Jiten Vora

Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men

background Conflicting views are reported on the association between advancing age and gradually diminishing concentrations of serum total testosterone in men. The putative loss of diurnal rhythm in serum total testosterone in older men is reported to be in part due to low concentrations in the morning when compared to concentrations found in young men. We have measured total, free and bioavailable testosterone along with SHBG in samples taken every 30 min throughout a 24‐h period in 10 young and eight middle‐aged men.

Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool diabetic eye study

Abstrac Objective: To evaluate different methods for community based screening for sight threatening diabetic eye disease. Design: Prospective study. Setting: Mobile screening unit visiting inner city community clinics; hospital assessment clinic (tertiary centre). Subjects: 395 diabetic patients registered with four general practices in an inner city location. Interventions: Community based photography with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced ophthalmologist, both compared with reference standard of slit lamp biomicroscopy by a consultant specialist in medical retinal disease. Main outcome measures: Sensitivity and specificity of screening method and prevalence of sight threatening diabetic eye disease (moderate preproliferative retinopathy, circinate maculopathy, exudate within 1 disc diameter of fixation, other diabetes related eye disease). Results: 358 subjects underwent photography, 326 attended hospital clinic for ophthalmoscopy, and six were ungradable on photographs and biomicroscopy, leaving 320 for analysis. Of these 295 (91%) attended clinic within four months of photography. Sensitivity of detection of eye disease by photography was 89% (95% confidence interval 80% to 98%), significantly better than for direct ophthalmoscopy (65% (51% to 79%)). Analysis of patients with false negative results indicated possible improvement of photographic sensitivity to 93% by addition of stereoscopic macular pair photographs. Specificity of detection of sight threatening eye disease was 86% (82% to 90%) for photography and 97% (95% to 99%) for direct ophthalmoscopy. Conclusions: Since high sensitivity is essential for an effective screening programme, a photographic method should be considered as preferred option in national, community based screening programmes. Even in the hands of an experienced ophthalmologist, direct ophthalmoscopy is limited by weaknesses inherent to the instrument.

Incidence of sight-threatening retinopathy in patients with type 2 diabetes in the Liverpool Diabetic Eye Study: a cohort study.

BACKGROUND Incidence data on which to base targets and protocols for screening for sight-threatening diabetic retinopathy are few. We aimed to investigate yearly and cumulative incidence of any retinopathy, maculopathy, and sight-threatening diabetic retinopathy in patients with type 2 diabetes in an established systematic programme and to calculate optimum screening intervals according to retinopathy grade at baseline. METHODS We investigated all patients with type 2 diabetes registered with enrolled general practices (except those who were attending an ophthalmologist) who had retinopathy data available at baseline and at least one further screening event. To screen patients, we used non-stereoscopic three-field mydriatic photography and modified Wisconsin grading. Sight-threatening diabetic retinopathy was defined as moderate preproliferative retinopathy or worse, or clinically significant maculopathy in either or both eyes. FINDINGS Results were obtained from 20 570 screening events. Yearly incidence of sight-threatening diabetic retinopathy in patients without retinopathy at baseline was 0.3% (95% CI 0.1-0.5) in the first year, rising to 1.8% (1.2-2.5) in the fifth year; cumulative incidence at 5 years was 3.9% (2.8-5.0). Rates of progression to sight-threatening diabetic retinopathy in year 1 by baseline status were: background 5.0% (3.5-6.5), and mild preproliferative 15% (10.2-19.8). For a 95% probability of remaining free of sight-threatening diabetic retinopathy, mean screening intervals by baseline status were: no retinopathy 5.4 years (95% CI 4.7-6.3), background 1.0 years (0.7-1.3), and mild preproliferative 0.3 years (0.2-0.5). INTERPRETATION A 3-year screening interval could be safely adopted for patients with no retinopathy, but yearly or more frequent screening is needed for patients with higher grades of retinopathy.

Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia.

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascuLar disease (CVD) and reduced Life expectancy, over and above that imposed by their mentaL illness through suicide. Several Levels of evidence from data Linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metaboLic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.

Cost effectiveness analysis of screening for sight threatening diabetic eye disease

Abstract Objective: To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. Design: Cost effectiveness analysis Setting: Liverpool. Subjects: A target population of 5000 diabetic patients invited for screening. Main outcome measures: Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. Results: Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was £209 (sensitivity 89%, specificity 86%, compliance 80%, annual cost £104 996) and of the opportunistic programme was £289 (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost £99 981). The incremental cost effectiveness of completely replacing the opportunistic programme was £32. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. Conclusion: Replacing existing programmes with systematic screening for diabetic eye disease is justified.

Incidence of sight-threatening retinopathy in Type 1 diabetes in a systematic screening programme.

Aim To measure the cumulative incidence of any retinopathy, maculopathy and sight‐threatening diabetic retinopathy (STDR), and calculate optimal screening intervals by retinopathy grade at baseline for patients with Type 1 diabetes attending an established systematic retinal screening programme.

Prevalence of diabetic eye disease in an inner city population: The liverpool diabetic eye study

Purpose To measure the population prevalence of diabetic eye disease in an inner city setting.Methods As part of a systematic screening programme all adult diabetic patients in four general practices were invited to attend for slit-lamp biomicroscopy by a retinal specialist. Data on non-attenders were available from community-based photography.Results Of 395 diabetic patients identified, 326 attended biomicroscopy with photographic data available on a further 31, giving a 90% compliance rate. Point prevalence of diabetes in the target population was 12.4/ 1000. Demographic data included: mean age 60 years (range 13-92 years); type of control: type I 49, type II insulin-requiring (IR) 40, type II non-insulin-requiring (NIR) 268. Prevalences were as follows: any retinopathy: of all diabetic patients 33.6%, type I 36.7%, type II IR 45.0%, type II NIR 31.3%; proliferativel advanced: all 1.1%, type I 2.0%, type II IR 0, type II NIR 1.1%; clinically significant macular oedema: all 6.4%, type I 2.3%, type II IR 16.2%, type II NIR 5.7%. The percentage of patients with retinopathy requiring follow-up by an ophthalmologist was 4.5%, and 9.2% had macular exudates within 1 disc diameter of fixation or significant circinate maculopathy. Sight-threatening diabetic eye disease (STED) was found in 13.4%. A visual acuity of ≤ 6/24 in the better eye occurred in 12 (3.4%) patients and of ≤ 6/60 in the better eye in 3 (0.8%). Conclusions Compared with previous population studies, prevalences appear to have declined in type I, but remain high in type II diabetic patients and especially in those requiring insulin.

Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement.

OBJECTIVE Adult growth hormone deficiency (AGHD) is characterized by abnormalities in body composition and a poor perceived quality of life (QoL). Weight‐based high‐dose growth hormone replacement (GHR) results in improvements in body composition and QoL in AGHD. However, a high patient percentage reported side‐effects on high‐dose GHR resulting in a high rate of patient withdrawal from growth hormone (GH) treatment. High‐dose GH therapy also leads to supraphysiological serum insulin‐like growth factor‐I (IGF‐I) concentrations that have been associated with breast and prostate cancer, raising major concerns over the use of such high‐dose GH regimen in AGHD. The aim of this study was to assess the effects of low‐dose growth hormone replacement (GHR) on body composition and QoL as early as 1 and 3 months.

Current concepts of renal hemodynamics in diabetes

Glomerular hyperfiltration has long been recognized in insulin-dependent diabetes, and has been more recently recognized in patients with non-insulin dependent diabetes mellitus as well. Experimentally, glomerular hyperfiltration has been shown to result from elevations in the glomerular capillary blood flow and the glomerular capillary hydraulic pressure (PGC). Of the hemodynamic determinants of hyperfiltration, it is glomerular hypertension that is most damaging to the glomerulus. Experimental and clinical studies have confirmed that antihypertensive agents that lower PGC more consistently slow the progression of injury than do those that fail to control glomerular hypertension. The pathogenesis of diabetic hyperfiltration is multifactoral. Many mediators have been proposed, including changes due to the altered metabolic milieu, and alterations in endogenous levels of such vasoactive mediators as atrial natriuretic peptide, endothelial-derived relaxing factor, angiotensin II, prostaglandins, thromboxanes, and kinins, among others. It has more recently been suggested that local renal tissue levels, rather than circulating levels, play the more profound role in hemodynamic regulation. For example, the renin-angiotensin system (RAS) appears to be disproportionately active in the renal tissue, potentially explaining the renal vascular responsiveness to angiotensin-converting enzyme inhibition despite absence of systemic RAS activation. Little is yet known of the mechanisms by which glomerular hypertension leads to injury. Innovative new in vitro systems have been developed to address this question. These studies postulate that glomerular hemodynamic factors (shear stress, pulsatile flow) modify the growth and activity of glomerular component cells, inducing the expression of cytokines and other mediators, which then stimulate matrix production and promote structural injury.

Prevalence of diabetic eye disease in patients entering a systematic primary care-based eye screening programme.

Aims Large‐scale, baseline prevalence measurements in a population at the institution of systematic retinal screening are currently unavailable. We report the prevalence of all grades of retinopathy at entry into a systematic primary care‐based diabetic eye screening programme.