Benzodiazepines and related drugs are initiated frequently in persons with Alzheimer’s disease already before the diagnosis, and their use becomes even more common after the diagnosis, shows a recent study from the University of Eastern Finland. Benzodiazepines and related drugs are used as a sleep medication and for anxiolytic purposes. These drugs were initiated more frequently in persons with Alzheimer’s disease than in persons not diagnosed with AD. Compared to persons not diagnosed with AD, it was three times more likely for persons with Alzheimer’s disease to initiate benzodiazepine use after the diagnosis, and benzodiazepines were most commonly initiated six months after the diagnosis.

The findings are based on data from the Finnish Medication Use and Alzheimer’s Disease Study, Medalz. Medalz comprises nationwide, extensive register-based data from the Finnish health care registers, and it includes all persons diagnosed with Alzheimer’s disease in Finland between 2005 and 2011. The study, analysed the initiation of benzodiazepines and related drugs in 51,981 persons diagnosed with AD. Their use of drugs was monitored for a period of five years, and the follow-up started already two years before the diagnosis. The findings were compared to persons not diagnosed with Alzheimer’s disease who were matched based on age and gender.

According to the Finnish Current Care Guidelines, benzodiazepines can be used on a short-term basis to treat behavioural problems associated with Alzheimer’s disease. However, data on the benefits of these drugs in the treatment of behavioural problems is insufficient, but it is known that these drugs increase the risk of falls and cause cognitive impairment.

One of the earlier studies on Medalz study found that in Finland, benzodiazepines are used for extensive periods in persons with Alzheimer’s disease. This, together with the current finding of frequent initiations of these drugs, paints a picture of a possible delay in AD diagnoses and concerning practice of symptom-based treatment before and around diagnosis.

University of Eastern Finland www.uef.fi/en/-/bentsodiatsepiinien-ja-niiden-kaltaisten-laakkeiden-kaytto-yleistyy-alzheimerin-taudin-toteamisen-aikoihin

Watching millions of neurons in the brain interacting with each other is the ultimate dream of neuroscientists! A new imaging method now makes it possible to observe the activation of large neural circuits, currently up to the size of a small-animal brain, in real time and three dimensions. Researchers at the Helmholtz Zentrum Munchen and the Technical University of Munich have recently reported on their new findings.
Nowadays it is well recognized that most brain functions may not be comprehended through inspection of single neurons. To advance meaningfully, neuroscientists need the ability to monitor the activity of millions of neurons, both individually and collectively. However, such observations were so far not possible due to the limited penetration depth of optical microscopy techniques into a living brain.
A team headed by Prof. Dr. Daniel Razansky, a group leader at the Institute of Biological and Molecular Imaging (IBMI), Helmholtz Zentrum Munchen, and Professor of Molecular Imaging Engineering at the Technical University of Munich, has now found a way to address this challenge. The new method is based on the so-called optoacoustics, which allows non-invasive interrogation of living tissues at centimetre scale depths.
‘We discovered that optoacoustics can be made sensitive to the differences in calcium ion concentrations resulting from neural activity and devised a rapid functional optoacoustic neuro-tomography (FONT) system that can simultaneously record signals from a very large number of neurons’, said Dr. Xose Luis Dean-Ben, first author of the study. Experiments performed by the scientists in brains of adult zebrafish (Danio rerio) expressing genetically encoded calcium indicator GCaMP5G demonstrated, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the longstanding penetration barrier of optical imaging in opaque brains. The technique was also able to trace neural activity during unrestrained motion of the animals.
‘So far we demonstrated real-time analysis on whole brains of adult animals with roughly 2x3x4 millimetre dimensions (approximately 24 mm3),’ says the study’s leader Razansky. State-of-the-art optical microscopy methods are currently limited to volumes well below a cubic millimetre when it comes to imaging of fast neural activity, according to the researchers. In addition, their FONT method is already capable of visualizing volumes of more than 1000 cubic millimetres with temporal resolution of 10 milliseconds.
Large-scale observation of neural activity is the key to understanding how the brain works, both under normal and diseased conditions. ‘Thanks to our method, one can now capture fast activity of millions of neurons simultaneously. Parallel neural networks with the social media: in the past, we were able to read along when someone (in this case, a nerve cell) placed a message with a neighbour. Now we can also see how this message spreads like wildfire,’ explains Razansky. ‘This new imaging tool is expected not only to significantly promote our knowledge on brain function and its pathophysiology but also accelerate development of novel therapies targeting neurological and neuropsychiatric disorders,’ he concludes.

Technical University of Munich http://tinyurl.com/goxtrm5

Researchers have evaluated the long-term efficacy and safety of long duration dual anti-platelet therapy (L-DAPT) compared to short duration DAPT (S-DAPT) after drug-eluting stent (DES) implantation. The current meta-analysis is the first to compare outcomes between S-DAPT and L-DAPT in a meta-analysis restricted to trials with patient follow-up of 24 months or longer.
DAPT using a combination of aspirin and a P2Y12 inhibitor is used for the prevention of ischemic complications after DES implantation. It is estimated that more than 10 million DES have been implanted globally, however, the optimal duration of DAPT after DES implantation remains unclear.
“A major limitation of most randomized control trials (RCTs) and previous meta-analyses was a short period of follow-up,” stated Abhishek Sharma, MD, of the Division of Cardiovascular Medicine at State University of New York Downstate Medical Center. “Between the small number of stent thrombosis (ST) events due to the low risk of ST with newer generation DES and the possibility that very-late ST events were not captured due to inadequate follow up, individual trials and even previous meta-analysis were probably underpowered to detect a definitive difference in reduction of very-late ST with L-DAPT. This limitation was addressed in our study by pooling data from only those RCTs, which have reported outcomes after a follow up of at least 24 months or longer.”
Researchers identified five RCTs in which 19,760 patients were randomized to S-DAPT (N59,810) and L-DAPT (n59,950), respectively. Compared with L-DAPT, S-DAPT was associated with higher rate of myocardial infarction (MI) (odds ratio [OR] 1.48, 95% confidence interval (CI) [1.04, 2.10]). There were no significant differences between S-DAPT and L-DAPT in terms of all-cause mortality, cardiac mortality, ST, TVR or stroke (OR 0.90, 95% CI [0.73, 1.12]; OR 1.02, 95% CI [0.80, 1.30]; OR 1.59, 95% CI [0.77, 3.27]; OR 0.87 95% CI [0.67, 1.14]; and OR 1.08 95% CI [0.81, 1.46], respectively). However, rate of thrombolysis in myocardial infarction (TIMI) major bleeding was significantly lower with S-DAPT compared to L-DAPT (OR 0.64, 95% CI [0.41, 0.99]).
“Our results support the importance of carefully choosing DAPT durations based on an individual patient’s ischemic and bleeding risks,” Sharma continued. “However, the clinical trials included in the current meta-analysis have mostly used clopidogrel as second agent. With increasing adoption of more potent P2Y12 inhibitors in clinical practice, the relative benefit-to-risk profile of S-DAPT vs L-DAPT using these agents remains to be established in future studies.”

The Society for Cardiovascular Angiography and Interventions
www.scai.org/Press/detail.aspx?cid=c76825de-20ca-4fae-bf48-9416611df29d#.WWP0Q_-GP5Y

Pulsed cavitation ultrasound (PCU) can be used to remotely soften human degenerative calcified biosprosthetic valves and may significantly improve the valve opening function, according to a study.
Olivier Villemain, MD, et al., examined the effects of PCU on human bioprosthetic heart valves that were removed from patients because they were heavily calcified and were non-functional. PCU, also called histotripsy, uses short-pulses of focused high pressure ultrasound to soften biological tissue. The ultrasound is delivered by a transducer that can be placed outside of the body and directed in a focused manner to the area of interest.
The removed valves were surgically implanted in sheep or were studied in an experimental bath apparatus in order to examine the longer-term effects of PCU. The researchers found that the PCU was able to soften the stiff calcified valves and improve the function of the valves. The amount of stenosis of the calcified aortic valves decreased by about two-fold on average in both the animal model and the experimental apparatus. The researchers believe that this new non-invasive approach has the potential to improve the outcome of patients with severe calcified bioprosthesis stenosis by avoiding risky surgical or transcatheter reintervention.
This study was designed as a proof of concept study and did not evaluate the potential risk of PCU causing pieces of the calcified aortic valve breaking off and causing an embolic stroke.
"The results of this experimental study must be regarded as provisional because neither the safety nor efficacy of this technique have been evaluated in humans," commented Douglas L. Mann, MD, FACC, editor-in-chief of JACC: Basic to Translational Science. "However, the concept of using high energy ultrasound to restore the function of calcified artificial tissue valves, analogous to the manner in which nephrologists use ultrasound to break up kidney stones, is both provocative and exciting. The ultrasound devices to perform this type of therapy exist today, so the ability to translate these concepts to patients can move very quickly."

American College of Cardiology www.acc.org/latest-in-cardiology/articles/2017/06/16/10/40/can-pulsed-cultivation-ultrasound-improve-valve-function?w_nav=LC

A Canadian-led research group has developed and validated a rule that could let half of women with unexplained vein blood clots stop taking blood thinners for life.

Over 1.5 million Canadians will experience a vein blood clot their lifetime, known as venous thrombosis. If part of the clot breaks off and travels to the lungs, it can be fatal. Half of these blood clots happen for no apparent reason, and are known as unexplained or unprovoked clots.

Once an unprovoked vein clot is treated, guidelines recommend that patients take blood thinners for the rest of their lives. If they do not, their risk of having a second clot is 30 to 40 percent in the next 10 years. Taking life-long blood thinners virtually eliminates this risk, but comes at a cost of a 1.2 percent chance of major bleeding per year.

‘Patients can get very anxious trying to balance the risks of the treatment with the risks of another blood clot,’ said Dr. Marc Rodger, senior scientist and thrombosis specialist at The Ottawa Hospital and professor at the University of Ottawa. ‘With this rule we can confidently tell half of the women we see that they are at low risk of having another blood clot. This means they can stop taking blood thinners once their initial clot is treated, sparing them the cost, inconvenience and risks of taking life-long medication.’

The HERDOO2 rule, so named to help physicians remember the criteria, was developed by an international team led by Dr. Rodger and published in 2008. According to the rule, if a woman has one or none of the following risk factors she is at low risk for having another blood clot:

Discoloration, redness or swelling in either leg (HER= Hyperpigmentation, (o)edema or redness)

High levels of a clotting marker (D-dimer) in the blood

Body mass index of 30 kg/m2 or more (Obesity)

Older than age 65

The team could not find factors to identify low-risk men.

The Ottawa Hospital Research Institute www.ohri.ca/newsroom/newsstory.asp?ID=903