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Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time.
FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n = 69), 3 months (n = 29) and 12 months (n = 36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point.
Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed ‘enhancement’ followed by ‘coping with unpleasant affect’ and ‘social motive’ more highly for their cannabis use than any other reason. ‘Conformity and acceptance’ followed closely. ‘Relief of positive symptoms and side effects’ was the least endorsed motive.
Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated ‘enhancement’ most highly for their cannabis use.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
A systematic review and meta-analysis were conducted to determine the efficacy of selective dry-cow antimicrobial therapy compared to blanket therapy (all quarters/all cows). Controlled trials were eligible if any of the following were assessed: incidence of clinical mastitis during the first 30 DIM, frequency of intramammary infection (IMI) at calving, or frequency of IMI during the first 30 DIM. From 3480 identified records, nine trials were data extracted for IMI at calving. There was an insufficient number of trials to conduct meta-analysis for the other outcomes. Risk of IMI at calving in selectively treated cows was higher than blanket therapy (RR = 1.34, 95% CI = 1.13, 1.16), but substantial heterogeneity was present (I2 = 58%). Subgroup analysis showed that, for trials using internal teat sealants, there was no difference in IMI risk at calving between groups, and no heterogeneity was present. For trials not using internal teat sealants, there was an increased risk in cows assigned to a selective dry-cow therapy protocol, compared to blanket treatment, with substantial heterogeneity in this subgroup. However, the small number of trials and heterogeneity in the subgroup without internal teat sealants suggests that the relative risk between treatments may differ from the determined point estimates based on other unmeasured factors.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.
We conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.
In this manuscript we use realistic data to conduct a network meta-analysis using a Bayesian approach to analysis. The purpose of this manuscript is to explain, in lay terms, how to interpret the output of such an analysis. Many readers are familiar with the forest plot as an approach to presenting the results of a pairwise meta-analysis. However when presented with the results of network meta-analysis, which often does not include the forest plot, the output and results can be difficult to understand. Further, one of the advantages of Bayesian network meta-analyses is in the novel outputs such as treatment rankings and the probability distributions are more commonly presented for network meta-analysis. Our goal here is to provide a tutorial for how to read the outcome of network meta-analysis rather than how to conduct or assess the risk of bias in a network meta-analysis.
Vaccination against putative causal organisms is a frequently used and preferred approach to controlling bovine respiratory disease complex (BRD) because it reduces the need for antibiotic use. Because approximately 90% of feedlots use and 90% of beef cattle receive vaccines in the USA, information about their comparative efficacy would be useful for selecting a vaccine. We conducted a systematic review and network meta-analysis of studies assessing the comparative efficacy of vaccines to control BRD when administered to beef cattle at or near their arrival at the feedlot. We searched MEDLINE, MEDLINE In-Process, MEDLINE Daily Epub Ahead of Print, AGRICOLA, Cambridge Agricultural and Biological Index, Science Citation Index, and Conference Proceedings Citation Index – Science and hand-searched the conference proceedings of the American Association of Bovine Practitioners and World Buiatrics Congress. We found 53 studies that reported BRD morbidity within 45 days of feedlot arrival. The largest connected network of studies, which involved 17 vaccine protocols from 14 studies, was included in the meta-analysis. Consistent with previous reviews, we found little compelling evidence that vaccines used at or near arrival at the feedlot reduce the incidence of BRD diagnosis.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy for clinical mastitis in lactating dairy cattle. Controlled trials in lactating dairy cattle with natural disease exposure were eligible if they compared an antimicrobial treatment to a non-treated control, placebo, or a different antimicrobial, for the treatment of clinical mastitis, and assessed clinical or bacteriologic cure. Potential for bias was assessed using a modified Cochrane Risk of Bias 2.0 tool. From 14775 initially identified records, 54 trials were assessed as eligible. Networks were established for bacteriologic cure by bacterial species group, and clinical cure. Disparate networks among bacteriologic cures precluded meta-analysis. Network meta-analysis was conducted for trials assessing clinical cure, but lack of precision of point estimates resulted in wide credibility intervals for all treatments, with no definitive conclusions regarding relative efficacy. Consideration of network geometry can inform future research to increase the utility of current and previous work. Replication of intervention arms and consideration of connection to existing networks would improve the future ability to determine relative efficacy. Challenges in the evaluation of bias in primary research stemmed from a lack of reporting. Consideration of reporting guidelines would also improve the utility of future research.
Early in a foodborne disease outbreak investigation, illness incubation periods can help focus case interviews, case definitions, clinical and environmental evaluations and predict an aetiology. Data describing incubation periods are limited. We examined foodborne disease outbreaks from laboratory-confirmed, single aetiology, enteric bacterial and viral pathogens reported to United States foodborne disease outbreak surveillance from 1998–2013. We grouped pathogens by clinical presentation and analysed the reported median incubation period among all illnesses from the implicated pathogen for each outbreak as the outbreak incubation period. Outbreaks from preformed bacterial toxins (Staphylococcus aureus, Bacillus cereus and Clostridium perfringens) had the shortest outbreak incubation periods (4–10 h medians), distinct from that of Vibrio parahaemolyticus (17 h median). Norovirus, salmonella and shigella had longer but similar outbreak incubation periods (32–45 h medians); campylobacter and Shiga toxin-producing Escherichia coli had the longest among bacteria (62–87 h medians); hepatitis A had the longest overall (672 h median). Our results can help guide diagnostic and investigative strategies early in an outbreak investigation to suggest or rule out specific etiologies or, when the pathogen is known, the likely timeframe for exposure. They also point to possible differences in pathogenesis among pathogens causing broadly similar syndromes.
Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol (‘low-level response’) imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: http://clinicaltrials.gov/ct2/show/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.
Veno-arterial extracorporeal membrane oxygenation is frequently used in patients with cardiac disease. We evaluated short-term outcomes and identified factors associated with hospital mortality in cardiac patients supported with veno-arterial extracorporeal membrane oxygenation.
A retrospective review of patients supported with veno-arterial extracorporeal membrane oxygenation at a university-affiliated children’s hospital was performed.
A total of 253 patients with cardiac disease managed with extracorporeal membrane oxygenation were identified; survival to discharge was 48%, which significantly improved from 39% in an earlier era (1995–2001) (p=0.01). Patients were categorised into surgical versus non-surgical groups on the basis of whether they had undergone cardiac surgery before or not, respectively. The most common indication for extracorporeal membrane oxygenation was extracorporeal cardiopulmonary resuscitation: 96 (51%) in the surgical group and 45 (68%) in the non-surgical group. In a multiple covariate analysis, single-ventricle physiology (p=0.01), duration of extracorporeal membrane oxygenation (p<0.01), and length of hospital stay (p=0.03) were associated with hospital mortality. Weekend or night shift cannulation was associated with mortality in non-surgical patients (p=0.05).
We report improvement in survival compared with an earlier era in cardiac patients supported with extracorporeal membrane oxygenation. Single-ventricle physiology continues to negatively impact survival, along with evidence of organ dysfunction during extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, and length of stay.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Core-collapse supernova explosions are driven by a central engine that converts a small fraction of the gravitational binding energy released during core collapse to outgoing kinetic energy. The suspected mode for this energy conversion is the neutrino mechanism, where a fraction of the neutrinos emitted from the newly formed protoneutron star are absorbed by and heat the matter behind the supernova shock. Accurate neutrino-matter interaction terms are crucial for simulating these explosions. In this proceedings for IAUS 331, SN 1987A, 30 years later, we explore several corrections to the neutrino-nucleon scattering opacity and demonstrate the effect on the dynamics of the core-collapse supernova central engine via two dimensional neutrino-radiation-hydrodynamics simulations. Our results reveal that the explosion properties are sensitive to corrections to the neutral-current scattering cross section at the 10-20% level, but only for densities at or above ~1012 g cm−3.
Over 300 cases of acute toxoplasmosis are confirmed by reference testing in England and Wales annually. We conducted a case-control study to identify risk factors for Toxoplasma gondii infection to inform prevention strategies. Twenty-eight cases and 27 seronegative controls participated. We compared their food history and environmental exposures using logistic regression to calculate odds ratios (OR) and 95% confidence intervals in a model controlling for age and sex. Univariable analysis showed that the odds of eating beef (OR 10·7, P < 0·001), poultry (OR 6·4, P = 0·01) or lamb/mutton (OR 4·9, P = 0·01) was higher for cases than controls. After adjustment for potential confounders a strong association between beef and infection remained (OR 5·6, P = 0·01). The small sample size was a significant limitation and larger studies are needed to fully investigate potential risk factors. The study findings emphasize the need to ensure food is thoroughly cooked and handled hygienically, especially for those in vulnerable groups.
Infectious bovine keratoconjunctivitis (IBK) is a common and important disease of calves. Without effective vaccines, antibiotic therapy is often implemented to minimize the impact of IBK. This review updates a previously published systematic review regarding comparative efficacy for antibiotic treatments of IBK. Available years of Centre for Biosciences and Agriculture International and MEDLINE databases were searched, including non-English results. Also searched were the American Association of Bovine Practitioners and World Buiatrics Congress conference proceedings from 1996 to 2016, reviews since 2013, reference lists from relevant trials, and U.S. Food and Drug Administration New Animal Drug Application summaries. Eligible studies assessed antibiotic treatment of naturally-occurring IBK in calves randomly allocated to group at the individual level. Outcomes of interest were clinical score, healing time, unhealed ulcer risk, and ulcer surface area. A mixed-effects model comparing active drug with placebo was employed for all outcomes. Heterogeneity was assessed visually and using Cochran's Q-test. Thirteen trials assessing nine treatments were included. Compared with placebo, most antibiotic treatments were effective. There was evidence that the treatment effect differed by day of outcome measurement. Visually, the largest differences were observed 7–14 days post-treatment. These results indicate improved IBK healing with many antibiotics and suggest the need for randomized trials comparing different antibiotic treatments.
Implementation intentions link triggers for self-harm with coping skills
and appear to create an automatic tendency to invoke coping responses
when faced with a triggering situation.
To test the effectiveness of implementation intentions in reducing
suicidal ideation and behaviour in a high-risk group.
Two hundred and twenty-six patients who had self-harmed were randomised
to: (a) forming implementation intentions with a ‘volitional help sheet’;
(b) self-generating implementation intentions without help; or (c)
thinking about triggers and coping, but not forming implementation
intentions. We measured self-reported suicidal ideation and behaviour,
threats of suicide and likelihood of future suicide attempt at baseline
and then again at the 3-month follow-up.
All suicide-related outcome measures were significantly lower at
follow-up among patients forming implementation intentions compared with
those in the control condition (ds>0.35). The
volitional help sheet resulted in fewer suicide threats
(d = 0.59) and lowered the likelihood of future
suicide attempts (d = 0.29) compared with patients who
self-generated implementation intentions.
Implementation intention-based interventions, particularly when supported
by a volitional help sheet, show promise in reducing future suicidal
ideation and behaviour.
Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations.
A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively.
Both ‘bad’ and ‘enjoyable’ experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population.
These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more ‘bad’ and ‘enjoyable’ experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms.