To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
A prior systematic review on the efficacy of halofuginone (HFG) treatment to prevent or treat cryptosporidiosis in bovine calves was inconclusive. We undertook an updated synthesis and meta-analyses on key outcomes for the treatment of calves with HFG. Evaluated outcomes were oocyst shedding, diarrhoea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Most doses were 100–150 mcg kg−1 day−1. Results were subgrouped by study design, experiments with the lowest risk of bias and lack of industry funding. Eighteen articles were found that described 25 experiments. Most evidence came from randomized controlled trials in Europe. Significantly lower incidence of oocyst shedding, diarrhoea burden and mortality was reported when treatment started before calves were 5 days old. Most studies reported on outcomes for animals up to at least 28 days old. Publication bias was possible in all outcomes and seemed especially likely for diarrhoea outcomes. Beneficial results when HFG treatment was initiated in calves older than 5 days were also found. Prophylactic treatment to prevent cryptosporidiosis is effective in preventing multiple negative outcomes and is beneficial to calf health and will result in a reduction of environmental contamination by Cryptosporidium oocysts.
The recent COVID-19 pandemic has altered the face of biology, social interaction and public health worldwide. It has had a destructive effect upon millions of people and is approaching a devastating one million fatalities. Emerging evidence has suggested a link between the infection and gut microbiome status. This is one of the several factors that may contribute towards severity of infection. Given the fact that the gut is heavily linked to immunity, inflammatory status and the ability to challenge pathogens, it is worthwhile to consider dietary intervention of the gut microbiota as means of potentially challenging the viral outcome. In this context, probiotics and prebiotics have been used to mitigate similar respiratory infections. Here, we summarise links between the gut microbiome and COVID-19 infection, as well as propose mechanisms whereby probiotic and prebiotic interventions may act.
Healthcare employees were tested for antibodies against severe acute respiratory coronavirus virus 2 (SARS-CoV-2). Among 734 employees, the prevalence of SARS-CoV-2 antibodies was 1.6%. Employees with heavy coronavirus disease 2019 (COVID-19) exposure had similar antibody prevalence as those with limited or no exposure. Guidelines for PPE use seem effective for preventing COVID-19 infection in healthcare workers.
Increasing evidence suggests that circulating factors and immune dysfunction may contribute to the pathogenesis of schizophrenia. In particular, proinflammatory cytokines, complement and autoantibodies against CNS epitopes have recently been associated with psychosis. Related concepts in previous decades led to several clinical trials of dialysis and plasmapheresis as treatments for schizophrenia. These trials may have relevance for the current understanding of schizophrenia. We aimed to identify whether dialysis or plasmapheresis are beneficial interventions in schizophrenia. We conducted a systematic search in major electronic databases for high-quality studies (double-blinded randomised trials with sham controls) applying either haemodialysis or plasmapheresis as an intervention in patients with schizophrenia, published in English from the start of records until September 2018. We found nine studies meeting inclusion criteria, reporting on 105 patients in total who received either sham or active intervention. One out of eight studies reported a beneficial effect of haemodialysis on schizophrenia, one a detrimental effect and six no effect. The sole trial of plasmapheresis found it to be ineffective. Adverse events were reported in 23% of patients. Studies were at unclear or high risk of bias. It is unlikely that haemodialysis is a beneficial treatment in schizophrenia, although the studies were of small size and could not consider potential subgroups. Plasmapheresis was only addressed by one study and warrants further exploration as a treatment modality in schizophrenia.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Despite advances in the last decade, people with schizophrenia remain disabled by negative symptoms and function poorly in community settings. Until recently negative symptoms were neglected as a treatment target despite apparent recognition of their importance among clinicians.
To examine the impact of negative symptoms on psychosocial functioning in order to assess the importance of such symptoms as a potential treatment target.
295 community based participants with DSM4R schizophrenia were recruited in 11 different European centres and assessed using the following scales: PANSS, GAF, Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Recovery Scale in Schizophrenia (FRSS) and PsychoSocial Remission in Schizophrenia (PSRS). Relationships between and negative symptoms and functionality were examined using standard statistical approaches.
In this European cohort negative symptom scores were highly correlated with poor psychosocial functioning in participants living in the community. This significant trend occurred across different scales for measuring functional assessment.
The pharmacological treatment of schizophrenia appears rather becalmed at present. First and second generation antipsychotics appear to have similar efficacy for positive symptoms, different side effect profiles, but little impact on negative symptoms. This study shows a close relationship between negative symptoms and psychosocial functioning: high negative symptom scores are associated with poor functioning. This work supports the view that negative symptoms are a key target for drug development with significant potential benefit for the functioning of individuals. Drug development will increasingly focus on negative symptoms and develop effective adjunctive medication used with existing antipsychotics.
The effect of minor orthopaedic day surgery (MiODS) on patient's mood.
A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of General Anaesthesia (GA) were included. The Medical Outcomes Study-Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and postoperatively.
The mean physical component score of SF-36 before surgery was 45.3 (SD = ±10.1) and 8 weeks following surgery was 44.9 (SD = ±11.04) [n = 148, p = 0.51, 95%CI = (-1.03 -1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov = 69.44) corresponded to a correlation coefficient, r = 0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with χ2 (df = 1) = 0.86 for which p = 0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected.
MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.
Many patients with schizophrenia suffer from poor social functioning, with high levels of unemployment being one particular consequence. Negative symptoms tend to persist during periods of clinical stability and may have a detrimental effect on function. This paper aims to investigate the relationship between negative symptoms and ability to function.
The EGOFORS study measured negative symptoms in 295 schizophrenia patients in 11 European sites using the PANSS Negative Subscale and assessment scales for psychosocial function: Global Assessment of Functioning (GAF), Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Remission of General Schizophrenia (FROGS), Psychosocial Remission in Schizophrenia (PSRS) and Subjective Wellbeing under Neuroleptics (SWN). The relationships between the PANSS Negative Subscale and the functional scales were investigated, adjusting for differences between study sites. Being in work, duration of illness, age of onset and number of years of education were also investigated for a relationship with function.
There were strong, statistically significant correlations between PANSS Negative Subscale and all of the function scales (95% confidence intervals for the correlation coefficients: PSRS 0.77–0.91; FROGS 0.74–0.89; QLS 0.74–0.92; GAF 0.64–0.78; PSP 0.63–0.80) except the SWN. All of the functional scales except SWN were at least moderately related to one another. All of the items in each of the PANSS Negative Subscale and the function scales contributed to the relationships between them. Better functioning correlated strongly with participants being in work.
This study shows a strong and significant relationship between negative symptoms and psychosocial functioning. Given the impact of negative symptoms on psychosocial function, much more emphasis should be placed on developing effective treatments for negative symptoms, given that most patients with schizophrenia now live in community settings and require to function adequately to support their quality of life.
ll antipsychotics act via dopaminergic receptor antagonism. This pharmacology is shared by all first (FGA) & second (SGA) generation antipsychotics. We reviewed the efficacy & safety of all antipsychotics in clinical use for BMJ Clinical Evidence (Barry et al 2012).
Methods & questions
Our paper summarises key results from this systematic review based on comprehensive literature search of the Medline, Embase, Cochrane Library, and other databases including safety information from the FDA and MHRA in UK. The main clinical questions of interest were: What is the efficacy of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? How effective are treatments for people with schizophrenia resistant to standard antipsychotic drugs?
We found 51 systematic reviews, RCTs, or observational studies that met our inclusion/quality criteria and performed GRADE analysis to assess quality of evidence. Key results are presented for efficacy & safety for: amisulpiride, chlorpromazine, clozapine, depot haloperidol, haloperidol, olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine, aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol, zuclopenthixol, depot zuclopenthixol, and clozapine.
The evidence for some ‘standard’ treatments is surprisingly weak. Up to 1/3 -1/2 of patients fail to respond to currently available antipsychotics, and all antipsychotics cause side effects in most people. This downbeat conclusion is not surprising, given clinical experience and the common mechanism of action of all antipsychotics. More efficacious antipsychotic medication will only be developed from understanding the biological pathogenesis of schizophrenia.Barry S, Gaughin T, and Hunter R. Schizophrenia. BMJ Clinical Evidence 13 July 2012.
Extended brief interventions (EBIs) are effective in targeting alcohol misuse in the general population. However, little is known on the effects of EBI in adults with intellectual (also known as learning disabilities).
In this feasibility trial we compared EBI with usual care for alcohol misuse in adults with mild to moderate intellectual disability (ID).
The study took place in three community ID services in England. Participants aged 18–65 years with reported alcohol problems, a score > 8 on the alcohol use disorder identification test (AUDIT), and IQ < 70 (+/5% CI) were recruited and were randomly allocated to either EBI (5 weekly sessions and 1 follow-up at 8 weeks) and usual care or usual care alone. Research assessments took place at baseline, two and three months.
Thirty individuals were randomised (15 in each arm). In regard to harmful drinking, at baseline, all the participants exceeded the relevant threshold. At 8 weeks, the proportion of participants with harmful drinking decreased to 60% for both groups, at 12 weeks it was decreased by 66.7% and 46.7% for the intervention and the control group respectively. The unit cost for the delivery of EBI is £ 430.
Recruitment to this trial has been proven challenging as prevalence of alcohol misuse in the targeted population was lower than anticipated. EBI may provide an effective low intensity treatment for this population. Participants’ and carers’ feedback on their experience was overall positive.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Evidence suggests that dietary intake of UK children is currently suboptimal. It is therefore imperative to identify effective and sustainable methods of improving dietary habits and knowledge in this population, whilst also promoting the value of healthiness of food products beyond price. Schools are ideally placed to influence children's knowledge and health, and Project Daire, in partnership with schools, food industry partners and stakeholders, aims to improve children's knowledge of, and interest in, food to improve health, wellbeing and educational attainment.
Daire is a randomised-controlled, factorial design trial evaluating two interventions. In total, n = 880 Key Stage (KS) 1 and 2 pupils have been recruited from 18 primary schools in the North West of Northern Ireland and will be randomised to one of four 6-month intervention arms: i) ‘Engage’, ii) ‘Nourish’, iii) ‘Engage’ and ‘Nourish’ and iv) Delayed. ‘Engage’ is an age-appropriate, cross-curricular educational intervention on food, agriculture, science and careers linked to the current curriculum. ‘Nourish’ is an intervention aiming to alter schools’ food environments and increase exposure to local foods. Study outcomes include food knowledge, attitudes, trust, diet, behaviour, health and wellbeing and will be collected at baseline and six months. Qualitative data on teacher/pupil opinions will also be collected. The intervention phase is currently ongoing. We present baseline results from our involvement and food attitudes measure from all participating schools. Results were compared by Key Stage and sex using Pearson Chi-Squared test.
Baseline results from our food involvement and attitudes measure are presented for n = 880 KS1 (n = 454) and KS2 (n = 426) pupils. KS1 pupils were more likely to always or sometimes help with food shopping (89.0%) whilst KS2 pupils were more likely to always or sometimes help with food preparation (69.0%). A higher proportion of KS1 pupils reported liking to try new foods (66.1%) and that it was important that food looked (64.5%), tasted (71.1%) and smelled good (60.6%) compared with KS2 children (P < 0.01). Girls were more likely to always or sometimes help with food shopping (96.2%) and preparation (73%) when compared with boys; whilst a higher proportion of girls reported they liked to try new foods (48.2%) and that it was important that food looked (68%) smelled (50.5%) and tasted (71.8%) good compared with boys (P < 0.01).
Results suggest that involvement in food preparation and shopping, willingness to try new foods and attitudes towards food presentation varied by KS and sex in this cohort.
As consumer-directed care programmes become increasingly common in aged care provision, there is a heightened requirement for literature summarising the experience and perspectives of recipients. We conducted rapid evidence reviews on two components of consumer experience of home- and community-based aged care: (a) drivers of choice when looking for a service (Question 1 (Q1)); and (b) perceptions of quality of services (Question 2 (Q2)). We systematically searched MEDLINE and EMBASE databases, and conducted manual (non-systematic) searches of primary and grey literature (e.g. government reports) across CINAHL, Scopus, PsychINFO, and Web of Science, Trove and OpenGrey databases. Articles deemed eligible after abstract/full-text screening subsequently underwent risk-of-bias assessment to ensure their quality. The final included studies (Q1: N = 21; Q2: N = 19) comprised both quantitative and qualitative articles, which highlighted that consumer choices of services are driven by a combination of: desire for flexibility in service provision; optimising mobility; need for personal assistance, security and safety, interaction, and social/leisure activities; and to target and address previously unmet needs. Similarly, consumer perspectives of quality include control and autonomy, interpersonal interactions, flexibility of choice, and safety and affordability. Our reviews suggest that future model development should take into account consumers’ freedom to choose services in a flexible manner, and the value they place on interpersonal relationships and social interaction.
Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.
Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.
Intravenous dextrose aids in the resolution of ketosis in dehydrated patients not tolerating oral glucose and is often recommended in this clinical scenario. Our aim was to determine whether the addition of dextrose to intravenous rehydration solutions results in decreased hospital admissions or other clinically important benefits among dehydrated children or adults.
MEDLINE, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched by a medical librarian from inception through November 2017. The inclusion criteria were randomized controlled trials comparing dextrose containing intravenous solutions with intravenous solutions without dextrose in patients being treated for dehydration, and not already hospitalized.
The database and bibliographies search identified 1,472 unique citations. Only two trials (N = 333) met the inclusion criteria. Both compared normal saline with solutions of dextrose in normal saline. There was no statistically significant difference in admission rates (relative risk = 0.83; 95% confidence interval = 0.62 to 1.10) or revisits (relative risk = 0.54; 95% confidence interval = 0.24 to 1.22). Heterogeneity was low (I2 = 0). No other outcome results were eligible for pooling, but neither study found differences in any clinical outcomes. No adverse events were reported in either trial.
The addition of dextrose to intravenous saline has not been shown to improve clinical outcomes in dehydrated children presenting to the emergency department with gastroenteritis, but the confidence intervals around the estimate of effect are wide and include the possibility of substantial benefit.