Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

A theoretical model evaluating the angular distribution of luminescence emission in X-ray scintillating screens.

The aim of this study was to examine the angular distribution of the light emitted from radiation-excited scintillators in medical imaging detectors. This distribution diverges from Lambert's cosine law and affects the light emission efficiency of scintillators, hence it also affects the dose burden to the patient. In the present study, the angular distribution was theoretically modeled and was used to fit experimental data on various scintillator materials. Results of calculations revealed that the angular distribution is more directional than that predicted by Lambert's law. Divergence from this law is more pronounced for high values of light attenuation coefficient and thick scintillator layers (screens). This type of divergence reduces light emission efficiency and hence it increases the incident X-ray flux required for a given level of image brightness.     

Local mucosal immunoglobulin E production: does allergy exist in non‐allergic rhinitis?

In this review, we critically evaluate the evidence for local IgE production in allergic rhinitis mucosa and the concept of local allergy in non-atopic idiopathic rhinitis. Significantly, fewer studies have focused on the disease pathways associated with non-allergic rhinitis compared with their allergic counterparts. Recently, there's been a revival of the hypothesis concerning the existence of local tissue-specific allergic disease confined to the nasal mucosa of some systemically non-atopic rhinitis subjects. Providing the evidence for local mucosal IgE production in allergic rhinitis is a pre-requisite to reviewing its existence in non-allergic rhinitis. In addition, practical and theoretical approaches useful in the detection of allergy in non-allergic rhinitis will be discussed. Furthermore, successful therapeutic regimens used in the treatment of non-allergic rhinitis will be examined as these could provide an insight into the underlying pathophysiology of this common but poorly understood disease.     

Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.     

Special needs of adolescent and young women in accessing reproductive health: promoting partnerships between young people and health care providers.

This article considers the unique challenges and opportunities that health care providers (HCPs) face when they address the sexual and reproductive health and rights of young women accessing services. Some of the difficulties that HCPs encounter in their work are highlighted, including poor remuneration, the impact of their personal biases and the effect of an under-equipped working environment. The financial, logistical and emotional challenges young people face in accessing services are also described, as well as some small changes that could promote fruitful partnerships between HCPs and their young clientele. Also considered is how international documents concerning reproductive health can be utilized as advocacy tools to ensure that, when governments speak of making young people's needs a priority, resources are also made a priority-so that reproductive health can become a reality for all young people.     

Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Laparoscopic vs open subtotal colectomy for benign and malignant disease

AIM: The present meta-analysis aims to compare short-term and long-term outcomes in patients undergoing laparoscopic or open subtotal colectomy for benign and malignant disease. METHODS: A literature search of Medline, Ovid, Embase and Cochrane databases was performed to identify studies published between 1992 and 2005, comparing laparoscopic (LSC) and open (OSC) subtotal colectomy. A random effect meta-analytical technique was used and sensitivity analysis performed on studies published since the beginning of 2000, higher quality papers, those reporting on more than 40 patients, and those studies reporting on adult cases or acute colitis. RESULTS: A total of eight studies satisfied the criteria for inclusion. These included outcomes on 336 patients, 143 (42.6%) of whom had undergone laparoscopic resection, with an overall conversion rate to open surgery of 5% (range 0-11.8%). Operative time was significantly longer in the laparoscopic group by 86.2 min (P < 0.001) and throughout subgroup analysis, although it was only in patients with acute colitis that this finding was without significant heterogeneity. Operative blood loss was less in the laparoscopic group by 57.5 millilitres in high quality and studies published since 2000, and 65.3 millilitres in those reporting on more than 40 patients. There was no significant difference in early or long-term complications between the groups. A statistically significant reduction in length of postoperative stay was observed in the laparoscopic groups by 2.9 days (P < 0.001). CONCLUSION: Laparoscopic subtotal colectomy was associated with longer operating times but a reduced length of stay compared to open surgery. Although short-term outcomes were equivalent in both groups, the suggested benefits in terms of reduced long-term obstructive complications were not supported by this meta-analysis.     

Andrologische Diagnostik

Andrology was included as a further subject for continuing education in the Model Ordinance on Continuing Education at the 106th German Physicians’ Meeting in Cologne in 2003. In addition to fertility disorders, this discipline comprises medical care for men with fertility disorders, erectile dysfunction, disorders of libido, ejaculation, and coitus, various forms of hypogonadism, and delayed puberty. Furthermore, this field also covers questions concerning male contraception, gynecomastia, and male senescence. Diagnostic procedures in andrology require close interdisciplinary cooperation with practitioners of gynecology, human genetics, and psychosomatic medicine. It includes medical history, clinical examination, and laboratory analyses. Except to confirm azoospermia, it is not possible to make a definitive prognosis for fertility based on semen analysis. Functional tests allow a better assessment of the spermatozoa’s fertility since 25–30% of men desiring a child exhibit reduced spermatozoal functions, which cannot be verified on routine semen analysis.