Novel agent outperforms ACE inhibitor in large HF trial

The investigational agent LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), has demonstrated superior efficacy to a widely used ACE inhibitor in the treatment of patients with chronic heart failure, according to a study presented at the recent European Society of Cardiology (ESC) Congress in Barcelona, Spain.

In the PARADIGM-HF* trial, LCZ696, a combination of the ARB valsartan and neprilysin inhibitor sacubitril, showed a significant 20 percent greater effect over enalapril 20 mg/day in reducing cardiovascular death or hospitalization for heart failure (21.8 vs 26.5 percent; p=0.0000002). [N Engl J Med 2014, e-pub 30 Aug, DOI: 10.1056/NEJMoa1409077]

When components of the composite primary endpoint were analyzed separately, LCZ696 demonstrated a 20 percent greater reduction in cardiovascular death (13.3 vs 16.5 percent; p=0.00004) and a 21 percent greater reduction in hospitalization for heart failure (12.8 vs 15.6 percent; p=0.0004) compared with enalapril.

“The trial was stopped early in April, after a median follow-up of 27 months, for an overwhelming benefit of LCZ696 on cardiovascular mortality,” said co-principal investigator Dr. Milton Packer of the Southwestern Medical Center in Dallas, Texas, US.

The ARNI also reduced all-cause mortality, a secondary endpoint of the trial, by an incremental 16 percent compared with enalapril (17 vs 19.8 percent; p<0.0001).

Symptoms and physical limitations of heart failure, measured on the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 8 months, significantly improved in patients receiving LCZ696 vs enalapril (KCCQ score, -2.99 vs -4.63; p=0.001).

“Enalapril 20 mg/day is the current gold-standard therapy in CHF. Results of the PARADIGM-HF trial provide compelling evidence that LCZ696 should replace current use of ACEIs and ARBs in the management of patients with mild to moderately severe CHF,” said Packer.

“The major benefit of LCZ696 is that it changes the natural course of CHF,” he pointed out. “It doubles the benefit of current cornerstone treatment with ACEIs, which reduce cardiovascular death by 18 percent vs placebo.”

The PARADIGM-HF trial included 8,399 patients with class II to IV heart failure and an ejection fraction of 40 percent or below. The patients were randomized to receive LCZ696 200 mg twice daily (n=4,187) or enalapril 10 mg twice daily (n=4,212), in addition to recommended therapy.

“LCZ696 was better tolerated than enalapril,” reported Packer. “It was less likely than enalapril to cause cough, hyperkalemia or renal impairment, and less likely to be discontinued due to an adverse event.”

“Although more symptomatic hypotension was reported with LCZ696, this rarely required treatment discontinuation,” he continued. “Importantly, LCZ696 was not associated with an increased risk of serious angioedema, which was the main safety concern observed with a related medication known as omapatrilat in another trial.”

The survival advantage demonstrated in the trial has prompted the US FDA to grant Fast Track status to LCZ696. Its developer Novartis expects the FDA review to be completed by the end of 2014.

*PARADIGM-HF: Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure.

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Ebola in Texas: Second Health Care Worker Tests Positive

A second health care worker at Texas Health Presbyterian Hospital who cared for Thomas Eric Duncan has tested positive for Ebola, the state’s health department said Wednesday.

The worker reported a fever Tuesday and was immediately isolated, health department spokeswoman Carrie Williams said.

The preliminary Ebola test was done late Tuesday at the state public health laboratory in Austin, and the results came back around midnight. A second test will be conducted by the Centers for Disease Control and Prevention in Atlanta.
Mayor: ‘Concerned’ about Ebola spreading
Understanding Ebola protocols
Director: Nurse’s infection ‘unacceptable’

“Health officials have interviewed the latest patient to quickly identify any contacts or potential exposures, and those people will be monitored,” the health department said. “The type of monitoring depends on the nature of their interactions and the potential they were exposed to the virus.”

But the pool of contacts could be small, since Ebola can only be transmitted when an infected person shows symptoms. Less than a day passed between the onset of the worker’s symptoms and isolation at the hospital.

The latest infection marks the second-ever transmission of Ebola in the United States. Both stemmed from Texas Health Presbyterian Hospital.

Late last week, nurse Tina Pham tested positive for Ebola. She also took care of Duncan, the first person to be diagnosed with Ebola in the United States. Duncan died last week.

On Tuesday, Pham said she was doing well.

“I am blessed by the support of family and friends, and am blessed to be cared for by the best team of doctors and nurses in the world,” she said.

Also Tuesday, a union made troubling allegations about the hospital, claiming “guidelines were constantly changing” and “there were no protocols” about how to deal with the deadly virus.”

“The protocols that should have been in place in Dallas were not in place, and that those protocols are not in place anywhere in the United States as far as we can tell,” National Nurses United Executive Director RoseAnn DeMoro said. “We’re deeply alarmed.”

Source : CNN

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FDA approves first combination pill to treat hepatitis C

The U.S. Food and Drug Administration today approved Harvoni (ledipasvir and sofosbuvir) to treat chronic hepatitis C virus (HCV) genotype 1 infection.

Harvoni is the first combination pill approved to treat chronic HCV genotype 1 infection. It is also the first approved regimen that does not require administration with interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection.

Both drugs in Harvoni interfere with the enzymes needed by HCV to multiply. Sofosbuvir is a previously approved HCV drug marketed under the brand name Sovaldi. Harvoni also contains a new drug called ledipasvir.

“With the development and approval of new treatments for hepatitis C virus, we are changing the treatment paradigm for Americans living with the disease,” said Edward Cox, M.D., M.P.H., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “Until last year, the only available treatments for hepatitis C virus required administration with interferon and ribavirin. Now, patients and health care professionals have multiple treatment options, including a combination pill to help simplify treatment regimens.”

Harvoni is the third drug approved by the FDA in the past year to treat chronic HCV infection. The FDA approved Olysio (simeprevir) in November 2013 and Sovaldi in December 2013.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take decades.

Some people with chronic HCV infection develop scarring and poor liver function (cirrhosis) over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections and liver cancer. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and without proper treatment, 15-30 percent of these people will go on to develop cirrhosis.

Harvoni’s efficacy was evaluated in three clinical trials enrolling 1,518 participants who had not previously received treatment for their infection (treatment-naive) or had not responded to previous treatment (treatment-experienced), including participants with cirrhosis. Participants were randomly assigned to receive Harvoni with or without ribavirin. The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response, or SVR), indicating that a participant’s HCV infection has been cured.

In the first trial, comprised of treatment-naive participants, 94 percent of those who received Harvoni for eight weeks and 96 percent of those who received Harvoni for 12 weeks achieved SVR. The second trial showed 99 percent of such participants with and without cirrhosis achieved SVR after 12 weeks. And in the third trial, which examined Harvoni’s efficacy in treatment-experienced participants with and without cirrhosis, 94 percent of those who received Harvoni for 12 weeks and 99 percent of those who received Harvoni for 24 weeks achieved SVR. In all trials, ribavirin did not increase response rates in the participants.

The most common side effects reported in clinical trial participants were fatigue and headache.

Harvoni is the seventh new drug with breakthrough therapy designation to receive FDA approval. The FDA can designate a drug as a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening diseases. Harvoni was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness.

Harvoni and Sovaldi are marketed by Gilead, based in Foster City, California. Olysio is marketed by Janssen Pharmaceutical based in Raritan, New Jersey.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source : FDA News Release

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Ebola: WHO says death rate has increased to 70 per cent

A woman wears protective clothing during a tour of one of the Ebola Centers in Harare, Zimbabwe Tuesday, Sept. 23, 2014. (AP / Tsvangirayi Mukwazhi)
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GENEVA — WHO says there could be up to 10,000 new cases of Ebola per week in 2 months.

GENEVA – A World Health Organization official says the death rate in the current Ebola outbreak has increased to 70 per cent.

WHO assistant director-general Dr. Bruce Aylward gave the figure during a news conference Tuesday.

Aylward said that the 70 per cent death rate was “a high mortality disease” in any circumstance and that the U.N. health agency was still focused on trying to get sick people isolated and provide treatment as early as possible.

Previously, WHO had said the death rate was around 50 per cent.

THIS IS A BREAKING NEWS UPDATE.

A World Health Organization official says there could be up to 10,000 new cases of Ebola per week within two months.

WHO assistant director-general Dr. Bruce Aylward says if the response to the Ebola crisis isn’t stepped up within 60 days, “a lot more people will die” and there will be a huge need on the ground to deal with the spiraling numbers of cases. He said WHO estimated there could up to 10,000 cases per week in two months.

Aylward said for the last four weeks, there have been about 1,000 new cases per week, though that figure includes suspected, confirmed and probable cases. He said WHO is aiming to have 70 per cent of cases isolated within two months to reverse the outbreak.

WHO increased its Ebola death toll tally to 4,447, nearly all of them in West Africa, and the group said the number of probable and suspected cases was 8,914.

Sierra Leone, Guinea and Liberia have been hardest hit. Aylward said WHO was very concerned about the continued spread of Ebola in the three countries’ capital cities —Freetown, Conakry and Monrovia. He noted that while certain areas were seeing cases decline, “that doesn’t mean they will get to zero.”

He said the agency was still focused on trying to treat Ebola patients, despite the huge demands on the broken health systems in West Africa.

“It would be horrifically unethical to say that we’re just going to isolate people,” he said, noting that new strategies like handing out protective equipment to families and setting up very basic clinics — without much treatment — was a priority.

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Role of N-Acetyl Cysteine in Acute liver failure

21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg

Loading dose: 150 mg/kg (maximum: 15 g) infused over 60 minutes

Second dose: 50 mg/kg (maximum: 5 g) infused over 4 hours

Third dose: 100 mg/kg (maximum: 10 g)infused over 16 hours

21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg

Loading dose: 150 mg/kg (maximum: 15 g) infused over 60 minutes

Second dose: 50 mg/kg (maximum: 5 g) infused over 4 hours

Third dose: 100 mg/kg (maximum: 10 g)infused over 16 hours

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Dallas Ebola Patient Dies

DALLAS — Thomas Eric Duncan, 42, the patient with the first case of Ebola diagnosed in the United States and the Liberian man at the center of a widening public health scare, died in isolation at a hospital here on Wednesday, hospital authorities said.

Mr. Duncan died at 7:51 a.m. at Texas Health Presbyterian Hospital, more than a week after the virus was detected in him on Sept. 30. His condition had worsened in recent days to critical from serious as medical personnel worked to support his fluid and electrolyte levels, crucial to recovery in a disease that causes bleeding, vomiting and diarrhea. Mr. Duncan was also treated with an experimental antiviral drug, brincidofovir, after the Food and Drug Administration approved its use on an emergency basis.

“The past week has been an enormous test of our health system, but for one family it has been far more personal,” Dr. David Lakey, the commissioner of the Texas Department of State Health Services, said in a statement. “Today they lost a dear member of their family. They have our sincere condolences, and we are keeping them in our thoughts.”

The mayor of Dallas, Mike Rawlings, also offered some assurance to Dallas residents. “I remain confident in the abilities of our health care professionals and the medical advances here in the U.S.,” Mr. Rawlings said, “and reassure you we will stop the Ebola virus in its tracks from spreading into our community.”

After Mr. Duncan arrived at the Dallas/Fort Worth International Airport on Sept. 20, he set off a chain of events that raised questions about health officials’ preparedness to detect and contain the deadly virus. His case spread fear and anxiety among those he encountered, however briefly, and turned the places, vehicles and items he touched into biohazardous sites that were decontaminated, dismantled, stored or, in some cases, incinerated.

Mr. Duncan went to the airport in Liberia on Sept. 19 for his flight to the United States, landed in Dallas the next day and first went to the emergency room at Texas Health Presbyterian Hospital feeling ill on Sept. 25. He was released by the hospital, which had failed to view him as a potential Ebola case for reasons that remain unclear. He returned there and was admitted Sept. 28 after his condition worsened.

Mr. Duncan spent nearly two decades separated from the woman he had traveled to Dallas to be with, Louise Troh, 54, with whom he had a son. The couple were apparently rekindling their relationship. Yet in the last days of Mr. Duncan’s life, Mr. Duncan and Ms. Troh remained more apart than together. Each had been quarantined because of the risk of spreading Ebola, Mr. Duncan in virtually his own hospital ward and Ms. Troh in a four-bedroom home on a remote property that state health officials prohibited her, her 13-year-old son and two others from leaving, under threat of prosecution.

Mr. Duncan had been a driver at a cargo company in Monrovia, the Liberian capital, living alone in a small room he rented from the parents of Marthalene Williams, 19. A simple act of kindness probably exposed him to the virus that has killed more than 3,000 people in West Africa. In Monrovia, neighbors and Ms. Williams’s parents said Mr. Duncan helped the family take Ms. Williams to and from a hospital on Sept. 15, shortly before she died of Ebola. Some of the men and women who had direct contact with Ms. Williams, and who were also in contact with Mr. Duncan, have also died, including Ms. Williams’s brother, Sonny Boy Williams, 21.

Mr. Duncan helped carry her while she was sick with the virus and convulsing. The disease is contagious only if the infected person is experiencing active symptoms.

“He was holding her by the legs, the pa was holding her arms and Sonny Boy was holding her back,” said Arren Seyou, 31, who witnessed the scene and is a neighbor of Mr. Duncan.

Local, state and federal officials have expressed confidence that they have been able to limit the spread of the disease in Dallas and said that none of the people they were monitoring had shown any symptoms of Ebola.

Officials are monitoring 48 people in the Dallas area, most of whom have not been quarantined but are instead staying home while they are under observation. Ten of those are considered high risk, including seven health care workers and three relatives and community members who had contact with Mr. Duncan. The other 38 are considered low risk, and include people who may or may not have had direct or indirect contact with Mr. Duncan. One of those 38 is Michael Lively, a homeless man who rode in the ambulance that took Mr. Duncan to the hospital after the vehicle dropped Mr. Duncan off but before it was taken out of service and disinfected.

Mr. Lively briefly disappeared on Sunday before he was found by law enforcement officers, an indication of the unease being felt by some of those being monitored.

Source : NY Times

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CPR Guidelines – Adults

AHA CPR Guidelines 2010

NOTE: Sequence has changed from airway, breathing, chest compressions (ABC) to chest compressions, airway, breathing (CAB) per the 2010 AHA Guidelines

Untrained lay rescuers should do compression-only CPR; whereas, trained lay rescuers and healthcare providers (HCP) should include compressions and breathing

Compressions

check pulse at carotid
compression landmarks: lower half of sternum, between nipples
compression method: heel of one hand, other hand on top
compression depth: at least 2 inches (5 cm)allow complete chest recoil after each compression
compression rate: at least 100/min compression-ventilation ratio: 30:2 (1 or 2 rescuers)
minimize interruptions in compressions; limit interruptions to <10 seconds avoid excessive ventilation

Airway

head tilt-chin (HCP suspected trauma: use jaw thrust)

Breathing

ventilation with advanced airway: 1 breath every 6-8 seconds (8-10 breaths/min)
asynchronous with chest compressions
about 1 second per breath
visible chest rise

Defibrillation

attach and use AED as soon as available
minimize interruptions in chest compressions before and after shock
resume CPR beginning with compressions immediately after each shock