Behavioral profile of adults with Prader-Willi syndrome : correlations with individual and environmental variables

Background: Maladaptive behavior has been reported as a phenotypical feature in Prader–Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. Methods: The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. Results: Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. Conclusions: Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was related to a lower severity of symptoms. Some major behavioral problems, such as hyperphagia, may be well controlled if living circumstances are adapted to the specific requirements of individuals with PWS.

Alternate lower extremity resistance training to increase stability in young and elderly adults

Gemstone Team BALANCE

Both CD4+ and CD8+ lymphocytes participate in the IFN-y response to filamentous hemagglutinin from Bordetella pertussis in infants, children and adults

Infant CD4+ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8 + T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8 + T-cell responses upon Bordetella pertussis infection in infants, children, and adults and pertussis vaccination in infants. Filamentous hemagglutinin-specific IFN-γ secretion by circulating lymphocytes was blocked by anti-MHC-I or -MHC-II antibodies, suggesting that CD4 + and CD8 + T lymphocytes are involved in IFN-γ production. Flow cytometry analyses confirmed that both cell types synthesized antigen-specific IFN-γ, although CD4 + lymphocytes were the major source of this cytokine. IFN-γ synthesis by CD8 + cells was CD4 + T cell dependent, as evidenced by selective depletion experiments. Furthermore, IFN-γ synthesis by CD4 + cells was sometimes inhibited by CD8 + lymphocytes, suggesting the presence of CD8 + regulatory T cells. The role of this dual IFN-γ secretion by CD4 + and CD8 + T lymphocytes in pertussis remains to be investigated. © 2012 Violette Dirix et al.

Feeding and overwintering of Antarctic krill across its major habitats: The role of sea ice cover, water depth, and phytoplankton abundance

Antarctic krill (Euphausia superba) were sampled in contrasting habitats: a seasonally ice-covered deep ocean (Lazarev Sea), ice-free shelves at their northern range (South Georgia) and the Antarctic Peninsula (Bransfield Strait), and shelf and oceanic sites in the Scotia Sea. Across 92 stations, representing a year-round average, the food volume in krill stomachs comprised 71 +/- 29% algae, 17 +/- 21% protozoans, and 12 +/- 25% metazoans. Fatty acid trophic markers showed that copepods were consistently part of krill diet, not a switch food. In open waters, both diatom and copepod consumption increased with phytoplankton abundance. Under sea ice, ingestion of diatoms became rare, whereas feeding on copepods remained constant. During winter, larvae contained high but variable proportions of diatom markers, whereas in postlarvae the role of copepods increased with krill body length. Overwintering differed according to habitat. Krill from South Georgia had lower lipid stores than those from the Bransfield Strait or Lazarev Sea. Feeding effort was much reduced in Lazarev Sea krill, whereas most individuals from the Bransfield Strait and South Georgia contained phytoplankton and seabed detritus in their stomachs. Their retention of essential body reserves indicates that krill experienced most winter hardship in the Lazarev Sea, followed by South Georgia and then Bransfield Strait. This was reflected in the delayed development from juveniles to adults in the Lazarev Sea. Circumpolar comparisons of length frequencies suggest that krill growth conditions are more favorable in the southwest Atlantic than in the Lazarev Sea or off East Antarctica because of longer phytoplankton bloom periods and rewarding access to benthic food.

Neuroactive substances and associated major muscle systems in Bucephaloides gracilescens (Trematoda : Digenea) metacercaria and adult

Cholinergic, serotoninergic and neuropeptidergic components of the nervous system were examined and compared in the progenetic metacercaria and adult gasterostome trematode, Bucephaloides gracilescens in order to provide baseline information on neuronal control of the musculature involved in egg-assembly. Enzyme cytochemistry and indirect immunocytochemical techniques interfaced with confocal scanning laser microscopy demonstrated all three classes of neuroactive substance throughout the central and peripheral nervous systems. A comparable orthogonal arrangement of the central nervous system (CNS) and peripheral array of nerve plexuses was observed in both metacercaria and adult. Staining patterns for cholinergic and peptidergic substances showed significant overlap, while the serotoninergic system was confined to a separate set of neurons. Immunostaining for FMRFamide-related peptides (FaRPs) was strong in the CNS and peripheral innervation to the attachment apparatus of metacercaria and adult but was only found in the innervation of the ootype in ovigerous adults, implicating FaRPs in neuronal control of the muscle of the female reproductive tract during egg-assembly.

Job Strain and Tobacco Smoking:An Individual-Participant Data Meta-Analysis of 166 130 Adults in 15 European Studies

BACKGROUND: Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults. METHODOLOGY AND PRINCIPAL FINDINGS: We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking. CONCLUSIONS: Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.

Smoking is a major cause of premature death worldwide

Question. How many deaths were attributable to smoking in 2000 worldwide? Study design. Statistical extrapolation of epidemiological and clinical data. Main results. In the year 2000, about 12% of adults died prematurely from smoking (estimated 4.83 million uncertainty range 3.94-5.93 million). Leading causes of death attributable to smoking were cardiovascular diseases (1.69 million deaths), chronic obstructive pulmonary disease (0.97 million deaths) and lung cancer (0.85 million deaths; 71% of lung cancers were smoking related). Smoking related deaths in men were about 3 times more common than women in industrial countries, and about 7 times more common in developing countries. Authors' conclusions. Smoking was a major cause of death worldwide in 2000. © 2004 Elsevier Ltd. All rights reserved.

Lung consequences in adults born prematurely

Although survival has improved significantly in recent years, prematurity remains a major cause of infant and childhood mortality and morbidity. Preterm births (<37 weeks of gestation) account for 8% of live births representing >50 000 live births each year in the UK. Preterm birth, irrespective of whether babies require neonatal intensive care, is associated with increased respiratory symptoms, partially reversible airflow obstruction and abnormal thoracic imaging in childhood and in young adulthood compared with those born at term. Having failed to reach their optimal peak lung function in early adulthood, there are as yet unsubstantiated concerns of accelerated lung function decline especially if exposed to noxious substances leading to chronic respiratory illness; even if the rate of decline in lung function is normal, the threshold for respiratory symptoms will be crossed early. Few adult respiratory physicians enquire about the neonatal period in their clinical practice. The management of these subjects in adulthood is largely evidence free. They are often labelled as asthmatic although the underlying mechanisms are likely to be very different. Smoking cessation, maintaining physical fitness, annual influenza immunisation and a general healthy lifestyle should be endorsed irrespective of any symptoms. There are a number of clinical and research priorities to maximise the quality of life and lung health in the longer term not least understanding the underlying mechanisms and optimising treatment, rather than extrapolating from other airway diseases.

Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report

BACKGROUND: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.

METHODS: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology.

RESULTS: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate.

CONCLUSIONS: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Smoking and All-cause Mortality in Older Adults: Results From the CHANCES Consortium

INTRODUCTION: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years.

METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.

RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively.

CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.

Prevalence of cataract and pseudophakia/aphakia among adults in the United States.

OBJECTIVES:

To determine the prevalence of cataract and pseudophakia/aphakia in the United States and to project the expected change in these prevalence figures by 2020.

METHODS:

Summary prevalence estimates of cataract and of pseudophakia/aphakia were prepared separately for black, white, and Hispanic persons (for whom only cataract surgery data were available) in 5-year age intervals starting at 40 years for women and men. The estimates were based on a standardized definition of various types of cataract: cortical, greater than 25% of the lens involved; posterior subcapsular, present according to the grading system used in each study; and nuclear, greater than or equal to the penultimate grade in the system used. Data were collected from major population-based studies in the United States, and, where appropriate, Australia, Barbados, and Western Europe. The age-, gender-, and race/ethnicity-specific rates were applied to 2000 US Census data, and projected population figures for 2020, to obtain overall estimates.

RESULTS:

An estimated 20.5 million (17.2%) Americans older than 40 years have cataract in either eye, and 6.1 million (5.1%) have pseudophakia/aphakia. Women have a significantly (odds ratio = 1.37; 95% confidence interval, 1.26-1.50) higher age-adjusted prevalence of cataract than men in the United States. The total number of persons who have cataract is estimated to rise to 30.1 million by 2020; and for those who are expected to have pseudophakia/aphakia, to 9.5 million.

CONCLUSION:

The number of Americans affected by cataract and undergoing cataract surgery will dramatically increase over the next 20 years as the US population ages.

Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Management of refractory status epilepticus in adults: still more questions than answers.

Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

Association of major and minor ECG abnormalities with coronary heart disease events.

CONTEXT: In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction. OBJECTIVE: To determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events. DESIGN, SETTING, AND PARTICIPANTS: A population-based study of 2192 white and black older adults aged 70 to 79 years from the Health, Aging, and Body Composition Study (Health ABC Study) without known cardiovascular disease. Adjudicated CHD events were collected over 8 years between 1997-1998 and 2006-2007. Baseline and 4-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict CHD events. MAIN OUTCOME MEASURE: Adjudicated CHD events (acute myocardial infarction [MI], CHD death, and hospitalization for angina or coronary revascularization). RESULTS: At baseline, 276 participants (13%) had minor and 506 (23%) had major ECG abnormalities. During follow-up, 351 participants had CHD events (96 CHD deaths, 101 acute MIs, and 154 hospitalizations for angina or coronary revascularizations). Both baseline minor and major ECG abnormalities were associated with an increased risk of CHD after adjustment for traditional risk factors (17.2 per 1000 person-years among those with no abnormalities; 29.3 per 1000 person-years; hazard ratio [HR], 1.35; 95% CI, 1.02-1.81; for minor abnormalities; and 31.6 per 1000 person-years; HR, 1.51; 95% CI, 1.20-1.90; for major abnormalities). When ECG abnormalities were added to a model containing traditional risk factors alone, 13.6% of intermediate-risk participants with both major and minor ECG abnormalities were correctly reclassified (overall net reclassification improvement [NRI], 7.4%; 95% CI, 3.1%-19.0%; integrated discrimination improvement, 0.99%; 95% CI, 0.32%-2.15%). After 4 years, 208 participants had new and 416 had persistent abnormalities. Both new and persistent ECG abnormalities were associated with an increased risk of subsequent CHD events (HR, 2.01; 95% CI, 1.33-3.02; and HR, 1.66; 95% CI, 1.18-2.34; respectively). When added to the Framingham Risk Score, the NRI was not significant (5.7%; 95% CI, -0.4% to 11.8%). CONCLUSIONS: Major and minor ECG abnormalities among older adults were associated with an increased risk of CHD events. Depending on the model, adding ECG abnormalities was associated with improved risk prediction beyond traditional risk factors.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.