Modeling Respiratory Syncytial Virus Adult Vaccination in the United States With a Dynamic Transmission Model.

BACKGROUND: Respiratory syncytial virus (RSV) is shown to cause substantial morbidity, hospitalization, and mortality in infants and older adults. Population-level modeling of RSV allows to estimate the full burden of disease and the potential epidemiological impact of novel prophylactics. METHODS: We modeled the RSV epidemiology in the United States across all ages using a deterministic compartmental transmission model. Population-level symptomatic RSV acute respiratory tract infection (ARI) cases were projected across different natural history scenarios with and without vaccination of adults aged ≥60 years. The impact of vaccine efficacy against ARIs, infectiousness and vaccine coverage on ARI incidence were assessed. The impact on medical attendance, hospitalization, complications, death, and other outcomes was also derived. RESULTS: Without a vaccine, we project 17.5-22.6 million symptomatic RSV ARI cases annually in adults aged ≥18 years in the US, with 3.6-4.8 million/year occurring in adults aged ≥60 years. Modeling indicates that up to 2.0 million symptomatic RSV-ARI cases could be prevented annually in ≥60-year-olds with a hypothetical vaccine (70% vaccine efficacy against symptomatic ARI and 60% vaccine coverage) and that up to 0.69 million/year could be prevented in the nonvaccinated population, assuming 50% vaccine impact on infectiousness. CONCLUSIONS: The model provides estimated burden of RSV in the US across all age groups, with substantial burden projected specifically in older adults. Vaccination of adults aged ≥60 years could significantly reduce the burden of disease in this population, with additional indirect effect in adults aged <60 years due to reduced transmissibility.

Increased Incident Alzheimer's Disease among Individuals with Varicose Veins: A Population-Based Cohort Study.

BACKGROUND: Varicose vein may be related to increased risk of comorbidities and decreased cognitive function in the elderly, but little is known about the association between varicose vein and Alzheimer's disease. OBJECTIVES: To evaluate whether there is an association between varicose veins and Alzheimer's disease. DESIGN: The study subjects of this cohort study were selected based on Chang Gung Research Database from January 1, 2003, to December 31, 2012. Follow-up ended December 31, 2017. SETTING: A population-based study Participants: Patients aged 45 years and older with varicose veins were enrolled, and the participants of control group were selected by matching with gender, age, and index date at a 4:1 ratio. MEASUREMENTS: The hazard ratios associated with varicose veins were estimated using Cox regression analysis with competitive risk model. Incidence rates of Alzheimer's disease, was assessed in people with and without varicose veins. RESULTS: A total of 9,601 patients with varicose veins and 38,404 matched controls were enrolled in the study. The varicose veins group had higher incidence rates than the control group for Alzheimer's disease (12.60 vs 6.24 per 10,000 person-years; Hazard ratio, 1.647 [95% confidence interval, 1.326- 2.045, p<0.001]). Patients with complicated varicose veins had increased incidence of Alzheimer's disease than uncomplicated cases (adjusted HR, 1.474; 95% CI, 1.034-2.101, P=0.032). CONCLUSION: The present study demonstrated a positive association between the varicose veins and Alzheimer's disease. Physicians should be alerted to cognitive function in patients with varicose veins, especially those with presence of inflammation and ulcerations.

The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA.

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Magnetic anisotropy manipulation of the femtosecond laser-excited spin wave modes in full-Heusler Co2Fe1-x Mn x Al films.

Spin-wave dynamics in full-Heusler Co2Fe1-x Mn x Al films have been investigated using all-optical pump-probe magneto-optical polar Kerr spectroscopy. We find magnetic damping and anisotropy can be modulated by composition x. Damon-Eshbach (DE) spin wave occurs only in the samples which present intrinsic magnetic damping and have huge uniaxial magnetic anisotropy, implying that intrinsic magnetic damping and huge uniaxial magnetic anisotropy is the necessary conditions to excite coherent DE spin wave. Kittel spin wave appears in low uniaxial magnetic anisotropic samples and presents extrinsic magnetic damping. Therefore, laser-excited spin-wave modes can be manipulated by magnetic anisotropy, whose physical picture is discussed phenomenologically.

Intervention of Online Percent Coefficient of Variation Reporting System Reduces the Variability of Tacrolimus Trough Concentration in Kidney Transplant Recipients.

BACKGROUND: The online percent coefficient of variation reporting system could monitor the variation of tacrolimus trough level (T0) and identify kidney transplant recipients (KTRs) with a higher percent coefficient of variation (%CV) instantly. Consequently, transplant doctors and pharmacists could take actions to improve drug variability. The purpose of this study was to determine the efficacy of the system for higher intrapatient variability of T0 in KTRs. METHODS: The T0 data were collected with KTRs routinely followed up at an outpatient clinic between June 2016 and November 2016. The %CV was calculated with T0 data within 6 months before and after the index date. The last outpatient clinic visit date was before December 1, 2016. The KTRs with %CV of T0 greater than 22% were enrolled. RESULTS: The study consisted of 183 KTRs (96 male, 87 female), the median age was 50 years (interquartile range [IQR], 41.0-57.0), and the median years post-kidney transplantation was 7 years (IQR, 3.0-12.4). The median T0 and creatinine level at baseline were 6.09 ng/mL (IQR, 4.80-7.52) and 1.33 mg/dL (IQR, 1.03-1.72), respectively. After the intervention, the median %CV of T0 was significantly lower than before, 32% (IQR, 26%-42%) vs 22% (IQR, 15%-33%), P < .001. The average improvement of %CV was also significantly better in KTRs with %CV ≥ 30% (median, from 41% to 25%) than KTRs with %CV between 22% and 30% (median, from 26% to 20%), P < .001. CONCLUSIONS: The results of this study indicate that continuously aggressive intervention with an online %CV reporting system effectively improves intrapatient variability of T0 in KTRs.

Epidemiological characteristics and associated factors of acute hepatitis A outbreak among HIV-coinfected men who have sex with men in Taiwan, June 2015-December 2016.

In Taiwan, an outbreak of acute hepatitis A (AHA) infection has been identified since June 2015. Approximately half of the cases occurred in HIV-infected men who have sex with men (MSM). We used the Taiwan Centers for Disease Control (TCDC)-operated National Disease Surveillance Systems (NDSS) to identify the incidence of AHA during 2011-2016. Between June 2015 and December 2016, a total of 1268 AHA cases were documented, and 601 cases (47.4%) were co-infected with HIV; the majority of whom were MSM (98.4%). Each AHA case was matched to two HIV-infected controls without AHA reported in the NDSS on age (± 5 years), risk factor of HIV infection, HIV diagnosis date (± 30 days) and county/city of residence at HIV diagnosis. Three hundred forty-three HIV/AHA cases were matched to 686 controls. In multivariable conditional logistic regression analysis, a previous gonorrhoea (adjusted OR=1.77, 95% CI 1.16-2.70) and recent (aOR=6.77, 95% CI 4.34-10.55) or remote syphilis report (aOR=3.56, 95% CI 2.48-5.13) were independently associated with AHA. The epidemic persisted till December 2016, and the cases with a new diagnosis of HIV infection after AHA (28/301, 9.3%) increased after July 2016 (P = .001). HIV/AHA cases were centralized in northern and central metropolitan areas and HIV-infected MSM with a recent history of sexually transmitted diseases in Taiwan. We recommend surveillance of associated behavioural and virologic characteristics and HAV counselling and testing for HIV-infected men.

Epidemiology, risk factors and characteristics of pediatric stroke: a nationwide population-based study.

BACKGROUND: Stroke, classically characterized as an acute acquired neurological deficit, is an important leading cause of death and chronic morbidity in children. AIMS: This study reported the period prevalence, incidence and risk factors of pediatric stroke in Taiwan. METHODS AND PROCEDURES: All Taiwan inhabitants aged 1 month to 18 years registered in the National Health Insurance Research Database between 2010 and 2011 were enrolled in this study. Factors including age, sex, location and household income levels were collected. Incidence, period prevalence, mortality rate and the possible risks were completely evaluated. Outcomes and results: Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke (27.6% vs. 10.2%, P<0.05). Risk factors or underlying diseases for stroke were identified in 77.8% of the patients and 16.2% had more than one risk factor. The most common risk factors were vascular diseases (26.3%), infection (14.0%) and cardiac disorders (9.1%). CONCLUSIONS AND IMPLICATIONS: Infants younger than 2 years, boys and children in lower socioeconomic status have a significantly higher risk of stroke. Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke. More than half of the children with stroke had underlying diseases and the causes of hemorrhagic stroke are significantly different from ischemic stroke.

Type 2 diabetes mellitus severity correlates with risk of hip fracture in patients with osteoporosis.

BACKGROUND: Osteoporosis is a major public health problem because of its associated fractures and the resulting complications. The objective of this study was to identify the association between the severity of type 2 diabetes mellitus (T2DM) and the risk of hip fracture in osteoporotic patients. METHODS: The patients who received a diagnosis of osteoporosis between 2006 and 2010, with an adequate follow-up between 2006 and 2015, were enrolled in this study. Among patients with T2DM, the severity of the disease was evaluated using the Diabetes Complication Severity Index (DCSI). Logistic regression models were used to calculate the odds ratios and to predict the risk of hip fracture in diabetic osteoporotic patients. RESULTS: A total of 1188 patients were enrolled in the final study, 87 patients had hip fractures in the follow-up period between 2006 and 2015. Among the diabetic patients, each level of the continuous DCSI was associated with a 1.56-fold greater risk of hip fracture. In further stratification, patients with a DCSI > 3 had a significantly higher risk of hip fracture in comparison with those with a DCSI ≤ 1. The categorical DCSI (DCSI > 3), HbA1c level on the diagnosis of T2DM and duration of diabetes, facilitate predicting the risk of hip fracture. CONCLUSION: The severity of T2DM reflects the risk of hip fracture in osteoporotic patients. Physicians should pay attention to osteoporotic patients presenting with a high HbA1c level on diagnosis of T2DM and a higher DCSI because of their vulnerability to hip fracture.

Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

BACKGROUND: Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. METHODS: We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. RESULTS: There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. CONCLUSIONS: PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.

Autophagy inhibition increased the anti-tumor effect of cisplatin on drug-resistant esophageal cancer cells.

The sensitivity of tumor cells to treatment can be affected by autophagy. The drug resistance of esophageal cancer cells against cisplatin occurs during the long period of chemotherapy drug treatment. This study was designed to observe the effect autophagy has on the occurrence of esophageal cancer cell drug resistance against cisplatin and investigate its molecular mechanism in order to provide new details and strategies for the clinical treatment of esophageal cancer, especially cisplatin treatment. The detection methods used in this study were 3-(4,5-dimethylthiazd-2-yl)-2,5-dipheny-ltetrazolium bromide (MTT) colorimetric assay, clone survival technique, small interfering RNA (siRNA) transfection, and Western blot. Autophagy is a protection mechanism of drug-resistant cells processed by cisplatin, and maintains the cell clone survival ability. Autophagy activation requires the involvement of Atg5 and Atg7.

Emerging Role for Mammalian Target of Rapamycin in Male Fertility.

Male fertility is modulated by environmental, endocrine, paracrine, and metabolic cues. Mammalian target of rapamycin (mTOR) coordinates many cellular events in response to those signals. Here, we discuss how the mTOR pathway integrates and mediates signals throughout the male reproductive system, acting as a central player in the control of spermatogenesis.

Vitamin D insufficiency and cognitive impairment in Asians: a multi-ethnic population-based study and meta-analysis.

BACKGROUND: The relationship between vitamin D insufficiency and cognitive impairment remains equivocal in Asians. We examined the association between circulating 25-hydroxyvitamin D (25OHD) concentration and cognitive performance in a large multi-ethnic Singaporean population-based study. We also conducted a meta-analysis of 25OHD concentrations amongst cognitively impaired older adults in Asia. METHODS: Our population-based cross-sectional study included 2273 persons ≥60 years of age from the Singapore Epidemiology of Eye Diseases (SEED) study (mean ± SD age 70.4 ± 6.2 years; 44.7% female), who were categorized according to 25OHD concentration (i.e. ≤10, 10.1-20 and >20 ng mL(-1) ). The 25OHD concentration was measured and adjusted to reflect a deseasonalized value. Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Global cognitive impairment was defined as AMT score of ≤6 if 0-6 years of education and AMT score of ≤8 if >7 years of education. Fully adjusted multivariate models were used. We included seven studies in a meta-analysis of 25OHD and cognition in Asia (6068 participants; 1179 cognitively impaired cases). RESULTS: Participants with 25OHD levels >20 ng mL(-1) (n = 1302) had higher AMT total scores (mean ± SD 8.5 ± 1.9) and were less likely to have cognitive impairment (14.1%) than participants with lower 25OHD levels (overall P < 0.001, P-trend < 0.001). Deseasonalized 25OHD concentration was associated with AMT score (ß = 0.10 per 10 ng mL(-1) , P = 0.035). Vitamin D insufficiency (25OHD ≤20 ng mL(-1) ) was associated with global cognitive impairment (OR 1.56, P = 0.028). Specifically, 25OHD concentration correlated with semantic memory (r = 0.08, P = 0.009) and orientation in time (r = 0.09, P = 0.003). In the meta-analysis, the pooled mean 25OHD difference was -6.83 ng mL(-1) (95% confidence interval -11.36; -2.30), indicating lower 25OHD concentrations amongst cognitively impaired compared to cognitively healthy participants in Asia. CONCLUSION: Vitamin D insufficiency is associated with a greater likelihood of and more severe cognitive impairment in Asian populations.

Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS).

WHAT IS KNOWN AND OBJECTIVE: Febuxostat is recommended as an alternative drug for gouty patients with a history of allopurinol hypersensitivity or carrying the HLA-B*5801 allele. CASE SUMMARY: An 81-year-old man with the medical history of gout presented to our clinic with generalized rashes for 2 days. After taking febuxostat for 2 days, he developed generalized skin rash with high fever. Laboratory tests showed elevated liver enzymes and acute kidney injury. WHAT IS KNOWN AND OBJECTIVE: This is the first identified case of febuxostat-associated DRESS. Febuxostat should be withdrawn immediately when DRESS is observed to avoid further serious complications.

Inhibition of melanogenesis by ß-caryophyllene from lime mint essential oil in mouse B16 melanoma cells.

OBJECTIVE: Volatile essential oils of mint species are used for cosmetics and in skin care products. In this study, we evaluated the main chemical components of the lime mint and the anti-melanogenic properties of its main components. METHODS: The essential oil was analysed by gas chromatography-mass spectrometry (GC/MS). The anti-melanogenic effects of mint essential oil and ß-caryophyllene were investigated in B16F10 murine melanoma cells. RESULTS: The main components of lime mint essential oil were found to be D-limonene (41.10%), D-carvone (8.58%), δ-selinene (6.73%) and ß-caryophyllene (6.24%). The lime mint essential oil reduced melanin production in a dose-dependent manner in murine B16F10 cells. ß-Caryophyllene, one of the main compounds in lime mint essential oil, could reduce melanogenesis by down-regulating the expression of MITF, TRP-1, TRP-2 and tyrosinase, resulting in a decrease in melanin content decrease. CONCLUSION: These results reveal that lime mint essential oil and ß-caryophyllene are considered to be valuable as potential skin-whitening agents.