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 email@example.com
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.
Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.
Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).
Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a ‘good’ response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36–3.41; I2 = 48.9) and ‘any’ response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35–3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on ‘any’ response (74.7% v. 65%; RR 1.15; 95% CI 0.82–1.62).
Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.
Community advisory boards (CABs) are a valuable strategy for engaging and partnering with communities in research. Eighty-nine percent of Clinical and Translational Science Awardees (CTSA) responding to a 2011 survey reported having a CAB. CTSAs’ experiences with CABs are valuable for informing future practice. This study was conducted to describe common CAB implementation practices among CTSAs; document perceived benefits, challenges, and contributions; and examine their progress toward desirable outcomes. A cross-CTSA collaborative team collected survey data from respondents representing academic and/or community members affiliated with CTSAs with CABs. Data representing 44 CTSAs with CABs were analyzed using descriptive statistics. A majority of respondents reported practices reflecting respect for CAB members’ expertise and input such as compensation (75%), advisory purview beyond their CTSA’s Community Engagement program (88%), and influence over CAB operations. Three-quarters provide members with orientation and training on roles and responsibilities and 89% reported evaluating their CAB. Almost all respondents indicated their CTSA incorporates the feedback of their CABs to some degree; over half do so a lot or completely. This study profiles practices that inform CTSAs implementing a CAB and provide an evaluative benchmark for those with existing CABs.
Single patient or ‘n-of-1’ trials are a pragmatic method to achieve optimal, evidence-based treatments for individual patients. Such trials could be particularly valuable in chronic, heterogeneous, difficult to treat illnesses such as schizophrenia.
To identify how often, and in what way, n-of-1 trials have been used in schizophrenia.
We performed a systematic search in the major electronic databases for studies adopting n-of-1 methodology in schizophrenia, published in English from the start of records until the end of January 2017.
We identified six studies meeting inclusion criteria. There was wide variability in study methodology and analysis. Each trial reported positive outcomes for their respective intervention, but all studies were at high risk of bias.
In conclusion, n-of-1 trials are currently underutilised in schizophrenia. Existing trials suggest the method is well tolerated and potentially effective in achieving optimal treatments for patients, but more standardised methods of design, execution and analysis are required in future trials.
Declaration of interest
S.M.L. has received grants and personal fees from Janssen, and personal fees from Otsuka and Sunovion, in the past 3 years, outside the submitted work.
Effective translational research requires engagement and collaboration between communities, researchers, and practitioners. We describe a community scientist academy (CSA) developed at the suggestion of our Clinical and Translational Science Awards’ (CTSA) community advisory board to engage and capacitate community members by (1) increasing community members’ and patients’ understanding about the research process and (2) increasing their access to opportunities to influence and participate in research. A joint CTSA/community planning committee developed this 8-hour workshop including sessions on: (1) research definitions and processes; (2) study design; (3) study implementation; and (4) ways to get involved in research. The workshop format includes interactive exercises, content slides and videos, and researcher and community presenters.
Community-based information sessions allowed assessment of community interest before piloting. Two pilots of the CSA were conducted with community members and patients. Participant data and a pre/post knowledge and feedback survey provide evaluation data.
The pilot included 24 diverse participants, over half of whom had not previously participated in research. Evaluation data suggest knowledge gains. Post-CSA, one-third have reviewed CTSA pilot grants and over 80% want to attend further training.
The CSA can demystify the research process for those underrepresented in research and facilitate their engagement and influence within CTSAs.
We carried out a cross-sectional study to assess cognitive function in a sample of adult CHD patients, within the Functioning in Adult Congenital Heart Disease study London. The association between cognitive functioning and disease complexity was examined.
A total of 310 patients participated in this study. Patients were classified into four structural complexity groups – tetralogy of Fallot, transposition of the great arteries, single ventricle, and simple conditions. Each patient underwent neuropsychological assessment to evaluate cognitive function, including memory and executive function, and completed questionnaires to assess depression and anxiety.
Among all, 41% of the sample showed impaired performance (>1.5 SD below the normative mean) on at least three tests of cognitive function compared with established normative data. This was higher than the 8% that was expected in a normal population. The sample exhibited significant deficits in divided attention, motor function, and executive functioning. There was a significant group difference in divided attention (F=5.01, p=0.002) and the mean total composite score (F=5.19, p=0.002) between different structural complexity groups, with the simple group displaying better cognitive function.
The results indicate that many adult CHD patients display impaired cognitive function relative to a healthy population, which differs in relation to disease complexity. These findings may have implications for clinical decision making in this group of patients during childhood. Possible mechanisms underlying these deficits and how they may be reduced or prevented are discussed; however, further work is needed to draw conclusive judgements.
Objectives: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers.
Methods: We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3).
Results: A wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type.
Conclusions: Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks.
Ulúa-style marble vases played important social, political, economic, and religious roles in southern Mesoamerica during the seventh through eleventh centuries A.D. However, most such vessels known to archaeologists are part of looted collections or else were unearthed before the advent of modern archaeological practices. As a result, little is known about the context, use, and chronology of these objects. Recent investigations at the site of Palos Blancos in northwest Honduras discovered an Ulúa-style marble vase in an undisturbed mortuary context. Excavation of the burial context, along with bioarchaeological and stable isotope analysis of the human remains, suggests that the vase was placed as an offering, possibly to an ancestor of the residential group. Phosphate and pollen studies indicate that the vase once held a corn-based beverage . Radiocarbon dating of four charcoal samples from immediately below and adjacent to the vase yielded a range of dates from the beginning of the Late Classic period, ca.A.D. 600-800. Through analyses of the context and contents of the vase, this research contributes to a more holistic understanding of the use and meaning of Ulúa-style marble vases in southern Mesoamerica.
To identify factors associated with the presence and severity of food insecurity among a sample of Honduran caregivers of young children.
Cross-sectional study in which the dependent variable, household food insecurity, was measured using a fourteen-item questionnaire developed and validated in a population of similar cultural context. A predictive modelling strategy used backwards elimination in logistic regression and multinomial logit regression models to compute odds ratios and 95 % confidence intervals for food insecurity.
Rural Honduras in the department of Intibucá, between March and April 2009.
Two-hundred and ninety-eight Honduran caregivers of children aged 6–18 months.
Ninety-three per cent of households were classified as having some degree of food insecurity (mild, moderate or severe). After controlling for caregiver age and marital status, compared with caregivers with more than primary-school education, those with less than primary-school education had 3·47 (95 % CI 1·34, 8·99) times the odds of severe food insecurity and 2·29 (95 % CI 1·00, 5·25) times the odds of moderate food insecurity. Our results also found that child anthropometric status was not associated with the presence or severity of food insecurity.
These results show that among the sociodemographic factors assessed, food insecurity in rural Honduras is associated with maternal education. Understanding key factors associated with food insecurity that are unique to Honduras can inform the design of interventions to effectively mitigate the negative impact of food insecurity on children.
This study examined homemade masks as an alternative to commercial face masks.
Several household materials were evaluated for the capacity to block bacterial and viral aerosols. Twenty-one healthy volunteers made their own face masks from cotton t-shirts; the masks were then tested for fit. The number of microorganisms isolated from coughs of healthy volunteers wearing their homemade mask, a surgical mask, or no mask was compared using several air-sampling techniques.
The median-fit factor of the homemade masks was one-half that of the surgical masks. Both masks significantly reduced the number of microorganisms expelled by volunteers, although the surgical mask was 3 times more effective in blocking transmission than the homemade mask.
Our findings suggest that a homemade mask should only be considered as a last resort to prevent droplet transmission from infected individuals, but it would be better than no protection. (Disaster Med Public Health Preparedness. 2013;0:1–6)
Closure of tanks containing high-level radioactive waste (HLW) is a challenging problem involving potentially competing influences from economic, societal, and technological considerations. The U.S. Department of Energy (DOE) is faced with protecting public health and the environment while making economically responsible decisions. Risk (i.e., annual dose) is becoming more prominent as DOE's metric to evaluate the economic consequences of its decisions. Risks are assessed through modeling and calculations commonly known as performance assessment (PA). In the process of tank closure, the U.S. Nuclear Regulatory Commission (NRC) is typically consulted to perform an independent review of DOE's PAs.
The NRC staff developed a generic PA model, applicable to HLW tank closure, which NRC utilizes to complete its independent review. The model was developed using the generic simulation software, GoldSim, because of its probabilistic capabilities and its adaptability to different problems . The NRC staff uses the resultant risk from the generic models to evaluate the reasonableness of performance assessment models submitted by DOE. Large differences in the estimates of risk between the generic PA model and the DOE PA would likely indicate a need for stronger technical basis for processes significantly contributing to annual dose (risk) reduction.
Disperse Red 1 (DR1) doped TiO2-SiO2 inorganic-organic hybrid polymers were prepared by an anhydrous sol-gel process and second harmonic generation (SHG) of the fundamental 1053nm in these polymeric thin films was measured using Maker-fringe method. The nonlinear optical activity of DR1 in the thin films was studied by corona poling at different temperature (from room temperature to 140°C), and the stability of SHG after switching off corona power was evaluated by analyzing the SHG decay dynamics. Experimental results showed that the stability of the SHG of DR1 significantly increases with the cross-linkage degree of the TiO2SiO2 hybrid polymer network, and that the second harmonic coefficient d33 increases as the DR1 concentration increases. TiO2-doping can promote the polymerization of unsaturated C=C double bonds in the hybrid thin films during in-situ hot poling, enhancing the cross-linkage of the network of the hybrid material, and resulting in a great improvement of the stability of SHG. The excellent stability of second harmonic generation in the hybrid polymer thin films suggests that TiO2-doped inorganic-organic hybrid polymer is promising for chromophore doping for nonlinear optical applications.