Coping style and depression influence the healing of diabetic foot ulcers: observational and mechanistic evidence.

AIMS/HYPOTHESIS: Experimental evidence suggests that the healing of diabetic foot ulcers is affected by psychosocial factors such as distress. We examined this proposal in a prospective study, in which we considered the role of psychological distress and coping style in the healing of diabetic foot ulcers over a 24 week period. We also explored the role of salivary cortisol and matrix metalloproteinases (MMPs) as potential mechanisms. METHODS: For this prospective observational study we recruited 93 (68 men; mean age 60 years) patients with neuropathic or neuroischaemic diabetic foot ulcers from specialist podiatry clinics in secondary care. Clinical and demographic determinants of healing, psychological distress, coping, salivary cortisol and both MMP2 and MMP9 were assessed at baseline. Ulcers were assessed at baseline and at 6, 12 and 24 weeks post-baseline. The primary outcome was ulcer status at 24 weeks, i.e. healed vs not healed. RESULTS: After controlling for clinical and demographic determinants of healing, ulcer healing at 24 weeks was predicted by confrontation coping, but not by depression or anxiety. Patients with unhealed ulcers exhibited greater confrontation coping (model including depression: OR 0.809, 95% CI 0.704-0.929, p = 0.003; model including anxiety: OR 0.810, 95% CI 0.704-0.930, p = 0.003). However, change in ulcer size over the observation period was associated with depression only (p = 0.04, d = 0.31). Healed ulcers by 24 weeks were also associated with lower evening cortisol, higher precursor MMP2 and a greater cortisol awakening response. CONCLUSIONS/INTERPRETATION: Confrontation coping and depression predict ulcer healing. Our preliminary enquiry into biological mechanisms suggests that cortisol and precursor MMP2 may underlie these relationships.

An investigation into the effects of social evaluation on cardiovascular and endocrine responses to the CO2 stress test in humans.

The present study examined whether social evaluation could heighten individuals' physiological responses to the CO(2) stress test, and the hypothalamic-pituitary-adrenal (HPA) response in particular. Twenty-five healthy volunteers undertook the CO(2) test under three conditions: (i) standard CO(2) protocol, (ii) standard CO(2) protocol conducted in front of a full-length mirror (mirror) and (iii) standard CO(2) protocol conducted in front of a video camera deemed to be transmitting live images of the procedure to investigators evaluating participant performance (video). Despite counterbalancing for task order, there were significant differences in anger and depression among the conditions. Repeated measures analysis of variances (ANOVAs), controlling for these mood indices, revealed that salivary cortisol, heart rate and systolic blood pressure responses to the CO(2) test were not affected by social evaluation (i.e. mirror or video). Although the data provide no evidence that endocrine and cardiovascular responses to the CO(2) test are affected by social evaluation, the potency of the social evaluation manipulation in this study is in question. Thus, further research is warranted which includes evidence of, or instructions suggesting negative social evaluation.

Methodologic issues in the study of the relationship between histologic indicators of intraamniotic infection and clinical outcomes.

GOAL: To determine the structure of the relationships of the histology scores for acute intraamniotic infection collected in the Collaborative Perinatal Project (CPP). MATERIALS AND METHODS: 44,427 subjects of the CPP had complete histology scores available for the 9 measures that related to acute intraamniotic infection (i.e., neutrophil infiltrates in umbilical cord, amnion of extraplacental membranes and chorionic plate, decidua, chorionic plate and fetal chorionic vessels). Confirmatory factor analysis was used to determine the relationships among the different markers of maternal inflammatory responses (in amnion, chorion and decidua) and fetal inflammatory responses (in umbilical cord and fetal chorionic vessels). RESULTS: A single CFA model could not be developed across all CPP sites. A well-fit model was developed from the Boston site (N=10,803) and the factor loadings applied to the histology scores from the other CPP sites. The resultant scores for the latent variables (maternal and fetal inflammatory responses) were compared across sites. There was not only considerable variability in factor loadings, and the signs of factor loadings were also inconsistent across sites. CONCLUSION: Histopathology scores of neutrophil infiltrates performed by different observers do not have the same interrelationships and, by extension, the latent variables they are supposed to reflect may not be equivalent. The lack of measurement invariance renders their use as indicators of the underlying processes of maternal and fetal inflammatory responses problematic in analysis with any clinical outcome.

An assessment of the effects of exposure to vibration, smoking, alcohol and diabetes on the prevalence of Dupuytren's disease in 97,537 miners.

A consecutive sample of 97,537 miners seeking compensation for Hand-Arm Vibration Syndrome were examined in a medical assessment process which included documentation of age, hand dominance, Dupuytren's disease, years of vibration exposure, history of diabetes, smoking habits and units of alcohol consumption per week. The prime determinant of prevalence of Dupuytren's disease was age, and all other factors investigated were corrected for age. There was no statistically significant correlation between years of exposure to vibration and the prevalence of Dupuytren's disease. There was a statistically significant association with smoking, alcohol consumption and diabetes mellitus, with the heaviest smokers having an odds ratio (OR) of 1.31 (95% CI, 1.17, 1.47), the heaviest drinkers (in excess of 22 units a week) having an OR of 1.59 (95% CI, 1.47, 1.72) and diabetes mellitus patients having an increase in the odds of having Dupuytren's disease of 1.52 (95% CI 1.30, 1.77).

Contamination in trials of educational interventions.

OBJECTIVES: To consider the effects of contamination on the magnitude and statistical significance (or precision) of the estimated effect of an educational intervention, to investigate the mechanisms of contamination, and to consider how contamination can be avoided. DATA SOURCES: Major electronic databases were searched up to May 2005. METHODS: An exploratory literature search was conducted. The results of trials included in previous relevant systematic reviews were then analysed to see whether studies that avoided contamination resulted in larger effect estimates than those that did not. Experts' opinions were elicited about factors more or less likely to lead to contamination. We simulated contamination processes to compare contamination biases between cluster and individually randomised trials. Statistical adjustment was made for contamination using Complier Average Causal Effect analytic methods, using published and simulated data. The bias and power of cluster and individually randomised trials were compared, as were Complier Average Causal Effect, intention-to-treat and per protocol methods of analysis. RESULTS: Few relevant studies quantified contamination. Experts largely agreed on where contamination was more or less likely. Simulation of contamination processes showed that, with various combinations of timing, intensity and baseline dependence of contamination, cluster randomised trials might produce biases greater than or similar to those of individually randomised trials. Complier Average Causal Effect analyses produced results that were less biased than intention-to-treat or per protocol analyses. They also showed that individually randomised trials would in most situations be more powerful than cluster randomised trials despite contamination. CONCLUSIONS: The probability, nature and process of contamination should be considered when designing and analysing controlled trials of educational interventions in health. Cluster randomisation may or may not be appropriate and should not be uncritically assumed always to be a solution. Complier Average Causal Effect models are an appropriate way to adjust for contamination if it can be measured. When conducting such trials in future, it is a priority to report the extent, nature and effects of contamination.

Non-cardiac chest pain: a retrospective cohort study of patients who attended a Rapid Access Chest Pain Clinic.

BACKGROUND: Rapid Access Chest Pain Clinics have recently been introduced to assist in the management of primary care patients experiencing suspected cardiac chest pain. OBJECTIVE: To study the longer term outcome for patients referred to a Rapid Access Chest Pain Clinic and then given a non-cardiac diagnosis. METHODS: The study collected retrospective data from a cohort of all patients attending the Rapid Access Chest Pain Clinic based in the cardiorespiratory Department at the York District Hospital, England. Questionnaires were sent to all patients who attended the Rapid Access Chest Pain Clinic during the previous 14 months and were diagnosed with non-cardiac chest pain. Participants reported on their chest pain, subsequent episodes of primary and secondary care and their beliefs about causation of pain. RESULTS: Of the patients referred to the Rapid Access Chest Pain Clinic, 235 (52%) did not have cardiac chest pain. Of these patients, 161 (69%) returned the questionnaire, nearly half of whom reported ongoing chest pain. The mean time since Clinic attendance was approximately 8 months and the median duration of ongoing chest pain was 5.4 months. Women were twice as likely as men to continue to be experiencing pain but did not report more frequent or severe pain on average. More than 50% of the non-cardiac group were not convinced by their negative cardiac diagnosis. CONCLUSION: There is an ongoing challenge to support patients with non-cardiac chest pain, including the provision of reassurance that their pain is very unlikely to be caused by their heart.

Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women.

BACKGROUND: Seasonal Affective Disorder (SAD) is a sub-type of depression that only occurs during the winter months. A reduction in vitamin D may be linked to SAD. Since vitamin D deficiency has been reported to be common in older people, vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group. OBJECTIVE: To assess the effect of vitamin D supplementation on the mental health of older women. SETTING: Primary care in three areas of the UK (Herts, Newcastle, York). SUBJECTS: Women aged 70 years or more recruited to the trial in the months May-October. INTERVENTION: Eligible women were randomised to receive calcium and vitamin D supplementation or no supplementation. OUTCOME MEASURE: At baseline and the six monthly assessment the mental component score (MCS), calculated from the SF-12 questionnaire was used to assess participants' subjective psychological well-being. RESULTS: A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October (1205 woman in the control group and 912 women in the intervention group). Of these women, 1621 had a MCS score at baseline and six months. Comparison of the six month mean MCS scores, adjusting for baseline MCS score and age, showed there was no significant difference between the two scores (p = 0.262). CONCLUSIONS: Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores.

The use of unequal randomisation ratios in clinical trials: a review.

OBJECTIVE: To examine reasons given for the use of unequal randomisation in randomised controlled trials (RCTs). MAIN MEASURES: Setting of the trial; intervention being tested; randomisation ratio; sample size calculation; reason given for randomisation. METHODS: Review of trials using unequal randomisation. DATABASES AND SOURCES: Cochrane library, Medline, Pub Med and Science Citation Index. RESULTS: A total of 65 trials were identified; 56 were two-armed trials and nine trials had more than two arms. Of the two-arm trials, 50 trials recruited patients in favour of the experimental group. Various reasons for the use of unequal randomisation were given. Six studies stated that they used unequal randomisation to reduce the cost of the trial, with one screening trial limited by the availability of the intervention. Other reasons for using unequal allocation were: avoiding loss of power from drop-out or cross-over, ethics and the gaining of additional information on the treatment. Thirty seven trials papers (57%) did not state why they had used unequal randomisation and only 14 trials (22%) appeared to have taken the unequal randomisation into account in their sample size calculation. CONCLUSION: Although unequal randomisation offers a number of advantages to trials the method is rarely used and is especially under-utilised to reduce trial costs. Unequal randomisation should be considered more in trial design especially where there are large differences between treatment costs.

Does position of syndesmotic screw affect functional and radiological outcome in ankle fractures?

The optimum level of syndesmotic screw used in ankle fractures with a tibiofibular diastasis is not clear in the literature. In a retrospective cohort study, we evaluated the clinical and radiological outcomes in two groups of patients-those who had a syndesmotic screw placed through the syndesmosis itself (transsyndesmotic, 17 patients) and those who had a syndesmotic screw placed just above the syndesmosis (suprasyndesmotic, 19 patients). The study suggests that the two groups do not differ significantly in terms of clinical and radiological outcomes.

Carpal tunnel syndrome in association with hand-arm vibration syndrome: a review of claimants seeking compensation in the Mining Industry.

Twenty six thousand eight hundred and forty-two miners seeking compensation were clinically assessed for vascular and neurosensory impairment arising from exposure to occupational hand-arm vibration (Hand-Arm Vibration Syndrome). They were also assessed clinically for Carpal Tunnel Syndrome which, if present, would result in additional compensation. Fifteen per cent were assessed as having both HAVS and CTS. Thirty-eight per cent of claimants had nocturnal wakening, 1.3% wasting of abductor pollicis brevis, 15% had a positive Tinel's test and 20% had a positive Phalen's test. The 15% prevalence reported is lower than the rates cited previously in several small population studies of workers exposed to vibration. This paper reports the results of the assessment process and discusses the difficulty of discriminating Carpal Tunnel Syndrome from diffuse neurosensory impairment arising from HAVS.

Criticizing and reassuring oneself: An exploration of forms, styles and reasons in female students.

OBJECTIVES: Self-critical people, compared with those who self-reassure, are at increased risk of psychopathology. However, there has been little work on the different forms and functions of these self-experiences. This study developed two self-report scales to measure forms and functions of self-criticism and self-reassurance and explore their relationship to depression. METHODS: A self-report scale measuring forms of self-criticism and self-reassuring, and a scale measuring possible functions of self-criticism, together with a measure of depression and another self-criticism scale (LOSC), were given to 246 female students. RESULTS: Self-criticizing vs. self-reassuring separated into two components. Forms of self-criticizing separated into two components related to: being self-critical, dwelling on mistakes and sense of inadequacy; and a second component of wanting to hurt the self and feeling self-disgust/hate. The reasons/functions for self-criticism separated into two components. One was related to desires to try to self-improve (called self-improving/correction), and the other to take revenge on, harm or hurt the self for failures (called self-harming/persecuting). Mediation analysis suggested that wanting to harm the self may be particularly pathogenic and is positively mediated by the effects of hating the self and negatively mediated by being able to self-reassure and focus on one's positives. CONCLUSIONS: Self-criticism is not a single process but has different forms, functions, and underpinning emotions. This indicates a need for more detailed research into the variations of self-criticism and the mechanisms for developing self-reassurance.

Cold provocation testing and hand-arm vibration syndrome--an audit of the results of the Department of Trade and Industry scheme for the evaluation of miners.

BACKGROUND: Hand-arm vibration syndrome (HAVS) is a major industrial disease that causes considerable morbidity among workers exposed to vibration. Compensation is paid to those affected in civil claims against employers and (in the UK) in claims made under Social Security legislation rules for Prescribed Disease A11. Diagnostic tests have been proposed but most are not objective. The cold provocation test (CPT), which is objective, is often included in the evaluation of HAVS. METHODS: A continuous audit was made of the findings recorded at the 18 HAVS test centres in the UK established to evaluate miners. The audit, and its outcome, were monitored by the Medical Reference Panel who advise the Department of Trade and Industry. This audit report constitutes the second analysis of the findings relating to the CPT. RESULTS: The CPT, with measurement of digital rewarming times, is of no value in assessing vibration-induced damage to the hands. CONCLUSION: In its present format, the CPT should not be used for evaluating the vascular component of HAVS.

Relationship of anhedonia and anxiety to social rank, defeat and entrapment.

There is good evidence to suggest that depression is highly correlated with perceptions of low rank and subordinate status (i.e. feeling inferior, low-self esteem, feeling that others look down on the self, and submissive behaviour). However, it is possible for people to feel inferior and anxious, and behave submissively but not necessarily be depressed. More recently two other processes, defeat and entrapment, have attracted attention as possible processes linked specifically to depression and anhedonia. This research explored the relationship of these variables (social rank variables and defeat and entrapment) to two measures of hedonic tone (low positive affectivity and anhedonia) and anxiety in both a clinical and student population. All variables were strongly associated with lowered hedonic tone and anxiety. However, partial correlations, and a structural equation model fitted to the data from combined groups, suggests that perceptions of defeat play a specifically important role in anhedonia as measured by low positive affect. Framed within an evolutionary model the data suggest that the mechanisms which evolved to help animals accommodate and respond to defeats may have important regulatory effects over positive affect, reducing exploration of and engagement with the environment.

The influence of high contrast acuity and normalised low contrast acuity upon self-reported situation avoidance and driving crashes.

The aim of this study was to determine the cues used to signal avoidance of difficult driving situations and to test the hypothesis that drivers with relatively poor high contrast visual acuity (HCVA) have fewer crashes than drivers with relatively poor normalised low contrast visual acuity (NLCVA). This is because those with poorer HCVA are well aware of their difficulties and avoid dangerous driving situations while those poorer NLCVA are often unaware of the extent of their problem. Age, self-reported situation avoidance and HCVA were collected during a practice based study of 690 drivers. Screening was also carried out on 7254 drivers at various venues, mainly motorway sites, throughout the UK. Age, self-reported situation avoidance and prior crash involvement were recorded and Titmus vision screeners were used to measure HCVA and NLCVA. Situation avoidance increased in reduced visibility conditions and was influenced by age and HCVA. Only half of the drivers used visual cues to signal situation avoidance and most of these drivers used high rather than low contrast cues. A statistical model designed to remove confounding interrelationships between variables showed, for drivers that did not report situation avoidance, that crash involvement decreased for drivers with below average HCVA and increased for those with below average NLCVA. These relationships accounted for less than 1% of the crash variance, so the hypothesis was not strongly supported.