Researchers investigating a key signalling protein in Huntington’s disease describe deleterious effects on heart function, going beyond the disease’s devastating neurological impact. By adjusting protein levels affecting an important biological pathway, the researchers improved heart function in experimental animals, shedding light on the biology of this fatal disease.
“Heart disease is the second leading cause of death in Huntington’s disease patients, but its biology remains poorly understood,” said study leader Beverly L. Davidson, PhD, Director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at Children’s Hospital of Philadelphia (CHOP), where she is an expert on gene therapy for inherited brain disorders. “Better knowledge of the underlying biology of Huntington’s disease will improve the development of effective therapies.”
Huntington’s disease (HD) is an incurable, inherited disease with progressive loss of brain cells and motor function, usually beginning in midlife. A defective gene produces repeated copies of a protein called huntingtin, or HTT. The mutant HTT protein (mHTT) particularly damages a brain region called the striatum, resulting in involuntary movements and severe cognitive and emotional disturbances.
Because mHTT disrupts multiple fundamental processes in cells throughout the body, it impairs multiple organ systems. The current study focused on heart function in mouse models of HD. The mutant protein mHTT disrupts functioning along the mTORC1 pathway, named for the signalling protein complex mTORC1 that promotes cellular growth and metabolism.
Researchers already knew that mTORC1 function plays a key role in the neurology of HD. The current study showed that mTORC1 activity was lower in HD mice than in healthy mice. The HD mice also had smaller-than-normal hearts. Crucially, the study team found that HD mice were less able to adapt to stress on their hearts, and had higher mortality from that stress.
When the researchers restored mTORC1 activation in the HD mice by using genetic techniques to knock down the mutant HTT protein, the mice were better able to adapt to cardiac stress and had higher survival over the course of the study.
“If the mHTT protein has a similar effect on human hearts as in the mice, it may explain the heart-related mortality seen in HT patients,” said Davidson, adding that future studies in HT should investigate that question. Given that there are currently clinical trials of HTT-lowering therapy in Huntington’s disease patients, it is important to better understand how HD affects organs outside the central nervous system.
In addition, some researchers propose using mTORC1 inhibitors to treat HD, but the new study suggests that this approach could cause unintended effects on cardiac function. “We know from our previous studies that improving mTORC1 functioning may have a protective effect in HD, but this would require carefully adjusting the pathway to restore normal mTORC1 levels,” said Davidson.

Children’s Hospital of Philadelphiahttps://tinyurl.com/y9g68vfe

Entry submissions for the 2018 International Hospital Federation Awards is now open. Hospitals and healthcare organizations that have innovations, outstanding achievements and best practices can enter their projects and programs in one of the four categories.

The IHF/Dr Kwang Tae Kim Grand Award is open only to IHF Full and Associate Members. This Award honors excellence and achievements at health system or facility level in multiple areas including quality and patient safety, corporate social responsibility, innovations in service delivery at affordable costs, and healthcare leadership and management practices.

The IHF/EOH Excellence Award for Leadership and Management in Healthcare recognizes outstanding projects that are enhancing governance, leadership, management policies and practices, fostering a new culture of service, effectively managing finance and resources, and major breakthroughs in productivity improvements or innovations in healthcare delivery or process management.

The Excellence Award for Quality & Safety and Patient-centered Care recognizes exceptional programs that promote quality and safety, enhances patient education, engagement and empowerment, and promote ethical approaches and evidence-based practices.

The final category, the IHF/Bionexo Excellence Award for Corporate Social Responsibility, is for projects that demonstrate excellence in providing quality healthcare services at affordable costs, promoting volunteer contribution to community care, promoting sustainable environment, energy and green initiatives, reducing inequalities in healthcare service delivery to the community and advancing healthcare for emerging and developing nations.

Winning an IHF Award is a prestigious accolade in the healthcare industry and all public and private healthcare service providers are encouraged to join.

Submitting an entry is the first step in an extensive process to determine this year’s award winners, who will be announced at the Awards Ceremony during the 2018 World Hospital Congress in Brisbane, Australia.

Entries can be submitted online through the IHF Awards submission website, find out more here.

Deadline of entries is on 13 April 2018.

For more information visit: https://congress.ihf-fih.org/ihf_awards

Cleveland Clinic researchers found that implementing a four-step protocol for the most severe type of heart attack not only improved outcomes and reduced mortality in both men and women, but eliminated or reduced the gender disparities in care and outcomes typically seen in this type of event.
Cardiovascular disease is the leading cause of death in women, and STEMI (ST elevation myocardial infarction, caused by an abrupt and prolonged blockage of the blood supply to the heart, impacts about one million women each year.  Previous studies have shown that women with STEMI have worse clinical outcomes, including higher mortality and higher rates of in-hospital adverse events. Studies have shown women also typically have higher door-to-balloon times (time from when they arrive at the hospital to when they receive a coronary intervention like angioplasty and stenting). They receive lower rates of guideline-directed medical therapy: for example, they are treated with lower rates of aspirin within 24 hours.  Previous studies have attributed the differences in care and outcomes in women with STEMI to their being older and higher risk patients than men, suggesting that these disparities may be inevitable.
In this study, Cleveland Clinic researchers put in place a comprehensive four-step protocol for STEMI patients, designed to minimize variability in care.  It included: (1) standardized emergency department (ED) cardiac catheterization lab activation criteria, (2) a STEMI Safe Handoff Checklist, (3) immediate transfer to an available catheterization lab, and (4) using the radial artery in the wrist as the first option for percutaneous (under the skin) coronary intervention, like stenting. This approach has been shown to have fewer bleeding complications and improved survival when compared to using the femoral artery.
The results of the study showed improvements in both genders after implementation of the protocol, and substantial reductions in care differences between men and women.
Prior to the protocol, women had significantly higher 30-day mortality than men (10.7 percent vs 4.6 percent) prior to the protocol.  Providers were able to lower the overall mortality rates for both men and women, and the difference between the genders was no longer statistically significant (6.5 percent vs. 3.3 percent).  In-hospital deaths of women with STEMI were reduced by about 50 percent.
In addition, there was also no difference in rates of major adverse events such as in-hospital stroke, bleeding, vascular complication and transfusions after implementation.  Prior to the protocol, mean door-to-balloon time for women was an average of 20 minutes longer compared to men, but afterwards, the times were equal between men and women. The system also resulted in equal rates of guideline-directed medical therapy in women.
“It’s long been known that the gender gap for these types of critical heart attacks is a real issue.  However, there is very little data demonstrating successful strategies and no formal recommendation on how a system should be designed to provide the best possible care for women,” said Umesh Khot, M.D., vice chairman of Cardiovascular Medicine at Cleveland Clinic and senior author of the study. “Our research shows that putting into  place a system that minimizes care variability raises the level of care for everyone and could be the first step to resolving the long-standing gender disparities.”
Cleveland Clinicnewsroom.clevelandclinic.org/2018/03/10/heart-attack-protocol-can-improve-outcomes-reduce-disparities-between-men-and-women/?_ga=2.175176674.1737011640.1520690703-370679601.1520690703

In the latest of their numerous innovative studies of the symptoms and experiences of neonatal intensive care unit (NICU) babies with trouble swallowing (dysphagia), physicians and researchers at Nationwide Children’s Hospital and The Ohio State University College of Medicine have identified and refined which symptoms suggest treatment-worthy gastroesophageal reflux disease (GERD). The team believes its body of work on the topic will make future GERD diagnosis and treatment in infants more appropriate.
More than 10 percent of NICU babies are believed to have GERD. Despite several risks associated with acid-suppressive medication in NICU babies, such as nosocomial infections, enterocolitis, osteopenia and malabsorption of nutrients, these tiny patients are often medically treated for GERD when any common symptom of the condition is present. In such young babies, these symptoms can include feeding difficulties, gagging, coughing, arching the back or acting irritable, grimacing, vomiting, sneezing, flushing, or grunting.
“NICU infants have many aerodigestive symptoms on a daily basis. There is a perceived myth that these symptoms are due to acid GERD and therefore using acid-suppressive medications will ameliorate the symptoms. This myth is not true, and can be dangerous,” says Sudarshan Jadcherla, MD, director of the Neonatal and Infant Feeding Disorders Program at Nationwide Children’s, member of the hospital’s Division of Neonatology and senior author on the publication, released earlier this year in Dysphagia. “Using acid-suppressive therapy without a definite diagnosis and symptom association probability not only diverts attention from what might be a different, undiagnosed problem, but also creates the new problem of dealing with dosing, treatment duration decisions, side effects and sequelae.”
Dr. Jadcherla acknowledges the practical challenges to confirming acid GERD and symptom association probability, however. “Accurate documentation of troublesome symptoms is required in a timely manner so that comparisons with the actual GER event characteristics can be made,” he says.
To help overcome this clinical disconnect and determine which symptoms merit acid suppression therapy, Dr. Jadcherla and his colleagues performed 24-hour pH-impedance tests on 53 infants in the NICU at Nationwide Children’s. More than 2000 acid reflux events (AREs) were documented, allowing the team to determine whether the babies’ GERD symptoms correlated with the presence and location of acid in the esophagus.
Their findings suggest that treating apparent GERD with proton pump inhibitors may be appropriate when the baby’s acid reflux index (ARI) score is greater than 7, AREs reach the middle or proximal areas of the esophagus, and there is abnormal symptom correlation between the ARI and ARE based on pH-impedance testing.
“This approach will separate false positives from true positives, thus providing opportunities to test the effect of therapies for those with the probability of acid-GERD,” Dr. Jadcherla says. “We still have to learn whether a placebo or acid-suppressive therapy can produce the same benefits, both in the short term and long term.”
Dr. Jadcherla hopes that this research and eventual randomized control trials evaluating GERD therapies using pH-impedance testing will move neonatologists closer to an actionable, objective and more specific treatment criteria for GERD management in NICU babies.

Nationwide Children’shttps://tinyurl.com/y9d83jey

Extended shift work has historically been linked to interrupted sleep patterns and risk of injury, and is a persistent problem for emergency medical services (EMS) personnel who are tasked with delivering acute care under significant pressure.
New guidelines, written by a team led by University of Pittsburgh School of Medicine scientists and published aim to mitigate the effects of fatigue by addressing the impact of shift work and scheduling.
“The problem of fatigued EMS personnel is widespread and not isolated to one type of EMS operation or category of EMS clinician. Administrators of EMS organizations are not sufficiently equipped to address fatigue in the workplace, in part because of the absence of guidelines for fatigue risk management in the EMS setting,” said Daniel Patterson, Ph.D., lead author and assistant professor of emergency medicine at the Pitt School of Medicine
After review and analysis of more than 38,000 journal articles, conference presentations and other publications, Patterson and his colleagues gathered information on fatigue and shift work to develop the evidence-based guidelines for fatigue risk management and test the impact of the findings to create a biomathematical model for use by the EMS community to aid in shift-scheduling decisions.
The guidelines consist of five recommendations:

• Use of fatigue/sleepiness surveys to measure and monitor EMS personnel fatigue.
• Limit EMS shifts to less than 24 hours in duration.
• Give EMS personnel access to caffeine to help stave off fatigue.
• Allow EMS personnel the opportunity to nap while on duty.
• Provide education and training in fatigue risk management to EMS personnel.

Patterson and his team expect the guidelines to have a wide impact on improving practice and policies to alleviate EMS personnel fatigue, whether when driving an ambulance or caring for patients.
 “Operating the ambulance is only one aspect of EMS care,” said Patterson. “Most of the work EMS clinicians do is actually patient care. Fatigue affects decision-making abilities and overall performance, and with the pressure of delivering acute care, one wrong decision can be detrimental.”
Pitt Health Scienceshttps://tinyurl.com/y835qdwx