Nearly a third of all antibiotics prescribed for hospitalized children globally were intended to prevent potential infections rather than to treat disease, according to the results of a worldwide survey.  A large proportion of these preventive, or prophylactic, prescriptions also were for broad-spectrum antibiotics or combinations of antibiotics, or were for prolonged periods, which can hasten the development of antibiotic-resistant bacteria and drug-resistant infections.
“This pattern and high rate of prophylactic prescribing indicates a clear overuse of antibiotics,” said study author Markus Hufnagel, of the University of Freiburg in Germany. “Hopefully, our study results will help to raise awareness among health professionals about appropriate prescribing of antibiotics in children,” Dr. Hufnagel said.
The study provides a snapshot of antibiotic prescriptions for 6,818 children who were inpatients at 226 paediatric hospitals in 41 countries, including four hospitals in the United States, during one day in 2012. There were 11,899 total prescriptions for antibiotics, and 28.6 percent of these were for prophylactic use, researchers found. Among hospitalized children who received at least one antibiotic prescription, 32.9 percent (2,242 children) were prescribed an antibiotic to prevent a potential infection rather than to treat a current one.
Of the antibiotics prescribed for prophylactic use, 26.6 percent were to prevent potential infections associated with an upcoming surgery, and the vast majority of these antibiotics were given for more than one day. The remaining 73.4 percent of the prophylactic prescriptions were intended to potentially prevent other types of infections. Approximately half (51.8 percent) of all preventive antibiotic prescriptions were for broad-spectrum antibiotics. In 36.7 percent of cases, two or more systemic antibiotics were prescribed at the same time.
These patterns contradict current recommendations for appropriate prophylactic antibiotic use. Guidelines often call for using narrow-spectrum antibiotics for shorter periods, in an effort to limit the development of antibiotic resistance. The study findings suggest clear targets for improving antibiotic prescribing in paediatric patients, according to the authors. These include reducing prolonged, preventive antibiotic use before surgery, limiting the use of broad-spectrum and combinations of antibiotics, and reducing antibiotic use, overall, for prophylactic rather than therapeutic use.
Additional education for clinicians and improved implementation of current guidelines for antibiotic use to prevent surgical infections are needed, Dr. Hufnagel said. More in-depth guidelines that address the use of prophylactic antibiotics for a broader range of medical conditions than current guidelines do are also needed, as well as efforts to communicate these guidelines to health care providers and to analyze how the recommendations are used.
Pediatric Infectious Diseases Societywww.pids.org/news/611-antibiotics-often-inappropriately-prescribed-for-hospitalized-kids-global-study-suggests.html

A study by researchers at the University of Birmingham has found that people whose heart rhythm returns to normal continue to be at high risk of stroke and should continue to be treated
Patients with an abnormal heart rhythm that can leave them at a higher risk of suffering from stroke still need treatment even after their heart rhythm seems to have returned to normal, say researchers at the University of Birmingham.
Atrial fibrillation is the most common heart rhythm disturbance, affecting around 1.6 million people in the UK. Those with atrial fibrillation may be aware of noticeable heart palpitations, where their heart feels like it’s pounding, fluttering or beating irregularly. Sometimes atrial fibrillation does not cause any symptoms and a person who has it is completely unaware that their heart rate is irregular.
People with atrial fibrillation are much more likely to develop blood clots and suffer from strokes. To avoid strokes it is important for them to take drugs to prevent blood clotting. Sometimes atrial fibrillation seems to go away and the heart goes back to its normal rhythm –the condition may then be deemed to have ‘resolved’. Up until now it has been unclear as to whether the clot-prevention drugs can be safely stopped when the condition is ‘resolved’.
Now a study by researchers at the University of Birmingham has found that people whose heart rhythm returns to normal continue to be at high risk of stroke and should continue to be treated.
Researchers looked at patient records from 640 general practices throughout the UK and compared the frequency of strokes in three groups of people: those with ongoing atrial fibrillation; those whose records said that atrial fibrillation had resolved; and those who never had atrial fibrillation.
Dr Nicola Adderley, of the University of Birmingham’s Institute of Applied Health Research, said: “What we found was that strokes were least common in people who never had atrial fibrillation, and much more common in people whose records said their atrial fibrillation had been resolved.
“Significantly, in recent years we found that strokes were nearly as common in people whose atrial fibrillation had resolved as in those with ongoing atrial fibrillation.
“Therefore, we can conclude that people with resolved atrial fibrillation continue to be at high risk of stroke.”
The researchers also looked at patient treatment. What they found was that, while most people deemed to have atrial fibrillation as an ongoing condition continue to get the clot-prevention drugs they need, the vast majority of those whose atrial fibrillation had ‘resolved’ do not.
Dr Krish Nirantharakumar, of the University of Birmingham’s Institute of Applied Health Research, added: “Our research demonstrates that although people with resolved atrial fibrillation continue to be at high risk of stroke, they are not getting their prevention drugs.
“Worryingly, we found that the problem seems to be becoming more common, with our research showing an increasing number of people are recorded as having atrial fibrillation as resolved and are highly unlikely to be given medication to prevent stroke.”

University of Birminghamwww.birmingham.ac.uk/news/latest/2018/05/irregular-heart-beat-research.aspx

A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.
There is a critical need to non-invasively and remotely manipulate cells at a distance, particularly for translational applications in animals and humans, researchers said.
The team developed an innovative approach to use mechanogenetics—a field of science that focuses on how physical forces and changes in the mechanical properties of cells and tissues influence gene expression—for the remote control of gene and cell activations. Researchers used ultrasound to mechanically perturb T cells, and then converted the mechanical signals into genetic control of cells.
In this study, researchers show how their remote-controlled mechanogenetics system can be used to engineer chimeric antigen receptor (CAR)-expressing T cells that can target and kill cancer cells. The engineered CAR-T cells have mechano-sensors and genetic transducing modules that can be remotely activated by ultrasound via microbubble amplification.
“CAR-T cell therapy is becoming a paradigm-shifting therapeutic approach for cancer treatment,” said bioengineering professor Peter Yingxiao Wang at the University of California San Diego. “However, major challenges remain before CAR-based immunotherapy can become widely adopted. For instance, the non-specific targeting of CAR-T cells against non-malignant tissues can be life-threatening. This work could ultimately lead to an unprecedented precision and efficiency in CAR-T cell immunotherapy against solid tumours, while minimizing off-tumour toxicities.”
The team brings together the laboratories of professors Wang and Shu Chien, both bioengineering professors at the Jacobs School of Engineering and the Institute of Engineering in Medicine at UC San Diego, in collaboration with professors Kirk Shung of the University of Southern California and Michel Sadelain at Memorial Sloan Kettering Cancer Center in New York. Researchers present their findings in the Jan. 15 issue of the Proceedings of the National Academy of Sciences, with UC San Diego Ph.D. candidate Yijia Pan as the first author.
Researchers found that microbubbles conjugated to streptavidin can be coupled to the surface of a cell, where mechanosensitive Piezo1 ion channels are expressed. Upon exposure to ultrasound waves, microbubbles vibrate and mechanically stimulate Piezo1 ion channels to let calcium ions inside the cell. This triggers downstream pathways, including calcineurin activation, NFAT dephoshorylation and translocation into the nucleus. The nucleus-translocated NFAT can bind to upstream response elements of genetic transducing modules to initiate gene expression of chimeric antigen receptor (CAR) for the recognition and killing of target cancer cells.
University of California – San Diegoucsdnews.ucsd.edu/pressrelease/researchers_develop_a_remote_controlled_cancer_immunotherapy_system

About one in every 100 people in the world takes glucocorticoids long term to treat immune-mediated diseases. However, glucocorticoids, such as prednisone, have a side effect — they induce the bone loss called osteoporosis, causing an estimated yearly bone fracture rate of 5 percent.
An alternative treatment option now appears promising, according to results of an international study. The study was headed by Kenneth Saag, M.D., the Jane Knight Lowe Professor of Medicine at the University of Alabama at Birmingham.
Saag and colleagues compared the monoclonal antibody denosumab against a standard treatment for glucocorticoid-induced secondary osteoporosis, the bisphosphonate risedronate. In the 12-month results of their 24-month study, they have found that denosumab was superior to risedronate, as measured by increased bone density in the lower spine.
“To our knowledge, ours is the first large, randomized controlled trial of denosumab in patients with glucocorticoid-induced osteoporosis who were either prevalent glucocorticoid users or newly initiating glucocorticoid therapy,” they wrote. “Denosumab could be a useful addition to the treatment armamentarium for glucocorticoid-induced osteoporosis.”
The double-blind study enrolled 795 patients at 79 health care centres in Europe, Latin America, Asia and North America. Of these, 505 were glucocorticoid-continuing patients who had received glucocorticoids for at least three months, and 290 were glucocorticoid-initiating patients who had received glucocorticoids for less than three months.
Glucocorticoids, such as prednisone, have a side effect — they induce the bone loss called osteoporosis, causing an estimated yearly bone fracture rate of 5 percent.
Patients were randomly assigned to one of two groups. The denosumab group got a shot of denosumab underneath the skin every six months and took a placebo pill every day. The risedronate group got a placebo shot every six months and took oral risedronate every day.
Besides the superior lumbar spine bone density with denosumab after 12 months, researchers also found that denosumab was superior to risedronate for bone density measured in the total hip and at the neck of the femur, the large bone of the thigh.
The two treatment groups had similar safety profiles.
The researchers note that the study compared denosumab with risedronate, so the relative performance of denosumab compared with osteoporosis treatments besides risedronate has not yet been established.

University of Alabama at Birminghamwww.uab.edu/news/research/item/9372-uab-led-study-shows-drug-effectiveness-in-reducing-glucocorticoid-induced-bone-loss
 

The type of needle used during a lumbar puncture makes a significant difference in the subsequent occurrence of headache, nerve irritation and hearing disturbance in patients, according to a study by McMaster researchers.
As well, they found the pencil-point atraumatic needle with the better tip design has been available for about 70 years, but few physicians have been using it because they have not been aware of its benefits over the conventional bevelled traumatic needles.
The implications on clinical care are huge, said Dr. Saleh Almenawer, the senior author of the study and a neurosurgeon at Hamilton Health Sciences who worked with a team of researchers at McMaster University including Sheila Singh, Alex Koziarz and Siddharth Nath.
“There is a more than 50 per cent reduction in the occurrence of headaches with the atraumatic needles, and also more than a 50 per cent reduction in patient readmissions and return to emergency rooms for narcotics or blood patches,” said Almenawer.
Post-dural puncture headaches appear in about 35 per cent of patients, sometimes causing debilitating pain that can lead to a return to hospital for painkillers or more invasive treatment.
The study says using atraumatic needles rather than conventional traumatic needles for lumbar punctures is just as effective and results in a significant decrease in complications such as the headaches.
“The two needles differ in how they penetrate the thick membrane, called the dura, surrounding the nerves,” said Almenawer.
He explained that the sharp edges of the tip of a conventional needle cuts its way through, while the tip of an atraumatic needle causes the tissue to dilate and contract around it. The tiny hole left in the dura by the atraumatic needle makes it significantly more difficult for cerebrospinal fluid to leak through, thus diminishing the frequency of headaches, readmissions and treatment.
Atraumatic needles have been around for decades, but their use remains significantly limited, according to the researchers. They also found the atraumatic needles cost the same or up to three times as much as the more conventional type.
“Several surveys from around the world showed that only a fraction of physicians know atraumatic needles exist, and among those even a smaller portion use the atraumatic type,” said Almenawer.
McMasters Universityhttps://tinyurl.com/y9qmsmm6