Day: 03/18/2011

Implementation in a Large Health System of a Program to Identify Women at High Risk for Breast Cancer

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Patients at high risk for developing breast cancer can be identified using a validated predictive tool: the Gail model. Patients thus identified can undergo careful breast cancer screening and be considered for preventive measures, such as chemoprevention with tamoxifen or raloxifene. An organized health system can create a screening and high-risk intervention program for breast cancer and potentially save lives and resources. Multiple components of the health system must work together in a multidisciplinary manner to successfully implement such a program.

Methods: Aurora Health Care is a large health system in Wisconsin. In 2007, a medical center within Aurora initiated a program to identify patients at high risk for developing breast cancer and intervene with screening and prevention. The program used the Gail model, which was administered to patients presenting for comprehensive physical examination at the women’s center.

Results: During the first year, 5,718 Gail model scores were calculated, and 15.2% of patients were deemed high risk. Most were counseled by their primary care providers, and few underwent screening with magnetic resonance imaging, genetics consultation, or chemoprevention. Primary care providers expressed concerns regarding the accuracy of the Gail model, the additional time necessary for patient counseling, how few patients underwent chemoprevention, and perceived medicolegal risk. The program was altered to address these concerns.

Conclusion: Success of a breast cancer risk and intervention program in a large health system is more likely if concerns of participating disciplines are acknowledged and addressed.

source: journal of oncology practice

 

Neural Correlates of Response Inhibition and Cigarette Smoking in Late Adolescence

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Smoking is usually initiated in adolescence, and is the leading preventable cause of death in the United States. Little is known, however, about the links between smoking and neurobiological function in adolescent smokers. This study aimed to probe prefrontal cortical function in late adolescent smokers, using a response inhibition task, and to assess possible relationships between inhibition-related brain activity, clinical features of smoking behavior, and exposure to cigarette smoking. Participants in this study were otherwise healthy late adolescent smokers (15–21 years of age; n=25), who reported daily smoking for at least the 6 months before testing, and age- and education-matched nonsmokers (16–21 years of age; n=25), who each reported smoking fewer than five cigarettes in their lifetimes. The subjects performed the Stop-signal Task, while undergoing functional magnetic resonance imaging. There were no significant group differences in prefrontal cortical activity during response inhibition, but the Heaviness of Smoking Index, a measure of smoking behavior and dependence, was negatively related to neural function in cortical regions of the smokers. These findings suggest that smoking can modulate prefrontal cortical function. Given the late development of the prefrontal cortex, which continues through adolescence, it is possible that smoking may influence the trajectory of brain development during this critical developmental period.

source: nature journal of neuropsychopharrmacology

 

Previous adult attention-deficit and hyperactivity disorder symptoms and risk of dementia with Lewy bodies: a case–control study

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Previous reports have shown that in Dementia with Lewy body (DLB) and attention-deficit and hyperactivity disorder (ADHD) a hypodopaminergic and noradrenergic substrate seems to play a central role in developing the diseases. We investigated the hypothesis that attention deficit may precede DLB expressed as adult ADHD symptoms long before the clinical onset of dementia.

Methods: Patients with DLB, Alzheimer disease type (ADT) and controls were recruited from the membership of the Italian Hospital Medical Care Program in Argentina from 2000 to 2005. The DSM-IV criteria adapted for the identification of adult patients with ADHD and validated to Spanish Wender Utah Rating Scale were used to identify individuals with preceding ADHD symptoms during their adult life. Analysis of categorical variables was carried out using chi-square. Mann–Whitney test was used for continuous variables. Statistical significance was P < 0.05.

Results: A total of 109 patients with DLB and 251 patients with ADT were matched by age, sex and year of education with 149 controls. The frequency of preceding ADHD symptoms in DLB cases was 47.8% in ADT 15.2% and 15.1% in the control group. The prevalence of ADHD symptoms in DLB cases was significantly higher compared with the control group (P ≤ 0.001, OR 5.1 95%CI 2.7–9.6) and also higher when compared with ADT (P ≤ 0.001, OR 4.9, 95%CI 2.8–8.4).

Conclusion: We found a higher risk of DLB in patients with preceding adult ADHD symptoms. To date, there is no clear explanation for the association found; however, further investigation will widen our understanding about both disorders.

source: European journal of neurology

Screening for tumours in paraneoplastic syndromes: report of an EFNS Task Force

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Paraneoplastic neurological syndromes (PNS) almost invariably predate detection of the malignancy. Screening for tumours is important in PNS as the tumour directly affects prognosis and treatment and should be performed as soon as possible.

Objectives: An overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome (LEMS), myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability.

Methods: Many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations grade A–C were possible, but good practice points were agreed by consensus.

Recommendations: The nature of antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region, a CT-thorax is recommended, which if negative is followed by fluorodeoxyglucose-positron emission tomography (FDG-PET). Breast cancer is screened for by mammography, followed by MRI. For the pelvic region, ultrasound (US) is the investigation of first choice followed by CT. Dermatomyositis patients should have CT-thorax/abdomen, US of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3–6 months and screen every 6 months up till 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients have a malignancy, tumour markers have additional value to predict a probable malignancy.

source: European journal of neurology

EFNS guidelines on diagnosis and treatment of primary dystonias

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Primary dystonias are classified as pure dystonia, dystonia plus or paroxysmal dystonia syndromes. Assessment should be performed using a validated rating scale for dystonia. Genetic testing may be performed after establishing the clinical diagnosis. DYT1 testing is recommended for patients with primary dystonia with limb onset before age 30, and in those with an affected relative with early-onset dystonia. DYT6 testing is recommended in early-onset or familial cases with cranio-cervical dystonia or after exclusion of DYT1. Individuals with early-onset myoclonus should be tested for mutations in the DYT11 gene. If direct sequencing of the DYT11 gene is negative, additional gene dosage is required to improve the proportion of mutations detected. A levodopa trial is warranted in every patient with early-onset primary dystonia without an alternative diagnosis. In patients with idiopathic dystonia, neurophysiological tests can help with describing the pathophysiological mechanisms underlying the disorder.

Treatment: Botulinum toxin (BoNT) type A is the first-line treatment for primary cranial (excluding oromandibular) or cervical dystonia; it is also effective on writing dystonia. BoNT/B is not inferior to BoNT/A in cervical dystonia. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for primary generalized or cervical dystonia, after medication or BoNT have failed. DBS is less effective in secondary dystonia. This treatment requires a specialized expertise and a multidisciplinary team.

source: European journal of neurology

Novel adenovirus-based helper system to support production of recombinant parvovirus

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Preclinical studies using various cell culture and animal systems highlight the potential of recombinant rodent parvoviruses (recPVs) for cancer therapy. Production of these viruses is, however, not efficient and this hampers the clinical applications of these agents. In this study, we show that the adenovirus genes E2a, E4(orf6) and VA RNA increase the production of recPVs by more than 10-fold and reduce the time of production from 3 to 2 days in HEK293T cells. The helper effects of these genes can be observed with different recPVs, regardless of the nature and size of the inserted transgene. Furthermore, we generated a recombinant Adenovirus 5 carrying the parvovirus VP transcription unit. This helper, named Ad-VP, allows recPVs to be efficiently produced through a protocol based only on cell infection, making possible to use cell lines, such as NB324K, which are good producers of parvoviruses but are hardly transfectable. Hence, we could further improve viral titers and reduce time and costs of production. This Ad-VP helper-based protocol could be scaled up to a bioreactor format for the generation of the large amounts of recPVs needed for future clinical applications.

source: cancer gene therapy

 

Prevention of Microalbuminuria with Olmesartan

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This drug delayed onset slightly but did not change overall incidence.

In patients with diabetes mellitus (DM), microalbuminuria predicts early development of nephropathy and cardiovascular (CV) disease; treatment with angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is recommended for patients with established microalbuminuria. In this trial, investigators assessed the value of the ARB olmesartan (Benicar) for preventing development of microalbuminuria. The drug’s maker funded the study, and most of the authors had financial relationships with the company.

About 4400 patients (mean age, 58) with type 2 DM, normoalbuminuria, and mean blood pressure of 136/81 mm Hg were randomized to daily olmesartan (40 mg) or placebo, with unrestricted use of antihypertensives other than ARBs or ACE inhibitors. Most patients in both groups achieved blood pressures <130/80 mm Hg. During median follow-up of 3.2 years, the incidence of microalbuminuria did not differ significantly between the olmesartan and placebo groups (8.2% vs. 9.8%), but onset was delayed significantly in the olmesartan group (median, 722 days vs. 576 days). Mean glomerular filtration rate declined more with olmesartan than with placebo (–5 vs. –1 mL/minute/1.73 m2). In a secondary endpoint, significantly more olmesartan patients died from any CV cause (0.7% vs. 0.1%).

Comment: The authors emphasize the 5-month delay in onset of microalbuminuria with olmesartan, but the clinical importance of this outcome is unclear. In addition, the authors concede that whether the observed parallel decline in GFR and albuminuria with olmesartan represents “a favorable hemodynamic (functional) response to lower glomerular pressure or an adverse underlying structural change” is unclear. Even more worrisome was the excess risk for fatal CV events. In our view, olmesartan should not be used as preemptive therapy in diabetic patients who have reasonably controlled blood pressure and no microalbuminuria.

Published in Journal Watch General Medicine

 

This drug delayed onset slightly but did not change overall incidence.

In patients with diabetes mellitus (DM), microalbuminuria predicts early development of nephropathy and cardiovascular (CV) disease; treatment with angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is recommended for patients with established microalbuminuria. In this trial, investigators assessed the value of the ARB olmesartan (Benicar) for preventing development of microalbuminuria. The drug’s maker funded the study, and most of the authors had financial relationships with the company.

About 4400 patients (mean age, 58) with type 2 DM, normoalbuminuria, and mean blood pressure of 136/81 mm Hg were randomized to daily olmesartan (40 mg) or placebo, with unrestricted use of antihypertensives other than ARBs or ACE inhibitors. Most patients in both groups achieved blood pressures <130/80 mm Hg. During median follow-up of 3.2 years, the incidence of microalbuminuria did not differ significantly between the olmesartan and placebo groups (8.2% vs. 9.8%), but onset was delayed significantly in the olmesartan group (median, 722 days vs. 576 days). Mean glomerular filtration rate declined more with olmesartan than with placebo (–5 vs. –1 mL/minute/1.73 m2). In a secondary endpoint, significantly more olmesartan patients died from any CV cause (0.7% vs. 0.1%).

Comment: The authors emphasize the 5-month delay in onset of microalbuminuria with olmesartan, but the clinical importance of this outcome is unclear. In addition, the authors concede that whether the observed parallel decline in GFR and albuminuria with olmesartan represents “a favorable hemodynamic (functional) response to lower glomerular pressure or an adverse underlying structural change” is unclear. Even more worrisome was the excess risk for fatal CV events. In our view, olmesartan should not be used as preemptive therapy in diabetic patients who have reasonably controlled blood pressure and no microalbuminuria.

Published in Journal Watch General Medicine

 

Palliative Care in Urology

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Urological malignancies, especially prostate cancer, are relatively common, but patients may live many years before eventually dying of the disease. Caring for these patients is an important role for urologists, although medical training often does not adequately prepare urologists for the palliative care of patients with advanced malignancies. Palliative care is no longer equated with end-of-life care, but rather integrated throughout illness, even when cure is impossible. This article focuses on the various palliative treatments available for the 3 most common urological malignancies: prostate, bladder, and renal cancers.

source: science direct

Meta-Analysis Favors Pioglitazone in ‘Real World’ Settings

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In an analysis of observational studies comparing pioglitazone versus rosiglitazone, pioglitazone emerges as the safer of the two.

Analyzing studies comprising over 800,000 patients with type 2 diabetes, researchers report in BMJ that use of rosiglitazone was associated with a “modest but statistically significant increase in the odds of myocardial infarction, congestive heart failure, and death compared with patients receiving pioglitazone in real world settings.”

In 2010, the European Medicines Agency recommended withdrawal of rosiglitazone from the market, and the U.S. FDA placed restrictions on its use.

Editorialists ask why, despite the association with increased risks for heart failure and the availability of other agents, thiazolidinediones remain among the leading prescribed drugs in the U.S. That popularity, they conclude, “says much about how healthcare has become less about promoting patients’ interests … and much more about promoting other interests, including those of the drug industry.”

Source:BMJ