HIV Testing in the U.S.: Good News and Bad.


Some infections are diagnosed promptly, but most are not.

With the ideal national testing strategy, all individuals with new HIV infections would be identified as soon as possible after infection. How close are we to this goal?

CDC researchers analyzed HIV testing histories reported by 57,000 individuals from 18 cities and states around the country who received new HIV diagnoses between 2006 and 2009. The majority (60%) reported having a previous negative test: 42% of them within the year before the positive test, 21% from 1 year to 2 years before, and the rest >2 years before.

The groups with the highest percentages of people identified within a year of HIV seroconversion were whites, individuals aged 13 to 29, and males reporting male-to-male sexual contact as their sole risk factor. The groups with the highest percentages of no previous HIV testing were blacks, those aged 50 and older, individuals of both sexes reporting heterosexual contact as their sole risk factor, and males reporting injection-drug use as their sole risk factor. Not surprisingly, those with no previous HIV testing were more likely than the others to progress to AIDS within 6 months of their HIV diagnosis (37% vs. 20%)

Comment: These data come with the caveat that people who know their HIV testing history precisely may not be representative of the larger at-risk population. Still, the data contain both good and bad news. They suggest that recent efforts to emphasize testing among young men who have sex with men may be producing results. However, they also show that among those traditionally less likely to acknowledge their HIV risk, including heterosexuals, older individuals, and blacks, many infections are still being diagnosed far too late.

Source: Journal Watch HIV/AIDS Clinical Care

GlaxoSmithKline to pay $3bn in US drug fraud scandal.


(GSK) is to pay $3bn (£1.9bn) in the largest healthcare fraud settlement in US history.

The drug giant is to plead guilty to promoting two drugs for unapproved uses and failing to report safety data about a diabetes drug to the Food and Drug Administration (FDA).

The settlement will cover criminal fines as well as civil settlements with the federal and state governments.

The case concerns the drugs Paxil, Wellbutrin and Avandia.

Deputy US Attorney General James Cole told a news conference in Washington DC that the settlement was “unprecedented in both size and scope”.

Doctors bribed

GSK, one of the world’s largest healthcare and pharmaceuticals companies, admitted  to promoting antidepressants Paxil and Wellbutrin for unapproved uses, including treatment of children and adolescents.

The illegal practice is known as off-label marketing.

The company also conceded charges that it held back data and made unsupported safety claims over its diabetes drug Avandia.

In addition, GSK has been found guilty of paying kickbacks to doctors.

“The sales force bribed physicians to prescribe GSK products using every imaginable form of high-priced entertainment, from Hawaiian vacations [and] paying doctors millions of dollars to go on speaking tours, to tickets to Madonna concerts,” said US attorney Carmin Ortiz.

As part of the settlement, GSK agreed to be monitored by government officials for five years.

GSK said in a statement it would pay the fines through existing cash resources.

Andrew Witty, the firm’s chief executive, said procedures for compliance, marketing and selling had been changed at GSK’s US unit.

“We have learnt from the mistakes that were made,” Mr Witty said. “When necessary, we have removed employees who have engaged in misconduct.”

Source: BBC Heath.

Indirect revascularization for nonmoyamoya intracranial arterial stenoses: clinical and angiographic outcomes.


Symptomatic intracranial arterial stenoses have a high rate of recurrent stroke despite medical and endovascular treatments. The authors present clinical and angiographic quantitative outcomes of indirect revascularization for patients with symptomatic intracranial stenosis.

Methods

Patients treated for symptomatic intracranial arterial stenosis by indirect revascularization were included. The patient population comprised those in whom medical management had failed and for whom endovascular therapy was unsuitable or had failed. Patients underwent encephaloduroarteriosynangiosis (EDAS) with or without bur holes. Preoperative and postoperative angiograms were evaluated for change in caliber of extracranial blood vessels (superficial temporal artery [STA] and middle meningeal artery [MMA]) and for evidence of neovascularization.

Results

Thirteen patients underwent EDAS. Ischemic symptoms ceased within the follow-up period in all patients, returning in a delayed fashion in only 2. No other patients had recurrent TIAs or strokes after the initial postoperative period. Donor blood vessels increased in size relative to preoperative sizes in all but 1 case (average increase of 52% for proximal STA [p = 0.01], 74% for midpoint of STA [p = 0.01], and 84% for the MMA [p = 0.02]). In addition, 8 of 11 patients demonstrated direct spontaneous anastomoses from extracranial to middle cerebral artery branches, and all patients demonstrated angiographic evidence of vascular blush and/or new branches from the STA and/or MMA.

Conclusions

Indirect revascularization appears to be a safe and effective method to improve blood flow to ischemic brain due to intracranial arterial stenosis. Neovascularization and enlargement of the branches of the ECA were observed in all patients and correlated with improvement in ischemic symptoms. Indirect revascularization is an option for patients in whom medical therapy has failed and who are not suitable for endovascular treatment.

Source: Journal of neurosurgery.

 

 

 

 

 

 

 

 

 

 

 

 

Annual rupture risk of growing unruptured cerebral aneurysms detected by magnetic resonance angiography.


In this paper, the authors’ goals were to clarify the characteristics of growing unruptured cerebral aneurysms detected by serial MR angiography and to establish the recommended follow-up interval.

Methods

A total of 1002 patients with 1325 unruptured cerebral aneurysms were retrospectively identified. These patients had undergone follow-up evaluation at least twice. Aneurysm growth was defined as an increase in maximum aneurysm diameter by 1.5 times or the appearance of a bleb.

Results

Aneurysm growth was observed in 18 patients during the period of this study (1.8%/person-year). The annual rupture risk after growth was 18.5%/person-year. The proportion of females among patients with growing aneurysms was significantly larger than those without growing aneurysms (p = 0.0281). The aneurysm wall was reddish, thin, and fragile on intraoperative findings. Frequent follow-up examination is recommended to detect aneurysm growth before rupture.

Conclusions

Despite the relatively short period, the annual rupture risk of growing unruptured cerebral aneurysms detected by MR angiography was not as low as previously reported. Surgical or endovascular treatment can be considered if aneurysm growth is detected during the follow-up period.

Source: Journal of neurosurgery.

cerebral aneurysm, magnetic resonance angiography, rupture, vascular disorders

 

 

Cost-effectiveness of carotid artery stent placement versus endarterectomy in patients with carotid artery stenosis

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated that the risk of the primary composite outcome of stroke, myocardial infarction (MI), or death did not differ significantly in patients with an average surgical risk undergoing carotid artery stenting (CAS) and those undergoing carotid endarterectomy (CEA). However, the cost associated with CAS may limit its broad applicability. The authors’ goal in this paper was to determine the cost-effectiveness of CAS with an embolic-protection device versus CEA in patients with moderate to severe carotid artery stenosis who are at average surgical risk.

Methods

The probability of the primary outcome was obtained from the results of the CREST trial. The quality-adjusted life years (QALYs) associated with each treatment modality were estimated by adjusting for the incidence of each quality-adjusted outcome (QALY weights of ipsilateral stroke, MI, death, and postprocedure QALYs). The total cost associated with each intervention was derived from hospitalization cost and cost associated with primary outcomes including stroke, MI, and death in each group. Costs are expressed in US dollars accounting for inflation up to October 2010. Incremental cost-effectiveness ratios (ICERs) were estimated for the 4-year period after the procedure. All values are expressed as means and 95% confidence intervals.

Results

The estimated net costs for patients after treatment with CAS and CEA after consideration of the primary outcome were $18,335 and $13,276, respectively, from the definitive presimulation analysis. Postsimulation values were $19,210 (range $18,264–$20,156) and $14,080 (range $13,076–$15,084), respectively. Overall, QALYs for the CAS and CEA groups were 0.712 and 0.702, respectively (ranging from 0.0 [death] to 0.815 [no adverse events]). The estimated ICER for CAS versus CEA treatment was $229,429.

Conclusions

Although the CREST demonstrated equivalent results with CAS (compared with CEA) in patients at average surgical risk with severe carotid artery stenosis, broad applicability of CAS might be limited by the higher cost associated with this procedure.

Source: Journal of neurosurgery.

 

Timing of clinical grade assessment and poor outcome in patients with aneurysmal subarachnoid hemorrhage.


Timing of clinical grading has not been fully studied in patients with aneurysmal subarachnoid hemorrhage (SAH). The primary objective of this study was to identify at which time point clinical assessment using the World Federation of Neurosurgical Societies (WFNS) grading scale and the Glasgow Coma Scale (GCS) is most predictive of poor functional outcome.

Methods

This study is a retrospective cohort study on the association between poor outcome and clinical grading determined at presentation, nadir, and postresuscitation. Poor functional outcome was defined as a Glasgow Outcome Scale score of 1–3 at 6 months after SAH.

Results

The authors identified 186 consecutive patients admitted to a teaching hospital between January 2002 and June 2008. The patients’ mean age (± SD) was 56.9 ± 13.7 years, and 63% were women. Twenty-four percent had poor functional outcome (the mortality rate was 17%). On univariable logistic regression analyses, GCS score determined at presentation (OR 0.80, p < 0.0001), nadir (OR 0.73, p < 0.0001), and postresuscitation (OR 0.53, p < 0.0001); modified Fisher scale (OR 2.21, p = 0.0013); WFNS grade assessed at presentation (OR 1.92, p < 0.0001), nadir (OR 3.51, < 0.0001), and postresuscitation (OR 3.91, p < 0.0001); intracerebral hematoma on initial CT (OR 4.55, p < 0.0002); acute hydrocephalus (OR 2.29, p = 0.0375); and cerebral infarction (OR 4.84, p < 0.0001) were associated with poor outcome. On multivariable logistic regression analysis, only cerebral infarction (OR 5.80, p = 0.0013) and WFNS grade postresuscitation (OR 3.43, p < 0.0001) were associated with poor outcome. Receiver operating characteristic/area under the curve (AUC) analysis demonstrated that WFNS grade determined postresuscitation had a stronger association with poor outcome (AUC 0.90) than WFNS grade assessed upon admission or at nadir.

Conclusions

Timing of WFNS grade assessment affects its prognostic value. Outcome after aneurysmal SAH is best predicted by assessing WFNS grade after neurological resuscitation.

Source: Journal of neurosurgery.

 

 

 

Interactive virtual simulation using a 3D computer graphics model for microvascular decompression surgery.


The purpose of this paper is to report on the authors’ advanced presurgical interactive virtual simulation technique using a 3D computer graphics model for microvascular decompression (MVD) surgery.

Methods

The authors performed interactive virtual simulation prior to surgery in 26 patients with trigeminal neuralgia or hemifacial spasm. The 3D computer graphics models for interactive virtual simulation were composed of the brainstem, cerebellum, cranial nerves, vessels, and skull individually created by the image analysis, including segmentation, surface rendering, and data fusion for data collected by 3-T MRI and 64-row multidetector CT systems. Interactive virtual simulation was performed by employing novel computer-aided design software with manipulation of a haptic device to imitate the surgical procedures of bone drilling and retraction of the cerebellum. The findings were compared with intraoperative findings.

Results

In all patients, interactive virtual simulation provided detailed and realistic surgical perspectives, of sufficient quality, representing the lateral suboccipital route. The causes of trigeminal neuralgia or hemifacial spasm determined by observing 3D computer graphics models were concordant with those identified intraoperatively in 25 (96%) of 26 patients, which was a significantly higher rate than the 73% concordance rate (concordance in 19 of 26 patients) obtained by review of 2D images only (p < 0.05). Surgeons evaluated interactive virtual simulation as having “prominent” utility for carrying out the entire surgical procedure in 50% of cases. It was evaluated as moderately useful or “supportive” in the other 50% of cases. There were no cases in which it was evaluated as having no utility. The utilities of interactive virtual simulation were associated with atypical or complex forms of neurovascular compression and structural restrictions in the surgical window. Finally, MVD procedures were performed as simulated in 23 (88%) of the 26 patients .

Conclusions

Our interactive virtual simulation using a 3D computer graphics model provided a realistic environment for performing virtual simulations prior to MVD surgery and enabled us to ascertain complex microsurgical anatomy.

Source: Journal of neurosurgery.

 

Effects of aging on behavioral assessment performance: implications for clinically relevant models of neurological disease.


Despite the role of aging in development of neurological and neurodegenerative diseases, the effects of age are often disregarded in experimental design of preclinical studies. Functional assessment increases the clinical relevance of animal models of neurological disease and adds value beyond traditional histological measures. However, the relationship between age and functional impairment has not been systematically assessed through a battery of functional tests.

Methods

In this study, various sensorimotor and behavioral tests were used to evaluate effects of aging on functional performance in naive animals. Sensorimotor measures included locomotor activity; Rotarod, inclined plane, and grip-strength testing; and modified Neurological Severity Score. The Morris water maze was used to examine differences in learning and memory, and the elevated plus maze and forced swim test were used to assess anxiety-like and depressive-like behaviors, respectively.

Results

Older Sprague-Dawley rats (18–20 months) were found to perform significantly worse on the inclined plane tests, and they exhibited alterations in elevated-plus maze and forced swim test compared with young adult rats (3–4 months). Specifically, older rats exhibited reduced exploration of open arms in elevated plus maze and higher immobility time in forced swim test. Spatial acquisition and reference memory were diminished in older rats compared with those in young adult rats.

Conclusions

This study demonstrates clear differences between naive young adult and older animals, which may have implications in functional assessment for preclinical models of neurological disease.

Source: Journal of neurosurgery.

 

 

 

A novel tissue engineering approach using an endothelial progenitor cell–seeded biopolymer to treat intracranial saccular aneurysms.


Recurrence after endovascular coiling of intracranial aneurysms is reported in up to 42% of cases and is attributed to the lack of endothelialization across the neck. In this study the authors used a novel tissue engineering approach to promote endothelialization by seeding endothelial progenitor cells (EPCs) within a fibrin polymer injected endovascularly into the aneurysm.

Methods

Experimental aneurysms were created in New Zealand White rabbits and were left untreated, surgically clipped, or embolized with platinum coils, fibrin biopolymer alone, or fibrin combined with autologous cultured EPCs.

Results

In aneurysms treated with EPCs, a confluent monolayer of endothelial cells with underlying neointima was demonstrated across the neck at 16 weeks posttreatment, which was not observed with aneurysms treated using the other methods.

Conclusions

This novel technique may address reasons for the limited durability of standard coil embolization and provides further avenues for the development of improved devices for the care of patients with aneurysms.

Source: Journal of neurosurgery.

 

 

Discontinuing Bevacizumab in Patients with Glioblastoma: An Ethical Analysis.


Glioblastoma (GBM) is a highly lethal malignant brain tumor that expresses proangiogenic factors, including vascular endothelial growth factor (VEGF). Bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA), a monoclonal antibody against VEGF, is routinely used in the U.S. to treat GBM patients whose tumors have progressed following initial therapy. The Ethics Advisory Committee at the Dana-Farber Cancer Institute was asked to provide consultation on two cases involving patients with recurrent GBM who were receiving bevacizumab. Despite evidence of disease progression, family members advocated for the continued use of bevacizumab because of its mild toxicity profile and concern that discontinuation would impair quality of life. However, continuing bevacizumab in this setting posed physical and financial risks to the patients and raised ethical concerns about resource allocation and justice.

We analyze the ethical questions regarding bevacizumab discontinuation in the setting of progressive GBM. We articulate the potential benefits and harms of continuing the drug and identify guiding principles for drug discontinuation that should be made transparent to patients and families. With the increasing availability of new, modestly toxic, expensive drugs for patients with advanced cancer, questions of when to stop these drugs will become increasingly relevant.

Source: the Oncologist.

 

 

 

A New Era for the Systemic Therapy of Neuroendocrine Tumors.


Carcinoids and pancreatic neuroendocrine tumors are becoming increasingly common, with the majority of patients presenting with either lymph node involvement or metastatic disease. An improved understanding of the molecular mechanisms involved in these tumors has implicated several pathways that have led to new therapeutic approaches. In this manuscript, we describe the biology of neuroendocrine tumors and approaches to systemic therapy. We review early data regarding the use of cytotoxics and several recent studies employing more targeted approaches that promise to change the standard of care. Specifically, phase III studies indicate that pharmacologic inhibition of the vascular endothelial growth factor pathway with sunitinib, and of the mammalian target of rapamycin pathway with everolimus, appears to have altered the natural history of these diseases. These successes set the stage for further advances in the management of patients with neuroendocrine tumors.

Source: the Oncologist.