Lipid-lowering treatment for all could substantially reduce the burden of macrovascular complications of diabetes patients in the Netherlands

BACKGROUND: We aimed to quantify the potential health benefits of increased use of lipid-lowering treatment (LLT), according to current guidelines, for the Dutch diabetes population. DESIGN: Simulation study. METHODS: We compared the long-term health outcomes for a scenario in which all diabetes patients received LLT to those in a 'current practice' scenario, in which 28% received LLT. The model reflected the Dutch diabetes population 40-80 years of age, in 2003. Sensitivity analyses were performed, using more conservative assumptions. RESULTS: Over the lifetime, LLT for all diabetes patients reduced the expected cumulative incidences of coronary heart disease (CHD) and stroke by, respectively, 6 and 9%. Average life expectancy of Dutch diabetes patients would increase by 0.33 years, ranging from 0.14 years for patients aged 70-79 years, to 0.84 years for patients aged 40-49 years at the start of the simulation. Life-long treatment for patients aged 50-59 contributed most to the life years gained (55,000 out of 146,000). With reduced effectiveness of LLT and fewer patients starting LLT, the cumulative incidences of both CHD and stroke would decrease by approximately 2%. The number needed to treat to prevent one incident case of cardiovascular disease over lifetime was 20 for CHD and 44 for stroke. CONCLUSION: This simulation study shows that increased use of LLT can substantially reduce the expected future burden of CHD and stroke in the Dutch diabetes population.     

Neuro-ophthalmic complications in giant cell arteritis

Giant cell arteritis (GCA) is a medical emergency characterized by systemic inflammation and critical ischemia. Neuro-ophthalmic complications occur early, with permanent vision loss in up to one fifth of patients. This mainly results from failure of prompt recognition and treatment. Diagnosis of GCA is often preceded by unrecognized symptoms, including constitutional upset and jaw claudication. Features predictive of permanent visual loss include jaw claudication and temporal artery abnormalities on physical examination. These patients often do not mount high inflammatory responses. Modern imaging techniques show diagnostic promise, and have led to an increased recognition of major artery involvement in GCA. However, temporal artery biopsy remains the gold standard for investigation. Intimal hyperplasia on histologic examination is associated with neuro-ophthalmic complications. The mainstay of therapy remains corticosteroids. Experience using conventional disease-modifying drugs has been mixed, and biologic therapies require further evaluation for their steroid-sparing potential.     

Predictors of treatment contact among individuals with cannabis dependence

Epidemiological studies have repeatedly shown that cannabis is the most commonly used illegal drug in the United States. Furthermore, individuals with cannabis dependence have high rates of comorbid substance use disorders and depression. A significant proportion of individuals with addictive disorders develop withdrawal symptoms, cannot control their drug use despite substantial adverse psychosocial consequences, and frequently have a coexisting psychiatric disorder. Nevertheless, only a minority of persons with cannabis dependence ever seek treatment. We were unable to locate epidemiological reports regarding treatment seeking behavior among persons with cannabis dependence. Epidemiological studies of populations with substance disorders have observed that employment, higher educational level, previous use of treatment, major depression, and a co-occurring substance dependency increased the probability of seeking treatment for alcohol dependence. Thus we hypothesized that the same variables would predict service use among persons with cannabis dependence. The main findings of this study were that persons with cannabis dependence were more likely to contact a professional during the past year if they previously sought treatment and had alcohol dependence with major depression. Prospective, longitudinal studies of adolescents would increase our understanding of the processes by which individuals identify themselves as having problems related to their habitual use of marijuana, and why some seek help while others do not.     

Erythropoietin: Novel Approaches to Neuroprotection in Human Brain Disease

With the increased life expectancy in western industrialized countries, the incidence and prevalence of brain diseases dramatically increased. Stroke and a wide spectrum of neuropsychiatric illnesses such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, traumatic head injury, and schizophrenia all lead to severe disability. However, targeted effective therapies for treatment of these diseases are lacking. Even more frustrating is the fact that we do not yet clearly understand the basic mechanisms underlying the disease processes in these conditions. We propose a hypothesis of loss of neuronal function via a final common deleterious pathway in this clinically very heterogeneous disease group. This review presents a novel neuroprotective concept for treatment of brain disease: Erythropoietin (EPO). EPO is a natural body-own-protein hormone that has been used for treatment of anemia for more than a decade. The neuroprotective approach using EPO in brain disease represents a totally new frontier. The “Göttingen EPO-stroke trial” represents the first effective use in man of a neuroprotective therapy in an acute brain disease while the experimental EPO therapy to combat cognitive decline in patients with schizophrenia will be introduced as an example of a neuroprotective strategy for a chronic brain disease.     

Reversible kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene

Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone (T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg(622)X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty.     

Drug use patterns and mental health of regular amphetamine users during a reported 'heroin drought'

Aims: The present study extends the findings of a pilot study conducted among regular amphetamine users in Newcastle, NSW, in 1998. It compares key features between current participants in a state capital city (Brisbane) and a regional city (Newcastle) and between the 1998 and current Newcastle sample. DESIGN: Cross-sectional survey. Setting Brisbane and Newcastle, Australia. PARTICIPANTS: The survey was conducted among 214 regular amphetamine users within the context of a randomized controlled trial of brief interventions for amphetamine use. MEASUREMENTS: Demographic characteristics, past and present alcohol and other drug use and mental health, treatment, amphetamine-related harms and severity of dependence. FINDINGS: The main findings were as follows: (i). the rate of mental health problems was high among regular amphetamine users and these problems commonly emerged after commencement of regular amphetamine use; (ii). there were regional differences in drug use with greater accessibility to a wider range of drugs in a state capital city and greater levels of injecting risk-taking behaviour outside the capital city environment; and (iii). there was a significant increase in level of amphetamine use and percentage of alcohol users, a trend for a higher level of amphetamine dependence and a significant reduction in the percentage of people using heroin and benzodiazepines among the 2002 Newcastle cohort compared to the 1998 cohort. CONCLUSIONS: Further longitudinal research is needed to elucidate transitions from one drug type to another and from recreational to injecting and regular use and the relationship between drug use and mental health in prospective studies among users. IMPLICATIONS: Intervention research should evaluate the effectiveness of interventions aimed at: preventing transition to injecting and regular use of amphetamines; toward reducing levels of depression among amphetamine users and interventions among people with severe psychopathology and personality disorders; and toward reducing the prevalence of tobacco dependence among amphetamine users.     

Enhanced external counterpulsation does not alter arterial stiffness in patients with angina

BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive treatment for angina that acutely augments diastolic pressure and reduces cardiac afterload. However, the mechanism of the sustained clinical benefit seen with this therapy is not known. HYPOTHESIS: The study aimed to determine whether EECP leads to an improvement in arterial stiffness. METHODS: In all, 22 men and 1 woman with angina (age 63.6 +/- 6.7 years, mean +/- SD) were studied prior to and after 35 h of EECP therapy over 7 weeks. We measured carotid-radial (C-R) pulse wave velocity (PWV), and aortic augmentation index (AI) was derived from radial and carotid artery waveforms using applanation tonometry. Seventeen patients underwent treadmill exercise testing before and after the 7 weeks of EECP. RESULTS: After EECP therapy, despite a significant improvement in treadmill exercise time and a reduction in systolic and diastolic blood pressures, there was no significant change in any arterial stiffness parameters: Mean C-R PWV was 8.4 +/- 0.8 m/s at baseline and 8.0 +/- 1.2 m/s after 7 weeks of EECP, mean change: -0.4, 95% confidence interval (CI): -1.0, + 0.2, p = 0.17. Mean radial-derived AI was 25.7 +/- 10.4% before and 24.6 +/- 10.8% after, mean change: +1.1%, 95% CI: -2.3, +4.5, p = 0.53. Median AI-carotid was 31.5% before and 28.7% after; median change: -0.5, interquartile range: -9.5, +3.5, p = 0.32. Nineteen patients returned for 6-month recordings; neither blood pressure nor arterial stiffness readings were significantly different from baseline. CONCLUSION: Enhanced external counterpulsation therapy does not significantly alter arterial stiffness. Other than an initial reduction in blood pressure, the sustained clinical benefit seen with this therapy is unlikely to be effected through alterations in arterial wall mechanical properties.