Foot ulceration and its association with mortality in diabetes mellitus: a meta-analysis.

BACKGROUND: Diabetic foot ulcers portend an almost twofold increase in all-cause mortality compared with diabetes on its own. AIM: To investigate the association between diabetic foot ulcers and risk of death. METHODS: We performed a meta-analysis of all observational studies investigating the association between diabetic foot ulcers and all-cause mortality. Risk ratios and risk differences were pooled in a random-effects model. The I2 statistic was used to quantify heterogeneity between studies. RESULTS: Altogether, we identified 11 studies that reported 84 131 deaths from any cause in 446 916 participants with diabetes during a total of 643 499 person-years of follow-up. The crude event rate for all-cause mortality in individuals with diabetes who did not develop foot ulceration was 22% lower at 181.5 deaths (per 1000 person-years) than in those who developed foot ulcers (230.8 per 1000 person-years). Diabetic foot ulceration was associated with an increased risk of all-cause mortality (pooled relative risk 2.45, 95% CI 1.85-2.85). We did not observe any tangible differences in risk of all-cause mortality from diagnosis in studies reporting a mean duration of follow-up of ≤3 years (relative risk 2.43, 95% CI 2.27-2.61) or >3 years (relative risk 2.26, 95% CI 2.13-2.40) years. Funnel plot inspection revealed no significant publication bias among studies included in this meta-analysis. CONCLUSIONS: Our study shows an excess rate of all-cause mortality in people with diabetic foot ulceration when compared to those without foot ulceration. It is imperative that early interventions to prevent foot ulceration and modify cardiovascular disease risk factors are put in place to reduce excess mortality.

Developing a foot ulcer risk model: what is needed to do this in a real-world primary care setting?

AIM: To determine how routinely collected data can inform a risk model to predict de novo foot ulcer presentation in the primary care setting. METHODS: Data were available on 15 727 individuals without foot ulcers and 1125 individuals with new foot ulcers over a 12-year follow-up in UK primary care. We examined known risk factors and added putative risk factors in our logistic model. RESULTS: People with foot ulcers were 4.2 years older (95% CI 3.1-5.2) than those without, and had higher HbA1c % (mean 7.9 ± 1.9 vs 7.5 ± 1.7) / HbA1c mmol/mol (63 ± 21 vs 59 ± 19) (p<0.0001) concentration [+0.45 (95% CI 0.33-0.56), creatinine level [+6.9 µmol/L (95% CI 4.1-9.8)] and Townsend score [+0.055 (95% CI 0.033-0.077)]. Absence of monofilament sensation was more common in people with foot ulcers (28% vs 21%; P<0.0001), as was absence of foot pulses (6.4% vs 4.8%; P=0.017). There was no difference between people with or without foot ulcers in smoking status, gender, history of stroke or foot deformity, although foot deformity was extremely rare (0.4% in people with foot ulcers, 0.6% in people without foot ulcers). Combining risk factors in a single logistic regression model gave modest predictive power, with an area under the receiver-operating characteristic curve of 0.65 (95% CI 0.62-0.67). The prevalence of ulceration in the bottom decile of risk was 1.8% and in the top decile it was 13.4% (compared with an overall prevalence of 6.5%); thus, the presence of all six risk factors gave a relative risk of 7.4 for development of a foot ulcer over 12 years. CONCLUSION: We have made some progress towards defining a variable set that can be used to create a foot ulcer prediction model. More accurate determination of foot deformity/pedal circulation in primary care may improve the predictive value of such a future risk model, as will identification of additional risk variables.

Psychological treatments for early psychosis can be beneficial or harmful, depending on the therapeutic alliance: an instrumental variable analysis.

BACKGROUND: The quality of the therapeutic alliance (TA) has been invoked to explain the equal effectiveness of different psychotherapies, but prior research is correlational, and does not address the possibility that individuals who form good alliances may have good outcomes without therapy. METHOD: We evaluated the causal effect of TA using instrumental variable (structural equation) modelling on data from a three-arm, randomized controlled trial of 308 people in an acute first or second episode of a non-affective psychosis. The trial compared cognitive behavioural therapy (CBT) over 6 weeks plus routine care (RC) v. supportive counselling (SC) plus RC v. RC alone. We examined the effect of TA, as measured by the client-rated CALPAS, on the primary trial 18-month outcome of symptom severity (PANSS), which was assessed blind to treatment allocation. RESULTS: Both adjunctive CBT and SC improved 18-month outcomes, compared to RC. We showed that, for both psychological treatments, improving TA improves symptomatic outcome. With a good TA, attending more sessions causes a significantly better outcome on PANSS total score [effect size -2.91, 95% confidence interval (CI) -0.90 to -4.91]. With a poor TA, attending more sessions is detrimental (effect size +7.74, 95% CI +1.03 to +14.45). CONCLUSIONS: This is the first ever demonstration that TA has a causal effect on symptomatic outcome of a psychological treatment, and that poor TA is actively detrimental. These effects may extend to other therapeutic modalities and disorders.

Cognitive-behavioural suicide prevention for male prisoners: a pilot randomized controlled trial.

BACKGROUND: Prisoners have an exceptional risk of suicide. Cognitive-behavioural therapy for suicidal behaviour has been shown to offer considerable potential, but has yet to be formally evaluated within prisons. This study investigated the feasibility of delivering and evaluating a novel, manualized cognitive-behavioural suicide prevention (CBSP) therapy for suicidal male prisoners. METHOD: A pilot randomized controlled trial of CBSP in addition to treatment as usual (CBSP; n = 31) compared with treatment as usual (TAU; n = 31) alone was conducted in a male prison in England. The primary outcome was self-injurious behaviour occurring within the past 6 months. Secondary outcomes were dimensions of suicidal ideation, psychiatric symptomatology, personality dysfunction and psychological determinants of suicide, including depression and hopelessness. The trial was prospectively registered (number ISRCTN59909209). RESULTS: Relative to TAU, participants receiving CBSP therapy achieved a significantly greater reduction in suicidal behaviours with a moderate treatment effect [Cohen's d = -0.72, 95% confidence interval -1.71 to 0.09; baseline mean TAU: 1.39 (S.D. = 3.28) v. CBSP: 1.06 (S.D. = 2.10), 6 months mean TAU: 1.48 (S.D. = 3.23) v. CBSP: 0.58 (S.D. = 1.52)]. Significant improvements were achieved on measures of psychiatric symptomatology and personality dysfunction. Improvements on psychological determinants of suicide were non-significant. More than half of the participants in the CBSP group achieved a clinically significant recovery by the end of therapy, compared with a quarter of the TAU group. CONCLUSIONS: The delivery and evaluation of CBSP therapy within a prison is feasible. CBSP therapy offers significant promise in the prevention of prison suicide and an adequately powered randomized controlled trial is warranted.

Understanding jumping to conclusions in patients with persecutory delusions: working memory and intolerance of uncertainty.

BACKGROUND: Persecutory delusions are a key psychotic experience. A reasoning style known as 'jumping to conclusions' (JTC) - limited information gathering before reaching certainty in decision making - has been identified as a contributory factor in the occurrence of delusions. The cognitive processes that underpin JTC need to be determined in order to develop effective interventions for delusions. In the current study two alternative perspectives were tested: that JTC partially results from impairment in information-processing capabilities and that JTC is a motivated strategy to avoid uncertainty. METHOD: A group of 123 patients with persistent persecutory delusions completed assessments of JTC (the 60:40 beads task), IQ, working memory, intolerance of uncertainty, and psychiatric symptoms. Patients showing JTC were compared with patients not showing JTC. RESULTS: A total of 30 (24%) patients with delusions showed JTC. There were no differences between patients who did and did not jump to conclusions in overall psychopathology. Patients who jumped to conclusions had poorer working memory performance, lower IQ, lower intolerance of uncertainty and lower levels of worry. Working memory and worry independently predicted the presence of JTC. CONCLUSIONS: Hasty decision making in patients with delusions may partly arise from difficulties in keeping information in mind. Interventions for JTC are likely to benefit from addressing working memory performance, while in vivo techniques for patients with delusions will benefit from limiting the demands on working memory. The study provides little evidence for a contribution to JTC from top-down motivational beliefs about uncertainty.

Microbial water quality communication: public and practitioner insights from British Columbia, Canada.

This work examines the communication interactions of water suppliers and health authorities with the general public regarding microbial source water quality for recreational and drinking water. We compare current approaches to risk communication observable in British Columbia (BC), Canada, with best practices derived from the communications literature, finding significant gaps between theory and practice. By considering public views and government practices together, we identify key disconnects, leading to the conclusion that at present, neither the public's needs nor public health officials' goals are being met. We find: (1) there is a general lack of awareness and poor understanding by the public of microbial threats to water and the associated health implications; (2) the public often does not know where to find water quality information; (3) public information needs are not identified or met; (4) information sharing by authorities is predominantly one-way and reactive (crisis-oriented); and (5) the effectiveness of communications is not evaluated. There is a need for both improved public understanding of water quality-related risks, and new approaches to ensure information related to water quality reaches audiences. Overall, greater attention should be given to planning and goal setting related to microbial water risk communication.

Patients' beliefs about the causes, persistence and control of psychotic experiences predict take-up of effective cognitive behaviour therapy for psychosis.

BACKGROUND: There is evidence that patients with schizophrenia benefit from standard cognitive behaviour therapy (CBT) only if active techniques are used ('full therapy'). By contrast, attending sessions but not proceeding beyond engagement and assessment strategies ('partial therapy'), or simply not attending sessions ('no therapy'), is not associated with better outcomes. The factors leading to full therapy are unknown. We hypothesized that patients' initial ideas about the nature and extent of their problems would predict use of CBT. A match between patients' views of their problems and the principles underlying treatment would lead to better outcomes. METHOD: Ninety-two patients with a recent relapse of psychosis completed the Illness Perception Questionnaire (IPQ) before receiving CBT. We examined whether their illness perceptions predicted the take-up of therapy. RESULTS: Patients who did not attend sessions believed their problems would not last as long as those who attended them. Those who attended sessions but did not proceed to full therapy had a lower sense of control over their problems and a more biological view of their causes. Patients who took up full therapy were more likely to attribute the cause of their problems to their personality and state of mind. The take-up of therapy was predicted neither by levels of psychiatric symptoms nor by insight. CONCLUSIONS: People with psychosis who have psychologically orientated views of their problems, including the potential to gain control over them, may be more likely to engage fully and do well with standard CBT for psychosis, irrespective of the severity of their problems.

Paranoia and post-traumatic stress disorder in the months after a physical assault: a longitudinal study examining shared and differential predictors.

BACKGROUND: Being physically assaulted is known to increase the risk of the occurrence of post-traumatic stress disorder (PTSD) symptoms but it may also skew judgements about the intentions of other people. The objectives of the study were to assess paranoia and PTSD after an assault and to test whether theory-derived cognitive factors predicted the persistence of these problems. METHOD: At 4 weeks after hospital attendance due to an assault, 106 people were assessed on multiple symptom measures (including virtual reality) and cognitive factors from models of paranoia and PTSD. The symptom measures were repeated 3 and 6 months later. RESULTS: Factor analysis indicated that paranoia and PTSD were distinct experiences, though positively correlated. At 4 weeks, 33% of participants met diagnostic criteria for PTSD, falling to 16% at follow-up. Of the group at the first assessment, 80% reported that since the assault they were excessively fearful of other people, which over time fell to 66%. Almost all the cognitive factors (including information-processing style during the trauma, mental defeat, qualities of unwanted memories, self-blame, negative thoughts about self, worry, safety behaviours, anomalous internal experiences and cognitive inflexibility) predicted later paranoia and PTSD, but there was little evidence of differential prediction. CONCLUSIONS: Paranoia after an assault may be common and distinguishable from PTSD but predicted by a strikingly similar range of factors.

Rediscovering contact inhibition in the embryo.

The cellular reaction called contact inhibition of locomotion was initially characterised by Michael Abercrombie more than 60 years ago. In his most general definition, it is defined as the stopping of the continued locomotion of a cell in the direction which has produced a collision with another cell. This deceptively simple response has been widely studied in vitro in a number of cell types over the years, yet it is still often misunderstood by the scientific community. Abercrombie spent much of his life studying the failure of the response shown by cancer cell types and how this might lead to malignant invasion of normal tissue. However, since Abercrombie's time, a role for this response in living organisms has been left to the realm of speculation. Here, we discuss the history of contact inhibition research, clarify some of the misconceptions about the response and reclaim misused terminology. We will also highlight our recent work, which for the first time elucidates a functional role for contact inhibition in vivo during embryogenesis.

Cognitive-self consciousness and metacognitive beliefs: Stress sensitization in individuals at ultra-high risk of developing psychosis.

OBJECTIVE: Metacognitive beliefs (MCB) may guide information and attention processes, increasing affective and symptomatic reactions to stressful events. Cognitive self-consciousness (CSC; i.e., a preoccupation with one's thoughts) may increase awareness of MCB, potentially triggering the onset of psychotic symptoms. This study tested the hypotheses that (1), MCB would moderate affective and symptomatic reactions to stress in individuals at ultra-high risk (UHR) of developing psychosis, and (2), greater CSC would precede worsening in psychotic symptoms in individuals with strong MCB. METHOD: Twenty-seven individuals at UHR of developing psychosis completed a self-report diary when prompted by an electronic wristwatch several times each day for 6 days (experience sampling). RESULTS: MCB moderated the association between affective, but not symptomatic, responses to social stress. CSC preceded the subsequent occurrence of hallucinations in individuals who reported strong beliefs about the need to control their thoughts. CONCLUSIONS: The data suggest that MCB sensitize an individual to social stressors. CSC may represent times where an individual is aware that their thoughts are uncontrollable, and therefore contradicting their MCB, motivating them to make an external attribution. The findings have implications for improving the effectiveness of interventions for people experiencing hallucinations.

Rapid Establishment of a Biospecimen Resource To Study the Global Impact of COVID-19 Vaccines.

The emergence and explosive spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 highlighted the need to rapidly develop curated biobanks to inform the etiology, diagnosis, and treatment options for global outbreaks of communicable diseases. Recently, we undertook efforts to develop a repository of biospecimens from individuals aged 12 and older who were to be vaccinated against coronavirus disease 19 (COVID-19) with vaccines developed with support from the United States Government. We planned to establish 40 or more clinical study sites in at least six countries to collect biospecimens from 1,000 individuals, 75% of whom were to be SARS-CoV-2 naive at the time of enrollment. Specimens would be used to (i) ensure quality control of future diagnostic tests, (ii) understand immune responses to multiple COVID-19 vaccines, and (iii) provide reference reagents for the development of new drugs, biologics, and vaccines. Biospecimens included serum, plasma, whole blood, and nasal secretions. Large-volume collections of peripheral blood mononuclear cells (PBMCs) and defibrinated plasma were also planned for a subset of subjects. Participant sampling was planned at intervals prior to and following vaccination over a 1-year period. Here, we describe the selection of clinical sites for specimen collection and processing, standard operating procedure (SOP) development, design of a training program for tracking specimen quality, and specimen transport to a repository for interim storage. This approach allowed us to enroll our first participants within 21 weeks from the study's initiation. Lessons learned from this experience should benefit the development of biobanks in response to future global epidemics. IMPORTANCE The ability to rapidly create a biobank of high-quality specimens in response to emergent infectious diseases is critical to allow for the development of prevention and treatment, as well as to effectively monitor the spread of the disease. In this paper, we report on a novel approach to getting global clinical sites up and running within a short time frame and to monitor the quality of specimens collected to ensure their value in future research efforts. Our results have important implications for the monitoring of the quality of biospecimens collected and to design effective interventions to address shortcomings, where needed.

Depressive symptoms and pragmatic rehabilitation for chronic fatigue syndrome.

BACKGROUND: Previous research has suggested that depressed mood may predict outcome and moderate response to treatment in chronic fatigue syndrome, although findings have differed between studies. AIMS: To examine potential moderators of response to pragmatic rehabilitation v. general practitioner treatment as usual in a recent randomised trial for patients with chronic fatigue syndrome in primary care (IRCTN74156610). METHOD: Simple regressions, with weighting adjustments to allow for missing data, were calculated. Demographic, medical and psychological variables, and treatment arm, were entered separately and as an interaction term. The outcome variable in each case was change in Chalder Fatigue Scale scores, from baseline to 1-year follow-up, our primary outcome point. RESULTS: Longer illness durations predicted poorer outcome across the two treatment arms. For patients allocated to pragmatic rehabilitation compared with those allocated to treatment as usual, higher levels of depressive symptoms at baseline were associated with smaller improvements in fatigue (P = 0.022). CONCLUSIONS: For patients in primary care with higher levels of depressive symptoms, either more intensive or longer pragmatic rehabilitation, or cognitive-behavioural therapy, may be required in order to show a significant improvement in fatigue.

Emotional and symptomatic reactivity to stress in individuals at ultra-high risk of developing psychosis.

BACKGROUND: The stress-vulnerability model of psychosis continues to be influential. The aim of this study was to compare emotional and symptomatic responses to stress in individuals at ultra-high risk (UHR) of developing psychosis, in age- and gender-matched healthy controls, and in patients with non-affective psychosis. METHOD: A total of 27 UHR, 27 psychotic and 27 healthy individuals completed the experience sampling method, an ambulant diary technique, where they were required to fill in self-assessment questions about their emotions, symptoms and perceived stress at semi-random times of the day for 6 days. Quesionnaire and interview assessments were also completed. RESULTS: Multilevel regression analyses showed that individuals at UHR of developing psychosis reported greater negative emotions in response to stress than the healthy individuals. Against the initial hypotheses, the UHR individuals also experienced greater emotional reactivity to stress when compared with the patient group. No significant differences were observed between the patients and the non-clinical sample. Stress measures significantly predicted the intensity of psychotic symptoms in UHR individuals and patients, but the extent of this did not significantly differ between the groups. CONCLUSIONS: Individuals at UHR of developing psychosis may be particularly sensitive to everyday stressors. This effect may diminish after transition to psychosis is made and in periods of stability. Subtle increases in psychotic phenomena occur in response to stressful events across the continuum of psychosis.

Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification.

BACKGROUND: Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. METHOD: The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. RESULTS: Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. CONCLUSIONS: Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

Effects of drop-out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia.

OBJECTIVE: Our aim was to find out how Cochrane reviews of five popular or frequently prescribed second-generation antipsychotics in the UK (olanzapine, risperidone, quetiapine, amisulpride and aripiprazole) approached the problem of high drop-out in placebo-controlled trials. METHOD: We examined the following: (i) whether reviews included data from studies with a level of drop-out exceeding their stated exclusion criterion; (ii) the level of missing data each efficacy outcome in each review relied upon; and (iii) impact of excluding studies with high drop-out. RESULTS: All reviews included data they stated they would exclude because of unacceptable levels of attrition, four (risperidone, olanzapine, amisulpride, aripiprazole) without clear acknowledgement or justification. Several reviews also excluded data from a number of relatively low-attrition studies because of missing standard deviations. CONCLUSION: Cochrane reviews of five popular antipsychotics for schizophrenia misrepresented the available evidence on their efficacy. The impact of including high-attrition studies was difficult to quantify because of the exclusion of relevant low-attrition studies. Further analysis of the efficacy of these drugs in studies with acceptable rates of attrition is required. To reduce the problem of high attrition, trialists should gather follow-up data from people who leave the double-blind process early.

Affective variability predicts suicidal ideation in individuals at ultra-high risk of developing psychosis: an experience sampling study.

OBJECTIVE: There is a suggestion in the literature that more variable affect increases suicidal ideation through the repeated re-activation of latent suicidal cognitions. The hypothesis that affective variability would be a better predictor of suicidal ideation and related behaviour than affect level was tested in individuals at ultra-high risk of developing psychosis. This study also examined the prediction that affective variability is a suicide-specific mechanism and would not predict levels of attenuated psychotic phenomena. METHOD: Twenty-seven ultra-high risk individuals were required to complete ambulant ratings of their affect when prompted by an electronic wristwatch for six days (the experience sampling method). In the debriefing session, participants were assessed with a semi-structured interview (the Comprehensive Assessment of At-Risk Mental State), which assessed the severity and frequency of suicidality and psychosis-related phenomena. RESULTS: The variability of negative and positive affect was predictive of the frequency of suicidal thoughts and behaviour. More variable negative, but not positive affect, was also associated with more severe suicidal ideation and related behaviour. Affect variability was not significantly related to the severity of attenuated psychotic phenomena. CONCLUSION: Affective variability appears to be a specific risk factor for suicidal ideation in individuals at ultra-high risk of developing psychosis. Early intervention should focus on providing individuals with skills for regulating their own affect.

The Genetic Counseling Outcome Scale: a new patient-reported outcome measure for clinical genetics services.

The aim of this study was to develop a patient-reported outcome measure (PROM) for clinical genetics services. Previous research was used to develop a draft 84-item questionnaire, which was completed by 527 members of patient support groups. Responses were subjected to exploratory factor analysis (EFA). Parallel analysis was used to identify the number of factors to extract using oblique rotation. Twenty-four questions were selected to form the Genetic Counseling Outcome Scale (GCOS-24). Two hundred and forty-one patients completed a questionnaire pack before and after attendance at a genetics clinic that included the GCOS-24, and validated measures of health locus of control, perceived personal control, anxiety, depression, satisfaction with life and authenticity. Concurrent validity of the GCOS-24 was assessed using bivariate correlation. Sensitivity to change of the GCOS-24 was assessed using analysis of variance. EFA identified a single overarching construct consisting of seven dimensions. Internal consistency (α = 0.87) and test-retest reliability (r = 0.86) are good. The GCOS-24 shows convergent and divergent validities, and sensitivity to change over time with a medium-to-large effect size (Cohen's d = 0.70). The GCOS-24 has potential as a clinical genetics-specific PROM.

Extracellular control of cell size.

Both cell growth (cell mass increase) and progression through the cell division cycle are required for sustained cell proliferation. Proliferating cells in culture tend to double in mass before each division, but it is not known how growth and division rates are co-ordinated to ensure that cell size is maintained. The prevailing view is that coordination is achieved because cell growth is rate-limiting for cell-cycle progression. Here, we challenge this view. We have investigated the relationship between cell growth and cell-cycle progression in purified rat Schwann cells, using two extracellular signal proteins that are known to influence these cells. We find that glial growth factor (GGF) can stimulate cell-cycle progression without promoting cell growth. We have used this restricted action of GGF to show that, for cultured Schwann cells, cell growth rate alone does not determine the rate of cell-cycle progression and that cell size at division is variable and depends on the concentrations of extracellular signal proteins that stimulate cell-cycle progression, cell growth, or both.

Experience sampling research in individuals with mental illness: reflections and guidance.

OBJECTIVE: The experience sampling method (ESM) represents a valuable way of assessing clinical phenomena in real world settings and across time. Despite its theoretical advantages, using this methodology in psychiatric populations is challenging. This paper acts as a guide to researchers wishing to employ this approach when investigating mental illness. METHOD: The contents represent the opinions of researchers around the United Kingdom and the Netherlands who are experienced at using the ESM. RESULTS: In ESM studies, participants are required to fill in questions about their current thoughts, feelings and experiences when prompted by an electronic device (e.g. a wristwatch, PDA). Entries are typically made at fixed or random intervals over 6 days. This article outlines how to design and validate an ESM diary. We then discuss which sampling procedure to use and how to increase compliance through effective briefing and telephone sessions. Debriefing, data management and analytical issues are considered, before suggestions for future clinical uses of the ESM are made. CONCLUSION: The last decade has seen an increase in the number of studies employing the ESM in clinical research. Further research is needed to examine the optimal equipment and procedure for different clinical groups.