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The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
Glycaemic index (GI) and glycaemic load (GL) values of some commonly consumed foods in the United Arab Emirates were determined with an aim of adding these values to the existing international table of GI and GL values. In all, eighteen test foods categorised into breads (n 5), entrée dishes (n 3), main dishes (n 5) and sweet dishes (n 5) were tested. For each test food, at least fifteen healthy participants consumed 25 or 50 g available carbohydrate portions of a reference food (glucose), which was tested three times, and a test food after an overnight fast, was tested once, on separate occasions. Capillary blood samples were obtained by finger-prick and blood glucose was measured using clinical chemistry analyser. A fasting blood sample was obtained at baseline and before consumption of test foods. Additional blood samples were obtained at 15, 30, 45, 60, 90 and 120 min after the consumption of each test food. The GI value of each test food was calculated as the percentage of the incremental area under the blood glucose curve (IAUC) for the test food of each participant divided by the average IAUC for the reference food of the same participant. The GI values of tested foods ranged from low (55 or less) to high (70 or more). The GI values of various breads and rice-containing dishes were comparable with previously published values. This study provides GI and GL values of previously untested traditional Emirati foods which could provide a useful guide on dietary recommendations for the Emirati population.
Apathy, characterized by diminished motivation, is a highly prevalent neuropsychiatric symptom in dementia. However, there is a substantial knowledge gap with regard to prevalence rates, neurobiological underpinnings, and effective treatments for apathy in pre-dementia states, including mild cognitive impairment (MCI) and mild behavioral impairment (MBI).
We conducted a comprehensive literature search using MEDLINE, Embase, and PsycINFO databases to identify available research on apathy in prodromal dementia.
Apathy has consistently been detected in individuals with MCI with varying prevalence rates, and only recently has literature discussed the prevalence of apathy in MBI. Few pharmacological treatments have been utilized for apathy, with galantamine and risperidone showing mild reductions in apathetic behaviors. Non-pharmacological interventions in prodromal dementia are beginning to be explored and show promise, but few studies have replicated those results.
More comprehensive guidelines for diagnosing apathy and further research investigating neurobiological mechanisms of apathy in MCI and MBI are required in order to effectively treat apathetic patients in prodromal dementia.
Objectives: The Priorities and Evaluation Committee (PEC) funding recommendations for new cancer drugs in British Columbia, Canada have been based on both clinical and economic evidence. The British Columbia Ministry of Health makes funding decisions. We assessed the association between cost-effectiveness of cancer drugs considered from 1998 to 2008 and the subsequent funding decisions.
Methods: All proposals submitted to the PEC between 1998 and 2008 were reviewed, and the association between cost-effectiveness and funding decisions was examined by (i) using logistic regression to test the hypothesis that interventions with higher incremental cost-effectiveness ratios (ICERs) have a lower probability of receiving a positive funding decision and (ii) using parametric and nonparametric tests to determine if a statistically significant difference exists between the mean cost-effectiveness of funded versus not funded proposals. A sub-analysis was conducted to determine if the findings varied across different outcome measures.
Results: Of the 149 proposals reviewed, 78 reported cost-effectiveness using various outcome measures. In the proposals that used life-years gained as the outcome (n = 22), a statistically significant difference of nearly $115,000 was observed between the mean ICERs for funded proposals ($42,006) and for unfunded proposals ($156,967). An odds ratio indicating higher ICERs have a lower probability of being funded was also found to be statistically significant (p < .05).
Conclusions: Economic evidence appears to play a role in British Columbia cancer funding decisions from 1998 to 2008; other decision-making criteria may also have an important role in recommendations and subsequent funding decisions.
The use of ultrasound for assessing diaphragmatic dysfunction after paediatric cardiac surgery may be under-utilised. This study aimed to evaluate the role of bedside ultrasound performed by an intensivist to diagnose diaphragmatic dysfunction and the need for plication after paediatric cardiac surgery.
We carried out a retrospective cohort study on prospectively collected data of postoperative children admitted to the paediatric cardiac ICU during 2013. Diaphragmatic dysfunction was suspected based on difficulties in weaning from positive pressure ventilation or chest X-ray findings. Ultrasound studies were performed by the paediatric cardiac ICU intensivist and confirmed by a qualified radiologist.
Out of 344 postoperative patients, 32 needed diaphragm ultrasound for suspected dysfunction. Ultrasound studies confirmed diaphragmatic dysfunction in 17/32 (53%) patients with an average age and weight of 10.8±3.8 months and 6±1 kg, respectively. The incidence rate of diaphragmatic dysfunction was 4.9% in relation to the whole population. Diaphragmatic plication was needed in 9/17 cases (53%), with a rate of 2.6% in postoperative cardiac children. The mean plication time was 15.1±1.3 days after surgery. All patients who underwent plication were under 4 months of age. After plication, they were discharged with mean paediatric cardiac ICU and hospital stay of 19±3.5 and 42±8 days, respectively.
Critical-care ultrasound assessment of diaphragmatic movement is a useful and practical bedside tool that can be performed by a trained paediatric cardiac ICU intensivist. It may help in the early detection and management of diaphragmatic dysfunction after paediatric cardiac surgery through a decision-making algorithm that may have potential positive effects on morbidity and outcome.
Toxoplasmosis affects a third of the global population and is of particular concern for immunologically compromised individuals. Toxoplasmosis induces host physiological events ranging from immunological to metabolic responses across multiple biological compartments. To understand the sequence of host responses during acute and chronic Toxoplasma gondii infection, eight male BALB/c mice were infected with 2000 T. gondii ME49 tachyzoites with a further eight uninfected mice used as controls. Plasma cytokines status, urinary metabolic profiling and fecal microbial profiles were characterized to monitor temporal variation related to T. gondii infection. The results showed elevated serum interferon-γ (IFN-γ), interleukin-12p40 and necrosis factor-α during acute phase of infection with concomitant perturbation in host energy metabolism and host-gut microbiome co-metabolism of phenolics and a shift in microbial composition. However, the differences were less pronounced during the putative chronic phase of infection with elevated IFN-γ, differences in urinary N-acetyls and O-acetyls of glycoproteins with no shift in gut microbial composition. Structural equation modelling on the current data showed host immune responses as the main driver for changes observed in urinary metabolites and gut microbial composition. Such an approach can be applied to other models of infectious diseases to aid understanding of host–pathogen interactions and potential biomarker discovery.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
This study aimed to measure changes in disease-specific quality of life in children following tonsillectomy or adenotonsillectomy.
A multicentre prospective cohort study was performed involving seven ENT departments in England. A total of 276 children entered the study over a 2-month period: 107 underwent tonsillectomy and 128 adenotonsillectomy. Forty-one children referred with throat problems initially managed by watchful waiting were also recruited. The follow-up period was 12 months. Outcome measures were the T14, parental impressions of their child's quality of life and the number of days absent from school.
One-year follow-up data were obtained from 150 patients (52 per cent). The mean baseline T14 score in the non-surgical group was significantly lower (T14 = 23) than in the tonsillectomy group (T14 = 31) or the adenotonsillectomy group (T14 = 35; p < 0.001). There was a significant improvement in the T14 scores of responders in all groups at follow up. The effect size was 1.3 standard deviations (SD) for the non-surgical group, 2.1 SD for the tonsillectomy group and 1.9 SD for the adenotonsillectomy group. Between-group differences did not reach statistical significance. A third of children in the non-surgical group underwent surgery during the follow-up period.
Children who underwent surgical intervention achieved a significant improvement in disease-specific quality of life. Less severely affected children were managed conservatively and also improved over 12 months, but 1 in 3 crossed over to surgical intervention.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.
A novel formulation of the flight dynamic equations is presented that permits a rapid solution for the design of trajectory following autopilots for nonlinear aircraft dynamic models. A robust autopilot control structure is developed based on the combination of the good features of the nonlinear dynamic inversion (NDI) method, integrator backstepping method, time scale separation and control allocation methods. The aircraft equations of motion are formulated in suitable variables so that the matrices involved in the block backstepping control design method are diagonally dominant. This allows us to use a linear controller structure for a trajectory following autopilot for the nonlinear aircraft model using the well known loop by loop controller design approach. The resulting autopilot for the fixed-wing rigid-body aircraft with a cascaded structure is referred to as the diagonally dominant backstepping (DDBS) controller. The method is illustrated here for an aircraft auto-landing problem under unknown actuator failures and severe winds. The requirement of state and control surface limiting is also addressed in the context of the design of the DDBS controller.
This study investigated improvements in quality of life associated with eight weeks of montelukast and/or intranasal steroid treatment for moderate to severe allergic rhinitis.
A single-centre, prospective, randomised, double-blind, placebo-controlled study was carried out. Assessments were made using the Rhinoconjunctivitis Quality of Life Questionnaire and symptom scales.
A total of 128 patients (aged 13–51 years) were randomly assigned to one of two groups. In the montelukast group, patients were treated with montelukast tablets and fluticasone propionate nasal spray (n = 64). In the placebo group, treatment comprised a placebo and fluticasone propionate. The results showed significant improvements in symptom scores and quality of life scores for both groups after one month and two months of treatment, compared with baseline values; these improvements were significantly greater for the montelukast group compared with the placebo group. The mean number of loratadine tablets taken by each patient during the study period was only 0.73 for the montelukast group compared with 9 for the placebo group.
The combination of montelukast tablets and fluticasone propionate nasal spray improved symptom control and overall quality of life for moderate to severe allergic rhinitis patients.
Two types of TiN/HfOx/TiN devices have been fabricated where the top 200nm TiN electrode has been deposited by two different sputtering methods; reactive, using a titanium target in a nitrogen environment, and non-reactive, using a titanium nitride target. Characterization of the materials shows that the reactive TiN is single-phase stoichiometric TiN with a sheet resistance of 7Ω/square. The non-reactive TiN has a sheet resistance of 300Ω/square and was found to contain significant amounts of oxygen. The resistive switching behavior differs for both devices. The reactive stoichiometric TiN device results in bipolar switching with a Roff/Ron ratio of 50. The non-reactive TiN results in unipolar switching with a Roff/Ron ratio of more than 103, however this device shows poor reproducibility. These results show that an oxygen rich layer between the top electrode and insulator affects the Roff value. It supports the theory of oxygen vacancies leading to the formation of conductive filaments.