Impacts of Catch-Up Immunization program with the 13-Valent pneumococcal Conjugate vaccine in Taiwan: Focus on age-stratified differences and high-risk population (2001-2015).

BACKGROUND: Taiwan commenced a national catch-up immunization program with a 13-valent pneumococcal conjugate vaccine (PCV13) in 2013 for children aged 2-5 years old and in 2014 for children aged 1-5 years old. However, real-world nationwide evidence of both the direct protection and indirect protection of all-cause pneumonia and pneumococcal pneumonia has been scarce, especially among high-risk populations, defined as patients with chronic diseases or immunosuppression. The aim of this study was to examine the impact of the national PCV13 catch-up program on all-cause pneumonia and pneumococcal pneumonia among overall and high-risk populations using interrupted time series analysis. METHODS: Using the National Health Insurance Research Database (NHIRD) from January 2001 to December 2015, we assessed the impact of this catch-up program by interrupted time-series analyses age-stratified (0-1, 2-4, 5-9, 10-17, 18-34, 35-49, 50-64, 65 + years old) incidence of pneumococcal pneumonia and all-cause pneumonia (100,000 person-quarter) among the overall and high-risk populations. RESULTS: The impact of this program was most profound on the incidence of pneumococcal pneumonia in children aged 2-4 years old (level change -10.56 per 100,000 person-quarters, p = 0.04; trend change -2.93, p less than 0.01). Indirect protection among unvaccinated children (0-1 years old: trend change -1.19, p = 0.01; 5-9 years old: trend change -1.04, p = 0.03; 10-17 years old: level change -1.42 per 100,000 person-quarters, p = 0.03) was also found. The incidence of all-cause pneumonia also decreased in children aged 2-4 (level change -234.91 per 100,000 person-quarter, p = 0.058) and 5-9 years old (level change -173.96 per 100,000 person-quarter, p = 0.0424). However, we did not find a significant impact among most high-risk populations. CONCLUSIONS: Our study suggests that the introduction of this catch-up program with PCV13 was associated with significant declines in the incidence of pneumococcal pneumonia and all-cause pneumonia in vaccinated children, and indirect protection from the program was also found in unvaccinated children.

Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome.

To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).

Quantitative Detection of the Foot-And-Mouth Disease Virus Serotype O 146S Antigen for Vaccine Production Using a Double-Antibody Sandwich ELISA and Nonlinear Standard Curves.

The efficacy of an inactivated foot-and-mouth disease (FMD) vaccine is mainly dependent on the integrity of the foot-and-mouth disease virus (FMDV) particles. At present, the standard method to quantify the active component, the 146S antigen, of FMD vaccines is sucrose density gradient (SDG) analysis. However, this method is highly operator dependent and difficult to automate. In contrast, the enzyme-linked immunosorbent assay (ELISA) is a time-saving technique that provides greater simplicity and sensitivity. To establish a valid method to detect and quantify the 146S antigen of a serotype O FMD vaccine, a double-antibody sandwich (DAS) ELISA was compared with an SDG analysis. The DAS ELISA was highly correlated with the SDG method (R2 = 0.9215, P<0.01). In contrast to the SDG method, the DAS ELISA was rapid, robust, repeatable and highly sensitive, with a minimum quantification limit of 0.06 µg/mL. This method can be used to determine the effective antigen yields in inactivated vaccines and thus represents an alternative for assessing the potency of FMD vaccines in vitro. But it still needs to be prospectively validated by analyzing a new vaccine preparation and determining the proper protective dose followed by an in vivo vaccination-challenge study to confirm the ELISA findings.

The effects of different epidural analgesia formulas on labor and mode of delivery in nulliparous women.

OBJECTIVES: Patient-controlled epidural analgesia (PCEA) and continuous epidural infusion (CEI) are popular and effective methods for pain relief during labor; however, there are concerns about increasing rates of cesarean section (C/S) and instrumental delivery. This prospective study investigated the effect of PCEA and CEI with different formulas on labor and the mode of delivery in nulliparous women. MATERIALS AND METHODS: A total of 480 nulliparous women were randomized into four groups, with 120 in each. Group A received a loading dose of 10 mL of 1 mg/mL ropivacaine with 2 µg/mL fentanyl, then an intermittent bolus of 5 mL with a background infusion of 5 mL/hour by PCEA. Group B received the same PCEA formula as Group A with 0.8 mg/mL bupivacaine. Group C received the same formula as Group A by CEI with 1 mg/mL ropivacaine at a rate of 10 mL/hour. Group D received the same formula as Group C with 0.8 mg/mL bupivacaine. The rates of C/S and instrumental delivery and the incidence of side effects were recorded. RESULTS: The rates of C/S were significantly different between Groups A and C, Groups A and D, and Groups B and D. The rates of instrumental delivery for normal spontaneous delivery were significantly different between Groups A and B, A and D, B and C, and C and D. CONCLUSION: The C/S rate was higher in Groups C and D; however, the instrumental delivery rate was lower in Groups A and C. We conclude that PCEA with 1 mg/mL ropivacaine might provide the greatest benefit for labor analgesia.

Doppler measurement of the changes of fetal umbilical and middle cerebral artery velocimetric indices during continuous epidural labor analgesia.

OBJECTIVE: Although complications of the epidural technique are known to affect the fetus adversely, there are no data indicating that regional analgesia directly causes harmful effects to the fetus. Our purpose was to determine the effect of epidural labor analgesia on the Doppler velocimetric indices of the uterine and fetal umbilical and middle cerebral arteries. METHODS: Doppler velocimetry indices, systolic/diastolic ratios, pulsatility index, and resistance index, of the fetal umbilical artery and uterine artery were recorded in 15 women receiving continuous epidural analgesia with 0.075% bupivacaine and 0.0002% fentanyl during labor; the same indices were recorded of the fetal umbilical and middle cerebral arteries in 10 women receiving the same analgesia. The cerebroplacental Doppler ratio was calculated. Maternal and neonatal outcome data were also recorded. RESULTS: Velocimetric indices of the fetal umbilical and middle cerebral artery after epidural infusion were not significantly different from the pre-epidural infusion levels. Indices of the maternal uterine artery were significantly increased after epidural infusion. The cerebroplacental ratio did not change after the beginning of epidural infusion. Neonatal outcome parameters (1- and 5-min Apgar scores) were all within normal limits. CONCLUSIONS: These data suggest that although velocimetric indices of the maternal uterine artery are affected by continuous epidural labor analgesia, fetal circulation, as measured by Doppler velocimetric indices, is not altered.

Development and validation of a prokaryotically expressed foot-and-mouth disease virus non-structural protein 2C'3AB-based immunochromatographic strip to differentiate between infected and vaccinated animals.

BACKGROUND: Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cattle, pigs, sheep, goats, and many cloven-hoofed wild animals. FMDV serotypes O and Asia 1 have circulated separately in China during the last fifty years, and eliminating infected animals and vaccination are the main policies to prevent and control FMD. Antibodies to NSPs exist in infected animals, and were utilized to differentiate between infected and vaccinated animals. The reliability of detection of 3AB or 3ABC antibodies is higher than that of other NSPs. The test of 3AB is still credible because 3C protein's immunogenicity is the weakest. The 2C protein, immediately N-terminal of 3AB, was used to differentiate between infected and vaccinated animals. The use of the immunochromatographic strip is facile for clinical laboratories lacking specialized equipment and for rapid field diagnosis. RESULTS: In this study, an immunochromatographic strip with non-structural protein (NSP) 2C'3AB was developed and validated to differentiate foot-and-mouth disease infected from vaccinated animals. A part of N-terminal of 2C protein gene and whole 3AB gene were connected and prokaryotically expressed as the antigens labeled with colloidal gold was used as the detector, the 2C'3AB protein and rabbits anti-2C'3AB antibodies were blotted on the nitrocellulose(NC) membrane for the test and control lines, respectively. 387 serum samples were collected to evaluate the characteristics of the strip in comparison with existing commercial 3ABC antibody ELISA kit. The coincidence rate of pigs negative serum, pigs vaccinated serum, pigs infected serum was 100%, 97.2%, 95.0%, respectively. The coincidence rate of cattle negative serum, cattle vaccinated serum, cattle infected serum was 100%, 96.7%, 98.0%, respectively. The coincidence rate of sheep negative serum, sheep infected serum was 97.6%, 96.3%, respectively. The strip was shown to be of high specificity and sensitivity, good repeatability and stability. CONCLUSION: These data suggest that the immunochromatographic strip is a useful tool for rapid on-site diagnosing animals infected foot-and-mouth disease virus.

Cervicofacial subcutaneous emphysema following tonsillectomy: implications for anesthesiologists.

Cervicofacial subcutaneous emphysema is an unusual complication following tonsillectomy. We present a 37-year-old male patient who, after receiving tonsillectomy, developed cervicofacial subcutaneous emphysema immediately following endotracheal extubation. Valsalva maneuvers evidenced by coughing and straining of the patient, and positive pressure ventilation by mask to alleviate laryngospasm in an emergency were believed to induce and exacerbate the emphysema. Fortunately, the patient was re-intubated and protected from further complication of pneumomediastinum or pneumothorax. The emphysema resolved 7 days later with conservative treatment, including broad-spectrum antibiotics and abstention from enteral intake. This case serves as a reminder that an unusual and unexpected complication can occur in a routine procedure. Methods to prevent this complication are discussed.

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression.

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE epsilon4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.

The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression.

Brain-derived neurotrophic-factor (BDNF), the most abundant of the neurotrophins in the brain, has been implicated in both major depression and cognitive function. This study examines the association between the BDNF-gene Val66Met polymorphism and depression susceptibility and severity, age-of-onset, cognitive function and suicidal attempt history in an elderly Chinese sample population. We genotyped the BDNF-gene Val66Met polymorphism in 110 elderly inpatients diagnosed with major depression and 171 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. Suicide attempt history and age-of-onset of depression were evaluated by interview and medical record. The BDNF Val66Met genotype distribution was significantly different between depressed patients and control subjects (P=0.003) and there was a significant excess of Met allele in the depressed patients compared to the control group (P=0.001). The BDNF polymorphism did not affect age-of-onset, depression severity, cognitive function or suicidal attempt history. The results suggest that the BDNF Val66Met polymorphism is a relevant risk factor for geriatric depression.