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Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
There is an established link between birth parameters and risk of adult-onset cancers. The Developmental Origins of Health and Disease concept provides potential underlying mechanisms for such associations, including intrauterine exposure to endogenous hormones (androgens and estrogens), insulin-like growth factors, etc. However, there is conflicting evidence on the association between birth parameters and the cancer mortality risk. Therefore, we aimed to review and analyse the available data on the association linking birth weight and birth length with cancer mortality. Eleven studies were identified, published until April 2019. A significant association between birth weight and the prognosis of cancer (overall) was found (relative risk, RR 1.06, 95% confidence interval, CI: 1.01, 1.11), with low heterogeneity (I2 = 27.7%). In addition, higher birth weight was associated with poorer prognosis of prostate cancer (RR 1.21, 95% CI: 1.02, 1.44). However, the association of birth weight with breast cancer mortality risk in women was not significant (RR 1.16, 95% CI: 0.93, 1.44), which might be due to high statistical heterogeneity (I2 = 67.9%). Birth length was not associated with cancer mortality risk (RR 1.0, 95% CI: 0.90–1.11). It might be inferred that birth parameters are not associated with cancer mortality as strongly as with the risk of developing cancer. Also, the association between birth parameters and cancer mortality risk is not uniform and varies according to its subtypes, and study characteristics/design. This highlights the need for further prospective studies.
Sintered nanoparticle structures are macroscopically brittle but quite robust if deposited on a flexible substrate. The effects of a polymer substrate on the stretchability of both brittle and ductile coatings and traces are well established. Systematic effects of substrate properties on the fatigue resistance of aerosol printed nano-Ag are slightly more complex. The present work is focused on the early stages of fatigue, where the resistance increases significantly but cracks are not yet visible. Overall, the fatigue behavior is seen to vary with the combination of substrate modulus and viscoelastic deformation properties. Comparing two common polyimides, the rate of damage was seen to increase faster with increasing amplitude on the less compliant one. Consistently with this increasing the minimum strain in the cycle led to a significantly stronger reduction in damage rates. However, the damage rate remained lower on the less compliant substrate at all amplitudes and strain ranges of practical concern.
Animal sterols, plant sterols and bile acids in stool samples have been suggested as biomarkers of dietary intake. It is still unknown whether they also reflect long-term habitual dietary intake and can be used in aetiological research. In a subgroup of the Cooperative Health Research in the Augsburg Region (KORA FF4) study, habitual dietary intake was estimated based on repeated 24-h food list and a FFQ. Stool samples were collected according to a standard operating procedure and those meeting the quality criteria were extracted and analysed by means of a metabolomics technique. The present study is based on data from 513 men and 495 women with a mean age of 60 and 58 years, respectively, for which faecal animal and plant sterols and bile acids concentrations and dietary intake data were available. In adjusted regression models, the associations between food intake and log-normalised metabolite concentrations were analysed. Bonferroni correction was used to account for multiple testing. In this population-based sample, associations between habitual dietary intake and faecal concentrations of animal sterols were identified, while the impact of usual diet on bile acids was limited. A habitual diet high in ‘fruits’ and ‘nuts and seeds’ is associated with lower animal faecal sterols concentrations, whereas a diet high in ‘meat and meat products’ is positively related to faecal concentrations of animal sterols. A positive association between glycocholate and fruit consumption was found. Further studies are necessary for evaluation of faecal animal sterols as biomarkers of diet. The findings need to be confirmed in other populations with diverse dietary habits.
This descriptive paper aims to describe the design and implementation of a community engaged primary healthcare strategy in rural Australia, the Primary Healthcare Registered Nurse: Schools-Based strategy. This strategy seeks to address the health, education and social inequities confronting children and adolescents through community engaged service provision and nursing practice.
There have been increasing calls for primary healthcare approaches to address rural health inequities, including contextualised healthcare, enhanced healthcare access, community engagement in needs and solutions identification and local-level collaborations. However, rural healthcare can be poorly aligned to community contexts and needs and be firmly entrenched in health systems, marginalising community participation.
This strategy has been designed to enhance nursing service and practice responsiveness to the rural context, primary healthcare principles, and community experiences and expectations of healthcare. The strategy is underpinned by a cross-sector collaboration between a local health district, school education and a university department of rural health. A research framework is being developed to explore strategy impacts for service recipients, cross-sector systems, and the establishment and maintenance of a primary healthcare nursing workforce.
Although in the early stages of implementation, key learnings have been acquired and strategic, relationship, resource and workforce gains achieved.
We aimed to identify the validity and robustness of effect estimates for serious rare adverse events in clinical study reports of antidepressant trials, across different meta-analysis methods for rare binary events data (1,2).
Four serious rare adverse events (all-cause mortality, suicidality, aggressive behaviour and akathisia) were meta-analyzed using different methods (3). The Yusuf-Peto odds ratio (OR), which ignores studies with no events in the treatment arms, was compared with the alternative approaches of generalized linear mixed models (GLMM), conditional logistic regression, a Bayesian approach using Markov Chain Monte Carlo (MCMC) and a beta-binomial regression model.
Though the estimates for the four outcomes did not change substantially across the different analysis methods, the Yusuf-Peto method underestimated the treatment harm and overstimated its precision, especially when the estimated odds ratio (OR) deviated greatly from 1. For example the OR for suicidality for children and adolescents was 2.39 (95 percent Confidence Interval, CI 1.32 to 4.33, using the Yusuf-Peto method), but increased to 2.64 (95 percent CI 1.33 to 5.26) using conditional logistic regression, to 2.69 (95 percent CI 1.19 to 6.09) using beta-binomial, to 2.73 (95 percent CI 1.37 to 5.42) using the GLMM and finally to 2.87 (95 percent CI 1.42 to 5.98) using the MCMC approach.
The method used for meta-analysis of rare events data influences the estimates obtained and the exclusion of double zero-event studies can give misleading results. To ensure reduction of bias and erroneous inferences, sensitivity analyses should be performed using different methods and we recommend that the Yusuf-Peto approach should no longer be used. Other methods, in particular the beta-binomial method that was shown to be superior, should be considered instead.
Goats make up the largest group of ruminant livestock in Nigeria and are strategic in bridging animal protein supply gap and improving the economy of rural households. The hypervariable region 1 (HVR1) of the caprine mitochondrial genome was investigated to better understand genetic diversity important for improving selection for animal breeding and conservation programs. We sequenced and analysed the mitochondrial DNA (mtDNA) HVR1 in 291 unrelated indigenous Nigerian goats (West African Dwarf (WAD), Red Sokoto (RSO) and Sahel (SAH)), randomly sampled from around the country, and compared them with the HVR1 sequences of 336 Indian goats and 12 other sequences in five different species in the genus Capra (C. falconeri, C. ibex nubiana, C. aegagrus, C. cylindricornis and C. sibirica). A total of 139 polymorphic sites from 291 individuals were captured in 204 haplotypes. Within and among population variations were 77.25 and 22.74 percent, respectively. Nigerian goats showed high genetic diversity (0.87) and high FST values, and separate from Indian goats and other wild species. Haplogroups in WAD separates it from RSO and SAH concomitant with a different demographic history. Clear genetic structure was found among Nigerian goat breeds with appreciable variation in mtDNA HVR1 region. This study grouped Nigerian goat breeds into two major groups suggesting two different demographic origins for Northern and Southern breeds. High genetic admixing denotes different maternal origins and in contrast to evidence from goats from Levant and Central Asia, where goats were originally domesticated.
Documented prevalence of alcohol misuse among older adult patients at Birmingham Heartlands Hospital is significantly lower than the national prevalence. We aimed to evaluate our alcohol misuse screening protocol for older adults to identify possible shortcomings. Hospital protocol is to screen all adults for alcohol misuse in the accident and emergency (A&E) department using the Fast Alcohol Screening Test (FAST). One hundred consecutive consenting in-patients aged 65–94 admitted via A&E subsequently undertook an additional alcohol screening test (Michigan Alcoholism Screening Test-Geriatric version; MAST-G). Results of the two tests were compared.
FAST screening was completed for 71 patients and none were FAST-positive for alcohol misuse, yet using MAST-G, 18 patients scored positively for alcohol misuse. FAST screening failed to identify 8 patients with a documented history of alcohol misuse.
Older adult alcohol misuse prevalence is significantly underreported using FAST. Screening older adults for alcohol problems requires a different approach to screening the general population.
Social disability is a hallmark of severe mental illness yet individual
differences and factors predicting outcome are largely unknown.
To explore trajectories and predictors of social recovery following a
first episode of psychosis (FEP).
A sample of 764 individuals with FEP were assessed on entry into early
intervention in psychosis (EIP) services and followed up over 12 months.
Social recovery profiles were examined using latent class growth
Three types of social recovery profile were identified: Low Stable (66%),
Moderate-Increasing (27%), and High-Decreasing (7%). Poor social recovery
was predicted by male gender, ethnic minority status, younger age at
onset of psychosis, increased negative symptoms, and poor premorbid
Social disability is prevalent in FEP, although distinct recovery
profiles are evident. Where social disability is present on entry into
EIP services it can remain stable, highlighting a need for targeted
Early intervention services (EIS) comprise low-stigma, youth-friendly mental health teams for young people undergoing first-episode psychosis (FEP). Engaging with the family of the young person is central to EIS policy and practice.
By analysing carers' accounts of their daily lives and affective challenges during a relative's FEP against the background of wider research into EIS, this paper explores relationships between carers' experiences and EIS.
Semi-structured longitudinal interviews with 80 carers of young people with FEP treated through English EIS.
Our data suggest that EIS successfully aid carers to support their relatives, particularly through the provision of knowledge about psychosis and medications. However, paradoxical ramifications of these user-focused engagements also emerge; they risk leaving carers' emotions unacknowledged and compounding an existing lack of help-seeking.
By focusing on EIS's engagements with carers, this paper draws attention to an urgent broader question: as a continuing emphasis on care outside the clinic space places family members at the heart of the care of those with severe mental illness, we ask: who can, and should, support carers, and in what ways?
High performance materials that can withstand radiation, heat, multiaxial stresses, and corrosive environment are necessary for the deployment of advanced nuclear energy systems. Nondestructive in situ experimental techniques utilizing high energy x-rays from synchrotron sources can be an attractive set of tools for engineers and scientists to investigate the structure–processing–property relationship systematically at smaller length scales and help build better material models. In this study, two unique and interconnected experimental techniques, namely, simultaneous small-angle/wide-angle x-ray scattering (SAXS/WAXS) and far-field high-energy diffraction microscopy (FF-HEDM) are presented. The changes in material state as Fe-based alloys are heated to high temperatures or subject to irradiation are examined using these techniques.
Objectives: Colloquial evidence (CE) has been described as the informal evidence that helps provide context to other forms of evidence in guidance development. Despite challenges around quality, and the potential biases, the use of CE is becoming increasingly important in assessments where scientific literature is sparse and to also capture the experience of all stakeholders in discussions, including that of experts and patients. We aimed to ascertain how CE was being used at the National Institute for Health and Care Excellence (NICE).
Methods: Relevant data corresponding to the use of CE was extracted from all NICE technical and process manuals by two reviewers and quality assured and analyzed by a third reviewer. This was considered in light of the results of a focused literature review and a combined checklist for quality assessment was developed.
Results: At NICE, CE is utilised across all guidance producing programmes and at all stages of development. CE could range from information from experts and patient/carers, grey literature (including evidence from websites and policy reports) and testimony from stakeholders through consultation. Six tools for critical appraisal of CE were available from the literature and a combined best practice checklist has been proposed.
Conclusions: As decisions often need to be made in areas where there is a lack of published scientific evidence, CE is employed. Therefore to ensure its appropriateness the development of a validated CE data quality check-list to assist decision makers is essential and further research in this area is a priority.
In this paper, high temperature (>1400°C) thermal oxidation has been applied, for the first time, to 4H-SiC PiN diodes with thick (110 μm) drift regions, for the purpose of increasing the carrier lifetime in the semiconductor. PiN diodes were fabricated using 4H-SiC material that had undergone thermal oxidation performed at 1400°C, 1500°C and 1600°C, then were electrically characterized. Forward current-voltage (I-V) measurements showed that thermally oxidized PiN diodes exhibited considerably improved electrical characteristics, with devices oxidized at 1500°C having a forward voltage drop (VF) of 4.15 V and a differential on-resistance (Ron,diff) of 8.9 mΩ-cm2 at 100 A/cm2 and 25°C. Compared to typical control sample PiN diode characteristics, this equated to an improvement of 8% and 23% for VF and Ron,diff, respectively. From analysis of the reverse recovery characteristics, the carrier lifetime of the PiN diodes oxidized at 1500°C was found to be 1.05 μs, which was an improvement of around 30% compared to the control sample PiN diodes.
Retention of a nanostructure in thermoelectric materials through rapid sintering (e.g., field-assisted sintering) is generally associated with leaving certain amounts of porosity due to short sintering times. In this study, the influence of porosity on the thermoelectric transport properties in Bi2Te3-based alloys was studied by changing the sintering pressure during spark plasma sintering. N-type Bi2Te3 and p-type (Bi0.2Sb0.8)2Te3 were sintered at 673 K using pressures from 50 to 300 MPa to obtain different levels of porosity. Electrical resistivity, thermal conductivity, Seebeck coefficient, carrier concentrations, and Hall mobility were measured and characterized. The results show that increasing sintering pressure is effective in reducing porosity, which lowers electrical resistivity and increases the carrier concentrations. The transport properties were fitted to general effective medium equations and demonstrate that in p-type (Bi0.2Sb0.8)2Te3 sintered at high pressures, decreases in electrical resistivity and lattice thermal conductivity exceeded the Seebeck coefficient reduction, improving the thermoelectric figure of merit.