Vaccine effectiveness of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine during a pertussis outbreak in Maine.

BACKGROUND: Multiple school-associated pertussis outbreaks were reported in Maine from 2010 to 2011. These outbreaks were associated with an overall increase in pertussis cases statewide. Waning of protection in students recently vaccinated with tetanus, diphtheria, and acellular pertussis (Tdap) has been implicated in the increase in reported rates of pertussis nationally. METHODS: We conducted a retrospective cohort study to evaluate Tdap vaccine effectiveness (VE) among students aged 11-19 years in two schools reporting outbreaks in 2011. All pertussis cases reported from August through November, 2011 at the two schools were included. Vaccination history was verified using provider information, state vaccine registry data, and parental verification. Attack rates (AR) were calculated. VE and duration of protection was calculated as VE=1-(ARvaccinated/ARunvaccinated)×100% using a log binomial regression model. RESULTS: Of 416 students enrolled, 314 were included in the analyses. Twenty-nine cases collectively in Schools A and B. Tdap coverage was 65% at School A and 42% at School B before the start of the outbreak. Among students enrolled in the study, attack rates were 11.9% and 7.7% at Schools A and B, respectively. Overall VE was 68.5% (95% confidence interval (CI) 37.7-86.2). VE was 70.4% (95% CI 17.5-89.4) for School A and 65.2% (95% CI -19.2 to 89.9) for School B. VE <2 years versus ≥2 years from outbreak onset was not significantly different. CONCLUSIONS: Tdap was moderately effective in preventing disease among vaccinated students. Vaccine coverage of 65% or less was suboptimal and might contribute to outbreaks. Waning VE was not demonstrated. Increased vaccination coverage rates as well as further evaluation of the role of acellular vaccine on VE is needed.

Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.

Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects approximately 1% of the population worldwide. To identify genetic variants that increase the risk of BP, we genotyped on the Illumina HumanHap550 Beadchip 2,076 bipolar cases and 1,676 controls of European ancestry from the National Institute of Mental Health Human Genetics Initiative Repository, and the Prechter Repository and samples collected in London, Toronto, and Dundee. We imputed SNP genotypes and tested for SNP-BP association in each sample and then performed meta-analysis across samples. The strongest association P value for this 2-study meta-analysis was 2.4 x 10(-6). We next imputed SNP genotypes and tested for SNP-BP association based on the publicly available Affymetrix 500K genotype data from the Wellcome Trust Case Control Consortium for 1,868 BP cases and a reference set of 12,831 individuals. A 3-study meta-analysis of 3,683 nonoverlapping cases and 14,507 extended controls on >2.3 M genotyped and imputed SNPs resulted in 3 chromosomal regions with association P approximately 10(-7): 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (MCTP1). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, P = 1.8 x 10(-7)) is in the ITIH1 gene on chromosome 3, with other strongly associated nonsynonymous SNPs in GNL3, NEK4, and ITIH3. Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported ANK3 association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, P = 0.042). Although these results are promising, analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk.

Neuroticism: a non-informative marker of vulnerability to psychopathology.

BACKGROUND: Neuroticism measures are very popular in psychopathological research, but it is unclear how useful neuroticism is in studies of the aetiology of psychopathology. METHOD: A conceptual examination was made of the literature on the association of neuroticism and psychopathology, the ontological status of neuroticism, the purport of neuroticism questionnaires, and causal issues. RESULTS: The research on which neuroticism is built has historically been based solely on the factor analyses of the common adjectives used to describe usual behaviours. An abundance of studies have shown that neuroticism scores predict life stress, psychological distress, emotional disorders, psychotic symptoms, substance abuse, physical tension-related symptoms, medically unexplained physical symptoms, and health care utilisation. This evidence suggests that neuroticism scales index vulnerability to many forms of negative affect and psychiatric disorder. However, the associations do not clarify the nature of this vulnerability nor the underlying psychobiological mechanisms. We present evidence that neuroticism scores reflect a person's characteristic (or mean) level of distress over a protracted period of time. In this perspective, even prospective associations of neuroticism with mental health outcomes are basically futile, and largely tautological since scores on any characteristic with substantial within-subject stability will predict, by definition, that characteristic and related variables at later points in time. CONCLUSION: Neuroticism is not an explanatory concept in the aetiology of psychopathology, since it measures a person's characteristic level of distress over a protracted period of time. This situation will not change until knowledge becomes available about: (i) the mechanisms that produce high neuroticism scores (and, therefore, also psychopathology) and (ii) its neurobiological substrate. Only then will we understand why neuroticism appears to "predict" the outcomes it predicts.