Prevalence of oral human papillomavirus infection among the general adult population in Hong Kong.

A cross-sectional study in 2021-23 collected oral rinse gargle samples from an human papillomaviruses (HPV) vaccine-naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self-administered questionnaire. Altogether, 2323 subjects aged 18-75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high-risk, and low-risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45-54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.

Determining meteorologically-favorable zones for seasonal influenza activity in Hong Kong.

Investigations of simple and accurate meteorology classification systems for influenza epidemics, particularly in subtropical regions, are limited. To assist in preparing for potential upsurges in the demand on healthcare facilities during influenza seasons, our study aims to develop a set of meteorologically-favorable zones for epidemics of influenza A and B, defined as the intervals of meteorological variables with prediction performance optimized. We collected weekly detection rates of laboratory-confirmed influenza cases from four local major hospitals in Hong Kong between 2004 and 2019. Meteorological and air quality records for hospitals were collected from their closest monitoring stations. We employed classification and regression trees to identify zones that optimize the prediction performance of meteorological data in influenza epidemics, defined as a weekly rate > 50th percentile over a year. According to the results, a combination of temperature > 25.1℃ and relative humidity > 79% was favorable to epidemics in hot seasons, whereas either temperature < 16.4℃ or a combination of < 20.4℃ and relative humidity > 76% was favorable to epidemics in cold seasons. The area under the receiver operating characteristic curve (AUC) in model training achieved 0.80 (95% confidence interval [CI], 0.76-0.83) and was kept at 0.71 (95%CI, 0.65-0.77) in validation. The meteorologically-favorable zones for predicting influenza A or A and B epidemics together were similar, but the AUC for predicting influenza B epidemics was comparatively lower. In conclusion, we established meteorologically-favorable zones for influenza A and B epidemics with a satisfactory prediction performance, even though the influenza seasonality in this subtropical setting was weak and type-specific.

Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization.

BACKGROUND & AIMS: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.

Laboratory testing for the diagnosis of COVID-19.

Rapid and accurate laboratory diagnosis of active COVID-19 infection is one of the cornerstones of pandemic control. With the myriad of tests available in the market, the use of correct specimen type and laboratory-testing technique in the right clinical scenario could be challenging for non-specialists. In this mini-review, we will discuss the difference in diagnostic performance for different upper and lower respiratory tract specimens, and the role of blood and fecal specimens. We will analyze the performance characteristics of laboratory testing techniques of nucleic acid amplification tests, antigen detection tests, antibody detection tests, and point-of-care tests. Finally, the dynamics of viral replication and antibody production, and laboratory results interpretation in conjunction with clinical scenarios will be discussed.

Prospective Study Comparing Deep Throat Saliva With Other Respiratory Tract Specimens in the Diagnosis of Novel Coronavirus Disease 2019.

BACKGROUND: Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. METHODS: We performed a prospective study in 2 regional hospitals in Hong Kong. RESULTS: We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62-0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum. CONCLUSIONS: Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.

SARS-CoV-2 RNA Detection on Disposable Wooden Chopsticks, Hong Kong.

We detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on disposable wooden chopsticks used by 5 consecutive asymptomatic and postsymptomatic patients admitted for isolation and care at our hospital. Although we did not assess virus viability, our findings may suggest potential for transmission through shared eating utensils.

From SARS to Avian Influenza Preparedness in Hong Kong.

The first human H5N1 case was diagnosed in Hong Kong in 1997. Since then, experience in effective preparedness strategies that target novel influenza viruses has expanded. Here, we report on avian influenza preparedness in public hospitals in Hong Kong to illustrate policies and practices associated with control of emerging infectious diseases. The Hong Kong government's risk-based preparedness plan for influenza pandemics includes 3 response levels for command, control, and coordination frameworks for territory-wide responses. The tiered levels of alert, serious, and emergency response enable early detection based on epidemiological exposure followed by initiation of a care bundle. Information technology, laboratory preparedness, clinical and public health management, and infection control preparedness provide a comprehensive and generalizable preparedness plan for emerging infectious diseases.

Molecular Identification of Spirometra erinaceieuropaei Tapeworm in Cases of Human Sparganosis, Hong Kong.

Human sparganosis is a foodborne zoonosis endemic in Asia. We report a series of 9 histologically confirmed human sparganosis cases in Hong Kong, China. All parasites were retrospectively identified as Spirometra erinaceieuropaei. Skin and soft tissue swelling was the most common symptom, followed by central nervous system lesions.

Activity of temocillin and 15 other agents, including fosfomycin and colistin, against Enterobacteriaceae in Hong Kong.

Limited data are available on temocillin susceptibilities in Enterobacteriaceae from Asian countries where antimicrobial resistance is prevalent. The in vitro activities of temocillin and 15 commonly used antimicrobials against 613 non-duplicate blood (n = 310) and urine (with clinically significant bacteriuria; n = 303) isolates of Enterobacteriaceae from patients who attended 3 out of 7 clusters of public hospitals of the Hospital Authority, Hong Kong, during 2015/2016 were tested. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) microbroth dilution (agar dilution with fosfomycin). For temocillin, MICs were also obtained using the British Society of Antimicrobial Chemotherapy (BSAC) microbroth dilution method and interpreted using the BSAC breakpoints. Overall, 93.0% (570) isolates were susceptible to temocillin using BSAC systemic breakpoint (≤8 mg/L) and all except 2 isolates were susceptible using the urinary breakpoint (≤32 mg/L). The extended spectrum beta-lactamase (ESBL) positivity rate was 23.2% (118 out of 508 E. coli, Klebsiella spp., Proteus spp.). Temocillin resistance rate to ESBL-positive isolates was 16.1% using the systemic breakpoint of ≤8 mg/L (MIC50 and MIC90 were 8 mg/L and 16 mg/L respectively). Two isolates (1 E. coli, temocillin MIC 64 mg/L, 1 Klebsiella sp., MIC 32 mg/mL) were resistant to meropenem and possessed the NDM-5 and KPC-2 genes respectively. Other susceptibility rates were: amoxicillin/clavulanate (59.1%), trimethoprim/sulfamethoxazole (62.5%), ciprofloxacin (71.5%), ceftriaxone (75.4%), nitrofurantoin (76.4%), gentamicin (78.3%), cefepime (81.1%), ceftazidime (83.5%), piperacillin/tazobactam (86%), colistin (88.8%), tigecycline (89.4%), fosfomycin (92.8%), ertapenem (99.0%), amikacin (99.2%) and meropenem (99.7%). Temocillin may be a useful alternative for the treatment of infections caused by ESBL and multi-drug-resistant Enterobacteriaceae in Hong Kong, particularly as resistance rates to ciprofloxacin, nitrofurantoin and piperacillin/tazobactam are high.

Cutaneous hyalohyphomycosis due to Parengyodontium album gen. et comb. nov.

"Engyodontium album" is an environmental saprobic mould and an emerging opportunistic pathogen able to cause both superficial and systemic infections. In this study, we isolated a mould from the skin lesion biopsy specimen of the right shin in a patient who received renal transplantation for end-stage renal failure with prednisolone, tacrolimus, and azathioprine immunosuppressant therapy. Histology of the skin biopsy showed mild squamous hyperplasia and neutrophilic infiltrate in the epidermis, active chronic inflammation in the dermis, and fat necrosis in the subcutis, with numerous fungal elements within the serum crusts. On Sabouraud glucose agar, the fungus grew as white, cobweb-like, floccose colonies. Microscopically, conidiogenous cells were arranged in whorls of one to seven at wide angles, with zigzag-shaped terminal fertile regions and smooth, hyaline, oval, apiculate conidia. DNA sequencing showed the mould isolate belonged to "E. album" but matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) failed to identify the isolate. Phylogenetic analyses based on the internal transcribed spacer region, 28S nuclear ribosomal DNA, and ß-tubulin gene and MALDI-TOF MS coupled with hierarchical cluster analysis showed that "E. album" is distantly related to other Engyodontium species and should be transferred to a novel genus within the family Cordycipitaceae, for which the name Parengyodontium album gen. et comb. nov. is proposed. Three potential cryptic species within this species complex were also revealed. Antifungal susceptibility testing showed posaconazole and voriconazole had high activities against all clinical P. album isolates and may be better drug options for treating P. album infections.

Allergy in Hong Kong: an unmet need in service provision and training.

Many children in Hong Kong have allergic diseases and epidemiological data support a rising trend. Only a minority of children will grow out of their allergic diseases, so the heavy clinical burden will persist into adulthood. In an otherwise high-quality health care landscape in Hong Kong, allergy services and training are a seriously unmet need. There is one allergy specialist for 1.5 million people, which is low not only compared with international figures, but also compared with most other specialties in Hong Kong. The ratio of paediatric and adult allergists per person is around 1:460 000 and 1:2.8 million, respectively, so there is a severe lack of adult allergists, while the paediatric allergists only spend a fraction of their time working with allergy. There are no allergists and no dedicated allergy services in adult medicine in public hospitals. Laboratory support for allergy and immunology is not comprehensive and there is only one laboratory in the public sector supervised by accredited immunologists. These findings clearly have profound implications for the profession and the community of Hong Kong and should be remedied without delay. Key recommendations are proposed that could help bridge the gaps, including the creation of two new pilot allergy centres in a hub-and-spoke model in the public sector. This could require recruitment of specialists from overseas to develop the process if there are no accredited allergy specialists in Hong Kong who could fulfil this role.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

Chronic post-COVID neuropsychiatric symptoms persisting beyond one year from infection: a case-control study and network analysis.

Our study aims to delineate the phenotypes of chronic neuropsychiatric symptoms among adult subjects recovering from their first COVID that occurred more than one year ago. We also aim to explore the clinical and socioeconomic risk factors of having a high loading of chronic neuropsychiatric symptoms. We recruited a post-COVID group who suffered from their first pre-Omicron COVID more than a year ago, and a control group who had never had COVID. The subjects completed app-based questionnaires on demographic, socioeconomic and health status, a COVID symptoms checklist, mental and sleep health measures, and neurocognitive tests. The post-COVID group has a statistically significantly higher level of fatigue compared to the control group (p < 0.001). Among the post-COVID group, the lack of any COVID vaccination before the first COVID and a higher level of material deprivation before the COVID pandemic predicts a higher load of chronic post-COVID neuropsychiatric symptoms. Partial correlation network analysis suggests that the chronic post-COVID neuropsychiatric symptoms can be clustered into two major (cognitive complaints -fatigue and anxiety-depression) and one minor (headache-dizziness) cluster. A higher level of material deprivation predicts a higher number of symptoms in both major clusters, but the lack of any COVID vaccination before the first COVID only predicts a higher number of symptoms in the cognitive complaints-fatigue cluster. Our result suggests heterogeneity among chronic post-COVID neuropsychiatric symptoms, which are associated with the complex interplay of biological and socioeconomic factors.

Extent of Oral-Gut Transmission of Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Recent studies have provided evidence on the presence of an oral-gut microbiota axis in gastrointestinal diseases; however, whether a similar axis exists in healthy individuals is still in debate. Here, we characterized the bacterial and fungal microbiomes in paired oral rinse and stool samples collected from 470 healthy Chinese adults by sequencing the 16S rRNA V3-V4 and ITS1 regions, respectively. We hypothesized that there is limited oral-gut transmission of both the bacterial and fungal microbiota in healthy Chinese adults. Our results showed that the oral and gut microbiota in healthy individuals differed in taxonomic composition, alpha and beta diversity, metabolic potential, and network properties. Bayesian analysis showed that the vast majority of subjects had negligible or low bacterial and fungal oral-to-stool contribution. Detailed examination of the prevalent amplicon sequence variants (ASVs) also revealed limited cases of sharing between the oral and stool samples within the same individuals, except a few bacterial and fungal ASVs. Association analysis showed that sharing of the potentially transmissible fungal ASVs was associated with host factors, including an older age and a higher body mass index. Our findings indicate that oral-gut transmission of both bacterial and fungal microbiota in healthy adults is limited. Detection of a large amount of shared bacterial or fungal members between the oral and gut microbiome of an individual may indicate medical conditions that warrant detailed checkup. IMPORTANCE The oral-gut microbiota axis in health is a fundamentally important and clinically relevant topic; however, our current understanding of it remains biased and incomplete. By characterizing the bacterial and fungal microbiomes in paired oral rinse and stool samples from a large cohort of healthy Chinese adults, here we provided new evidence that oral-gut microbiota transmission is limited in non-Western population and across biological domains. Our study has established an important baseline of a healthy oral-gut microbiota axis, with which other disease conditions can be compared. Besides, our findings have practical implications that detection of a large amount of shared bacterial or fungal members between the oral cavity and gut within the same individual as an indicator of potential medical conditions.

Alterations in faecal microbiome and resistome in Chinese international travellers: a metagenomic analysis.

BACKGROUND: International travel increases the risk of acquisition of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Previous studies have characterized the changes in the gut microbiome and resistome of Western travellers; however, information on non-Western populations and the effects of travel-related risk factors on the gut microbiome and resistome remains limited. METHODS: We conducted a prospective observational study on a cohort of 90 healthy Chinese adult residents of Hong Kong. We characterized the microbiome and resistome in stools collected from the subjects before and after travelling to diverse international locations using shotgun metagenomic sequencing and examined their associations with travel-related variables. RESULTS: Our results showed that travel neither significantly changed the taxonomic composition of the faecal microbiota nor altered the alpha (Shannon) or beta diversity of the faecal microbiome or resistome. However, travel significantly increased the number of ARGs. Ten ARGs, including aadA, TEM, mgrB, mphA, qnrS9 and tetR, were significantly enriched in relative abundance after travel, eight of which were detected in metagenomic bins belonging to Escherichia/Shigella flexneri in the post-trip samples. In sum, 30 ARGs significantly increased in prevalence after travel, with the largest changes observed in tetD and a few qnrS variants (qnrS9, qnrS and qnrS8). We found that travel to low- or middle-income countries, or Africa or Southeast Asia, increased the number of ARG subtypes, whereas travel to low- or middle-income countries and the use of alcohol-based hand sanitizer (ABHS) or doxycycline as antimalarial prophylaxis during travel resulted in increased changes in the beta diversity of the faecal resistome. CONCLUSIONS: Our study highlights travel to low- or middle-income countries, Africa or Southeast Asia, a long travel duration, or the use of ABHS or doxycycline as antimalarial prophylaxis as important risk factors for the acquisition/enrichment of ARGs during international travel.

Characterization of upper airway microbiome across severity of COVID-19 during hospitalization and treatment.

Longitudinal studies on upper respiratory tract microbiome in coronavirus disease 2019 (COVID-19) without potential confounders such as antimicrobial therapy are limited. The objective of this study is to assess for longitudinal changes in the upper respiratory microbiome, its association with disease severity, and potential confounders in adult hospitalized patients with COVID-19. Serial nasopharyngeal and throat swabs (NPSTSs) were taken for 16S rRNA gene amplicon sequencing from adults hospitalized for COVID-19. Alpha and beta diversity was assessed between different groups. Principal coordinate analysis was used to assess beta diversity between groups. Linear discriminant analysis was used to identify discriminative bacterial taxa in NPSTS taken early during hospitalization on need for intensive care unit (ICU) admission. A total of 314 NPSTS samples from 197 subjects (asymptomatic = 14, mild/moderate = 106, and severe/critical = 51 patients with COVID-19; non-COVID-19 mechanically ventilated ICU patients = 11; and healthy volunteers = 15) were sequenced. Among all covariates, antibiotic treatment had the largest effect on upper airway microbiota. When samples taken after antibiotics were excluded, alpha diversity (Shannon, Simpson, richness, and evenness) was similar across severity of COVID-19, whereas beta diversity (weighted GUniFrac and Bray-Curtis distance) remained different. Thirteen bacterial genera from NPSTS taken within the first week of hospitalization were associated with a need for ICU admission (area under the receiver operating characteristic curve, 0.96; 95% CI, 0.91-0.99). Longitudinal analysis showed that the upper respiratory microbiota alpha and beta diversity was unchanged during hospitalization in the absence of antimicrobial therapy.

Longitudinal monitoring reveals the emergence and spread of blaGES-5-harboring carbapenem-resistant Klebsiella quasipneumoniae in a Hong Kong hospital wastewater discharge line.

Testing hospital wastewater (HWW) is potentially an effective, long-term approach for monitoring trends in antimicrobial resistance (AMR) patterns in health care institutions. Over a year, we collected wastewater samples from the clinical and non-clinical sites of a tertiary hospital and from a downstream wastewater treatment plant (WWTP). We focused on the extent of carbapenem resistance among Enterobacteriaceae isolates given their clinical importance. Escherichia coli and Klebsiella spp. were the most frequently isolated Enterobacteriaceae species at all sampling sites. Additionally, a small number of isolates belonging to ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), except K. pneumoniae, were detected. Of the 232 Klebsiella spp. isolates, 100 (43.1 %) were multi-drug resistant (MDR), with 46 being carbapenem-resistant. Most of these carbapenem-resistant isolates were K. quasipneumoniae (CRKQ) (n = 44). All CRKQ isolates were isolated from the wastewater of a clinical site that includes intensive care units, which also yielded significantly more multi-drug resistant isolates compared to all other sampling sites. Among the CRKQ isolates, blaGES-5 genes (n = 42) were the primary genetic determinant of carbapenem resistance. Notably, three different CRKQ isolates, collected within the same month in HWW and the influent and effluent flow of the WWTP, shared >99 % sequence similarity between their blaGES-5 genes and between their flanking regions and upstream integron-integrase region. The influent isolate was phylogenetically close to K. quasipnuemoniae isolates from wastewater collected in Japan. Its blaGES-5 gene and surrounding sequences were > 99 % identical to blaGES-24 genes found in the Japanese isolates. Our results suggest that testing samples from sites located closer to hospitals could support antibiotic stewardship programs compared to samples collected further downstream. Moreover, testing samples collected regularly from WWTPs may reflect the local and global spread of pathogens and their resistances.

Evaluation of the asthma control test: a reliable determinant of disease stability and a predictor of future exacerbations.

BACKGROUND AND OBJECTIVE: This study assessed the asthma control test (ACT) cut-off values for asthma control according to the Global Initiative for Asthma guideline in adults and the effectiveness of ACT scores in predicting exacerbations and serial changes in ACT scores over time in relation to treatment decisions. METHODS: Subjects completed ACT together with same-day spirometry and fractional concentration of exhaled nitric oxide (FeNO) measurement at baseline and at 3 months. Physicians, blinded to the ACT scores and FeNO values, assessed the patient's asthma control in the past month and adjusted the asthma medications according to management guidelines. Asthma exacerbations and urgent health-care utilization (HCU) at 6 months were recorded. RESULTS: Three hundred seventy-nine (120 men) asthmatics completed the study. The ACT cut-off for uncontrolled and partly controlled asthma were ≤19 (sensitivity 0.74, specificity 0.67, % correctly classified 69.5) and ≤22, respectively (sensitivity 0.73, specificity 0.71, % correctly classified 72.1). Baseline ACT score had an odds ratio of 2.34 (95% confidence interval: 1.48-3.69) and 2.66 (1.70-4.18) for urgent HCU and exacerbations, respectively, at 6 months (P < 0.0001). However, baseline FeNO and spirometry values had no association with urgent HCU and exacerbations. The 3-month ACT score of ≤20 correlated best with step-up of asthma medications (sensitivity 0.65, specificity 0.81, % correctly classified 72.8). For serial changes of ACT scores over 3 months, the cut-off value was best at ≤3 for treatment decisions with low sensitivity (0.23) and % correctly classified (57.3%) values. CONCLUSIONS: Single measurement of ACT is useful for assessing asthma control, prediction of exacerbation and changes in treatment decisions.

Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three.

RATIONALE: There is epidemiological evidence that the use of acetaminophen may increase the risk of developing asthma. OBJECTIVES: To investigate the risk of asthma and other allergic disorders associated with the current use of acetaminophen in 13- to 14-year-old children in different populations worldwide. METHODS: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, 13- to 14-year-old children completed written and video questionnaires obtaining data on current symptoms of asthma, rhinoconjunctivitis, and eczema, and a written environmental questionnaire obtaining data on putative risk factors, including acetaminophen use in the past 12 months. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the odds ratio (OR) of current asthma symptoms associated with acetaminophen use calculated by logistic regression. A total of 322,959 adolescent children from 113 centers in 50 countries participated. In the multivariate analyses the recent use of acetaminophen was associated with an exposure-dependent increased risk of current asthma symptoms (OR, 1.43 [95% confidence interval, 1.33-1.53] and 2.51 [95% confidence interval, 2.33-2.70] for medium and high versus no use, respectively). Acetaminophen use was also associated with an exposure-dependent increased risk of current symptoms of rhinoconjunctivitis and eczema. CONCLUSIONS: Acetaminophen use may represent an important risk factor for the development and/or maintenance of asthma, rhinoconjunctivitis, and eczema in adolescent children.

Overcoming the rising incidence and evolving mechanisms of antibiotic resistance by novel drug delivery approaches - An overview.

Antimicrobial resistance is a normal evolutionary process for microorganisms. Antibiotics exerted accelerated selective pressure that hasten bacterial resistance through mutation, and acquisition external genes. These genes often carry multiple antibiotic resistant determinants allowing the recipient microbe an instant "super-bug" status. The extent of Antimicrobial Resistance (AMR) has reached a level of global crisis, existing antimicrobials are no long effective in treating infections caused by AMR pathogens. The great majority of clinically available antimicrobial agents are administered through oral and intra-venous routes. Overcoming antibacterial resistance by novel drug delivery approach offered new hopes, particularly in the treatment of AMR pathogens in sites less assessible through systemic circulation such as the lung and skin. In the current review, we will revisit the mechanism and incidence of important AMR pathogens. Finally, we will discuss novel drug delivery approaches including novel local antibiotic delivery systems, hybrid antibiotics, and nanoparticle-based antibiotic delivery systems.