Infection fatality risk of the pandemic A(H1N1)2009 virus in Hong Kong.

One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60-69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.

Delayed oseltamivir treatment is associated with longer viral shedding of pandemic (H1N1) 2009 virus.

During the early phase of the influenza pandemic in 2009, all cases of laboratory-confirmed pandemic (H1N1) 2009 (pH1N1) infection required compulsory isolation in hospital. These cases were offered oseltamivir treatment and only allowed to be discharged from the hospital when three consecutive respiratory specimens were negative for the virus by reverse transcription-polymerase chain reaction (RT-PCR). We reviewed the case records of these patients to assess the viral shedding kinetics of the pH1N1 virus. We defined viral shedding duration as the interval from illness onset date to the date of collection of the last positive specimen from the patients. Fifty-six patients were included in the study, of whom 96% received oseltamivir. The median viral shedding duration of pH1N1 virus by viral culture and RT-PCR were 3 days and 4 days, respectively. Patients who started oseltamivir treatment >48 h after onset had a significantly longer median viral shedding duration by viral culture than those who started treatment within 48 h of onset (4 days vs. 2 days, P=0·014).

A school outbreak of pandemic (H1N1) 2009 infection: assessment of secondary household transmission and the protective role of oseltamivir.

In mid-June 2009, an outbreak of pandemic (H1N1) 2009 (pH1N1) infection occurred in a secondary school in Hong Kong. We carried out an epidemiological investigation to delineate the characteristics of the outbreak, gauge the extent of secondary household transmission, and assess the protective role of oseltamivir in household contacts. We interviewed pH1N1-confirmed cases using a standardized questionnaire. Sixty-five of 511 students in the school were affected. Of the 205 household contacts identified, 12 were confirmed as cases. All cases recovered. The estimated secondary household attack rate was 5·9% (95% CI 2·7-9·1). Household contacts aged <18 years were about 15 times more likely to be infected than older contacts. Household contacts who had received oseltamivir prophylaxis were less likely to acquire a secondary infection than those who had not (odds ratio=0). The estimated mean household serial interval of pH1N1 virus was 2·8 days (95% CI 2·1-3·4 days).

Evaluation of sentinel surveillance system for monitoring hand, foot and mouth disease in Hong Kong.

OBJECTIVES: A sentinel surveillance system (SSS) was set up in Hong Kong to monitor hand, foot and mouth disease (HFMD) trends. This evaluation assessed the performance of the SSS from 2001 to 2009, and aimed to identify areas for improvement. STUDY DESIGN: A retrospective review using structured guidelines for evaluating public health surveillance systems published by the US Centers for Disease Control and Prevention. METHODS: The effectiveness of the SSS was evaluated using routine service statistics, laboratory surveillance data, and results of an acceptability survey conducted among the sentinel doctors. This information was used to assess various attributes of the SSS including simplicity, flexibility, data quality, usefulness, sensitivity, specificity, positive predictive value (PPV), representativeness, timeliness and acceptability. RESULTS: The SSS was simple and flexible with high-quality data. It correlated well with the laboratory surveillance data (P < 0.001) and facilitated early detection of community epidemics. It helped to identify seasonal trends and high-risk groups. Specificity was high (83.4-88.5%), while sensitivity and PPV were borderline satisfactory (38.4-56.8%). The sentinel clinics were representative of the population distribution. The SSS was acceptable to the sentinel doctors, but 17.9-28.2% of them had delays in reporting. CONCLUSIONS: The SSS is effective for monitoring HFMD trends in Hong Kong, and is useful for initiating preventive measures.

Is hand, foot and mouth disease associated with meteorological parameters?

We examined the relationship between meteorological parameters and hand, foot and mouth disease (HFMD) activity. Meteorological data collected from 2000 to 2004 were tested for correlation with HFMD consultation rates calculated through the sentinel surveillance system in Hong Kong. The regression model constructed was used to predict HFMD consultation rates for 2005-2009. After adjusting for the effect of collinearity, mean temperature, diurnal difference in temperature, relative humidity, and wind speed were positively associated with HFMD consultation rates, and explained HFMD consultation rates well with 2 weeks' lag time (R²=0·119, P=0·010). The predicted HFMD consultation rates were also also well matched with the observed rates (Spearman's correlation coefficient=0·276, P=0·000) in 2005-2009. Sensitivity analysis showed that HFMD consultation rates were mostly affected by relative humidity and least affected by wind speed. Our model demonstrated that climate parameters help in predicting HFMD activity, which could assist in explaining the winter peak detected in recent years and in issuing early warning.

Community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections in Hong Kong.

Community-associated methicillin resistant Staphylococcus aureus is an emerging cause of skin and soft tissue infections in Hong Kong, especially among certain ethnic minorities.

Effect of flap design on periodontal healing after impacted third molar extraction: a systematic review and meta-analysis.

The extraction of an impacted third molar violates the surrounding soft and bony tissues. The surgeon's access to the tooth, for which there are various surgical approaches, has an important impact on the periodontium of the adjacent second molar. The aim of this review was to analyze the relationships between the different flap techniques and postoperative periodontal outcomes for the mandibular second molars (LM2) adjacent to the impacted mandibular third molars (LM3). An electronic search of MEDLINE and other databases was conducted to identify randomized controlled trials fulfilling the eligibility criteria. To assess the impact of flap design on the periodontal condition, the weighted mean difference of the probing depth reduction (WDPDR) and the weighted mean difference of the clinical attachment level gain (WDCAG) at the distal surface of LM2 were used as the primary outcomes. The results showed that, overall, the different flap techniques had no significant impact on the probing depth reduction (WDPDR -0.14mm, 95% confidence interval -0.44 to 0.17), or on the clinical attachment level gain (WDCAG 0.05mm, 95% confidence interval -0.84 to 0.94). However, a subgroup analysis revealed that the Szmyd and paramarginal flap designs may be the most effective in reducing the probing depth in impacted LM3 extraction, and the envelope flap may be the least effective.

Predicting clustered dental implant survival using frailty methods.

The purpose of this study was to predict future implant survival using information on risk factors and on the survival status of an individual's existing implant(s). We considered a retrospective cohort study with 677 individuals having 2349 implants placed. We proposed to predict the survival probabilities using the Cox proportional hazards frailty model, with three important risk factors: smoking status, timing of placement, and implant staging. For a non-smoking individual with 2 implants placed, an immediate implant and in one stage, the marginal probability that 1 implant would survive 12 months was 85.8% (95%CI: 77%, 91.7%), and the predicted joint probability of surviving for 12 months was 75.1% (95%CI: 62.1%, 84.7%). If 1 implant was placed earlier and had survived for 12 months, then the second implant had an 87.5% (95%CI: 80.3%, 92.4%) chance of surviving 12 months. Such conditional and joint predictions can assist in clinical decision-making for individuals.

Consumption of viscera as the most important risk factor in the largest outbreak of shellfish poisoning in Hong Kong, 2005.

Poisoning from shellfish toxins is associated with significant morbidity worldwide. During 10-15 March 2005, 36 clusters of shellfish poisoning related to consumption of fresh scallops (Atrina vexillum) were reported to the Center for Health Protection, Department of Health Hong Kong. We conducted a case-control study to identify the risk factors associated with shellfish poisoning. Detailed demographic, clinical, shellfish consumption data of these subjects were collected using standardized questionnaires. Fifty-eight cases and 44 controls were identified. The mean age for the cases was 37.5 years (range 10-81 years); 45% (n=26) were male. Ninety-five percent had onset of symptoms within 12 hours of consumption of scallops (range: 10 minutes to 30 hours, median: 45 minutes). Dizziness (87.9%) and blurred vision (53.4%) were the predominant symptoms. The mean number of pieces of scallop meat and viscera taken by the cases were 3.7 and 3.6, respectively, significantly higher than that for the controls, which were 1.6 (p<0.001) and 0.5 (p<0.001), respectively. Forty-two percent (n=22) and 19% (n=7) of cases and controls, respectively, took soup/sauce from the same dish that was cooked with the scallops (p=0.02). Consumption of scallop viscera was identified as the only significant risk factor (Adjusted OR=9.93, p=0.001) after adjusting for other risk factors. The result show that consumption of scallop viscera is an important risk factor for shellfish poisoning. The public should be warned specifically in health education messages to avoid eating viscera of scallops.

Frailty approach for the analysis of clustered failure time observations in dental research.

Because dental implant failure patterns tend to cluster within subjects, we hypothesized that the risk of implant failure varies among subjects. To address this hypothesis in the setting of clustered, correlated observations, we considered a retrospective cohort study where we identified a cohort having at least one implant placed. The cohort was composed of 677 patients who had 2349 implants placed. To test the hypothesis, we applied an innovative analytic method, i.e., the Cox proportional hazards model with frailty, to account for correlation within subjects and the heterogeneity of risk, i.e., frailty, among subjects for implant failure. Consistent with our hypothesis, risk for implant failure among subjects varied to a statistically significantly degree (p=0.041). In addition, the risk for implant failure is significantly associated with several factors, including tobacco use, implant length, immediate implant placement, staging, well size, and proximity of adjacent implants or teeth.

Multi-center randomized clinical trials in oral and maxillofacial surgery: modeling of fixed and random effects.

The multi-center randomized clinical trial (MCCT) is an important tool to evaluate treatment of rare diseases. An important and challenging analytic consideration is how to model the variability of the set of clinical centers composing an MCCT. The purpose of this paper was to demonstrate how changing the assumptions regarding the variability (fixed effect versus random effect) of the set of clinical centers may alter the results. The data for this paper were derived from a recently completed MCCT. The MCCT was designed as a prospective, randomized clinical trial comparing the stability of two techniques, i.e., wire versus rigid internal fixation (RIF), for stabilizing the mandible after bilateral sagittal split ramus osteotomy (BSSO) for patients requiring mandibular advancement. Three treatment centers were involved. The key outcome variable was change in mandibular position (B-point) over time. We developed two different analytic models by varying the underlying statistical assumptions regarding the variability of the clinical treatment centers, i.e., random or fixed effects. Analyses based on the random-effects model demonstrated no significant difference between treatment groups in terms of relapse (P=0.13). With the fixed-effects model, however, wire fixation had significantly more relapse at B-point over time than RIF (P=0.02). The results from these two sets of analyses demonstrate how changing assumptions regarding the variability of the set of clinical centers can alter the interpretation of the treatment effect. The choice of statistical modeling of the set of clinical centers is an important consideration when performing analyses of MCCTs and it is a decision that should be made prior to initiating the study.

Identifying dental panoramic radiograph features for the screening of low bone mass in postmenopausal women.

A retrospective cohort study was performed to evaluate the use of panoramic radiographs as a screening tool for low bone mass in postmenopausal women. Female subjects aged ≥50 years were included. The predictor variables were gonial angle, antegonial angle, mandibular cortical bone integrity, periodontal disease status, and number of remaining teeth. The primary outcome variable was bone mineral density status. Descriptive and logistic regression statistics were computed; P<0.05 was considered significant. The sample was composed of 273 subjects, aged 50-89 years. Visual assessment of mandibular cortical bone integrity demonstrated a statistically significant correlation with low bone mass diagnosis on univariate logistic regression (P=0.019), but lost significance on multivariate analysis with age, body mass index, and number of remaining teeth (P=0.6). A visual estimation of the mandibular cortical bone integrity from panoramic radiographs may be useful for identifying postmenopausal women at high risk for osteoporosis.

Botulinum toxin therapy for temporomandibular joint disorders: a systematic review of randomized controlled trials.

The objective of this study was to undertake a systematic review to assess the efficacy of botulinum toxin therapy (BTX) for temporomandibular joint disorders (TMDs). A comprehensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014. Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of randomized controlled trials comparing BTX versus any alternative intervention or placebo. Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations. The entire systematic search and selection process was done independently by two reviewers. Five relevant study trials were identified, involving 117 participants. Two trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal efficacy of pain relief on TMDs, while the remaining two trials showed no significant difference between the BTX and placebo groups. Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed. Based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs. A more rigorous design of trials should be carried out in future studies.

Pharmacokinetics of metoprolol enantiomers in Chinese subjects of major CYP2D6 genotypes.

OBJECTIVE: CYP2D6 mediates both alpha-hydroxylation and O-demethylation of metoprolol. In Chinese subjects, CYP2D6*1 (the wild-type) alleles are relatively uncommon. Subjects with P34S (C188-->T188) and S486T (G4268-->C4268) mutations (CYP2D6J or CYP2D6*10A) are more frequently seen. Recently, the CYP2D6*2 (CYP2D6L) genotype that results in R296C (C2938-->T2938) and S486T mutations was also found important. In this study, metoprolol pharmacokinetics was investigated in subjects of these 3 major genotypes. METHODS: Allele-specific polymerase chain reaction was used to differentiate CYP2D6*1 and CYP2D6*2 alleles from the common CYP2D6*10A allele in Chinese. Subjects with both CYP2D6*1 and CYP2D6*2 have homozygous C188 in the exon 1, whereas subjects with CYP2D6*10A have T188. Metoprolol pharmacokinetics was compared in 16 C188 subjects (6 homozygous CYP2D6*1 subjects and 10 heterozygous CYP2D6*1/CYP2D6*2 subjects), 12 heterozygous C/T188 subjects, and 12 homozygous T188 subjects. RESULTS: No significant difference in plasma concentration profile or urinary alpha-hydroxymetoprolol excretion could be found among subjects with R296C polymorphism (CYP2D6*1/CYP2D6*2). Therefore data from subjects with CYP2D6*1 and CYP2D6*2 were pooled to compare with data from subjects with CTP2D6*10A. The area under plasma concentration curves (AUC) of S-metoprolol was 1411+/-116 (mean +/- SEM, n = 16), 1899+/-120 (n = 12), and 3588+/-435 (n = 12) nmol x hr/L for homozygous C188, heterozygous C/T188, and homozygous T188 subjects, respectively. The urinary recovery of all 4 alpha-hydroxymetoprolol diastereomers was significantly lower in T188 subjects than in C188 subjects. CONCLUSION: The P34S polymorphism but not the R296C polymorphism resulted in higher metoprolol plasma concentrations and lower urinary metoprolol metabolite levels in Chinese subjects. This finding suggests that a lower dose of metoprolol may be used in subjects with T188 mutation (CYP2D6*10A allele).

Predicting dental implant survival by use of the marginal approach of the semi-parametric survival methods for clustered observations.

The analyses of clustered survival observations within the same subject are challenging. This study's purpose was to compare and contrast predicted dental implant survival estimates assuming the independence or dependence of clustered observations. Using a retrospective cohort composed of 677 patients (2,349 implants), we applied an innovative analytic marginal approach to produce point and variance estimates of survival predictions given the covariates smoking status, implant staging, and timing of placement adjusted for clustered observations (dependence method). We developed a second model assuming independence of the clustered observations (naïve method). The 95% confidence intervals for survival prediction point estimates given the naive method were 5.9% to 14.3% more narrow than the dependence method estimates, resulting in an increased risk for type I error and erroneous rejection of the null hypothesis. To obtain statistically valid confidence intervals for survival prediction of the Aalen-Breslow estimates, we recommend adjusting for dependence among clustered survival observations.

Kaplan-Meier analysis of dental implant survival: a strategy for estimating survival with clustered observations.

The study's purposes were to estimate dental implant survival in a statistically valid manner and to compare three models for estimating survival. We estimated survival using three different statistical models: (1) randomly selecting one implant per patient; (2) utilizing all implants, assuming independence among implants from the same subject; and (3) utilizing all implants, assuming dependence among implants from the same subject. The cohort was composed of 660 patients who had 2286 implants placed. Due to the high success rates of implants, the five-year survival point and standard error estimates varied little among the three models. Patients at high risk for implant failure (smokers) manifested greater variation in the standard error estimates among the three models, 8.2%, 4.0%, and 5.6%, respectively. To obtain statistically valid survival confidence intervals when performing Kaplan-Meier survival analyses, we recommend adjusting for dependence when there are multiple observations within the same subject.

Risk factors for dental implant failure: a strategy for the analysis of clustered failure-time observations.

This study's objective was to identify, in a statistically valid and efficient manner, the risk factors associated with dental implant failure. We hypothesize that factors exist which can be modified by clinicians to enhance outcome. A retrospective cohort study design was used. Cohort members had >or= one implant placed. Risk factors were classified as demographic, health status, implant-, anatomic-, or prosthetic-specific, and reconstructive variables. The outcome variable was implant failure. The cohort was composed of 677 patients who had 2349 implants placed. Based on the adjusted multivariate model, factors associated with implant failure were tobacco use, implant length, staging, well size, and immediate implants (p

Botulinum toxin decreases salivation from canine submandibular glands.

The objective of this study was to determine whether botulinum toxin types A and D reduced the production of saliva from the submandibular glands of 18 dogs. The left submandibular glands of 8 dogs were injected with increasing doses of botulinum type A toxin (range 10 to 70 units), and the left glands of 10 dogs were injected with botulinum type D toxin (50 or 100 units). The right gland of each dog was injected with equivalent volumes of saline solution to serve as control. Six days after the injection, the lingual nerve was electrically stimulated for 10 minutes (3 mAmp, 20 Hz). The resulting volume of saliva was collected and weighed. Overall, the glands injected with types A or D toxin produced significantly less saliva than comparable glands injected with saline solution. Six of 8 dogs injected with type A toxin showed a significant decrease in saliva production (range 10.1% to 19.2%, one-sided p value = 0.0375) when compared with the controls. Nine of 10 dogs injected with type D toxin demonstrated a highly significant reduction in saliva production (total average decrease = 60%, two-sided pvalue = 0.001) when compared with the controls. We concluded that intraglandular injections of botulinum toxin types A and D significantly reduced the production of saliva from canine submandibular glands. The potential applications of intraglandular injections of botulinum toxin are discussed.

Epidemiologic study of sound surface trends in a 10-year longitudinal study.

Longitudinal data of 589 men aged 30-65 yr, each followed for 10 yr, were analyzed to identify variables which may be associated with healthy tooth surface loss. A longitudinal linear growth curve model was used. As expected, older cohorts tended to have fewer sound surfaces (P < 0.02), but they also tended to have greater rates of sound surface loss (P < 0.01). Age, bone loss, number of teeth at baseline, gingivitis, pocket depth and calculus were individually correlated (P < 0.05) with the rate of sound surface loss. The number of filled or diseased surfaces at baseline was also marginally correlated (P < 0.06) with rate of sound surface loss.

Longitudinal statistical models for loss of sound surfaces.

Longitudinal data of 50-yr-old men, followed for 10 yr, were analyzed to identify variables which may be associated with healthy tooth surface loss. Three types of longitudinal models were used, arriving at similar conclusions. Predictors of sound tooth surface loss with aging included pocket depth, mobility, and recession.