How are family doctors serving the Hong Kong community during the COVID-19 outbreak? A survey of HKCFP members.

INTRODUCTION: This study evaluated the preparedness of family doctors during the early phase of the coronavirus disease 2019 (COVID-19) outbreak in Hong Kong. METHODS: All members of the Hong Kong College of Family Physicians were invited to participate in a cross-sectional online survey using a 20-item questionnaire to collect information on practice preparedness for the COVID-19 outbreak through an email followed by a reminder SMS message between 31 January 2020 and 3 February 2020. RESULTS: Of 1589 family doctors invited, 491 (31%) participated in the survey, including 242 (49%) from private sector. In all, 98% surveyed doctors continued to provide clinical services during the survey period, but reduced clinic service demands were observed in 45% private practices and 24% public clinics. Almost all wore masks during consultation and washed hands between or before patient contact. Significantly more private than public doctors (80% vs 26%, P<0.001) experienced difficulties in stocking personal protective equipment (PPE); more public doctors used guidelines to manage suspected patients. The main concern of the respondents was PPE shortage. Respondents appealed for effective public health interventions including border control, quarantine measures, designated clinic setup, and public education. CONCLUSION: Family doctors from public and private sectors demonstrated preparedness to serve the community from the early phase of the COVID-19 outbreak with heightened infection control measures and use of guidelines. However, there is a need for support from local health authorities to secure PPE supply and institute public health interventions.

Inverse relationship between hepatic steatosis and hepatitis B viremia: Results of a large case-control study.

The potential interaction between chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD), two of the most prevalent liver diseases worldwide, has not been well defined. We performed liver stiffness (LS) and controlled attenuation parameter (CAP) measurements using transient elastography in 1202 CHB patients. Of these, 601 steatotic patients were matched with nonsteatotic controls in a 1:1 ratio by age, gender, nucleoside analogue treatment status, and treatment duration. Severe fibrosis was defined according to EASL-ALEH criteria, and steatosis was defined as CAP ≥222 dB m-1 . Anthropometric measurements and metabolic-related parameters were recorded. The mean age of the 1202 patients (51.4% male) was 51.8 years. 696 patients (57.9%) were on nucleoside analogues for a median duration of 76.2 months. Among treatment-naïve patients, median serum HBV DNA was lower in steatotic individuals than in controls (3.0 vs 3.4 log IU mL-1 , P < .05), with this inverse relationship remaining significant in multivariate analysis (odds ratio 0.859, 95% CI 0.743-0.994, P < .05). With increased steatosis severity, there was a stepwise decrease in median HBV DNA levels (3.1 and 2.6 log IU mL-1 in no steatosis and severe steatosis, respectively, P = .032). Steatosis was associated with a higher median LS (5.4 kPa vs 5.0 kPa, P < .001). Severe steatosis, when compared to mild/moderate steatosis, was associated with an increased percentage of severe fibrosis (23.2% and 12.6%, respectively, P = .005). We conclude that severe steatosis was associated with increased fibrosis in CHB patients. Increasing steatosis was independently associated with lower serum HBV DNA levels, suggesting its potential negative effects on viral replication.

GlpC gene is responsible for biofilm formation and defense against phagocytes and imparts tolerance to pH and organic solvents in Proteus vulgaris.

Biofilm-forming bacteria are highly resistant to antibiotics, host immune defenses, and other external conditions. The formation of biofilms plays a key role in colonization and infection. To explore the mechanism of biofilm formation, mutant strains of Proteus vulgaris XC 2 were generated by Tn5 random transposon insertion. Only one biofilm defective bacterial species was identified from among 500 mutants. Inactivation of the glpC gene coding an anaerobic glycerol-3-phosphate dehydrogenase subunit C was identified by sequence analysis of the biofilm defective strain. Differences were detected in the growth phenotypes of the wild-type and mutant strains under pH, antibiotic, and organic solvent stress conditions. Furthermore, we observed an increase in the phagocytosis of the biofilm defective strain by the mouse macrophage RAW264.7 cell line compared to the wild-type strain. This study shows that the glpC gene plays an important role in biofilm formation, in addition to imparting pH, organic solvent, and antibiotic tolerance, and defense against phagocytosis to Proteus sp. The results further clarified the mechanism of biofilm formation at the genomic level, and indicated the importance of the glpC gene in this process. This data may provide innovative therapeutic measures against P. vulgaris infections; furthermore, as an important crocodile pathogen, this study also has important significance in the protection of Chinese alligators.

Microfluidic quantum sensing platform for lab-on-a-chip applications.

Lab-on-a-chip (LOC) applications have emerged as invaluable physical and life sciences tools. The advantages stem from advanced system miniaturization, thus, requiring far less sample volume while allowing for complex functionality, increased reproducibility, and high throughput. However, LOC applications necessitate extensive sensor miniaturization to leverage these inherent advantages fully. Atom-sized quantum sensors are highly promising to bridge this gap and have enabled measurements of temperature, electric and magnetic fields on the nano- to microscale. Nevertheless, the technical complexity of both disciplines has so far impeded an uncompromising combination of LOC systems and quantum sensors. Here, we present a fully integrated microfluidic platform for solid-state spin quantum sensors, like the nitrogen-vacancy (NV) center in diamond. Our platform fulfills all technical requirements, such as fast spin manipulation, enabling full quantum sensing capabilities, biocompatibility, and easy adaptability to arbitrary channel and chip geometries. To illustrate the vast potential of quantum sensors in LOC systems, we demonstrate various NV center-based sensing modalities for chemical analysis in our microfluidic platform, ranging from paramagnetic ion detection to high-resolution microscale NV-NMR. Consequently, our work opens the door for novel chemical analysis capabilities within LOC devices with applications in electrochemistry, high-throughput reaction screening, bioanalytics, organ-on-a-chip, or single-cell studies.

Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation.

Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW (+)-iutA (+)-rmpA (+)-silS (+) than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.

Participation of the protein Go in multiple aspects of behavior in C. elegans.

The goa-1 gene encoding the alpha subunit of the heterotrimeric guanosine triphosphate-binding protein (G protein) Go from Caenorhabditis elegans is expressed in most neurons, and in the muscles involved in egg laying and male mating. Reduction-of-function mutations in goa-1 caused a variety of behavioral defects including hyperactive movement, premature egg laying, and male impotence. Expression of the activated Go alpha subunit (G alpha o) in transgenic nematodes resulted in lethargic movement, delayed egg laying, and reduced mating efficiency. Induced expression of activated G alpha o in adults was sufficient to cause these phenotypes, indicating that G alpha o mediates behavior through its role in neuronal function and the functioning of specialized muscles.

Sensory regulation of male mating behavior in Caenorhabditis elegans.

C. elegans male mating behavior comprises a series of steps: response to contact with the hermaphrodite, backing along her body, turning around her head or tail, location of the vulva, insertion of the two copulatory spicules into the vulva, and sperm transfer. By ablation of male-specific copulatory structures and their associated neurons, we have identified sensory structures and neurons that participate in each of these steps: the sensory rays mediate response to contact and turning; the hook, the postcloacal sensilla, and the spicules mediate vulva location; the spicules also mediate spicule insertion and regulate sperm transfer. Generally, successful completion of each step places the male in a position to receive a cue for the next step in the pathway. However, the high degree of sensory regulation allows the male to execute some steps independently.

Laser ablations reveal functional relationships of segmental hindbrain neurons in zebrafish.

Segmentation of the vertebrate brain is most obvious in the hindbrain, where successive segments contain repeated neuronal types. One such set of three repeated reticulospinal neurons--the Mauthner cell, MiD2cm, and MiD3cm--is thought to produce different forms of the escape response that fish use to avoid predators. We used laser ablations in larval zebrafish to test the hypothesis that these segmental hindbrain cells form a functional group. Killing all three cells eliminated short-latency, high-performance escape responses to both head- and tail-directed stimuli. Killing just the Mauthner cell affected escapes from tail-directed but not from head-directed stimuli. These results reveal the contributions of one set of reticulospinal neurons to behavior and support the idea that serially repeated hindbrain neurons form functional groups.

Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia.

BACKGROUND: Gut dysbiosis may contribute to pain and bloating in patients with functional gastrointestinal disease. AIMS: To determine if treatment with rifaximin would improve the symptoms of functional dyspepsia in Chinese patients in a double-blinded, randomised, placebo-controlled trial. METHODS: Consecutive subjects with a diagnosis of functional dyspepsia as per the Rome III criteria were randomised to receive rifaximin 400 mg or placebo, all taken three times daily for 2 weeks. The investigators and study subjects were blinded to the treatment allocation. Subjects were followed up for 8 weeks. The primary end point was adequate relief of global dyspeptic symptoms (GDS). Secondary endpoints were relief of individual dyspeptic symptoms. RESULTS: Eighty-six subjects were recruited. At week 8, there were significantly more subjects in the rifaximin than in the placebo group who experienced adequate relief of GDS (78% vs. 52%, P = 0.02). A trend favouring rifaximin group was also noted in the preceding 4 weeks. Rifaximin was also superior to placebo in providing adequate relief of belching and post-prandial fullness/bloating (PPF) in subjects at week 4. Subgroup analysis revealed that female subjects had more significant response to rifaximin treatment (adequate relief of GDS at week 4: 76% vs. 42%, P = 0.006; week 8: 79% vs. 47%, P = 0.008), as well as improvements in their belching and PPF at week 4. The incidences of adverse effects were similar in both groups. CONCLUSIONS: Treatment with 2 weeks of rifaximin led to adequate relief of global dyspeptic symptoms, belching and post-prandial fullness/bloating in subjects with functional dyspepsia. The difference was more marked in females. (clinicaltrials.org NCT01643083).

Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B.

BACKGROUND: Factors influencing changes in liver stiffness measurements during long-term nucleoside analogue therapy for chronic hepatitis B (CHB) have not been thoroughly investigated. AIM: To identify determinants of on-treatment fibrosis regression in CHB. METHODS: We performed follow-up liver stiffness and controlled attenuation parameter measurements on nucleoside analogue-treated CHB patients with severe liver fibrosis, according to EASL-ALEH criteria, diagnosed by transient elastography in 2006-2008. Anthropometric measurements and different metabolic parameters were recorded. RESULTS: Among 257 patients with severe liver fibrosis by initial transient elastography, 123 (47.9%) were recruited for reassessment. Median treatment duration was 87.5 (interquartile range 75.3-102.2) months; 97.5% had undetectable HBV DNA. There was a significant reduction in median liver stiffness from 14.6 to 8.3 kPa (P < 0.001). A total of 29.3% had fibrosis regression, with lower rates of 17.9%, 14.9% and 11.5% noted in patients with body-mass index (BMI) ≥25 kg/m2 , metabolic syndrome and diabetes, respectively. Absence of BMI ≥25 kg/m2 , diabetes and metabolic syndrome, when compared with presence of any one of these three factors, was associated with increased fibrosis regression (43.1% vs. 16.9%, P = 0.001). Multivariate analysis found a lower BMI to be the only factor independently associated with fibrosis regression (P = 0.034, odds ratio 0.68, 95% CI 0.48-0.97). No association was noted between controlled attenuation parameter measurements and fibrosis regression (P > 0.05). CONCLUSION: An increased BMI hindered fibrosis regression in patients with chronic hepatitis B during nucleoside analogue treatment, suggesting that control of metabolic risk factors, in addition to virologic suppression via antiviral therapy, might be needed to halt the fibrogenic process in chronic hepatitis B.

Irritant effects of formaldehyde exposure in mobile homes.

This paper reports the irritant effects associated with formaldehyde exposures in mobile homes. Week-long, integrated formaldehyde concentrations were measured using passive monitors in summer and winter while the mobile home residents continued their normal activities. Information on acute health problems, chronic respiratory/allergic illnesses, smoking behavior, demographic variables, and time spent at home was obtained on over 1000 individuals during the sampling period. Measured formaldehyde concentrations varied from under the limit of detection (0.01 ppm) to 0.46 ppm. Formaldehyde exposure was estimated for each individual by multiplying the concentration measured in his or her home by the time he or she spent at home. Irritant effects were found to be associated with formaldehyde exposure after controlling for age, sex, smoking status, and chronic illnesses using a logistic procedure. Some of the interaction terms found to be significant indicated that there were synergistic effects between formaldehyde exposure and chronic health problems.

Zebrafish as a model system for studying neuronal circuits and behavior.

Zebrafish are best known as a model system for studies of the genetics of development. They do, however, also offer many advantages for the study of neuronal circuitry because the larvae are transparent, allowing optical studies of neuronal activity and noninvasive photoablations of individual neurons. The combination of these optical methods with genetics through the use of mutant and transgenic lines of fish should make the zebrafish model a unique and powerful one among vertebrates. Here we review the strengths of the model and the possibilities it offers for studies of the neural basis of behavior.

Intent-to-treat analysis for longitudinal clinical trials: coping with the challenge of missing values.

Drop-out is a common phenomenon in clinical trials of drug treatments involving longitudinal assessments for a fixed duration of follow-up. For these trials intent-to-treat (IT) analysis is usually preferred because time effects are seen in practice. The IT analysis mandates that all subjects randomized to a treatment arm should be included in the analysis. The purpose of the present paper is to acquaint both clinicians and statisticians with recent statistical methodological advances in handling drop-outs and their usage for IT analysis. We discuss a sensitivity analysis of 12-month outcome data to investigate the efficacy of drug therapy from a longitudinal double-blind placebo-controlled clinical trial in the maintenance therapy of geriatric major depressive illness. Outcome measures consist of monthly Hamilton depression scores. The sensitivity analysis includes endpoint analysis, last observation carried forward analysis, repeated measures models and imputation models. Imputation models are based on multiple imputations of missing responses deriving from an 'as-treated' model. The model used imputed doses from a plausible treatment scenario after drop-out and a 'propensity-adjusted' model where the imputations for the drop-outs were obtained from the adhering subjects with the same probability to remain on study (propensity) given the observed trajectory prior to withdrawal. Issues related to bias and efficiency of the estimates obtained by different analyses are discussed. We recommend a more widespread use of imputation models for the IT analysis.

Correlation between meteorological conditions and mutagenicity of airborne particulate samples in a tropical monsoon climate area from Kaohsiung City, Taiwan.

Kaohsiung is a city of 1.5 million located in the southern part of Taiwan. It has a serious air pollution problem mainly attributable to much industrial and commercial activity. In order to estimate the effects of traffic, season, and meteorological conditions on the mutagenicity of Kaohsiung City's urban ambient particulate matter, 624 airborne particulate samples were collected on a weekly basis from 12 locations for an entire year. The mutagenic potential of acetone extracts of air samples was evaluated by the Salmonella/microsomal test with S. typhimurium TA98 in the presence and absence of S9 mixtures. The air samples from November 1990 showed the highest direct and indirect mutagenicity among the 12 months, whereas those from June and July 1991 had the lowest direct and indirect mutagenic activity, respectively. The mutagenicity showed a good correlation with amounts of the acetone extractable matter of airborne particulates. The meteorological conditions, monthly mean precipitation, and wind speed also showed a good correspondence with mutagenicity. Wind direction and temperature had a moderate relationship. The major mutagenic fractions of air samples that had the highest mutagenic activity in a month were purified using Sephadex LH-20 column chromatography, and the contents of PAHs, 1-NP, and DNPs were analyzed by HPLC. The characteristic concentration ratios of PAHs indicated that, for the main pollution sources of airborne particulates from Kaohsiung city, the mobile sources were more important than the stationary ones. The total amounts of 1-NP and DNPs in airborne particulates seemed to correspond to their mutagenicity. Although the total amounts of 1-NP and DNPs in the air samples correlated with their mutagenicity, the major mutagenic chemicals in the airborne particulate samples from Kaohsiung City need further investigation.

Dynamic effects of self-efficacy on smoking lapse and relapse.

Self-efficacy (SE) is thought to be critical to success in smoking cessation both as an individual difference and as a dynamic process after a quit attempt. In this study, 214 smokers used palm-top computers to record day-to-day variations in SE during 4 weeks after quitting. SE remained at high and stable levels prior to a 1st lapse but decreased and became more variable thereafter. The authors used event history models with time-varying covariates to assess the effect of daily SE on lapse and relapse risk. Daily SE measures predicted an initial lapse on the subsequent day. However, this relationship was accounted for by stable baseline differences in SE (assessed by questionnaire), rather than by day-to-day dynamics in SE. Progression from 1st lapse to relapse was also examined. In this instance, daily SE predicted subsequent relapse risk, even when baseline SE and concurrent smoking were accounted for, suggesting the importance of SE dynamics for this stage of the relapse process.

Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving.

AIMS: To compare a transdermal nicotine patch designed for 24-hour wear with one designed for 16-hour wear for relief of craving and withdrawal, particularly in the morning hours. DESIGN: Smokers were randomly assigned to use one of two common patch regimens: NicoDerm/NiQuitin (24-hour wear, 21 mg nicotine) or Nicotrol/Nicorette (16-hour wear, 15 mg). In a double-dummy design, participants wore two patches during the day, one active, one placebo and one patch while sleeping. SETTING: A smoking cessation research clinic. PARTICIPANTS: Two hundred and forty-four smokers who suffered morning cravings. INTERVENTION: Two patch formulations approved and marketed for over-the-counter use in the US--NicoDerm CQ (labeled as 21 mg over 24 hours) and Nicotrol (labeled as 15 mg over 16 hours)--were each used according to its instructions. Smokers also received behavioral counseling. MEASUREMENTS: For a week of baseline and 2 weeks after quitting, smokers used palm-top computers to assess craving and withdrawal symptoms several times each day. FINDINGS: The 21 mg/24-hour patch yielded consistently better control of craving, not only during the morning hours, but throughout the day, and over the 2-week period of abstinence. Additionally, the 21 mg/24-hour patch yielded greater reductions in anxiety, irritability and restlessness. Smokers using the 21 mg/24-hour dosing regimen also experienced longer abstinence than those using the 15 mg/16-hour patch. CONCLUSIONS: These findings demonstrate that 24-hour dosing with a 21 mg patch affords superior relief of craving and withdrawal during the first 2 weeks of abstinence, when symptoms are at their peak, and when relapse is most likely. They confirm the importance of dosing parameters in nicotine replacement products.

Identification and case management in an HMO of patients at risk of preterm labor.

We carried out a study of pregnant patients in a health maintenance organization to identify and provide case management of women at risk of preterm labor and to determine important risk factors for preterm labor in a managed care population. Data were collected on 794 women who completed an initial prenatal care visit at HealthAmerica of Pittsburgh between July 15, 1994, and March 31, 1995, and delivered at a local Pittsburgh hospital. The patients were assessed during an initial call to schedule their first prenatal visit and also at the 8- to 15-week and 24- to 28-week prenatal visits. Patients scoring 10 or higher on the risk assessment form were referred to a nurse case manager who provided education and support. Results of a logistic regression analysis suggest that the risk assessment tool was effective in identifying women at risk for preterm labor. "Physical/stressful work", as assessed by the patient, history of a prior preterm birth, and multiple gestation were all statistically significant predictors of preterm birth. Further research is needed to confirm the finding that physical or stressful work is a significant predictor of preterm births and to determine which aspects of the work may increase the patient's risk. This study was based on 8 months of data; however, additional program implementation is needed to evaluate fully the potential long-term benefits of the program.

The distribution of lifetime cumulative exposures to radon for California residents.

The distribution of individual lifetime exposures to radon was estimated using data from studies on radon concentrations, mobility, and time-activity patterns in the state of California. The distributions of radon concentrations in various geographic regions were obtained from the results of year-long radon measurements of 310 residences. The mobility patterns were acquired through a survey of the moving histories of the members of 507 households. The indoor and outdoor time-activity data were collected for 1,780 individuals in 1,596 households. Based on these data, a computer simulation technique was used to estimate the distribution of radon exposures with a parametric (lognormal model) and a nonparametric approach (bootstrap method). The estimated average lifetime exposure for radon was 2,448 Bq.m-3.yr for the lognormal model and 2,487 Bq.m-3.yr for the bootstrap method. The standard deviation was 1,130 and 1,145 Bq.m-3.yr respectively. Assuming no move over the lifetime, the estimated average lifetime exposure to radon was 2,052 Bq.m-3.yr for the lognormal model and 2,078 Bq.m-3.yr for the bootstrap method, while the standard deviation increased to 1,378 Bq.m-3.yr for the lognormal model and 1,514 Bq.m-3.yr for the bootstrap method.