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Psychiatric disorders are associated with increased risk of ischaemic heart disease (IHD) and stroke, but it is not known whether the associations or the role of sociodemographic factors have changed over time.
To investigate the association between psychiatric disorders and IHD and stroke, by time period and sociodemographic factors.
We used Scottish population-based records from 1991 to 2015 to create retrospective cohorts with a hospital record for psychiatric disorders of interest (schizophrenia, bipolar disorder or depression) or no record of hospital admission for mental illness. We estimated incidence and relative risks of IHD and stroke in people with versus without psychiatric disorders by calendar year, age, gender and area-based deprivation level.
In all cohorts, incidence of IHD (645 393 events) and stroke (276 073 events) decreased over time, but relative risks decreased for depression only. In 2015, at the mean age at event onset, relative risks were 2- to 2.5-fold higher in people with versus without a psychiatric disorder. Age at incidence of outcome differed by cohort, gender and socioeconomic status. Relative but not absolute risks were generally higher in women than men. Increasing deprivation conveys a greater absolute risk of IHD for people with bipolar disorder or depression.
Despite declines in absolute rates of IHD and stroke, relative risks remain high in those with versus without psychiatric disorders. Cardiovascular disease monitoring and prevention approaches may need to be tailored by psychiatric disorder and cardiovascular outcome, and be targeted, for example, by age and deprivation level.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
The mass franchise led to more responsive government and a more equitable distribution of resources in the United States and other democracies. Recently in America, however, voter participation has been low and increasingly biased toward the wealthy. We investigate whether this electoral “class bias” shapes government ideology, the substance of economic policy, and distributional outcomes, thereby shedding light on both the old question of whether who votes matters and the newer question of how politics has contributed to growing income inequality. Because both lower and upper income groups try to use their resources to mobilize their supporters and demobilize their opponents, we argue that variation in class bias in turnout is a good indicator of the balance of power between upper and lower income groups. And because lower income voters favor more liberal governments and economic policies we expect that less class bias will be associated with these outcomes and a more equal income distribution. Our analysis of data from the U.S. states confirms that class bias matters for these outcomes.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Primary small cell neuroendocrine carcinoma of larynx is a rare, aggressive type of malignancy. As only about 200 cases worldwide have been reported, any larger institutional experience is valuable. This study reports our experience in managing this rare entity.
Of the nine patients identified, three had metastatic cancer at the time of diagnosis. Four patients underwent radical treatment: one was managed surgically followed by adjuvant chemotherapy and consolidation radiotherapy; the remaining three were treated with neoadjuvant chemotherapy and definitive radiotherapy.
Of the 4 patients treated with radical intent, 1 was alive and disease free after 99 months, 2 died of metastatic disease after 22 and 26 months, and 1 was alive after 20 months with a diagnosis of recurrent disease.
Our relatively small number of patients confirms other centres' experiences. This cancer has a poorer prognosis than most other head and neck cancers. Although the logistics would be challenging, there is a need for international multicentre trials for this disease modelled on those performed for other cancers, as has been done for paediatric malignancies.
Individuals with amnestic mild cognitive impairment (aMCI) show minor decrements in their instrumental activities of daily living (IADL). Sensitive measures of IADL performance are needed to capture the mild difficulties observed in aMCI groups. Routine naturalistic actions (NAs) are familiar IADL-type activities that require individuals to enact everyday tasks such as preparing coffee. In the current study we examined the extent to which NAs could be used to help facilitate differential diagnosis of aMCI relative to composite measures of episodic memory, semantic knowledge, and executive function. Healthy older adults (n=24) and individuals with aMCI (n=24) enacted two highly familiar NAs and completed tests of episodic memory, semantic knowledge, and executive function. Binary logistic regression was used to predict group membership (aMCI vs. control participants). The regression analyses indicated that NA performance could reliably predict group membership, over and above measures of cognitive functioning. These findings indicated that NA performance can be used to help facilitate differential diagnosis of healthy aging and aMCI and used as an outcome measure in intervention studies. (JINS, 2015, 21, 419–428)
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Parkinson's disease (PD) is a neurodegenerative disorder characterised by the progressive loss of midbrain dopaminergic neurons, which causes motor impairments. Current treatments involve dopamine replacement to address the disease symptoms rather than its cause. Factors that promote the survival of dopaminergic neurons have been proposed as novel therapies for PD. Several dopaminergic neurotrophic factors (NTFs) have been examined for their ability to protect and/or restore degenerating dopaminergic neurons, both in animal models and in clinical trials. These include glial cell line-derived neurotrophic factor, neurturin, cerebral dopamine neurotrophic factor and growth/differentiation factor 5. Delivery of these NTFs via injection or infusion to the brain raises several practical problems. A new delivery approach for NTFs involves the use of recombinant viral vectors to enable long-term expression of these factors in brain cells. Vectors used include those based on adenoviruses, adeno-associated viruses and lentiviruses. Here we review progress to date on the potential of each of these four NTFs as novel therapeutic strategies for PD, as well as the challenges that have arisen, from pre-clinical analysis to clinical trials. We conclude by discussing recently-developed approaches to optimise the delivery of NTF-carrying viral vectors to the brain.