Neil W. Scott

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7–12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery.

Environmental risk factors for parkinson's disease and parkinsonism : the geoparkinson study

Objective: To investigate the associations between Parkinson’s disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods: A case–control study of 959 prevalent cases of parkinsonism (767 with Parkinson’s disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson’s Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson’s disease. Results: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson’s disease/parkinsonism with an exposure–response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson’s disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson’s disease gave similar results. Conclusions: The association of pesticide exposure with Parkinson’s disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.

Five-year follow-up of a randomized trial to assess pain and numbness after laparoscopic or open repair of groin hernia.

Claims that laparoscopic groin hernia repair is followed by less persisting pain and numbness than open mesh repair were tested by follow‐up within a multicentre randomized clinical trial.

Psychological, surgical, and sociodemographic predictors of pain outcomes after breast cancer surgery: A population-based cohort study

Summary Risk factors for chronic pain up to 9 months after breast cancer surgery include younger age, psychological vulnerability, axillary clearance surgery, and severe acute postoperative pain. ABSTRACT Chronic postsurgical pain (CPSP) is a common postoperative adverse event affecting up to half of women undergoing breast cancer surgery, yet few epidemiological studies have prospectively investigated the role of preoperative, intraoperative, and postoperative risk factors for pain onset and chronicity. We prospectively investigated preoperative sociodemographic and psychological factors, intraoperative clinical factors, and acute postoperative pain in a prospective cohort of 362 women undergoing surgery for primary breast cancer. Intraoperative nerve handling (division or preservation) of the intercostobrachial nerve was recorded. At 4 and 9 months after surgery, incidence of chronic painful symptoms not present preoperatively was 68% and 63%, respectively. Univariate analysis revealed that multiple psychological factors and nerve division was associated with chronic pain at 4 and 9 months. In a multivariate model, independent predictors of CPSP at 4 months included younger age and acute postoperative pain (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.12 to 1.60), whereas preoperative psychological robustness (OR 0.70, 95% CI 0.49 to 0.99), a composite variable comprising high dispositional optimism, high positive affect, and low emotional distress, was protective. At 9 months, younger age, axillary node clearance (OR 2.97, 95% CI 1.09 to 8.06), and severity of acute postoperative pain (OR 1.17, 95% CI 1.00 to 1.37) were predictive of pain persistence. Of those with CPSP, 25% experienced moderate to severe pain and 40% were positive on Douleur Neuropathique 4 and Self‐Complete Leeds Assessment of Neuropathic Symptoms and Signs pain scales. Overall, a high proportion of women report painful symptoms, altered sensations, and numbness in the upper body within the first 9 months after resectional breast surgery and cancer treatment.

Gene‐environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study

Objectives: To investigate associations of Parkinson’s disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. Results: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). Conclusions: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.

A simulation study provided sample size guidance for differential item functioning (DIF) studies using short scales

OBJECTIVE Differential item functioning (DIF) analyses are increasingly used to evaluate health-related quality of life (HRQoL) instruments, which often include relatively short subscales. Computer simulations were used to explore how various factors including scale length affect analysis of DIF by ordinal logistic regression. STUDY DESIGN AND SETTING Simulated data, representative of HRQoL scales with four-category items, were generated. The power and type I error rates of the DIF method were then investigated when, respectively, DIF was deliberately introduced and when no DIF was added. The sample size, scale length, floor effects (FEs) and significance level were varied. RESULTS When there was no DIF, type I error rates were close to 5%. Detecting moderate uniform DIF in a two-item scale required a sample size of 300 per group for adequate (>80%) power. For longer scales, a sample size of 200 was adequate. Considerably larger sample sizes were required to detect nonuniform DIF, when there were extreme FEs or when a reduced type I error rate was required. CONCLUSION The impact of the number of items in the scale was relatively small. Ordinal logistic regression successfully detects DIF for HRQoL instruments with short scales. Sample size guidelines are provided.

Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

BackgroundDifferential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application.MethodsA review of logistic regression DIF analyses in HRQoL was undertaken. Methodological articles from other fields and using other DIF methods were also included if considered relevant.ResultsThere are many competing approaches for the conduct of DIF analyses and many criteria for determining what constitutes significant DIF. DIF in short scales, as commonly found in HRQL instruments, may be more difficult to interpret. Qualitative methods may aid interpretation of such DIF analyses.ConclusionsA number of methodological choices must be made when applying logistic regression for DIF analyses, and many of these affect the results. We provide recommendations based on reviewing the current evidence. Although the focus is on logistic regression, many of our results should be applicable to DIF analyses in general. There is a need for more empirical and theoretical work in this area.

Does mindfulness improve outcomes in patients with chronic pain? Systematic review and meta-analysis

BACKGROUND Chronic pain and its associated distress and disability are common reasons for seeking medical help. Patients with chronic pain use primary healthcare services five times more than the rest of the population. Mindfulness has become an increasingly popular self-management technique. AIM To assess the effectiveness of mindfulness-based interventions for patients with chronic pain. DESIGN AND SETTING Systematic review and meta-analysis including randomised controlled trials of mindfulness-based interventions for chronic pain. There was no restriction to study site or setting. METHOD The databases MEDLINE(®), Embase, AMED, CINAHL, PsycINFO, and Index to Theses were searched. Titles, abstracts, and full texts were screened iteratively against inclusion criteria of: randomised controlled trials of mindfulness-based intervention; patients with non-malignant chronic pain; and economic, clinical, or humanistic outcome reported. Included studies were assessed with the Yates Quality Rating Scale. Meta-analysis was conducted. RESULTS Eleven studies were included. Chronic pain conditions included: fibromyalgia, rheumatoid arthritis, chronic musculoskeletal pain, failed back surgery syndrome, and mixed aetiology. Papers were of mixed methodological quality. Main outcomes reported were pain intensity, depression, physical functioning, quality of life, pain acceptance, and mindfulness. Economic outcomes were rarely reported. Meta-analysis effect sizes for clinical outcomes ranged from 0.12 (95% confidence interval [CI] = -0.05 to 0.30) (depression) to 1.32 (95% CI = -1.19 to 3.82) (sleep quality), and for humanistic outcomes 0.03 (95% CI = -0.66 to 0.72) (mindfulness) to 1.58 (95% CI = -0.57 to 3.74) (pain acceptance). Studies with active, compared with inactive, control groups showed smaller effects. CONCLUSION There is limited evidence for effectiveness of mindfulness-based interventions for patients with chronic pain. Better-quality studies are required.

The use of differential item functioning analyses to identify cultural differences in responses to the EORTC QLQ-C30

IntroductionThe European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a widely used health-related quality of life instrument. The main aim of this study is to investigate whether there are international differences in response to the questionnaire that can be explained by cultural factors.MethodsAnalyses involved a database of 106 separate studies including data from over 28,000 respondents. Differential item functioning (DIF) analyses using logistic regression were conducted for each item of the EORTC QLQ-C30 with respect to cultural/geographic group. Results were qualitatively compared with previously reported DIF analyses by translation to explore whether the source of the DIF was more likely to be linguistic or cultural in nature.ResultsAlthough most response patterns were similar, there were a number of international differences in how the questionnaire was answered. The largest variations were found in the results for Eastern Europe and East Asia. Results for the UK, the US and Australia tended to be similar. Many of the European results followed patterns that were more clearly explained when grouped by translation than when grouped by geographical region.DiscussionOur results suggest that, in general, the EORTC QLQ-C30 is suitable for use in a wide variety of countries and settings. Some response variations that have the potential to affect the results of international studies were identified, but it was not always clear whether the source of the variation was primarily linguistic or cultural.

Age-, gender-, and socioeconomic status-specific incidence of Parkinson's disease and parkinsonism in North East Scotland: The PINE study

There have been few high quality incidence studies of Parkinsons disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I(2) 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.