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.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
Social and economic changes associated with new roads can bring about rapid nutritional transitions. To study this process, we: 1) describe trends in adult overweight and obesity (OW/OB) among rural Afro-Ecuadorians over time and across a gradient of community remoteness from the nearest commercial center; 2) examine the relationship between male and female adult OW/OB and factors associated with market integration such as changing livelihoods; and, 3) examine the co-occurrence of adult OW/OB and under-five stunting and anemia.
Adult anthropometry was collected through serial case-control studies repeated over a decade across twenty-eight communities. At the same time, anthropometry and hemoglobin were measured for all children under five in every community.
Northern coastal Ecuador.
Adults (N=1665) and children under five (N=2618).
From 2003 and 2013, OW/OB increased from 25.1% to 44.8% among men and 59.9% to 70.2% among women. The inverse relationship between remoteness and OW/OB in men was attenuated when adjusting for urban employment, suggesting that livelihoods mediated the remoteness-OW/OB relationship. No such relationship was observed among women. Communities with a higher prevalence of male OW/OB also had a greater prevalence of stunting, but not anemia, in children under five.
The association between male OW/OB and child stunting at the community level, but not the household level, suggests that changing food environments, rather than household- or individual-level factors, drove these trends. A closer examination of changing socioeconomic structures and food environments in communities undergoing rapid development could help mitigate future public health burdens.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Background: Stollery Children’s Hospital (SCH) is a tertiary-care pediatric hospital with a complex infrastructure: 3 NICUs located at 3 different hospitals, and all of the pediatric inpatient beds, PICU, PCICU, and a medical-surgical NICU at the main SCH site shared buildings with an academic adult hospital. We describe a collaborative process used to develop standardized SCH Infection Prevention and Control (IPC) recommendations. Methods: The SCH IPC formed a working group with Patient and Family-Centered Care (PFCC) and family representatives in 2014 to enhance the engagement of families in regards to IPC issues and initiatives. The working group identified inconsistent messages provided to families when a child was admitted as a patient requiring additional precautions (PRAP). The working group then developed a framework of key questions to be answered for family care providers of PRAP. The working group held several consultative meetings with frontline staff followed by a review of published guidelines and consultations with other pediatric hospitals about contentious issues. A consensus meeting with all key stakeholders was held to finalize IPC recommendations. Results: The key contentious issues included (1) whether personal protective equipment is required for family care providers who stay overnight with PRAP and (2) whether family care providers of PRAP are allowed to access nutrition centers on clinical units and family lounges in PCICU–PICU–NICU that were stocked with free hot meals for the families. No directly applicable recommendation was available IPC guidelines on these issues. Discussions of these topics were directed by PFCC at family councils of various clinical programs with efforts to seek opinions from more family representatives. Expert opinions and current practice were also obtained from Canadian hospitals through emails and from US hospitals through SHEA Open Forum by ICP. A final consensus meeting revisiting all available information was held, and a new Stollery IPC guideline was created with families as partners sharing the IPC vision of minimizing transmission risk at SCH. Conclusions: A consultative engagement and consensus process was successful in the development of IPC recommendations for family care providers for PRAP for implementation at a tertiary-care pediatric hospital with a complex infrastructure. The next step is to develop family-friendly educational and resource materials with clear and concise messages.
The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.
Case-Finding for Complex Chronic Conditions in Seniors 75+ (C5-75) is a systematic approach to identify frailty using gait speed and hand-grip strength and to screen for co-morbid conditions. We identified the C5-75 features offering the highest yield for identifying frailty and to streamline the screening program. Analyses included 1,948 C5-75 assessments completed from 2013 to 2018. Age 85 or older, less than regular physical activity, and more than two falls in the previous six months had the strongest associations with frailty. Exempting patients under 85 who reported regular physical activity and less than two falls excluded 39.1 per cent of the cohort while maintaining a sensitivity of 95.2 per cent and a negative predictive value of 99.4 per cent for frailty. These findings provide insight into optimizing screening for frailty, making it more feasible to implement and to identify co-existing conditions that may contribute to or be affected by frailty.
While extensive modelling - both physical and virtual - is imperative to develop right-first-time products, the parallel use of virtual and physical models gives rise to two interrelated issues: the lack of revision control for physical prototypes; and the need for designers to manually inspect, measure, and interpret modifications to either virtual or physical models, for subsequent update of the other. The Digital Twin paradigm addresses similar problems later in the product life-cycle, and while these digital twins, or the “twinning” process, have shown significant value, there is little work to date on their implementation in the earlier design stages. With large prospective benefits in increased product understanding, performance, and reduced design cycle time and cost, this paper explores the concept of using the Digital Twin in early design, including an introduction to digital twinning, examination of opportunities for and challenges of their implementation, a presentation of the structure of Early Stage Twins, and evaluation via two implementation cases.
Medicines regulation has become increasingly adaptive to support earlier patient access but the immature clinical data is often challenging for health technology assessment decision-makers due to high levels of uncertainty on long term risks and benefits. Scottish Medicines Consortium (SMC) is therefore exploring new, more adaptive approaches to help manage this challenge.
SMC consulted with key stakeholders including clinicians, the pharmaceutical industry and patient groups on a number of options that would allow the committee to make an interim decision that would be revisited based on later evidence. The ability to collect robust patient level data given data capabilities in National Health Service Scotland (NHSScotland) was an important consideration.
To ensure that additional evidence would be available to inform a re-assessment, the new approach applies to medicines with a Conditional Marketing Authorisation (MA) from the European Medicines Agency (EMA). This obligates the company to provide specified clinical data to the regulator within a pre-set timeframe. For these medicines, the SMC decision-making committee can accept or not recommend the medicine as at present but can also accept the medicine on an interim basis, if the regulator's mandated Specific Obligations are likely to address the uncertainties in the clinical evidence. When the regulator converts the MA from conditional to standard, the company is required to make a further SMC submission to allow a reassessment and a final decision. The company can also provide additional supplementary post-licensing patient level evidence at reassessment.
This new decision option allows SMC to test an approach to managing uncertainty targeted at a small number of promising new medicines where there is unmet patient need, with the reassurance that a final decision will be supported by additional clinical data.
Medicines for very rare conditions present challenges for healthcare globally due to uncertain evidence and often extremely high costs. In 2014, SMC introduced an ultra-orphan framework placing less emphasis on the cost per quality adjusted life year (QALY). Despite this, many medicines continued to be not recommended. A new pathway aimed at improved patient access based on further evidence collection is now being implemented.
The development of the new pathway has involved collaboration with key stakeholders including patient groups, the pharmaceutical industry, and clinicians. Medicines that meet a new definition (based on four criteria including the prevalence of the condition treated) will be appraised by the SMC committee and a data collection plan will then be agreed with the pharmaceutical company.
From April 2019, medicines validated as ultra-orphans will initially be appraised using the broader decision-making framework and the SMC committee will outline key uncertainties in the clinical effectiveness. The medicine will then be available for a period of at least three years while further data are gathered, potentially comprising ongoing clinical trials, registry data, and patient reported outcome measures. SMC will then re-assess the clinical and economic evidence to inform a final decision on routine use of the medicine in NHS Scotland.
The new pathway for ultra-orphan medicines will allow further evidence on their longer-term clinical benefits to be collected before a final decision on routine use. This approach reflects the current direction of travel in medicines regulation, by making medicines that address an unmet need available to patients at an earlier stage of development.
Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.
Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.
Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.
Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
Modern datasets provide the context necessary for accurate interpretations of isotopic data from archaeological faunal assemblages. In this study, we use the oxygen isotope ratios (δ18O) of modern small mammals from Chaco Canyon, New Mexico, to quantify expected isotopic variation in a local population. The δ18O values of local, modern small mammals encompass a broad range (−6.0‰ to 4.8‰ VPDB), which is expected given the extreme seasonal variation in the δ18O of precipitation on the Colorado Plateau (−11‰ to −3‰ VPDB). Isotopic ratios of small mammals obtained from excavated archaeological sites in Chaco Canyon (ca. AD 800 to 1200) show no significant differences with their modern counterparts, suggesting that there is no difference in the origins of the archaeological small-mammal collection and the modern, local Chaco Canyon small-mammal collection. In contrast, δ18O values of large mammals from Chaco archaeological sites are significantly different from those of modern specimens, reflecting a nonlocal, but also nonspecific, source in the past.
Mycobacterium marinum, a bacterium found in freshwater and saltwater, can infect persons with direct exposure to fish or aquariums. During December 2013, the New York City Department of Health and Mental Hygiene learned of four suspected or confirmed M. marinum skin or soft tissue infections (SSTIs) among persons who purchased whole fish from Chinese markets. Ninety-eight case-patients with non-tuberculous mycobacteria (NTM) SSTIs were identified with onset June 2013–March 2014. Of these, 77 (79%) were female. The median age was 62 years (range 30–91). Whole genome sequencing of clinical isolates revealed two main clusters and marked genetic diversity. Environmental samples from distributors yielded NTM though not M. marinum. We compared 56 case-patients with 185 control subjects who shopped in Chinese markets, frequency-matched by age group and sex. Risk factors for infection included skin injury to the finger or hand (odds ratio [OR]: 15·5; 95% confidence interval [CI]: 6·9–37·3), hand injury while preparing fish or seafood (OR 8·3; 95% CI 3·8–19·1), and purchasing tilapia (OR 3·6; 95% CI 1·1–13·9) or whiting (OR 2·7; 95% CI 1·1–6·6). A definitive environmental outbreak source was not identified.
Viewed from both an ethical and practical perspective, it is clearly desirable that public sector allocative and regulatory decisions should, so far as possible, reflect the preferences of individual members of society. It is therefore hardly surprising that, in appraising proposed safety improvements, public sector bodies have displayed an increasing tendency to estimate the benefits of such improvements on the basis of values of safety defined in such a way as to reflect the preferences and attitudes to safety of individual members of the public. However, given the technical complexity of many public sector safety decisions, it is also necessary to rely on expert analysis and informed judgement in reaching such decisions, so that preference-based values of safety should be regarded as being only one input to the decision-making process. In addition, the definition and estimation of the values themselves raise a number of practical and ethical questions. The purpose of this paper is to consider the role that preference-based values of safety can realistically be expected to play in these decision-making processes, given these difficulties and limitations.
This study examines the interplay between individual and social–developmental factors in the development of positive functioning, substance use problems, and mental health problems. This interplay is nested within positive and negative developmental cascades that span childhood, adolescence, the transition to adulthood, and adulthood. Data are drawn from the Seattle Social Development Project, a gender-balanced, ethnically diverse community sample of 808 participants interviewed 12 times from ages 10 to 33. Path modeling showed short- and long-term cascading effects of positive social environments, family history of depression, and substance-using social environments throughout development. Positive family social environments set a template for future partner social environment interaction and had positive influences on proximal individual functioning, both in the next developmental period and long term. Family history of depression adversely affected mental health functioning throughout adulthood. Family substance use began a cascade of substance-specific social environments across development, which was the pathway through which increasing severity of substance use problems flowed. The model also indicated that adolescent, but not adult, individual functioning influenced selection into positive social environments, and significant cross-domain effects were found in which substance-using social environments affected subsequent mental health.
Asian populations have a higher percentage body fat (%BF) and are at higher risk for CVD and related complications at a given BMI compared with those of European descent. We explored whether %BF was disproportionately elevated in rural Bangladeshi women with low BMI. Height, weight, mid-upper arm circumference, triceps and subscapular skinfolds and bioelectrical impedance analysis (BIA) were measured in 1555 women at 3 months postpartum. %BF was assessed by skinfolds and by BIA. BMI was calculated in adults and BMI Z-scores were calculated for females <20 years old. Receiver operating characteristic (ROC) curves found the BMI and BMI Z-score cut-offs that optimally classified women as having moderately excessive adipose tissue (defined as >30 % body fat). Linear regressions estimated the association between BMI and BMI Z-score (among adolescents) and %BF. Mean BMI was 19·2 (sd 2·2) kg/m2, and mean %BF was calculated as 23·7 (sd 4·8) % by skinfolds and 23·3 (sd 4·9) % by BIA. ROC analyses indicated that a BMI value of approximately 21 kg/m2 optimised sensitivity (83·6 %) and specificity (84·2 %) for classifying subjects with >30 % body fat according to BIA among adults. This BMI level is substantially lower than the WHO recommended standard cut-off point of BMI ≥ 25 kg/m2. The equivalent cut-off among adolescents was a BMI Z-score of –0·36, with a sensitivity of 81·3 % and specificity of 80·9 %. These findings suggest that Bangladeshi women exhibit excess adipose tissue at substantially lower BMI compared with non-South Asian populations. This is important for the identification and prevention of obesity-related metabolic diseases.
A patient with no risk factors for malaria was hospitalized in New York City with Plasmodium falciparum infection. After investigating all potential sources of infection, we concluded the patient had been exposed to malaria while hospitalized less than 3 weeks earlier. Molecular genotyping implicated patient-to-patient transmission in a hospital setting.
Infect. Control Hosp. Epidemiol. 2015;37(1):113–115