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After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
Environmental and biological factors contribute to sleep development during infancy. Parenting plays a particularly important role in modulating infant sleep, potentially via the serotonin system, which is itself involved in regulating infant sleep. We hypothesized that maternal neglect and serotonin system dysregulation would be associated with daytime sleep in infant rhesus monkeys. Subjects were nursery-reared infant rhesus macaques (n = 287). During the first month of life, daytime sleep-wake states were rated bihourly (0800–2100). Infants were considered neglected (n = 16) if before nursery-rearing, their mother repeatedly failed to retrieve them. Serotonin transporter genotype and concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) were used as markers of central serotonin system functioning. t tests showed that neglected infants were observed sleeping less frequently, weighed less, and had higher 5-HIAA than non-neglected nursery-reared infants. Regression revealed that serotonin transporter genotype moderated the relationship between 5-HIAA and daytime sleep: in subjects possessing the Ls genotype, there was a positive correlation between 5-HIAA and daytime sleep, whereas in subjects possessing the LL genotype there was no association. These results highlight the pivotal roles that parents and the serotonin system play in sleep development. Daytime sleep alterations observed in neglected infants may partially derive from serotonin system dysregulation.
Severe longitudinally extensive transverse myelitis (LETM) can cause quadriplegia, marked sensory dysfunction, and respiratory failure. Some patients are unresponsive to conventional immune therapy. We report two cases of severe immune-mediated LETM requiring intensive care admission that failed to respond to high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab. Disease cessation and significant recovery was achieved after cyclophosphamide induction. In patients with severe acute immune-mediated LETM who fail to respond to corticosteroids and plasma exchange, cyclophosphamide induction should be considered. This agent and regimen provides a robust immunosuppressive response and can be induced rapidly. Cyclophosphamide effects and supportive evidence are discussed.
Oregon's Fort Rock Cave is iconic in respect to both the archaeology of the northern Great Basin and the history of debate about when the Great Basin was colonized. In 1938, Luther Cressman recovered dozens of sagebrush bark sandals from beneath Mt. Mazama ash that were later radiocarbon dated to between 10,500 and 9350 cal B.P. In 1970, Stephen Bedwell reported finding lithic tools associated with a date of more than 15,000 cal B.P., a date dismissed as unreasonably old by most researchers. Now, with evidence of a nearly 15,000-year-old occupation at the nearby Paisley Five Mile Point Caves, we returned to Fort Rock Cave to evaluate the validity of Bedwell's claim, assess the stratigraphic integrity of remaining deposits, and determine the potential for future work at the site. Here, we report the results of additional fieldwork at Fort Rock Cave undertaken in 2015 and 2016, which supports the early Holocene occupation, but does not confirm a pre–10,500 cal B.P. human presence.
People with severe mental illness (SMI) have high rates of chronic disease and premature death.
To explore the strength of evidence for interventions to reduce risk of mortality in people with SMI.
In a meta-review of 16 systematic reviews of controlled studies, mortality was the primary outcome (8 reviews). Physiological health measures (body mass index, weight, glucose levels, lipid profiles and blood pressure) were secondary outcomes (14 reviews).
Antipsychotic and antidepressant medications had some protective effect on mortality, subject to treatment adherence. Integrative community care programmes may reduce physical morbidity and excess deaths, but the effective ingredients are unknown. Interventions to improve unhealthy lifestyles and risky behaviours can improve risk factor profiles, but longer follow-up is needed. Preventive interventions and improved medical care for comorbid chronic disease may reduce excess mortality, but data are lacking.
Improved adherence to pharmacological and physical health management guidelines is indicated.
Children and adolescents make up almost a quarter of the world's population with 85% living in low- and middle-income countries (LMICs). Globally, mental (and substance use) disorders are the leading cause of disability in young people; however, the representativeness or ‘coverage’ of the prevalence data is unknown. Coverage refers to the proportion of the target population (ages 5–17 years) represented by the available data.
Prevalence data for conduct disorder (CD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), eating disorders (EDs), depression, and anxiety disorders were sourced from systematic reviews conducted for the Global Burden of Disease Study 2010 (GBD 2010) and 2013 (GBD 2013). For each study, the location proportion was multiplied by the age proportion to give study coverage. Location proportion was calculated by dividing the total study location population by the total country population. Age proportion was calculated by dividing the population of the country aged within the age range of the study sample by the country population aged 5–17 years. If a study only sampled one sex, study coverage was halved. Coverage across studies was then summed for each country to give coverage by country. This method was repeated at the region and global level, and separately for GBD 2013 and GBD 2010.
Mean global coverage of prevalence data for mental disorders in ages 5–17 years was 6.7% (CD: 5.0%, ADHD: 5.5%, ASDs: 16.1%, EDs: 4.4%, depression: 6.2%, anxiety: 3.2%). Of 187 countries, 124 had no data for any disorder. Many LMICs were poorly represented in the available prevalence data, for example, no region in sub-Saharan Africa had more than 2% coverage for any disorder. While coverage increased between GBD 2010 and GBD 2013, this differed greatly between disorders and few new countries provided data.
The global coverage of prevalence data for mental disorders in children and adolescents is limited. Practical methodology must be developed and epidemiological surveys funded to provide representative prevalence estimates so as to inform appropriate resource allocation and support policies that address mental health needs of children and adolescents.
To examine: (1) gender-specific determinants of help-seeking for mental health, including health professional consultation and the use of non-clinical support services and self-management strategies (SS/SM) and; (2) gender differences among individuals with unmet perceived need for care.
Analyses focused on 689 males and 1075 females aged 16–85 years who met ICD-10 criteria for a past-year affective, anxiety or substance use disorder in an Australian community-representative survey. Two classifications of help-seeking for mental health in the previous year were created: (1) no health professional consultation or SS/SM, or health professional consultation, or SS/SM only, and; (2) no general practitioner (GP) or mental health professional consultation, or GP only consultation, or mental health professional consultation. Between- and within-gender help-seeking patterns were explored using multinomial logistic regression models. Characteristics of males and females with unmet perceived need for care were compared using chi-square tests.
Males with mental or substance use disorders had relatively lower odds than females of any health professional consultation (adjusted odds ratio [AOR] = 0.46), use of SS/SM only (AOR = 0.59), and GP only consultation (AOR = 0.29). Notably, males with severe disorders had substantially lower odds than females of any health professional consultation (AOR = 0.29) and GP only consultation (AOR = 0.14). Most correlates of help-seeking were need-related. Many applied to both genders (e.g., severity, disability, psychiatric comorbidity), although some were male-specific (e.g., past-year reaction to a traumatic event) or female-specific (e.g., past-year affective disorder). Certain enabling and predisposing factors increased the probability of health professional consultation for both genders (age 30+ years) or for males (unmarried, single parenthood, reliance on government pension). Males with unmet perceived need for care were more likely to have experienced a substance use disorder and to want medicine or tablets or social intervention, whereas their females peers were more likely to have experienced an anxiety disorder and to want counselling or talking therapy. For both genders, attitudinal/knowledge barriers to receiving the types of help wanted (e.g., not knowing where to get help) were more commonly reported than structural barriers (e.g., cost).
Findings suggest a need to address barriers to help-seeking in males with severe disorders, and promote GP consultation. Exploring gender-specific attitudinal/knowledge barriers to receiving help, and the types of help wanted, may assist in designing interventions to increase consultation. Mental health promotion/education efforts could incorporate information about the content and benefits of evidence-based treatments and encourage males to participate in other potentially beneficial actions (e.g., physical activity).
Education and related proxies for cognitive reserve (CR) are confounded by associations with environmental factors that correlate with cerebrovascular disease possibly explaining discrepancies between studies examining their relationships to cognitive aging and dementia. In contrast, sex-related memory differences may be a better proxy. Since they arise developmentally, they are less likely to reflect environmental confounds. Women outperform men on verbal and men generally outperform women on visuospatial memory tasks. Furthermore, memory declines during the preclinical stage of AD, when it is clinically indistinguishable from normal aging. To determine whether CR mitigates age-related memory decline, we examined the effects of gender and APOE genotype on longitudinal memory performances. Memory decline was assessed in a cohort of healthy men and women enriched for APOE ɛ4 who completed two verbal [Rey Auditory Verbal Learning Test (AVLT), Buschke Selective Reminding Test (SRT)] and two visuospatial [Rey-Osterrieth Complex Figure Test (CFT), and Benton Visual Retention Test (VRT)] memory tests, as well as in a separate larger and older cohort [National Alzheimer’s Coordinating Center (NACC)] who completed a verbal memory test (Logical Memory). Age-related memory decline was accelerated in APOE ɛ4 carriers on all verbal memory measures (AVLT, p=.03; SRT p<.001; logical memory p<.001) and on the VRT p=.006. Baseline sex associated differences were retained over time, but no sex differences in rate of decline were found for any measure in either cohort. Sex-based memory advantage does not mitigate age-related memory decline in either APOE ɛ4 carriers or non-carriers. (JINS, 2015, 21, 95–104)
Mortality-associated burden of disease estimates from the Global Burden of Disease 2010 (GBD 2010) may erroneously lead to the interpretation that premature death in people with mental, neurological and substance use disorders (MNSDs) is inconsequential when evidence shows that people with MNSDs experience a significant reduction in life expectancy. We explore differences between cause-specific and excess mortality of MNSDs estimated by GBD 2010.
GBD 2010 cause-specific death estimates were produced using the International Classification of Diseases death-coding system. Excess mortality (all-cause) was estimated using natural history models. Additional mortality attributed to MNSDs as underlying causes but not captured through GBD 2010 methodology is quantified in the comparative risk assessments.
In GBD 2010, MNSDs were estimated to be directly responsible for 840 000 deaths compared with more than 13 million excess deaths using natural history models.
Numbers of excess deaths and attributable deaths clearly demonstrate the high degree of mortality associated with these disorders. There is substantial evidence pointing to potential causal pathways for this premature mortality with evidence-based interventions available to address this mortality. The life expectancy gap between persons with MNSDs and the general population is high and should be a focus for health systems reform.
We used the winter of 2009–2010, which had minimal influenza circulation due to the earlier 2009 influenza A(H1N1) pandemic, to test the accuracy of ecological trend methods used to estimate influenza-related deaths and hospitalizations. We aggregated weekly counts of person-time, all-cause deaths, and hospitalizations for pneumonia/influenza and respiratory/circulatory conditions from seven healthcare systems. We predicted the incidence of the outcomes during the winter of 2009–2010 using three different methods: a cyclic (Serfling) regression model, a cyclic regression model with viral circulation data (virological regression), and an autoregressive, integrated moving average model with viral circulation data (ARIMAX). We compared predicted non-influenza incidence with actual winter incidence. All three models generally displayed high accuracy, with prediction errors for death ranging from −5% to −2%. For hospitalizations, errors ranged from −10% to −2% for pneumonia/influenza and from −3% to 0% for respiratory/circulatory. The Serfling and virological models consistently outperformed the ARIMAX model. The three methods tested could predict incidence of non-influenza deaths and hospitalizations during a winter with negligible influenza circulation. However, meaningful mis-estimation of the burden of influenza can still result with outcomes for which the contribution of influenza is low, such as all-cause mortality.
Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs.
A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010.
In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000.
ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.
The main aim of this paper is to compare and contrast the methodological approaches of the new Global Burden of Disease 2010 Study (GBD 2010) with the original study conducted for 1990 (GBD 1990), in terms of calculating burden for mental and substance use disorders.
We reviewed the conceptual and methodological changes to GBD burden calculations in the GBD 2010 study, compared with previous studies. We then discuss the possible implications of these changes with respect to burden estimates for mental and substance use disorders.
It is not possible to compare burden estimates arising from the GBD 1990 study with the most recent burden estimates. There have been important advances in the categorisation and definition of mental disorders, and the input and computation of epidemiological models for disease distribution. There have also been major changes to conceptual and social value choices aimed at addressing concerns that arose following publication of earlier GBD studies.
Advancements to the GBD conceptual framework and method of calculating burden estimates has led to more accurate and equitable consideration of the burden for mental and substance use disorders. Proposed annual updates of GBD estimates by the Institute of Health Metrics and Evaluation provide an opportunity to continue to advance the evidence base that underpins the quantification of disease burden.
When and why do women gain from increased descriptive representation in deliberating bodies? Using a large randomized experiment, and linking individual-level speech with assessments of speaker authority, we find that decision rules interact with the number of women in the group to shape the conversation dynamics and deliberative authority, an important form of influence. With majority rule and few women, women experience a negative balance of interruptions when speaking, and these women then lose influence in their own eyes and in others’. But when the group is assigned to unanimous rule, or when women are many, women experience a positive balance of interruptions, mitigating the deleterious effect of small numbers. Men do not experience this pattern. We draw implications for a type of representation that we call authoritative representation, and for democratic deliberation.
Despite their high prevalence, the global burden of anxiety disorders has never been calculated comprehensively. The new Global Burden of Disease (GBD) study has estimated burden due to morbidity and mortality caused by any anxiety disorder.
Prevalence was estimated using Bayesian meta-regression informed by data identified in a systematic review. Years of life lived with disability (YLDs) were calculated by multiplying prevalent cases by an average disability weight based on severity proportions (mild, moderate and severe). Disability-adjusted life years (DALYs) were then calculated and age standardized using global standard population figures. Estimates were also made for additional suicide mortality attributable to anxiety disorders. Findings are presented for YLDs, DALYs and attributable burden due to suicide for 21 world regions in 1990 and 2010.
Anxiety disorders were the sixth leading cause of disability, in terms of YLDs, in both high-income (HI) and low- and middle-income (LMI) countries. Globally, anxiety disorders accounted for 390 DALYs per 100 000 persons [95% uncertainty interval (UI) 191–371 DALYs per 100 000] in 2010, with no discernible change observed over time. Females accounted for about 65% of the DALYs caused by anxiety disorders, with the highest burden in both males and females experienced by those aged between 15 and 34 years. Although there was regional variation in prevalence, the overlap between uncertainty estimates means that substantive differences in burden between populations could not be identified.
Anxiety disorders are chronic, disabling conditions that are distributed across the globe. Future estimates of burden could be further improved by obtaining more representative data on severity state proportions.
We describe trends in incidence rates of methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected and HIV-uninfected patients enrolled in a large northern California Health Plan, and the ratio of MRSA to methicillin-susceptible S. aureus (MSSA) case counts. Between 1995 and 2010, 1549 MRSA infections were diagnosed in 14060 HIV-infected patients (11·0%) compared to 89546 MRSA infections in 6597396 HIV-uninfected patients (1·4%) (P = 0·00). A steady rise in MRSA infection rates began in 1995 in HIV-uninfected patients, peaking at 396·5 infections/100000 person-years in 2007. A more rapid rise in MRSA infection rates occurred in the HIV-infected group after 2000, peaking at 3592·8 infections/100000 in 2005. A declining trend in MRSA rates may have begun in 2008–2009. Comparing the ratio of MRSA to MSSA case counts, we observed that HIV-infected patients shouldered a greater burden of MRSA infection during most years of study follow-up compared to HIV-uninfected patients.