The neurobiology under the placebo effect.

The placebo effect is a phenomenon of great scientific interest that affects the response in both inactive and active treatments. It is broadly understood as the product of a central integration of positive expectations, reward learning and continuous conditioning inducing physiological changes in the brain. The placebo effect is accepted as a phenomenon which can be harnessed in clinical practice. It has emerged that there is not a single neurobiological mechanism involved in placebo responses, but many depending on the underlying disease. Molecular neuroimaging techniques with positron emission tomography and selective radiotracers have been significant in the understanding of the neurobiological systems involved in the placebo effect. The aim of this review was to summarize the key findings relating to the neurobiology behind the placebo effect.

Sustained moderate visual loss as a predictive end point for visual loss in non-proliferative diabetic retinopathy.

PURPOSE: In PKC-DRS2, the efficacy of the oral PKC-beta inhibitor, ruboxistaurin 32 mg/day, was measured by the primary end point of sustained moderate visual loss (SMVL: a > or = 15 letter decrease from baseline on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart sustained at least for the last 6 months of study participation). We now evaluate whether SMVL is more accurate than moderate visual loss (MVL: a single occurrence of a decrease from baseline of > or = 15 ETDRS letters) for predicting future visual loss. METHODS: Study eyes with moderately severe to very-severe non-proliferative diabetic retinopathy, best-corrected visual acuity of at least 45 letters on the ETDRS chart (approximately Snellen 20/125), and no prior pan retinal photocoagulation were evaluated in 506 patients (869 eyes) who completed 36 months of treatment. RESULTS: Sixty-five percentage (26/40) of study eyes with the onset of SMVL within 24 months of enrolment still had SMVL at study completion (36 months). In comparison, only 24% (30/126) with MVL within 24 months had SMVL at study completion. Analyses based on data from 6, 12, and 18 months of treatment were similar. CONCLUSIONS: SMVL is a more predictable measure of subsequent visual loss than is a single time point measure of MVL.

Diabetic macular oedema: a clinical overview.

Diabetic retinopathy is the leading cause of blindness in working aged-adults in westernised countries. Diabetic macular oedema (DMO) is a manifestation of diabetic retinopathy and is the leading cause of the visual impairment that occurs with diabetic retinopathy. There are multiple ways of classifying DMO; however, none appear to be wholly satisfactory. DMO occurs more frequently in type 2 diabetes mellitus, and appears to be more prevalent as the duration of diabetes increases, and as the severity of diabetic retinopathy worsens. There are multiple risk factors in common with diabetic retinopathy, such as hyperglycaemia, hypertension and dyslipidaemia; however, specific factors such as the presence of renal disease appear to be more significantly associated with DMO. Whereas the gold standard for diagnosis of DMO is via clinical examination, there is considerable variability involved, and hence, this has led to the advent of more objective methods of quantifying the degree of retinal thickness, such as optical coherence tomography. Laser photocoagulation appears to be the only universally acceptable treatment of choice to date; however, this is a destructive therapy, and its side effects coupled with the suboptimal efficacy has led to the advent of potential new therapies which will undoubtedly compliment the existing approaches, in the future management of a patient with DMO.

Diagnosed diabetic retinopathy in France, Italy, Spain, and the United Kingdom.

AIM: The objective of this study was to describe the proportion and characteristics of patients diagnosed with diabetic retinopathy (DR) in France, Italy, Spain, and the United Kingdom (UK). METHODS: To estimate the proportion of patients with type 1 and type 2 diabetes diagnosed with DR, we conducted a cross-sectional survey of general practitioners in each country using physician records. In addition, diabetes specialists were recruited in Italy and Spain. We extracted data from the medical notes of a sample of DR patients to characterize DR severity and clinical characteristics. RESULTS: The average number of physicians per country was 41 (range: 34-49). The proportion of diagnosed DR ranged from 10.3% (95% CI, 6.7-14.0%) in Spain to 19.6% (95% CI, 16.0-23.1%) in the UK. Of 752 DR patients studied, 53.9% were male; mean age (+/-SD) was 64.2+/-12.8 years. Consistently across countries, mild non-proliferative DR was the most common severity level of diagnosed DR. Proliferative DR (PDR) ranged from 19.7% (France) to 31.5% (UK). Diabetic macular oedema was reported in approximately 10% of patients. Hypertension (73.1%), dyslipidemia (63.2%), and neuropathy (52.1%) were the most common co-morbidities. CONCLUSIONS: Country-specific prevalence of diagnosed DR may reflect clinical management of diabetes, healthcare systems, or record-keeping accuracy. Across countries, up to 30% of DR patients had a diagnosis of PDR, which could suggest that patients are diagnosed only when their disease is advanced.

Diabetic microvascular complications: can patients at risk be identified? A review.

People with diabetes have an increased risk of developing microvascular complications, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy, which, if undetected or left untreated, can have a devastating impact on quality of life and place a significant burden on health care costs. In addition, diabetic microvascular complications can reduce life expectancy. The strongest risk factors are glycaemic control and diabetes duration; however, other modifiable risk factors such as hypertension, hyperlipidaemia and smoking, and unmodifiable risk factors including age at onset of diabetes and genetic factors may all play a part. Along with the presence of external risk factors, some associations have also been noted between diabetic microvascular complications themselves. There is evidence that diabetic retinopathy in association with increased blood pressure is an important risk factor for diabetic nephropathy progression. Significant correlations have also been shown between the presence of diabetic peripheral neuropathy and the presence of background or proliferative diabetic retinopathy. Clinical trials are currently in progress looking at a number of approaches to designing treatments to prevent the adverse effects of hyperglycaemia. It is essential however, that risk factors associated with the progression and development of diabetic microvascular complications are detected and treated at an early stage in order to further reduce morbidity and mortality. Considering all three complications as interrelated may well facilitate early detection of microvascular disease. Despite good long-term glycaemic and blood pressure control, diabetes remains a major cause of blindness, renal failure and amputations. As the incidence of diabetes continues to rise, the burden of diabetic microvascular complications will increase in future, hence the need for early detection. Considering the microvascular complications of diabetes as related, and enquiring proactively about complications, may well facilitate early detection of microvascular disease.

Epidemiology of diabetic retinopathy and macular oedema: a systematic review.

AIMS: To systematically review the literature on the prevalence and incidence of diabetic retinopathy (DR) and macular oedema (MO). METHODS: A search of the bibliographic databases (Medline, Embase, CINAHL) was conducted up to October 2001. Selected relevant studies were scrutinized and included in the review. RESULTS: A total of 359 studies were included. The studies were reported in nearly 100 different journals and in over 50 countries. The majority of the studies were US-based, with large studies such as the Wisconsin Epidemiologic Study of Diabetic Retinopathy dominating the literature. The studies were quite dated and highly heterogeneous in nature in terms of patient selection with variable inclusion criteria (age range, gender, diabetes duration and type, ethnicity, comorbidity, and DR status, assessment, and classification). CONCLUSIONS: There are inconsistencies between epidemiological studies, and differences in study methods may contribute to conflicting reports of prevalence and incidence of DR and MO in diabetic populations. As new therapies for DR and its associated complications emerge, the need to capture and monitor new epidemiological data becomes increasingly important to be able to assess the impact and effectiveness of these therapies. Robust, longitudinal capture of patient data is, therefore, essential to evaluate the impact of current practice on the epidemiology of diabetic eye complications.

A retrospective audit of the combined pituitary function test, using the insulin stress test, TRH and GnRH in a district laboratory.

OBJECTIVE: To assess the value of the combined insulin stress test (IST), thyrotrophin-releasing hormone (TRH) and gonadotrophin hormone-releasing hormone (GnRH) tests. DESIGN: A retrospective audit of 232 such tests performed between 1980 and 1989 inclusive. PATIENTS: One hundred and ninety-seven patients with known or suspected pituitary disease. MEASUREMENTS: IST, TRH and GnRH responses were retrieved from laboratory records. Case notes were surveyed for clinical data and additional results. RESULTS: A basal serum cortisol level of less than 100 nmol/l (or less than 200 nmol/l in patients who had recently received glucocorticoid replacement therapy) accurately predicted a subnormal response to hypoglycaemia. All patients with a basal cortisol level of greater than 400 nmol/l, except those who had recently received steroids, showed a normal cortisol response. In retrospect, by consideration of such basal values, 55% of ISTs could have been avoided if the only aim was to assess cortisol reserve. A deficient growth hormone (GH) response to hypoglycaemia was, however, common in patients with a normal cortisol response. Two-thirds of patients with GH deficiency would have been missed if an IST had been avoided on the basis either of basal cortisol levels alone, or of cortisol responses to an alternative test which did not test GH reserve. There was poor agreement between the pituitary response to TRH and GnRH and basal levels of thyroxine and gonadotrophins respectively, suggesting that these releasing hormone tests are misleading. CONCLUSIONS: The IST provides information regarding pituitary function not provided by other tests of the hypothalamic-pituitary-adrenal axis, so that the choice between the IST and alternative tests must depend on a critical assessment of what information is required. Routine TRH and GnRH testing appears to yield little information of practical clinical value.