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Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12–23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.
The AD 775 peak in Δ14C (henceforth, M12) was first measured by Miyake et al. and has since been confirmed globally. Here we present earlywood and latewood Δ14C values from tree rings of pinyon pine (Pinus edulis) from Mummy Cave, Canyon de Chelly National Monument, Chinle, Arizona, USA, for the period AD 770–780. These data reconfirm the timing of M12 and show a small rise in Δ14C in AD 774 latewood. Allowing for the delay in lateral transfer of radiocarbon produced at high latitude, this suggests that 14C peak production occurred in late winter or spring of AD 774. Additionally, Δ14C decreased slightly in the earlywood of AD 775 and increased in the latewood of AD 775 to a higher level than that observed in AD 774.
Background: Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, California (SHIELD OC) was a CDC-funded regional decolonization intervention from April 2017 through July 2019 involving 38 hospitals, nursing homes (NHs), and long-term acute-care hospitals (LTACHs) to reduce MDROs. Decolonization in NH and LTACHs consisted of universal antiseptic bathing with chlorhexidine (CHG) for routine bathing and showering plus nasal iodophor decolonization (Monday through Friday, twice daily every other week). Hospitals used universal CHG in ICUs and provided daily CHG and nasal iodophor to patients in contact precautions. We sought to evaluate whether decolonization reduced hospitalization and associated healthcare costs due to infections among residents of NHs participating in SHIELD compared to nonparticipating NHs. Methods: Medicaid insurer data covering NH residents in Orange County were used to calculate hospitalization rates due to a primary diagnosis of infection (counts per member quarter), hospital bed days/member-quarter, and expenditures/member quarter from the fourth quarter of 2015 to the second quarter of 2019. We used a time-series design and a segmented regression analysis to evaluate changes attributable to the SHIELD OC intervention among participating and nonparticipating NHs. Results: Across the SHIELD OC intervention period, intervention NHs experienced a 44% decrease in hospitalization rates, a 43% decrease in hospital bed days, and a 53% decrease in Medicaid expenditures when comparing the last quarter of the intervention to the baseline period (Fig. 1). These data translated to a significant downward slope, with a reduction of 4% per quarter in hospital admissions due to infection (P < .001), a reduction of 7% per quarter in hospitalization days due to infection (P < .001), and a reduction of 9% per quarter in Medicaid expenditures (P = .019) per NH resident. Conclusions: The universal CHG bathing and nasal decolonization intervention adopted by NHs in the SHIELD OC collaborative resulted in large, meaningful reductions in hospitalization events, hospitalization days, and healthcare expenditures among Medicaid-insured NH residents. The findings led CalOptima, the Medicaid provider in Orange County, California, to launch an NH incentive program that provides dedicated training and covers the cost of CHG and nasal iodophor for OC NHs that enroll.
Disclosures: Gabrielle M. Gussin, University of California, Irvine, Stryker (Sage Products): Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes.
Anthocyanins and bromelain have gained significant attention due to their antioxidative and anti-inflammatory properties. Both have been shown to improve endothelial function, blood pressure (BP) and oxygen utility capacity in humans; however, the combination of these two and the impacts on endothelial function, BP, total antioxidant capacity (TAC) and oxygen utility capacity have not been previously investigated. The purpose of this study was to investigate the impacts of a combined anthocyanins and bromelain supplement (BE) on endothelial function, BP, TAC, oxygen utility capacity and fatigability in healthy adults. Healthy adults (n 18, age 24 (sd 4) years) received BE or placebo in a randomised crossover design. Brachial artery flow-mediated dilation (FMD), BP, TAC, resting heart rate, oxygen utility capacity and fatigability were measured pre- and post-BE and placebo intake. The BE group showed significantly increased FMD, reduced systolic BP and improved oxygen utility capacity compared with the placebo group (P < 0·05). Tissue saturation and oxygenated Hb significantly increased following BE intake, while deoxygenated Hb significantly decreased (P < 0·05) during exercise. Additionally, TAC was significantly increased following BE intake (P < 0·05). There were no significant differences for resting heart rate, diastolic BP or fatigability index. These results suggest that BE intake is an effective nutritional therapy for improving endothelial function, BP, TAC and oxygen utility capacity, which may be beneficial to support vascular health in humans.
Patulous Eustachian tube appears to be caused by a concave defect in the anterolateral wall of the tubal valve of the Eustachian tube. This study aimed to compare the clinical features of patulous Eustachian tube patients with or without a defect in the anterolateral wall of the tubal valve.
Sixty-six patients with a patulous Eustachian tube completed a questionnaire, which was evaluated alongside endoscopic findings of the tympanic membrane, nasal cavity and Eustachian tube orifice.
Females were more frequently diagnosed with a patulous Eustachian tube, but the valve defect was more common in males (p = 0.007). The ratio of patulous Eustachian tube patients with or without defects in the anterolateral wall of the tubal valve was 1.6:1. Weight loss in the previous six months and being refractory to conservative management were significantly associated with the defect (p = 0.035 and 0.037, respectively). Symptom severity was significantly higher in patients with the defect.
Patulous Eustachian tube patients without a defect in the anterolateral wall of the tubal valve can be non-surgically treated more often than those with the defect. Identification of the defect could assist in making treatment decisions for patulous Eustachian tube patients.
To assess the Framingham risk score as a prognostic tool for idiopathic sudden sensorineural hearing loss patients.
Medical records were reviewed for unilateral idiopathic sudden sensorineural hearing loss patients between January 2010 and October 2017. The 10-year risk of developing cardiovascular disease was calculated. Patients were subdivided into groups: group 1 – Framingham risk score of less than 10 per cent (n = 28); group 2 – score of 10 to less than 20 per cent (n = 6); and group 3 – score of 20 per cent or higher (n = 5).
Initial pure tone average and Framingham risk score were not significantly associated (p = 0.32). Thirteen patients in group 1 recovered completely (46.4 per cent), but none in groups 2 and 3 showed complete recovery. Initial pure tone average and Framingham risk score were significantly associated in multivariable linear regression analysis (R2 = 0.36). The regression coefficient was 0.33 (p = 0.003) for initial pure tone average and −0.67 (p = 0.005) for Framingham risk score.
Framingham risk score may be useful in predicting outcomes for idiopathic sudden sensorineural hearing loss patients, as those with a higher score showed poorer hearing recovery.
There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.
The goal of this randomly-assigned placebo-controlled double-blind study was to determine if the addition of buspirone, a widely available 5-HT1A partial agonist, would enhance cognitive function, in subjects with schizophrenia treated with atypical antipsychotic drugs (AAPDs). Seventy-three patients with schizophrenia, who had been treated with an AAPD for at least three months, were randomly assigned to receive either buspirone, 30 mg/day, or matching placebo. All other medications remained unchanged. Attention, verbal fluency, verbal learning and memory, verbal working memory, and executive function, as well as psychopathology, were assessed at baseline, and 6 weeks, and 3 and 6 months after baseline. A significant Time x Group interaction effect was noted on the Digit Symbol Substitution Test, a measure of attention/speeded motor performance, due to better performance of the buspirone group compared to the placebo group at 3 months. No significant interaction effects were noted for other domains of cognition. Scores on the Brief Psychiatric Rating Scale (Total, Positive) were improved during treatment with buspirone but not placebo, but the effects did not reach statistical significance.
The results of this study showed a possible benefit of buspirone augmentation of AAPDs to enhance attention. However, we did not replicate the results of the previous study with tandospirone that improved executive function and verbal learning and memory, which may be due to the differences between tandospirone and buspirone, between typical antipsychotics and AAPDs, or a combination of the above. Further study to determine the usefulness of 5-HT1A agonist treatment in schizophrenia is indicated.
Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.
The aim of this study was to evaluate theprevalence of night eating syndrome (NES) and its correlates in schizophrenicoutpatients.
The 14 items of self-reported night eatingquestionnaire (NEQ) was administered to 201 schizophrenic patients in psychiatricoutpatient clinic. We examined demographic and clinical characteristics, bodymass index (BMI), subjective measures of mood, sleep, binge eating, andweight-related quality of life using Beck's Depression Inventory (BDI),Pittsburgh Sleep Quality Index (PSQI), Binge Eating Scale (BES) and Koreanversion of Obesity-Related Quality of Life Scale (KOQoL), respectively.
The prevalence of night eaters in schizophrenicoutpatients was 10.4% (21 of 201). Comparisons between NES group and non-NES grouprevealed no significant differences in sociodemographic characteristics, clinical status and BMI. Compared to non-NES, patients with NES reportedsignificantly greater depressed mood and sleep disturbance, more binge eatingpattern, and decreased weight-related quality of life. While 'morning anorexia'and 'delayed morning meal' (2 of 5 NES core components in NEQ) were notdiffered between groups, 'nocturnal ingestions', 'evening hyperphagia', and'mood/sleep' were more impaired in NES group.
These findings are the first to describe theprevalence and its correlates of night eaters in schizophrenic outpatients. These results suggest that NES has negative mental health implications, although it was not associated with obesity. Further study to generalize theseresults is required.
Thisstudy was to assess the prevalence and its correlates of restless legs syndrome(RLS) in outpatients with bipolar disorder.
A total of 100clinical stabilized bipolar outpatients were examined. The presence of RLS andits severity were assessed using the International Restless Legs Sydrome StudyGroup (IRLSSG) diagnostic criteria. Beck's Depression Inventory (BDI), Spielberg's StateAnxiety Inventory (STAI-X-1), Pittsburgh Sleep Quality Index (PSQI), Koreanversion Drug Attitude Inventory (KDAI-10), Subjective Well-Beings under NeurolepticTreatment Scale-Short Form(SWN-K) and Barnes Akathisia Rating Scale (BARS) wereused to evaluate the depressive symptomatology, level of anxiety, subjectivequality of sleep, subjective feeling of well-being, drug attitude, presence ofakathisia, respectively.
Of the 100 bipolar outpatients,7 (7%) were met to full criteria of IRLSSG and 36 (36%) have at least one ofthe 4 IRLSSG criterion. Because of relatively small sample size, non-parametricanalysis were done to compare the characteristics among 3 groups (full-RLS, 1≥positiveRLS-symptom and Non-RLS). There were no significant differences in sex, age, and other sociodemographic and clinical data among 3 groups. BDI, STAI-X-1 andPSQI are tended to be impaired in RLS and 1≥positive RLS-symptomgroups.
This is the first preliminarystudy for studying the prevalence and its correlates of RLS in bipolardisorder. The results shows that RLS was relatively smaller presentin bipolar disorder than schizophrenia. Sametendencies shown in schizophrenic patients were found that bipolar patientswith RLS had more depressive symptoms, state anxiety and poor subjective sleepquality.
Acute angle-closure glaucoma (AACG) is an ophthalmic emergency, accompanied with severe eye pain, headache, and visual changes because of acute intraocular pressure elevation. Among psychotropic drugs, several antidepressants, typical antipsychotics with strong anticholinergic effects, and topiramate have been known to increase a possibility of AACG. Benzodiazepines have been used widely in the treatment of mental and physical illnesses regardless of age or indication. Since benzodiazepines have some anticholinergic properties and affect pupillae muscles, their use could be theoretically a risk factor for AACG. However, it is unclear whether benzodiazepines actually increase the risk of AACG. To our knowledge, there was no population-based study on the risk of benzodiazepines to the occurrence of AACG.
To know whether benzodiazepines increase the risk of AACG in a geriatric population.
We will perform a case-control study using a geriatric cohort from the National Health Insurance database. Case subjects will be defined as cases diagnosed with AACG confirmed by the claim data of laser iridotomy, which is the definitive treatment of AACG. The controls, which were not diagnosed with AACG, will be matched with case subjects according to similar age, sex, and the scores of the Charlson comorbidity index.
The data handling and statistical analyses will be executed in autumn and winter 2016.
Any preliminary findings of this study will be presented at the EPA 2017. We will discuss the importance of a pharmaco-epidemiological study in the geriatric research.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The study aims to examine whether cognitive deficits are different between patients with early stage Alzheimer's disease (AD) and patients with early stage vascular dementia (VaD) using the Korean version of the CERAD neuropsychological battery (CERAD-K-N).
Patients with early stage dementia, global Clinical Dementia Rating (CDR) 0.5 or 1 were consecutively recruited among first visitors to a dementia clinic, 257 AD patients and 90 VaD patients completed the protocol of the Korean version of the CERAD clinical assessment battery. CERAD-K-N was administered for the comprehensive evaluation of the neuropsychological function.
Of the total 347 participants, 257 (69.1%) were AD group (CDR 0.5 = 66.9%) and 90 (21.9%) were VaD group (CDR 0.5 = 40.0%). Patients with very mild AD showed poorer performances in Boston naming test (BNT) (P = 0.028), word list memory test (P < 0.001), word list recall test (P < 0.001) and word list recognition test (WLRcT) (P = 0.006) than very mild VaD after adjustment of T score of MMSE-KC. However, the performance of trail making A (TMA) was more impaired in VaD group than in AD group. The performance of WLRcT (P < 0.001) was the worst among neuropsychological tests within AD group, whereas TMA was performed worst within VaD group.
Patients with early-stage AD have more cognitive deficits on memory and language while patients with early-stage VaD show worse cognitive function on attention/processing speed. In addition, as the first cognitive deficit, memory dysfunction comes in AD and deficit in attention/processing speed in VaD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Numerous studies reported on the frequency of, and factors associated with inappropriate or unnecessary emergency department (ED) visits using clinician judgment as the gold standard of appropriateness. This study evaluated the reliability of clinician judgment for assessing appropriateness of pediatric ED visit.
We conducted a retrospective cohort study comparing 3 clinicians’ determination of ED visit appropriateness with and without guidance from a three-question structured algorithm. We used a cohort of scheduled ED return visits deemed appropriate by the index treating clinician between May 1, 2012, and April 30, 2013. We measured the level of agreement among three clinician investigators with and without use of the structured algorithm.
A total of 207 scheduled ED return visits were reviewed by the primary clinician reviewer who agreed with the index treating clinician for 79/207 visits (38.2%). Among a random subset of 90 return visits reviewed by all three clinicians, agreement was 67% with a Fleiss’ Kappa of 0.30 (0.17–0.44). Using a three-question algorithm based on objective criteria, agreement with the index treating provider increased to 115/207 (55.6%).
Although an important contributor to pediatric ED overcrowding, unnecessary or inappropriate visits are difficult to identify. We demonstrated poor reliability of clinician judgment to determine appropriateness of ED return visits, likely due to variability in clinical decision-making and risk-tolerance, social and systems factors impacting access and use of health care. We recommend that future studies evaluating the appropriateness of ED use standardized, objective criteria rather than clinician judgment alone.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.