Keith Millar

Morbidity After Sentinel Lymph Node Biopsy in Primary Breast Cancer: Results From a Randomized Controlled Trial

PURPOSE Axillary lymph node dissection (ALND) as part of surgical treatment for patients with breast cancer is associated with significant morbidity. Sentinel lymph node biopsy (SLNB) is a newly developed method of staging the axilla and has the potential to avoid an ALND in lymph node-negative patients, thereby minimizing morbidity. The aim of this study was to investigate physical and psychological morbidity after SLNB in the treatment of early breast cancer in a randomized controlled trial. PATIENTS AND METHODS Between November 1999 and February 2003, 298 patients with early breast cancer (tumors 3 cm or less on ultrasound examination) who were clinically node negative were randomly allocated to undergo ALND (control group) or SLNB followed by ALND if subsequently found to be lymph node positive (study group). A detailed assessment of physical and psychological morbidity was performed during a 1-year period postoperatively. RESULTS A significant reduction in postoperative arm swelling, rate of seroma formation, numbness, loss of sensitivity to light touch and pinprick was observed in the study group. Although shoulder mobility was less impaired on average in the study group, this was significant only for abduction at 1 month and flexion at 3 months. Scores reflecting quality of life and psychological morbidity were significantly better in the study group in the immediate postoperative period, with fewer long-term differences. CONCLUSION SLNB in patients undergoing surgery for breast cancer results in a significant reduction in physical and psychological morbidity.

Long term neuropsychological outcome after head injury: relation to APOE genotype

Background: Existing evidence suggests that some patients who sustain a head injury suffer cognitive decline many years later, and that head injury and possession of the APOE ε4 allele are each risk factors for Alzheimer’s disease. Objective: To determine whether late cognitive decline after head injury is more prevalent among carriers of APOE ε4. Methods: A database of head injured patients was used. Initial assessment was at the time of their injury, between 1968 and 1985, and outcome data at six months were available. Their ages at the time of injury ranged between 2 and 70 years. A cohort of 396 subjects was reassessed at a mean of 18 years later, with determination of APOE genotype and detailed neuropyschological testing. Results: Judging by the Glasgow outcome scale, twice as many patients had deteriorated as improved between six months after injury and the late assessment; 22.2% of APOE ε4 carriers had a good late outcome compared with 30.5% of non-carriers (95% confidence interval for the difference, −0.7% to 17.2%; p = 0.084). There were no clear differences between ε4 carriers and non-carriers in detailed neuropsychological assessments. Conclusions: Although this study provides additional evidence that a late decline may occur after head injury, there was no clear relation to APOE genotype. Despite the follow up interval of 15 to 25 years, the cohort is still too young (mean age 42.1 years) to assess the risk of Alzheimer’s disease.

Assessment of personal qualities in relation to admission to medical school

Background  Recently there has been much scrutiny of the medical school admissions process by universities, the General Medical Council and the public. Improved objectivity, fairness and effectiveness of selection procedures are desirable. The ultimate outcome sought is the graduation of competent doctors who reflect the values of and are in tune with the communities they serve.

Socio-economic status is associated with epigenetic differences in the pSoBid cohort

BACKGROUND Epigenetic programming and epigenetic mechanisms driven by environmental factors are thought to play an important role in human health and ageing. Global DNA methylation has been postulated as an epigenetic marker for epidemiological studies as it is reflective of changes in gene expression linked to disease. How epigenetic mechanisms are affected by psychological, sociological and biological determinants of health still remains unclear. The aim of this study was to investigate the relationship between socio-economic and lifestyle factors and epigenetic status, as measured by global DNA methylation content, in the pSoBid cohort, which is characterized by an extreme socio-economic and health gradient. METHODS DNA was extracted from peripheral blood leukocytes using the Maxwell® 16 System and Maxwell® 16 Blood DNA Purification kit (Promega, UK). Global DNA methylation was assessed using Methylamp™ Global DNA Methylation Quantification Ultra kit (Epigentek, USA). Associations between global DNA methylation and socio-economic and lifestyle factors were investigated in linear regression models. RESULTS Global DNA hypomethylation was observed in the most socio-economically deprived subjects. Job status demonstrated a similar relationship, with manual workers having 24% lower DNA methylation content than non-manual. Additionally, associations were found between global DNA methylation content and biomarkers of cardiovascular disease (CVD) and inflammation, including fibrinogen and interleukin-6 (IL-6), after adjustment for socio-economic factors. CONCLUSIONS This study has indicated an association between epigenetic status and socio-economic status (SES). This relationship has direct implications for population health and is reflected in further associations between global DNA methylation content and emerging biomarkers of CVD.

Accelerated Telomere Attrition Is Associated with Relative Household Income, Diet and Inflammation in the pSoBid Cohort

Background It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences. Methods A total of 382 blood samples from the pSoBid study were available for telomere analysis. For each participant, data was available for socio-economic status factors, biochemical parameters and dietary intake. Statistical analyses were undertaken to investigate the association between telomere lengths and these aforementioned parameters. Results The rate of age-related telomere attrition was significantly associated with low relative income, housing tenure and poor diet. Notably, telomere length was positively associated with LDL and total cholesterol levels, but inversely correlated to circulating IL-6. Conclusions These data suggest lower socio-economic status and poor diet are relevant to accelerated biological ageing. They also suggest potential associations between elevated circulating IL-6, a measure known to predict cardiovascular disease and diabetes with biological ageing. These observations require further study to tease out potential mechanistic links.

Local or general anesthesia for open hernia repair: a randomized trial

ObjectiveTo compare patient outcome following repair of a primary groin hernia under local (LA) or general anesthesia (GA) in a randomized clinical trial. Summary Background DataLA hernia repair is thought to be safer for patients, causes less postoperative pain, cost less, and is associated with a more rapid recovery when compared with the same operation performed under GA. MethodsAll patients presenting to three surgeons during the study period with a primary groin hernia were considered eligible. Outcome parameters measured including tests of vigilance, divided attention, sustained attention, memory, cognitive function, pain, return to normal activity, and costs. ResultsTwo hundred seventy-nine patients were randomized to LA or GA hernia repair; 276 of these had an operation, with 138 participants in each group. At 6, 24, and 72 hours postoperatively there were no differences in vigilance or divided attention between the groups. Similarly, memory, sustained attention, and cognitive function were not impaired in either group. Although physical activity was significantly impaired at 24 hours, this and return to usual social activities were similar in both groups. While patients in the LA group had significantly less pain on moving, at 6 hours they were less likely to recommend the same operation to someone else. GA hernia repair cost 4% more than the same operation under LA. ConclusionsThere are no major differences in patient recovery after LA or GA hernia repair. Patients should be offered a choice of anesthesia, LA or GA, for repair of their groin hernia.

The prediction of self-care behaviors in end-stage renal disease patients using Leventhal's Self-Regulatory Model

OBJECTIVE To assess the utility of Leventhals Self-Regulatory Model (SRM) to predict self-care behavior with regard to dietary, medication, and fluid regimes in end-stage renal disease (ESRD) patients. METHODS In a prospective study, ESRD patients treated via hospital-based haemodialysis (N=73) were screened for cognitive deficits and completed questionnaires that enquired about illness perceptions, coping strategies, knowledge of kidney disease, and psychological distress at Time 1. Physiological proxy measures of self-care behaviors regarding diet (serum potassium levels), fluid intake (mean and standard deviation of interdialytic weight gain), and medication (serum phosphate levels) regimes were collected 3 weeks later at Time 2. RESULTS Illness representations (emotional and timeline perceptions) predicted self-care behaviors with regard to diet and medication. Emotion-focused coping strategies predicted higher levels of variation in adherence to fluid restrictions. Younger males were less likely to adhere to the fluid restrictions. CONCLUSIONS The SRM has predictive utility. Psychological interventions should focus on alleviating disease-specific distress and challenging erroneous timeline perceptions in order to increase adherence to dietary and medication regimes in ESRD patients. A more specific measure of coping for ESRD is required to clarify the role of coping strategies in this population. Younger, male patients should be targeted for extra support with fluid restrictions.

Differences in atherosclerosis according to area level socioeconomic deprivation: cross sectional, population based study

Objectives To examine the relation between area level social deprivation and ultrasound markers of atherosclerosis (common carotid intima-media thickness and plaque score), and to determine whether any differences can be explained by “classic” (currently recognised) or “emerging” (novel) cardiovascular risk factors. Design Cross sectional, population based study. Setting NHS Greater Glasgow Health Board area. Participants 666 participants were selected on the basis of how their area ranked in the Scottish Index of Multiple Deprivation 2004. Approximately equal numbers of participants from the most deprived areas and the least deprived areas were included, as well as equal numbers of men and women and equal numbers of participants from each age group studied (35-44, 45-54, and 55-64 years). Main outcome measures Carotid intima-media thickness and plaque score, as detected by ultrasound. Results The mean age and sex adjusted intima-media thickness was significantly higher in participants from the most deprived areas than in those from the least deprived areas (0.70 mm (standard deviation (SD) 0.16 mm) v 0.68 mm (SD 0.12 mm); P=0.015). On subgroup analysis, however, this difference was only apparent in the highest age tertile in men (56.3-66.5 years). The difference in unadjusted mean plaque score between participants from the most deprived and those from the least deprived areas was more striking than the difference in intima-media thickness (least deprived 1.0 (SD 1.5) v most deprived 1.7 (SD 2.0); P<0.0001). In addition, a significant difference in plaque score was apparent in the two highest age tertiles in men (46.8-56.2 years and 56.3-66.5 years; P=0.0073 and P<0.001) and the highest age tertile in women (56.3-66.5 years; P<0.001). The difference in intima-media thickness between most deprived and least deprived males remained significant after adjustment for classic risk factors, emerging risk factors, and individual level markers of socioeconomic status (P=0.010). Adjustment for classic risk factors and emerging cardiovascular risk factors, either alone or in combination, did not abolish the deprivation based difference in plaque presence (as a binary measure; adjusted odds ratio of 1.73, 95% confidence interval 1.07 to 2.82). However, adjustment for classic risk factors and individual level markers of early life socioeconomic status abolished the difference in plaque presence between the most deprived and the least deprived individuals (adjusted odds ratio 0.94, 95% CI 0.54 to 1.65; P=0.84). Conclusions Deprivation is associated with increased carotid plaque score and intima-media thickness. The association of deprivation with atherosclerosis is multifactorial and not adequately explained by classic or emerging risk factors.

Patient maintained sedation for colonoscopy using a target controlled infusion of propofol

In this study, we evaluated safety and recovery using a patient maintained, target controlled infusion of propofol for sedation in 20 patients undergoing colonoscopy. Using a handset with a two‐minute lockout interval, patients could make 0.2 µg.ml−1 increments to an initial target plasma concentration of 1 µg.ml−1 up to a maximum 4.5 µg.ml−1. Four patients became oversedated but required no airway or circulatory interventions. Subjects had a significant reduction in mean (SD) heart rate: 78.7 (15) vs. 69.8 (13.5) (p < 0.001) and in systolic blood pressure 121.1 (13.2) mmHg vs. 96.5 (8.6) mmHg (p < 0.001). Choice reaction time testing 15 min after colonoscopy showed a significant median (IQR [range]) rise of 162 (− 16, 383.3 [‐199–859]) ms (p < 0.05). Six patients had faster reaction times postcolonoscopy. All patients denied unpleasant recall and were satisfied with the system. Although oversedation was a problem in this model, we conclude that patient maintained propofol sedation could be possible for colonoscopy.

A partially blinded randomised controlled trial of patient-maintained propofol sedation and operator controlled midazolam sedation in third molar extractions

Patient‐maintained sedation using propofol has recently been shown to be effective for dental surgery. We compared this new technique to the established technique of operator administered midazolam. The two groups were compared before, during and after sedation. The two primary outcomes were time until discharge and oxygen saturation. Vital signs, anxiety and psychomotor skills were also compared. State anxiety was reduced to a greater extent in the propofol group (mean difference 10 (SD 4) mm; p = 0.010. Propofol patients recovered quicker (mean difference 7 (SD 1.4) min; p = 0.001). Propofol patients had a smaller reduction in arterial oxygen saturation (mean difference 0.8 (SD 0.3)%; p = 0.030), and a reduced increase in heart rate (mean difference 9 (SD 2) beats.min–1; p < 0.001). Both techniques were well tolerated and safe. Propofol sedation offered superior anxiolysis, quicker recovery, less amnesia and less depression of simple psychomotor function.