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Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: Older (age >=65 years) trauma patients suffer increased morbidity and mortality. This is due to under-triage of older trauma victims, resulting in lack of transfer to a trauma centre or failure to activate the trauma team. There are currently no Canadian guidelines for the management of older trauma patients. The objective of this study was to identify modifiers to the prehospital and emergency department (ED) phases of major trauma care for older adults based on expert consensus. Methods: We conducted a modified Delphi study to assess senior-friendly major trauma care modifiers based on national expert consensus. The panel consisted of 24 trauma care providers across Canada, including medical directors, paramedics, emergency physicians, emergency nurses, trauma surgeons and trauma administrators. Following a literature review, we developed an online Delphi survey consisting of 16 trauma care modifiers. Three online survey rounds were distributed and panelists were asked to score items on a 9-point Likert scale. The following predetermined thresholds were used: appropriate (median score 7–9, without disagreement); inappropriate (median score 1–3; without disagreement), and uncertain (any median score with disagreement). The disagreement index (DI) is a method for measuring consensus within groups. Agreement was defined a priori as a DI score <1. Results: There was a 100% response rate for all survey rounds. Three new trauma care modifiers were suggested by panelists. Of 19 trauma care modifiers, the expert panel achieved consensus agreement for 17 items. The prehospital modifier with the strongest agreement to transfer to a trauma centre was a respiratory rate <10 or >20 breaths/minute or needing ventilatory support (DI = 0.24). The ED modifier with the strongest level of agreement was obtaining a 12-lead electrocardiogram following the primary and secondary survey for all older adults (DI = 0.01). Two trauma care modifiers failed to reach consensus agreement: transporting older patients with ground level falls to a trauma centre and activating the trauma team based solely on an age >=65 years. Conclusion: Using a modified Delphi process, an expert panel agreed upon 17 trauma care modifiers for older adults in the prehospital and ED phases of care. These modifiers may improve the delivery of senior-friendly trauma care and should be considered when developing local and national trauma guidelines.
Introduction: Acute heart failure (AHF) is a common emergency department (ED) presentation and may be associated with poor outcomes. Conversely, many patients rapidly improve with ED treatment and may not need hospital admission. Because there is little evidence to guide disposition decisions by ED and admitting physicians, we sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We conducted prospective cohort studies at 9 tertiary care hospital EDs from 2007 to 2019, and enrolled adult patients who required treatment for AHF. Each patient was assessed for standardized real-time clinical and laboratory variables, as well as for SSO (defined as death within 30 days or intubation, non-invasive ventilation (NIV), myocardial infarction, coronary bypass surgery, or new hemodialysis after admission). The fully pre-specified, logistic regression model with 13 predictors (age, pCO2, and SaO2 were modeled using spline functions with 3 knots and heart rate and creatinine with 5 knots) was fitted to the 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions and estimated a sample size of 170 SSOs. Results: The 2,246 patients had mean age 77.4 years, male sex 54.5%, EMS arrival 41.1%, IV NTG 3.1%, ED NIV 5.2%, admission on initial visit 48.6%. Overall there were 174 (7.8%) SSOs including 70 deaths (3.1%). The final risk scale is comprised of five variables (points) and had c-statistic of 0.76 (95% CI: 0.73-0.80): 1.Valvular heart disease (1) 2.ED non-invasive ventilation (2) 3.Creatinine 150-300 (1) ≥300 (2) 4.Troponin 2x-4x URL (1) ≥5x URL (2) 5.Walk test failed (2) The probability of SSO ranged from 2.0% for a total score of 0 to 90.2% for a score of 10, showing good calibration. The model was stable over 1,000 bootstrap samples. Choosing a risk model total point admission threshold of >2 would yield a sensitivity of 80.5% (95% CI 73.9-86.1) for SSO with no change in admissions from current practice (48.6% vs 48.7%). Conclusion: Using a large prospectively collected dataset, we created a concise and sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of this risk scoring scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: An important challenge physicians face when treating acute heart failure (AHF) patients in the emergency department (ED) is deciding whether to admit or discharge, with or without early follow-up. The overall goal of our project was to improve care for AHF patients seen in the ED while avoiding unnecessary hospital admissions. The specific goal was to introduce hospital rapid referral clinics to ensure AHF patients were seen within 7 days of ED discharge. Methods: This prospective before-after study was conducted at two campuses of a large tertiary care hospital, including the EDs and specialty outpatient clinics. We enrolled AHF patients ≥50 years who presented to the ED with shortness of breath (<7 days). The 12-month before (control) period was separated from the 12-month after (intervention) period by a 3-month implementation period. Implementation included creation of rapid access AHF clinics staffed by cardiology and internal medicine, and development of referral procedures. There was extensive in-servicing of all ED staff. The primary outcome measure was hospital admission at the index visit or within 30 days. Secondary outcomes included mortality and actual access to rapid follow-up. We used segmented autoregression analysis of the monthly proportions to determine whether there was a change in admissions coinciding with the introduction of the intervention and estimated a sample size of 700 patients. Results: The patients in the before period (N = 355) and the after period (N = 374) were similar for age (77.8 vs. 78.1 years), arrival by ambulance (48.7% vs 51.1%), comorbidities, current medications, and need for non-invasive ventilation (10.4% vs. 6.7%). Comparing the before to the after periods, we observed a decrease in hospital admissions on index visit (from 57.7% to 42.0%; P <0.01), as well as all admissions within 30 days (from 65.1% to 53.5% (P < 0.01). The autoregression analysis, however, demonstrated a pre-existing trend to fewer admissions and could not attribute this to the intervention (P = 0.91). Attendance at a specialty clinic, amongst those discharged increased from 17.8% to 42.1% (P < 0.01) and the median days to clinic decreased from 13 to 6 days (P < 0.01). 30-day mortality did not change (4.5% vs. 4.0%; P = 0.76). Conclusion: Implementation of rapid-access dedicated AHF clinics led to considerably increased access to specialist care, much reduced follow-up times, and possible reduction in hospital admissions. Widespread use of this approach can improve AHF care in Canada.
There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer’s disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here.
The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer’s Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria.
Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.
The aim of the present study was to determine the frequency of emotional and disruptive behaviours and the rates of hyperactivity, conduct and emotional problems in school-aged children. The Rutter Children’s Behaviour Questionnaire for completion by teachers was used to assess psychiatric symptoms. A total deviance score is derived from the sum of scores for the individual items (n= 26). An emotional sub-score can be obtained from the sum of scores of four items (worried, miserable, fearful, tears on arrival at school), a conduct sub-score obtained from the sum of scores of six items (destructive, fights, disobedient, lies, steals, bullies) and a hyperactivity sub-score obtained from the sum of scores of three items (restless/overactive, poor concentration, fidgety/squirmy). The sample comprised 877 children (446 girls) with an age range between 6 and 11 years. Compared to girls, boys showed a significantly higher frequency of restless/overactive (15.8% vs. 5.8%), fidgety/squirmy (9.3% vs. 3.6%), fights (6.3% vs. 2.2%), disobedient (6.0% vs. 2.7%), bullies (5.3% vs. 2.0%) and irritable (5.1% vs. 1.8%) behaviours. Rates of conduct and hyperactivity behavioural problems were also significantly more frequent in boys than in girls (conduct problems: 17.9% vs. 8.1%; hyperactivity problems: 20.4% vs. 9.6%). The high rates of disruptive behaviours and problems in boys are in accordance with the literature.
Recent advances in biomarker technology have allowed for the development of highly predictive tests for Alzheimer's disease (AD) when combined with standard psychometric tests. Current research in AD utilizes the ADAS-Cog and/or the MMSE as standard measures; they do not exclusively address the specific deficits expected in an amnesic syndrome of the hippocampal type as express with AD.
Because episodic memory degradation is most strongly predictive of conversion from mild cognitive impairment (MCI) to AD, a clinical measure targeting this deficit is warranted.
To utilize current knowledge of neural correlates of different stages of episodic memory function and their modulation by AD to develop a psychometrically sound instrument.
The authors developed a brief scale that captures registration, storage and retrieval of information along four identified domains of episodic memory in AD. A second stage was to confirm BEMA in institutionalized subjects, and assess reliability and validity.
Preliminary results indicate good test-retest reliability and adequate sensitivity and specificity. the BEMA was positively and significantly correlated with other measures of episodic memory. the [insert scale name or abbreviation] yields a total score, scores for 3 lifetime periods and the duration of episodic memory impairment.
Findings suggest that a richer understanding of the memory deficits in AD can lead to the development of an instrument which taps different aspects of episodic memory function. This scale can aid in the screening, assessment and treatment of early AD and complement the newly developed one-plus-one strategy.
Relationships between the seven dimensions of the Cloninger's psychobiological model (1993) and the five factors of the Costa and McCrae's model (1990) were examined in this study of 200 subjects from French general population. The dimensions of temperament (novelty seeking, harm avoidance, reward dependence) and character (self-directedness, cooperativeness, self-transcendence) from the Cloninger's model were measured by the Temperament and Character Inventory-125 items (TCI-125) and the Five-Factor Model (FFM) (neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) was evaluated using the NEOPersonality Inventory-Revised (NEO-PI-R). Correlation and multiple regression analyses have highlighted that all the temperamental and character dimensions predict all Neo-PI-R domains and vice versa. There are particularly close relationships between harm avoidance, self-directedness, neuroticism and extraversion; between novelty seeking and extraversion, openness, conscientiousness; between reward dependence, cooperativeness, extraversion, openness and agreeableness; between persistence and conscientiousness; and finally between self-transcendence and agreeableness. As a result, due to their relationship with temperamental dimensions of psychobiological model, the FFM domains could be related to brain monoaminergic activities.
Cognitive Behaviour Therapy has a good track record of being able to achieve meaningful change for many disorders, among them schizophrenia. In this presentation we would like to present three cases of patients with a diagnosis of severe or chronic or treatment-resistant schizophrenia and how the creative and innovative use of cognitive behaviour therapy strategies achieved meaningful change. In all cases detailed pre and post treatment data will be presented. Detailed sessions narratives will be presented as well as creative adaptions of standard CBT techniques.
The setting of therapy is a low secure psychiatric hospital in England. Patients have been in psychiatric care for at least 15 years.
Case 1: 'I need to learn to become immune to water'
A case of not washing as a result of a waterphobia.
Case 2: 'Life is unfair, but I am making the best of it'.
Physical handicaps in combination with paranoid schizphrenia make life unfair and anger provocing for this patient. Will cognitive behaviour therapy be bale to help?
Case 3: When I feel afraid; I have to do something that scares me.
For this patient with paranoid schizophrenia, feeling anxious results in doing very scary things. Can he learn to become less vulnerable to anxiety with CBT?
All cases will be briefly presented with a focus on the results achieved AND the adaptations needed to standard cognitive behaviour therapy in order to achieve these results.
Prognostic models discriminate between groups of individuals likely to experience better or worse outcomes and to predict response to treatment.
The premise of the analysis was the assumption that baseline PANSS measurements could be a prognostic factor to inform decisions on the expected response (completion or early-termination) to treatment during participation in a clinical trial.
To examine early patterns/profiles based on PANSS and response to treatment (Study-Completer (SC), Early-Termination (ET)).
Receiver Operating Curves (ROC) was conducted on 809 subjects with SC versus ET. Factor structure assessed whether psychopathology constructs are comparable across SC and ET.
Positive-Symptoms: P5.Grandiosity, P7.Hostility and P4.Excitement are not as good as others in predicting ET. 91.1% ET would have scores of 5, 6 or 7 on P1.Delusions.
Negative-Symptoms: N5. Difficulty in Abstract Thinking and N6.Lack of Spontaneity and Flow of Conversation are not as good in predicting ET. 67.9% ET may have scores of 5, 6 or 7 on N1.Blunted Affect. General-Psychopathology: G3.Guilt Feelings, G6.Depression, G7.Motor Retardation, and G10.Disorientation are not as good in predicting ET. 73.2% ET have scores of 5, 6 or 7 on G9.Unusual Thought Content. Positive Factor accounted for the most variance 15.885%, then Negative factor=14.592%, then Hostile-Excitement=11.973% for SC. For ET, Negative Factor=13.713% variance, cognitive factor=12.451%, Excitement Factor=10.396%.
These findings represent patterns of early detection of response in clinical trials, and have led to the development of sophisticated algorithms that may allow investigators to identify ET and SC, which is important in trial success.
Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulation technique used in many indications, especially in psychiatry in the treatment of mood disorders. Although its efficacy in this treatment has been demonstrated, the study of predictive response factors currently remains a major challenge.
We conducted a retrospective study from the cohort of treatment-resistant depressed patients that received rTMS treatment in Esquirol Hospital in Limoges in order to identify response predictors at three months. Of the 416 patients treated between January 2007 and November 2015, 107 subjects have been included. The clinical characteristics of responders and nonresponders at three months after treatment, but also at the end of treatment and after one month were compared. Predictors of clinical improvement objectified by the Hamilton Depression Rating Scale (HDRS) were identified using a logistic regression model.
In our cohort, the response rates were 52% at the end of treatment, 61% at 1 month and 57% at 3 months. Psychiatric family history and the recurrence of thymic episodes were found to be negative predictors of response to rTMS treatment. Similarly, high subscore of depression core symptoms in HDRS could also predict a poorer response.
Our data from a naturalistic cohort tended to prove that a number of clinical features should be taken into account in determining the profile of the treatment-resistant depressed patients that could respond to rTMS treatment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
As the primary risk factor for cardiovascular disease (CVD), hypertension is the leading cause of preventable, premature mortality globally. Hypertension, or elevated blood pressure (BP), has a number of well-established risk factors, including genetics. A common C677T polymorphism in the gene encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) affects 10–12% of UK and Irish populations and has been linked with 24–87% increased risk of hypertension globally. Evidence from randomised controlled trials (RCTs) conducted at this Centre has shown BP to be highly responsive (by 5–13 mmHg) to supplementation with riboflavin (MTHFR co-factor), an effect confined to homozygous individuals (TT genotype). To date, our trials have focused on peripheral BP; however, additional measures of vascular health such as central pressure are reported to be more closely correlated with CVD risk. Investigation of central BP, augmentation index (AIx) and pulse pressure amplification (PPA) may thus offer further insight into the role of this gene-nutrient interaction in blood pressure. The present study aims to investigate BP, and measures of vascular health in healthy adults stratified by MTHFR 677 genotype. Apparently healthy adults aged 18–60 years were recruited from workplaces across Northern Ireland and screened for MTHFR genotype via buccal swab. Clinic BP, anthropometry and blood sample were measured in TT individuals (n 209) and age and sex-matched CC (n 98) and CT (n 102) controls. AIx and central BP were assessed using SphygmoCor® (AtCor Medical, Australia). Preliminary results demonstrate higher BP in individuals with the MTHFR 677TT genotype compared to non-TT controls (systolic BP 134.7 ± 13.8 mmHg vs 129.7 ± 12.4 mmHg, P < 0.001; diastolic BP 81.6 ± 9.5 mmHg vs 79.7 mmHg ± 8.9 mmHg, P = 0.023, respectively). The MTHFR 677TT genotype group had significantly higher central systolic BP (119.4 ± 11.8 vs 116.7 ± 10.9 mmHg, P = 0.018), central pulse pressure (P = 0.006) and central mean pressure (P = 0.011) compared to the non-TT group. No significant differences for central diastolic BP, pulse pressure amplification, pulse pressure ratio and augmentation index were observed. This study confirms the phenotype of elevated BP in individuals with the C677T polymorphism in the gene encoding MTHFR. For the first time, this study reports that individuals with the MTHFR 677TT genotype have higher central systolic BP, central mean pressure and pulse pressure. Further investigations through RCTs investigating the effect of the MTHFR cofactor, riboflavin, on central blood pressure in these genetically at-risk adults are warranted.
Vitamin B12 deficiency is common among older adults, even with dietary intakes well in excess of current recommendations. Severe clinical B12 deficiency (i.e. pernicious anaemia) leads to irreversible neurological damage, but once diagnosed, can be treated effectively with B12 injections. A much more common cause of low vitamin B12 status in older adults is food-bound malabsorption owing to atrophic gastritis. This in turn leads to reduced gastric acid secretion, thus limiting B12 absorption from food (given the essential role of gastric acid in releasing B12 from food proteins). Proton pump inhibitor (PPI) drugs reduce gastric acid secretion, similar to atrophic gastritis, thus there is a concern that these medications may lead to vitamin B12 malabsorption. Therefore, the aim of this study was to investigate biomarker status of vitamin B12 in relation to atrophic gastritis and PPI usage. Data were accessed from The Trinity Ulster Department of Agriculture (TUDA) Ageing Cohort Study, a cross-sectional study of community-dwelling adults (n 5186, ≥ 60 years) recruited across Northern Ireland and the Republic of Ireland (2008–2012). TUDA participants were classified into 3 groups; ‘healthy’ controls, atrophic gastritis and PPI users. Vitamin B12 status was assessed using a total of four biomarkers: serum total B12; serum holotranscobalamin, holoTC; plasma methylmalonic acid, MMA; plasma homocysteine. Atrophic gastritis was identified using pepsinogen analysis (via ELISA), with a pepsinogen I : II ratio of < 3 considered indicative of atrophic gastritis. Based on results from all four biomarkers, participants with atrophic gastritis were found to have significantly lower B12 status compared to healthy controls: e.g. mean (95% CI) serum total vitamin B12, 188 (156, 218) pmol/L vs. 262 (252, 272) pmol/L P < 0.001; holoTC, 46.0 (38.1, 53.8) pmol/L vs. 60.3 (57.8, 62.8) pmol/L P < 0.001; plasma MMA, 0.65 (0.52, 0.78) μmol/L vs. 0.37 (0.32, 0.42) μmol/L P = 0.001. No differences in B12 biomarker concentrations were observed between PPI users and healthy controls. Regular consumption of fortified foods (i.e. ≥ 5 portions per week) compared to non-regular consumption (i.e. 0–4 portions per week) impacted positively on B12 biomarker status in all participants. This effect however appeared insufficient to restore normal vitamin B12 status in those with atrophic gastritis. These results show that older adults with atrophic gastritis have significantly lower vitamin B12 biomarker status, particularly in those who did not regularly consume fortified foods. Further investigations of the effect of atrophic gastritis and PPI usage on B12 status are warranted.
Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA.
We conducted a scoping review (Medline and EMBASE, 2000–2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters.
Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters.
This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.