Health inequalities - why so little progress?

Studies of the health of the population of Scotland over many years have provided new insights to the basis of inequalities in life expectancy across the Scottish population. Conventional descriptions of health inequalities as being due predominantly to smoking, obesity and alcohol do not fully account for the situation in Scotland. The deeper insights obtained from comprehensive analysis have prompted new approaches to narrowing the gap. Opportunities for well-being are created within the complex system of a well functioning society and novel methods are required if the outcomes of such a complex system are to improve.

The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake.

Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy. However, the physiological mechanisms by which these agents modulate human energy balance are incompletely elucidated. Here, we describe a comprehensive clinical research study of taranabant, a structurally novel acyclic CB1R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [(18)F]MK-9470 confirmed central nervous system receptor occupancy levels ( approximately 10%-40%) associated with energy balance/weight-loss effects in animals. In a 12-week weight-loss study, taranabant induced statistically significant weight loss compared to placebo in obese subjects over the entire range of evaluated doses (0.5, 2, 4, and 6 mg once per day) (p < 0.001). Taranabant treatment was associated with dose-related increased incidence of clinical adverse events, including mild to moderate gastrointestinal and psychiatric effects. Mechanism-of-action studies suggest that engagement of the CB1R by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation.

Does deprivation affect breast cancer management?

We evaluated whether social deprivation affected decision-making for breast cancer surgery. Of 3419 patients, 53.6% had mastectomy and this was predicted by deprivation, age, tumour size and hospital, all of which retained significance on multivariate analysis, except deprivation. Pathological characteristics and surgical decision-making determined choice of operation not deprivation.

Three's a crowd.

Where do patients' rising expectations fit into the purchaser/provider relationship? John Spiers, Harry Burns and Michael Richards look at this question from a patient, purchase, and provider perspective.

Report on consensus conference on colorectal cancer: Royal College of Surgeons of Edinburgh 1993.

Colorectal cancer is the second commonest cause of death from cancer in Scotland. Recent developments in molecular biology, pre-symptomatic diagnosis, surgery and adjuvant treatment suggest that a substantial reduction in mortality is achievable. Some fear that major changes to the organisation of the NHS could undermine future attempts to coordinate major cancer screening studies or multicentre adjuvant trials. In contrast, others argue that a sharp focus on cost and benefits could encourage the development of clear guidelines based on a consensus of good practice. Thus, the time seems right for a consensus conference and this article summarises the outcome of such a recent conference held in Scotland. A group of 80 surgeons, radiation oncologists and medical oncologists were invited as a representative cross-section of clinicians with an interest in colorectal cancer. Seventy per cent of those attending were surgeons. A series of expert presentations were used to lead discussion in four sessions devoted respectively to epidemiology and screening, influence of surgical factors and outcome, the role of adjuvant therapy and planning for the future. Full discussion from delegates was encouraged and computer-collated, key-pad responses allowed documentation of the opinions of the audience in respect of pre-defined questions. For statistical purposes we have assumed that a consensus had been reached when there was a statistically significant difference (Chi-square) between the observed response from clinicians and the null hypothesis, i.e. a 50/50 split.

Resting and total energy expenditure in patients with ischemic heart disease.

Total energy expenditure (TEE) was measured by doubly labeled water in 13 preoperative patients undergoing elective coronary artery surgery and compared to resting energy expenditure (REE) measured by indirect calorimetry (IC) calculated from the Harris-Benedict (HB) formula or from formulas based on midarm circumference and arm muscle circumference. Mean REE measured by IC and calculated from the HB, midarm circumference, arm muscle circumference formulas were 62, 75, 62, and 69%, respectively, of TEE measured by doubly labeled water. REE measured by IC correlated significantly with that predicted by the HB (p = 0.006) but not the anthropometric formulas. The relationship between REE derived from anthropometric predictive formulas and REE measured by IC is altered in ischemic heart disease.

Effects of cardiac surgery and intraoperative hypothermia on energy expenditure as measured by doubly labelled water.

Total energy expenditure (TEE) was measured over two 10-day periods, before and after operation in 16 patients undergoing coronary artery surgery and randomized to have cardiopulmonary bypass with an intraoperative blood temperature of either 28 or 20 degrees C. TEE was measured with doubly labelled water containing stable isotopes of hydrogen and oxygen to allow calculation of TEE over fixed periods from the differential rate of excretion of the two isotopes. Results were available for eight patients in the 28 degrees C group but for only seven in the 20 degrees C group (one patient in this group was excluded as the temperature allocated was not achieved). The groups were similar with respect to body-weight and lean body mass. The 20 degrees C group received more grafts than the 28 degrees C group, resulting in an increase in cross-clamp and bypass times. Mean preoperative TEE was similar in both groups. The mean difference in fractional turnover rates of hydrogen and oxygen was not significantly different in the postoperative period. There was a non-significant increase in the mean 10-day postoperative TEE, calculated in total calories, of 4.7 per cent in the 28 degrees C and 5.1 per cent in the 20 degrees C group. When changes in postoperative TEE were calculated according to lean body mass, the mean increases were respectively 3.7 and 3.2 per cent. Cardiac surgery utilizing cardiopulmonary bypass and intraoperative hypothermia results in only a modest increase in postoperative TEE. In this study a more profound level of intraoperative hypothermia did not influence the change in postoperative TEE.

Comparison of various predictive formulae for the estimation of resting energy expenditure.

The accuracy of the Harris-Benedict (HB), Kleiber and Robertson-Reid predictive formulae and the Fleisch tables in estimating resting energy expenditure (REE) has been assessed in 114 cancer patients and 54 patients with nonmalignant illness. The effects of weight status and disease on the predictive ability of the formulae were assessed by comparison of the estimated REE value with that measured by indirect calorimetry. Underestimation of measured REE by greater than 10% occurred in 6-62% of patients, depending on the formula used. Weight loss did not affect predictive ability, whereas the presence of cancer resulted in inaccurate prediction of REE in female patients. Using a multiple comparison procedure, the Fleisch tables were the most accurate in all groups, while the HB formula was least accurate in male patients, irrespective of weight status or disease status. The use of predictive formulae and tables are inappropriate for the accurate estimation of REE in individual patients.

Influence of whole body protein turnover rate on resting energy expenditure in patients with cancer.

Whole body protein turnover and resting energy expenditure are measured simultaneously in weight stable and weight losing patients with lung (n = 22) or colorectal cancer (n = 38). These results were compared with those from weight stable and weight losing non-cancer controls (n = 22). Rates of whole body protein turnover were calculated from the plateau isotopic enrichment of urinary ammonia and urea following a primed, continuous, 24-h infusion of [15N]glycine. Resting energy expenditure was measured by indirect calorimetry. All groups of cancer patients had significantly elevated rates of whole body protein turnover (P less than 0.05) and synthesized, on average, 1.9 g/kg/day more protein compared with weight stable non-cancer controls. In contrast, the resting energy expenditure of cancer patients and controls was similar. Moreover, there was no correlation between individual rates of whole body protein turnover. Thus, although cancer patients had rates of whole body protein turnover which were 50-70% greater than controls, this did not result in a measurable increase in resting energy expenditure. The assumption that elevation of whole body protein turnover or resting energy expenditure causes weight loss in cancer patients must be an oversimplification. An acute phase protein response was observed in the majority of cancer patients. Although the presence of such an inflammatory response did not correlate with the rate of whole body protein turnover, the role of inflammatory mediators in the pathogenesis of disturbed protein metabolism in cancer patients merits further investigation.

The effects on resting energy expenditure of different tumor types.

The presence of a malignant tumor is said to influence the resting energy expenditure (REE) of the host. This study assesses the hypothesis that different tumor types exert differing effects on REE. REE was measured using indirect calorimetry in 84 cancer patients. Fifty-one patients had colorectal cancer, 22 had gastric cancer, and 11 had non-small cell bronchial cancer. For each tumor type, REE correlated significantly with body weight and lean body mass (LBM). The slope of the regression line for the bronchial cancer patients was significantly different from the colorectal (P less than 0.02) and gastric (P less than 0.02) cancer patients when REE was related to LBM. When related to body weight, the slope of the line of the bronchial cancer patients was significantly different from that of the gastric cancer patients only (P less than 0.05). The bronchial cancer patients had a significantly higher REE than the colorectal (P less than 0.005) and gastric (P less than 0.02) cancer patients when REE was expressed in terms of body weight. However, when corrected for LBM, no significant differences in REE were found between the groups. The presence of hepatic metastases did not influence REE in any of the tumor groups. Differing relationships between REE and indices of body size have been detected in differing tumor types. Consequently, the use of heterogeneous cancer groups may be inappropriate in studies of REE and cancer.

Effects of hepatic metastases on resting energy expenditure in patients with colorectal cancer.

There are frequent reports that cancer causes an increase in resting energy expenditure (REE), and the presence of hepatic metastases is said to increase REE further. The effect of tumour burden on REE has been measured in 24 patients before and following surgery for colorectal cancer. Fifteen patients had a 'curative' resection whereas nine patients were found to have hepatic metastases at the time of surgery. No significant differences in REE were found between the groups either before surgery or at follow-up, by which time all 15 curative resection patients were tumour free and the remaining nine had progression of their hepatic disease. It is concluded that neither surgical removal of the primary tumour nor progression of metastatic hepatic disease significantly alters REE in patients with colorectal cancer.

The relationship between resting energy expenditure and weight loss in benign and malignant disease.

The relationship between cancer, weight loss, and resting energy expenditure (REE) has been investigated in 136 patients using indirect calorimetry. Ninety-one patients had gastric, colorectal, or nonsmall cell bronchial neoplasm, seven patients had other malignancies, and 38 patients had nonmalignant illness. Four groups were studied: weight stable cancer patients (CWS: N = 56), weight losing cancer patients (CWL: N = 42), weight stable patients with nonmalignant illness (NCWS: N = 22), and weight losing patients with nonmalignant illness (NCWL: N = 16). In each group REE correlated significantly with body weight, metabolic body size, and lean body mass (LBM: estimated from total body water measurements). The closest correlation was between REE and lean body mass, with the slope of the CWL regression line differing significantly from that of the CWS (p less than 0.05) and NCWS (p less than 0.02) groups. However, there was no difference in REE expressed as kcal/kg LBM/d between the groups. The slopes of the regressions between REE and LBM were almost identical when all cancer patients were compared with all patients with nonmalignant illness. However, when all weight stable patients were compared with all weight losing patients, there was a highly significant difference between the slopes of the regressions (p less than 0.005). This indicates that the weight losing state rather than the presence or absence of cancer is responsible for an alteration in the relationship between REE and LBM. There were no differences in REE between the different tumor types. It is concluded that REE is not elevated in patients with gastric, colorectal, or nonsmall cell bronchial cancer. Elevation of REE contributes very little to the etiology of cancer cachexia.

A clinical assessment of electroanalgesia following abdominal operations.

A prospective randomized controlled trial was performed to assess the value of transcutaneous electrical stimulation as an analgesic technique for postoperative pain. Forty patients who underwent cholecystectomy were studied. Patients in group A (control group) complained of more severe wound pain than either patients in group B (wound stimulation) or group C (remote stimulation). However, the treated groups showed no evidence of a significant reduction in opiate demand or of improved ventilatory function.

Assessment of dopamine receptor densities in the human brain with carbon-11-labeled N-methylspiperone.

We describe the use of carbon-11-labeled 3-N-methylspiperone, a ligand that preferentially binds to dopamine receptors in vivo, to image the receptors by positron emission tomography scanning in baboons and, for the first time, in a human. The method has now been used in 58 humans for noninvasive assessment of the state of brain dopamine receptors under normal and pathological conditions.