Usefulness of three-dimensional echocardiography for assessment of left and right ventricular volumes in children,verified by cardiac magnetic resonance. Can we overcome the discrepancy?

IntroductionThe role of three-dimensional echocardiography (3D-ECHO) chamber quantification in children is still underestimated.Material and methodsIn 43 children 3D-ECHO measurements of end-diastolic (EDV) and end-systolic ventricular volumes (ESV) were compared to cardiac magnetic resonance (CMR) using Bland-Altman analysis and linear regression. The values of left and right ventricular volumes calculated in 3D-ECHO were compared with each other and verified by CMR.ResultsThe values of LV-EDV and LV-ESV measured in 3D-ECHO showed highly significant correlations with CMR (for LV-EDV r = 0.892, p < 0.00001; for LV-ESV r = 0.896, p < 0.00001). In the case of the right ventricle the correlation of 3D-ECHO results with CMR was still high (RV-EDV r = 0.848, p < 0.00001, RV-ESV r = 0.914, p < 0.00001), although mean RV-EDV and RV-ESV in 3D-ECHO were underestimated compared to CMR (by 38% for RV-EDV and 45% for RV-ESV). Correction of 3D-ECHO results using the coefficient of 1.38 and 1.45 for RV-EDV and RV-ESV, respectively, significantly improved the consistency of the results with CMR. 3D-ECHO offered lower mean values of right ventricular volumes compared to the left ventricle. The discrepancy was again reduced by the calculated coefficients.Conclusions3D-ECHO is a valuable tool for assessment of left ventricular volume, which strongly correlates and agrees with CMR. The right ventricular volumes calculated in 3D-ECHO tend to be significantly underestimated in comparison to CMR and corresponding left ventricular volumes obtained from 3D-ECHO. The use of coefficients developed by the study improves the consistency of right ventricular volumes measured by 3D-ECHO with results obtained by CMR and reduces the volumetric discrepancy between ventricles in 3D-ECHO.     

Increasing children's consumption of fruit and vegetables: does the type of exposure matter?

This study sought to determine how eight days of home exposure to information about healthful foods and eating behaviors in the form of children's books and a variety of fruit and vegetables interacted to affect 4- to 8-year-old children's (N=59) consumption of fruit and vegetables. Before and after the home exposure, children participated in a task in which their consumption of a variety of fruit and vegetables that ranged in familiarity was measured. Results indicated that exposure to food and books were both effective at increasing consumption of fruit, but not vegetables. Additionally, children who were exposed to books consumed more of an infrequently consumed fruit presented during the post-test, but only if they had not been exposed to food during the home exposure. Overall, children's fruit consumption increased more if their mothers did not pressure them to eat, and those who were less neophobic were more likely to try a novel fruit or vegetable during the post-test. These findings suggest that information and food variety both can be effective for increasing acceptance of fruit, and highlight the need for more research that investigates the efficacy of intervention strategies that promote vegetable consumption in young children.     

What are the Alternatives to Increasing Inhaled Corticosteroids for the Long Term Control of Asthma?

The Global Initiative for Asthma (GINA) guidelines stated the therapeutic goals for the management of asthma and, through a stepwise approach to treatment, defined the various grades of asthma severity and the therapeutic options available to the clinician at each step. This article considers the options at step 3; the management of a patient with poorly controlled asthma who is already taking low-dose inhaled corticosteroids. Before considering a change in therapy, the clinician should rule out alternative diagnoses, confirm compliance with treatment, explore potential exacerbants in the patient’s environment and, where possible, remove them. If a change in medication is necessary, the choice of drug will depend on the therapeutic goal that needs to be achieved. If the most important goal is the control of symptoms and optimisation of lung function, most studies support the addition of a long-acting β2-agonist to low dose inhaled corticosteroids. If recurrent severe exacerbations are a major feature of the poor control, increasing the dosage of inhaled corticosteroids may be most effective. The addition of a leukotriene antagonist may be the best choice if exercise-induced symptoms are prominent or in the setting of aspirin-sensitive asthma. General recommendations supported by the findings of large therapeutic trials do not allow for significant variability in the individual response to a particular drug. Receptor polymorphisms have recently been discovered that may account for variability in the response to β2-agonists and leukotriene receptor antagonists. However, until more is known about the reasons behind this variability, a therapeutic trial may be the most effective way of determining the best drug for an individual patient. One of the key developments in asthma over the past decade has been the acceptance of the concept of asthma as a chronic inflammatory disorder of the airways. However, the long term significance of this inflammation is not clear and the importance of control of inflammation beyond the suppression of symptoms, reduction of exacerbation frequency and the optimisation of lung function has not been established.     

Aging of the Immune System: How Much Can the Adaptive Immune System Adapt?

The competency of the adaptive immune function decreases with age, primarily because of the decline in production of naive lymphocytes in the bone marrow and thymus as well as the expansion of incompetent memory lymphocytes. Here I discuss the recent progress on age-associated changes in lymphocytes and their effect on the adaptive immune system.     

The Research Council System and the Politics of Medical and Agricultural Research for the British Colonial Empire, 1940–52

Historical accounts of colonial science and medicine have failed to engage with the Colonial Office’s shift in focus towards the support of research after 1940. A large new fund was created in 1940 to expand activities in the colonies described as fundamental research. With this new funding came a qualitative shift in the type of personnel and activity sought for colonial development and, as a result, a diverse group of medical and technical officers existed in Britain’s colonies by the 1950s. The fact that such variety existed amongst British officers in terms of their qualifications, institutional locations and also their relationships with colonial and metropolitan governments makes the use of the term ‘expert’ in much existing historical scholarship on scientific and medical aspects of empire problematic. This article will consider how the Colonial Office achieved this expansion of research activities and personnel after 1940. Specifically, it will focus on the reasons officials sought to engage individuals drawn from the British research councils to administer this work and the consequences of their involvement for the new apparatus established for colonial research after 1940. An understanding of the implications of the application of the research council system to the Colonial Empire requires engagement with the ideology promoted by the Agricultural Research Council (ARC) and Medical Research Council (MRC) which placed emphasis on the distinct and higher status of fundamental research and which privileged freedom for researchers. Keywords : Medical Research Council, Agricultural Research Council, Colonial Office, 1940 CDW Act, Colonial Medical Research Council, East Africa     

Can the laboratory affect the investigation and diagnosis of primary biliary cirrhosis?

BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by the presence of various laboratory abnormalities but the precise role of laboratory staff in initiating clinical referral and subsequent biopsy is not clear. OBJECTIVE: To examine the impact of laboratory abnormalities in the investigation of PBC. METHODS: In a retrospective study of laboratory results over nine years from 1996, computer records were reviewed to identify how many referrals for biopsy were initiated and subsequent diagnoses made as a result of clinical signs, raised serum alkaline phosphatase activity (ALP), raised IgM concentration, or positive mitochondrial antibodies accompanied by a clinical comment from the laboratory suggesting further action. RESULTS: 22 diagnoses of PBC were confirmed by histopathology. Eleven had high ALP activity which had follow up tests initiated by the laboratory (mitochondrial antibodies or IgM or both) and a comment added suggesting further investigation into the possibility of PBC. Seven had abnormal liver antibodies and one had a high polyclonal IgM concentration which prompted the relevant follow on testing and comments. One had an earlier diagnosis made on serological/clinical grounds and the biopsy was a confirmatory measure. One had no liver related antibodies. One had a request by laboratory staff for follow on tests but these were not asked for in subsequent samples by the requesting clinician. CONCLUSIONS: There is a positive role for laboratory staff in the diagnosis of PBC. Unexplained rises in ALP activity, positive mitochondrial antibodies, or raised IgM concentrations should be investigated more fully by laboratory staff and advice given to prompt a clinical referral for review and biopsy.     

How relevant is the impairment of smell for the quality of life in allergic rhinitis?

PURPOSE OF REVIEW: In the present review, the authors try to evaluate how relevant smell impairment is in patients suffering from allergic rhinitis and how it affects their quality of life. Smell dysfunction has a significant impact on the quality of life as it can lead to a wrong choice of food and intake, a reduction in appetite and eventually to weight loss, malnutrition, immunity reduction and worsening of medical illness. Patients with smell impairment are reported to use larger quantities of sugar and salt to highlight flavours, thus worsening their general health condition and increasing the risk of developing diabetes and hypertension. RECENT FINDINGS: Recent studies estimate that a complete loss of the sense of smell can be found in at least 1% of the US population, and that an impairment in the olfactory function can be highlighted in about 24% of individuals aged 53-97 years and 19% of individuals aged 20-92 years. Despite the high prevalence, subjective complaints do not accurately reflect the real disturbance experienced by the patient, and usually go unnoticed. SUMMARY: Current information in literature highlights the need for additional studies that concentrate on the impact of olfactory dysfunction on the quality of life of patients affected by allergic rhinitis.     

How can clinicians,specialty societies and others evaluate and improve the quality of apps for patient use?

Background

Health-related apps have great potential to enhance health and prevent disease globally, but their quality currently varies too much for clinicians to feel confident about recommending them to patients. The major quality concerns are dubious app content, loss of privacy associated with widespread sharing of the patient data they capture, inaccurate advice or risk estimates and the paucity of impact studies. This may explain why current evidence about app use by people with health-related conditions is scanty and inconsistent.

Main text

There are many concerns about health-related apps designed for use by patients, such as poor regulation and implicit trust in technology. However, there are several actions that various stakeholders, including users, developers, health professionals and app distributors, can take to tackle these concerns and thus improve app quality. This article focuses on the use of checklists that can be applied to apps, novel evaluation methods and suggestions for how clinical specialty organisations can develop a low-cost curated app repository with explicit risk and quality criteria.

Conclusions

Clinicians and professional societies must act now to ensure they are using good quality apps, support patients in choosing between available apps and improve the quality of apps under development. Funders must also invest in research to answer important questions about apps, such as how clinicians and patients decide which apps to use and which app factors are associated with effectiveness.

     

Can Google Searches Predict the Popularity and Harm of Psychoactive Agents?

Background

Predicting the popularity of and harm caused by psychoactive agents is a serious problem that would be difficult to do by a single simple method. However, because of the growing number of drugs it is very important to provide a simple and fast tool for predicting some characteristics of these substances. We were inspired by the Google Flu Trends study on the activity of the influenza virus, which showed that influenza virus activity worldwide can be monitored based on queries entered into the Google search engine.

Objective

Our aim was to propose a fast method for ranking the most popular and most harmful drugs based on easily available data gathered from the Internet.

Methods

We used the Google search engine to acquire data for the ranking lists. Subsequently, using the resulting list and the frequency of hits for the respective psychoactive drugs combined with the word “harm” or “harmful”, we estimated quickly how much harm is associated with each drug.

Results

We ranked the most popular and harmful psychoactive drugs. As we conducted the research over a period of several months, we noted that the relative popularity indexes tended to change depending on when we obtained them. This suggests that the data may be useful in monitoring changes over time in the use of each of these psychoactive agents.

Conclusions

Our data correlate well with the results from a multicriteria decision analysis of drug harms in the United Kingdom. We showed that Google search data can be a valuable source of information to assess the popularity of and harm caused by psychoactive agents and may help in monitoring drug use trends.     

Editorial At the Centre of a Science of Psychopathology? Characteristics and Limitations of Cognitive Research

In this brief paper I will suggest that the cognitive approach has four characteristics which must place it at the centre of any complete science of psychopathology: (1) it leads to testable hypotheses about abnormal mental states; (2) it establishes a link between normal psychology and abnormal mental processes, and therefore obviates the need to dichotomise behaviour into the normal and the abnormal; (3) it has the potential to make apparently bizarre and irrational behaviour understandable; and (4) it is neutral with regard to the relative contributions that biology and the environment make to the aetiology of psychiatric disorders. I also identify three limitations of contemporary cognitive models of psychiatric disorders: (1) an over-reliance on conventional methods of psychiatric classification; (2) an underemphasis on social aspects of cognition; and (3) a failure to integrate findings obtained from different models. Once these limitations are overcome, cognitive research is likely to lead to a revolution in our understanding of abnormal behaviour.     

Radiology Reporting in the Era of Patient-Centered Care: How Can We Improve Readability?

Radiology reports are consumed not only by referring physicians and healthcare providers, but also by patients. We assessed report readability in our enterprise and implemented a two-part quality improvement intervention with the goal of improving report accessibility. A total of 491,813 radiology reports from ten hospitals within the enterprise from May to October, 2018 were collected. We excluded echocardiograms, rehabilitation reports, administrator reports, and reports with negative scores leaving 461,219 reports and report impressions for analysis. A grade level (GL) was calculated for each report and impression by averaging four readability metrics. Next, we conducted a readability workshop and distributed weekly emails with readability GLs over a period of 6 months to each attending radiologist at our primary institution. Following this intervention, we utilized the same exclusion criteria and analyzed 473,612 reports from May to October, 2019. The mean GL for all reports and report impressions was above 13 at every hospital in the enterprise. Following our intervention, a statistically significant drop in GL for reports and impressions was demonstrated at all locations, but a larger and significant improvement was observed in impressions at our primary site. Radiology reports across the enterprise are written at an advanced reading level making them difficult for patients and their families to understand. We observed a significantly larger drop in GL for impressions at our primary site than at all other sites following our intervention. Radiologists at our home institution improved their report readability after becoming more aware of their writing practices.     

How robust is the evidence for viruses in the induction of type 1 diabetes?

Viruses associated with type 1 diabetes have eluded definition as causal, with the exception of rubella virus. False-negative results may have occurred due to the focus on subjects at symptomatic onset, who may be heterogeneous and differently affected by viruses. In addition, assays have not always been sufficiently sensitive to deal with transient infections, and pancreatic tissue is scarce. Longitudinal studies of at-risk subjects and more sensitive DNA techniques now reveal that at initiation of islet autoimmunity, enteroviruses have only a small role, but are more likely to be important at symptomatic onset. Rotaviruses remain associated with initiation of islet autoimmunity, and generate strong T cell responses in the young.     

Can an accelerometer enhance the utility of the Timed Up & Go Test when evaluating patients with Parkinson's disease?

IntroductionThe Timed Up and Go (TUG) test is a widely used measure of mobility and fall risk in older adults and in Parkinson's disease (PD). We tested the hypothesis that body-fixed accelerometers can provide insight into TUG performance in PD patients.MethodsWe examined 17 patients with PD (Hoehn and Yahr score: 2.7 ± 0.7; ON state) and 15 age-matched healthy controls; mean ages were 66.8 ± 5.9 years, 67.6 ± 9.6 years, respectively. Subjects wore a 3D-accelerometer (ADXL330, Analog Devices) on the lower back while performing the TUG test. Sit-to-Stand and Stand-to-Sit times were extracted from the anterior–posterior (AP) signal. Parameters included Sit-to-Stand, Stand-to-Sit durations, amplitude range (Range) and slopes (Jerk). Acceleration median and standard deviation (SD) were also calculated.ResultsStopwatch-based TUG duration tended to be higher for the PD patients compared to the control group, although not significantly (p = 0.08). In contrast, the TUG duration that was extracted from the acceleration signal was significantly (p < 0.02) higher in the PD group compared to the control group. Many acceleration-parameters were also significantly different (p < 0.05) between groups; most were not correlated with TUG duration.ConclusionsAccelerometer-derived parameters are sensitive to group differences, indicating that PD patients have poorer mobility during specific aspects of the TUG. In addition to test duration, these measures may serve as complementary and objective bio-markers of PD to augment the evaluation of disease progression and the response to therapeutic interventions.     

Can I be sued for that? Liability risk and the disclosure of clinically significant genetic research findings

Genomic researchers increasingly are faced with difficult decisions about whether, under what circumstances, and how to return research results and significant incidental findings to study participants. Many have argued that there is an ethical—maybe even a legal—obligation to disclose significant findings under some circumstances. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research. However, there is no explicit legal duty to disclose in the United States. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care. This article discusses liability risks associated with the disclosure of significant research findings for investigators in the United States.The return of individual research results and incidental findings to participants in genome research has stimulated extensive policy discussion and intense scholarly debate over the past several years. In the context of genome-wide research, it has been identified as one of the most pressing ethical challenges warranting immediate policy attention (Caulfield et al. 2008). Several professional bodies, in the United States and abroad, have published ethics recommendations suggesting an obligation to offer at least some individual research results to participants (National Bioethics Advisory Council 1999; Council for International Organizations of Medical Sciences 2002; United Nations Educational, Scientific and Cultural Organization 2003; Knoppers et al. 2006; Fabsitz et al. 2010; Office of Biorepositories and Biospecimen Research 2010; Cassa et al. 2012; World Medical Association 2013). Despite this, research suggests that genome scientists are not routinely returning research results or incidental findings to study participants (Heaney et al. 2010; Fullerton et al. 2012; McGuire et al. 2013; Ramoni et al. 2013). A survey of genome-wide association study (GWAS) investigators suggests that the fear of legal liability serves as both a motivation and a barrier to the return of results (Ramoni et al. 2013). On the one hand, investigators are concerned about their potential liability for failure to return results. In fact, Hank Greely suggests that not offering to return results may be illegal, at least in extreme circumstances where the results “pose a very high risk of a serious disease” (Greely 2007). On the other hand, investigators worry that they could be sued for adverse outcomes resulting from premature disclosure, the disclosure of inaccurate findings, or medical mismanagement resulting from disclosure. Yet, no United States regulations directly address this issue, and there is no clear case law to rely on. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care (Wennberg 2004).This article focuses on the disclosure of research results and clinically significant incidental findings (hereinafter “significant findings”) in the context of genetic research. We do not address the equally important and controversial issue of potential liability related to disclosure of incidental findings in the clinical context. We also focus specifically on genomic research but recognize that the liability issues are similar for other areas of research, such as neuroimaging research, where investigators are likely to discover clinically significant findings in the research context. We therefore look to case law in these other areas to help inform our analysis. We limit our discussion to findings that the researcher has knowledge of. Some have argued that there is a moral duty to hunt for significant findings, at least in the clinical context (Evans 2013). For example, the American College of Medical Genetics and Genomics (ACMG) recently published “Recommendations on Incidental Findings for Clinical Exome and Genome Sequencing” (Green et al. 2013) that suggests that clinical laboratories have a duty to seek out certain genetic variants that meet a high threshold of clinical utility. The recommendations are limited explicitly to clinical sequencing, and we do not think they should apply to research because of important differences between the nature of research and clinical care, which we describe elsewhere (Clayton and McGuire 2012) and summarize below. However, the authors of the “Recommendations” recognize that they may inform the development of research standards (Green et al. 2013). To the extent that they become widely adopted by the genome research community, they could create a new standard of care.Finally, we limit our analysis to United States law. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research (Open in a separate window     

How can directional and fluctuating asymmetry help in the prognosis of scoliosis along the course of the condition?

Fluctuating asymmetry (FA) is an indicator of developmental instability referred to random deviations from mean asymmetry. That average asymmetry is the directional asymmetry (DA), which, in the particular case of adolescent idiopathic scoliosis (AIS), corresponds to a right thoracic and left lumbar curves. Investigating the presence of FA and DA in AIS has never been done, and it is a key element of the pathophysiology of the scoliotic condition. Thirty-six X-rays of patients with AIS were digitized and analysed using Geometric Morphometric analyses to test for both statistical effects. The individual FA score for each patient was calculated using Procrustes ANOVA and a methodology based on the components of shape was used to estimate the individual DA score. DA is a stronger effect than FA (2.12 to 1), as it has been found in other clinical conditions. The individual DA score, with an effect size of 0.58, is a better predictor of the Cobb angle than FA score. The methodology presented in this paper to estimate DA score is a valid approach in the study of asymmetries in AIS. FA should be correlated in future studies with environmental covariates to serve as a variable in the medical prognosis, while DA will serve as a good predictor of the Cobb angle during the course of the condition, avoiding the abuse of X-rays. This potential use of DA should be tested on 3D shape due to the three-dimensional clinical presentation of AIS.     

Disconnection of man and the soil: reason for the asthma and atopy epidemic?

Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease.