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Compared to the general population, people with schizophrenia have a substantially higher risk of premature mortality which translates into a 10–15 year reduction in life expectancy. The aim of this investigation was to determine if symptoms (including aggression, hallucinations or delusions, and depression) or the environmental and functional status of people with schizophrenia contribute to the high mortality risk observed in this patient group.
We identified cases of schizophrenia, aged ≥15 years in a large secondary mental healthcare case register linked to national mortality tracing. We modelled the effect of specific symptoms, activities of daily living (ADLs), living conditions, occupational and recreational activities (Health of the Nation Outcome Scale [HoNOS] subscales) on all-cause mortality over a 4-year observation period (2007-10) using Cox regression.
We identified 4270 schizophrenia cases (170 deaths) in the observation period. After controlling for a broad range of covariates, mortality was not significantly associated with hallucinations and delusions or overactive-aggressive behaviour, but was associated with subclinical depression (adjusted HR 1.5; 95% CI 1.1-2.2) and ADL impairment (adjusted HR 1.8; 95% CI 1.2-2.9).
Severity of symptoms, such as delusions and hallucinations, was less important in predicting mortality than subclinical depression and difficulties carrying out activities of daily living. The overall picture appears to be one where the highest all-cause mortality risk is in service users who are least visible to clinical teams.
Public health monitoring is commonly undertaken in social media but has never been combined with data analysis from electronic health records. This study aimed to investigate the relationship between the emergence of novel psychoactive substances (NPS) in social media and their appearance in a large mental health database.
Insufficient numbers of mentions of other NPS in case records meant that the study focused on mephedrone. Data were extracted on the number of mephedrone (i) references in the clinical record at the South London and Maudsley NHS Trust, London, UK, (ii) mentions in Twitter, (iii) related searches in Google and (iv) visits in Wikipedia. The characteristics of current mephedrone users in the clinical record were also established.
Increased activity related to mephedrone searches in Google and visits in Wikipedia preceded a peak in mephedrone-related references in the clinical record followed by a spike in the other 3 data sources in early 2010, when mephedrone was assigned a ‘class B’ status. Features of current mephedrone users widely matched those from community studies.
Combined analysis of information from social media and data from mental health records may assist public health and clinical surveillance for certain substance-related events of interest. There exists potential for early warning systems for health-care practitioners.
Over the past decade, a growing interest has developed on the archaeology, palaeontology, and palaeoenvironments of the Arabian Peninsula. It is now clear that hominins repeatedly dispersed into Arabia, notably during pluvial interglacial periods when much of the peninsula was characterised by a semiarid grassland environment. During the intervening glacial phases, however, grasslands were replaced with arid and hyperarid deserts. These millennial-scale climatic fluctuations have subjected bones and fossils to a dramatic suite of environmental conditions, affecting their fossilisation and preservation. Yet, as relatively few palaeontological assemblages have been reported from the Pleistocene of Arabia, our understanding of the preservational pathways that skeletal elements can take in these types of environments is lacking. Here, we report the first widespread taxonomic and taphonomic assessment of Arabian fossil deposits. Novel fossil fauna are described and overall the fauna are consistent with a well-watered semiarid grassland environment. Likewise, the taphonomic results suggest that bones were deposited under more humid conditions than present in the region today. However, fossils often exhibit significant attrition, obscuring and fragmenting most finds. These are likely tied to wind abrasion, insolation, and salt weathering following fossilisation and exhumation, processes particularly prevalent in desert environments.
A longstanding issue in the field of nutrition is the potential inaccuracy of methods traditionally used for dietary assessment (i.e. food diaries and food frequency questionnaires). It is possible to overcome the limitations and biases of these techniques by combining them with analytical measurements in human biofluids. Metabolomic technologies are gaining popularity as nutritional tools due to their capacity to measure metabolic responses to external stimuli, such as the ingestion of certain foods. This project performed both LC-MS and 1H-NMR metabolomic profiling on serum samples collected as part of the NICOLA study (Northern Irish Cohort for the Longitudinal Study of Aging) in order to discover novel dietary biomarkers. A dietary validation cohort (NIDAS) was incorporated within NICOLA, involving 45 males and 50 females, aged 50 years and over. Participants provided detailed dietary data (4-day food diary) and blood samples at two time-points, six months apart. Serum samples were processed on two analytical platforms. 1H-NMR spectra were acquired using a Bruker 600 MHz Ascent coupled to a TCI cryoprobe and processed using Bayesil (University of Alberta, Canada). A Waters TQ-S coupled with an Acquity I-class UPLC was used in combination with a targeted commercially available kit (AbsoluteIDQ p180 kit, Biocrates). Mass spectra obtained were processed with MetIDQ and verified using MassLynx (v4.1). Data were tested for normality, and metabolite concentrations were correlated with recorded dietary intake of each food type using SPSS. Additional tests (PCA, PLS-DA, ROC Curves) were performed on MetaboAnalyst 4.0 (University of Alberta, Canada). More than 50 statistically significant (P < 0.05) food-metabolite correlations were detected, 15 of which remained significant after eliminating potential confounding from sex, age and BMI. The strongest correlations were between fruit consumption and acetic acid, and between dairy consumption and certain glycerophospholipids (e.g. LysoPC aa C20:3). Stratifying the cohort by gender yielded further correlations, including PC ae C38:2 (dairy; males), PC aa C34:4 (dairy; females), PC aa C36:4 (dairy; females) and trans-4-Hydroxyproline (meat; males). A number of potential blood-based food biomarkers were detected, many of which are gender-specific, and some are corroborated by previously published studies. However, further validation work is required. For example, biological plausibility needs to be established, and the findings need to be reproduced in other cohorts to demonstrate their applicability in larger and more diverse populations. These results contribute greatly to the ongoing efforts to discover and validate reliable nutritional biomarkers as an objective and unbiased measurement of food intake.
To update current estimates of non–device-associated pneumonia (ND pneumonia) rates and their frequency relative to ventilator associated pneumonia (VAP), and identify risk factors for ND pneumonia.
Academic teaching hospital.
All adult hospitalizations between 2013 and 2017 were included. Pneumonia (device associated and non–device associated) were captured through comprehensive, hospital-wide active surveillance using CDC definitions and methodology.
From 2013 to 2017, there were 163,386 hospitalizations (97,485 unique patients) and 771 pneumonia cases (520 ND pneumonia and 191 VAP). The rate of ND pneumonia remained stable, with 4.15 and 4.54 ND pneumonia cases per 10,000 hospitalization days in 2013 and 2017 respectively (P = .65). In 2017, 74% of pneumonia cases were ND pneumonia. Male sex and increasing age we both associated with increased risk of ND pneumonia. Additionally, patients with chronic bronchitis or emphysema (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.40–3.06), congestive heart failure (HR, 1.48; 95% CI, 1.07–2.05), or paralysis (HR, 1.72; 95% CI, 1.09–2.73) were also at increased risk, as were those who were immunosuppressed (HR, 1.54; 95% CI, 1.18–2.00) or in the ICU (HR, 1.49; 95% CI, 1.06–2.09). We did not detect a change in ND pneumonia risk with use of chlorhexidine mouthwash, total parenteral nutrition, all medications of interest, and prior ventilation.
The incidence rate of ND pneumonia did not change from 2013 to 2017, and 3 of 4 nosocomial pneumonia cases were non–device associated. Hospital infection prevention programs should consider expanding the scope of surveillance to include non-ventilated patients. Future research should continue to look for modifiable risk factors and should assess potential prevention strategies.
To update current estimates of non–device-associated urinary tract infection (ND-UTI) rates and their frequency relative to catheter-associated UTIs (CA-UTIs) and to identify risk factors for ND-UTIs.
Academic teaching hospital.
All adult hospitalizations between 2013 and 2017 were included. UTIs (device and non-device associated) were captured through comprehensive, hospital-wide active surveillance using Centers for Disease Control and Prevention case definitions and methodology.
From 2013 to 2017 there were 163,386 hospitalizations (97,485 unique patients) and 1,273 UTIs (715 ND-UTIs and 558 CA-UTIs). The rate of ND-UTIs remained stable, decreasing slightly from 6.14 to 5.57 ND-UTIs per 10,000 hospitalization days during the study period (P = .15). However, the proportion of UTIs that were non–device related increased from 52% to 72% (P < .0001). Female sex (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.50–2.50) and increasing age were associated with increased ND-UTI risk. Additionally, the following conditions were associated with increased risk: peptic ulcer disease (HR, 2.25; 95% CI, 1.04–4.86), immunosuppression (HR, 1.48; 95% CI, 1.15–1.91), trauma admissions (HR, 1.36; 95% CI, 1.02–1.81), total parenteral nutrition (HR, 1.99; 95% CI, 1.35–2.94) and opioid use (HR, 1.62; 95% CI, 1.10–2.32). Urinary retention (HR, 1.41; 95% CI, 0.96–2.07), suprapubic catheterization (HR, 2.28; 95% CI, 0.88–5.91), and nephrostomy tubes (HR, 2.02; 95% CI, 0.83–4.93) may also increase risk, but estimates were imprecise.
Greater than 70% of UTIs are now non–device associated. Current targeted surveillance practices should be reconsidered in light of this changing landscape. We identified several modifiable risk factors for ND-UTIs, and future research should explore the impact of prevention strategies that target these factors.
This article involved a broad search of applied sciences for milestone technologies we deem to be the most significant innovations applied by the North American pork industry, during the past 10 to 12 years. Several innovations shifted the trajectory of improvement or resolved significant production limitations. Each is being integrated into practice, with the exception being gene editing technology, which is undergoing the federal approval process. Advances in molecular genomics have been applied to gene editing for control of porcine reproductive and respiratory syndrome and to identify piglet genome contributions from each parent. Post-cervical artificial insemination technology is not novel, but this technology is now used extensively to accelerate the rate of genetic progress. A milestone was achieved with the discovery that dietary essential fatty acids, during lactation, were limiting reproduction. Their provision resulted in a dose-related response for pregnancy, pregnancy maintenance and litter size, especially in maturing sows and ultimately resolved seasonal infertility. The benefit of segregated early weaning (12 to 14 days of age) was realized for specific pathogen removal for genetic nucleus and multiplication. Application was premature for commercial practice, as piglet mortality and morbidity increased. Early weaning impairs intestinal barrier and mucosal innate immune development, which coincides with diminished resilience to pathogens and viability later in life. Two important milestones were achieved to improve precision nutrition for growing pigs. The first involved the updated publication of the National Research Council nutrient requirements for pigs, a collaboration between scientists from America and Canada. Precision nutrition advanced further when ingredient description, for metabolically available amino acids and net energy (by source plant), became a private sector nutrition product. The past decade also led to fortuitous discoveries of health-improving components in ingredients (xylanase, soybeans). Finally, two technologies converged to facilitate timely detection of multiple pathogens in a population: oral fluids sampling and polymerase chain reaction (PCR) for pathogen analysis. Most critical diseases in North America are now routinely monitored by oral fluid sampling and prepared for analysis using PCR methods.
Heat stress due to increasing extremes in ambient temperature and humidity results in reduced semen quality in boars. This has caused reduced efficiency of the swine industry, requiring more boars to breed the same number of sows. Vitamins such as vitamin C (VC) and E (VE) have been shown to improve semen quality in boars. Recently, vitamin D has been shown to improve semen quality in boars. The purpose of this experiment was to evaluate the effects of increased supplemental vitamins on boar reproduction during the summer season in a commercial boar stud. One hundred and sixty Pig Improvement Company (PIC) terminal line boars (n = 32 per treatment) and 39 maternal, heat-sensitive boars (n = 7 or 8 per treatment) were randomly allocated to treatment and fed a corn and soybean meal-based diet adjusted based on individual boar body condition score. A control (CNT) diet was used that met PIC recommendations for boars. Increased supplementation of specific vitamins was given in the form of a top-dress and consisted of CNT wheat middlings, CNT plus VC (560 mg/day), CNT plus 25-hydroxy vitamin D3 (VD) (125 µg/day), CNT plus VE (275 mg/day) and CNT plus VC, VD and VE (CDE). The experiment was split into three periods based on maximum daily high temperatures in the barn, where period 1 was weeks 1 to 4, period 2 was weeks 5 to 11 and period 3 was weeks 12 to 14. Semen was collected from boars as needed using the stud’s normal production schedule and was analyzed for sperm quantity and quality characteristics. There were no dietary effects on semen volume, sperm concentration or total sperm production (P ≥ 0.553). Total motility of sperm was not impacted by diet (P = 0.115); although, VC tended (P = 0.064) to have a greater progressive motility than CDE. Percentages of morphologically normal sperm and normal acrosomes were not affected by dietary supplementation (P ≥ 0.157). Period effects were observed for most semen quality parameters, with quality generally becoming reduced over time. The present study demonstrates that increased supplementation of vitamins beyond PIC recommendations was not beneficial for boar reproduction during the summer.
Natalizumab is an efficacious disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS), often limited by risk of progressive multifocal leukoencephalopathy. We describe the clinical course of RRMS patients switched from natalizumab to another DMT. We identified all RRMS patients treated with natalizumab ≥3 months with JC virus antibody positivity who switched to another DMT. Overall, 84 individuals switched DMT with 57 (68%) beginning fingolimod. On fingolimod, survival without a relapse was 74% (55.8–85.6%) at 36 months and survival without disease progression was 78% (62.6–87.6%) at 36 months. In conclusion, fingolimod is an effective therapy post-natalizumab.
Public involvement in service change has been identified as a key facilitator of health care transformation (Foley et al., 2017) but little is known about how health policy influences whether and how organisations involve the public in change processes. This qualitative study compares policy and practice for involving the public in major service changes across the UK's four health systems (England, Northern Ireland, Wales and Scotland). We analysed policy documents, and conducted interviews with officials, stakeholders, NHS staff and public campaigners (total number of interviewees = 47). Involving the public in major service change was acknowledged as a policy challenge in all four systems. Despite ostensible similarities, there were some clear differences between the four health systems' processes for involving patients and the public in major changes to health services. The extent of central Government oversight, the prescriptiveness of Government guidance, the role for intermediary bodies and arrangements for independent scrutiny of contentious decisions all vary. We analyse how health policy in the four systems has used ‘sticks’ and ‘sermons’ to promote particular approaches, and conclude that both policy and the wider system context within which health care organisations try to effect change are significant, and understudied aspect of contemporary practice.
In an on-demand media environment, the 2016 presidential primary debates provided a ratings and economic boost to host networks surpassing all prior primary debates and even major sporting events in viewership. In turn, millions of viewers were exposed to and subtly influenced by the ways in which these candidates were visually presented. We analyze how the Republican and Democratic presidential candidates were presented in their initial two debates (Fox News and CNN; CNN and CBS, respectively). Candidates are considered in terms of visual priming through aggregate camera time and average camera fixation time and how contenders were visually framed through the proportion of different camera shot types used (solo, split screen, side by side, multiple candidate, and audience reaction). Findings suggest that while the front-runners from both political parties benefited from preferential visual coverage, Donald Trump stood out in terms of the visual priming and framing that presented him as a serious contender.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
Under current Australian industry pre-slaughter guidelines, lambs may be off feed for up to 48 h before slaughter. The purpose of this study was to examine what proportion of circulating metabolites at slaughter are due to stress and feed deprivation and if this response differs between Merino and Terminal genotypes. In addition the effect of feed deprivation on carcass weight and meat quality was examined. Jugular blood samples were collected from 88 Merino and Terminal sired lambs at rest and at slaughter following 24, 36 and 48 h of feed deprivation and plasma analysed for glucose, lactate, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHOB). From the same carcasses hot carcass weight (HCWT) were measured as well as a suite of meat quality traits measured such as M. longissimus lumborum (loin) and M. semitendinosus pH at 24 h postmortem. Loin samples were also analysed for intramuscular fat content and Warner–Bratzer Shear Force. Merino sired lambs had a higher NEFA response compared to Terminal sired lambs at slaughter after 24, 36 and 48 h of feed deprivation, with NEFA levels up to 35% higher than previously reported in the same animals at rest in animal house conditions, whereas BHOB response to feed deprivation was not affected by sire type (P>0.05) and similar to previously reported at rest. In addition to the metabolic effects, increasing feed deprivation from 36 h was associated with a 3% reduction in HCWT and dressing percentage as well as causing increased ultimate pH in the M. semitendinosus in Merino sired lambs. Findings from this study demonstrate that Merino and Terminal sired lambs differ in their metabolic response to feed deprivation under commercial slaughter conditions. In addition, commercial feed deprivation appears to have a negative effect on ultimate pH and carcass weight and warrants further investigation.