New antiviral approved just in time for flu season

There’s a new treatment for the influenza virus, just in time for a new season of infections.


Xofluza (baloxavir marboxil) was approved in late October by the U.S. Food and Drug Administration (FDA) for treatment of acute, uncomplicated influenza in patients aged 12 and older who have been symptomatic for no more than two days. 

The first flu treatment approved by FDA in 20 years, Xofluza offers clinicians another option to fight the flu virus—although FDA officials warn that this treatment is not a substitute for annual flu vaccination.

The antiviral treatment, taken as a single oral dose, has been shown in clinical trials to reduce the duration of flu symptoms by 23 to 28 hours. Adverse reactions to the treatment included diarrhea and bronchitis, according to FDA.

Debra Birnkrant, MD, director of the Division of Antiviral Products in the Office of Antimicrobial Products for the FDA, said Xofluza will be added to the standard arsenal of medications used to treat the flu— oseltamivir, zanamivir, and peramivir. While there is no real cure for the flu, Birnkrant said, Xofluza may help lessen the severity and duration of infection, like other treatments.

“We know that when started within 48 hours of flu symptoms, antiviral drugs can lessen symptoms and shorten the time patients feel sick,” Birnkrant said. “Having more treatment options that work in different ways to attack the virus is important because flu viruses can become resistant to antiviral drugs.”

Priority review and final approval of the new medication was granted to Japan’s Shionogi & Co., Ltd., but Xofluza is being developed and commercialized globally with the Roche Group, including Genetech in the U.S. Doses are expected to be available to clinicians in the coming weeks.

Mark D. Eisner, MD, MPH, vice president of Product Development Immunology, Infectious Disease and Ophthalmology at Genentech, said the development of new antiviral treatments for the flu is important considering that 3 percent to 11 percent of the U.S. is infected with the flu virus each year, and more than 900,000 hospitalizations and 80,000 deaths resulted from influenza last year alone.

Eisner said Xofluza is the first single-dose oral medicine to fight the flu, and works by blocking enzymes within the flu virus to stop viral replication early in the virus’ life cycle. Other approved flu treatments must be taken in multiple doses and attack the flu virus at much later stages in their life cycle.

Forty percent of cancers linked to overweight or obesity

Being overweight or obese significantly increased the risk of developing at least 13 types of cancer, according to a report by the Centers for Disease

Now that a larger proportion of the American population is overweight or obese, the rates of obesity-related cancers have increased. Between 2005 and 2014, the rate of obesity-related cancers, excluding colorectal cancer, increased by 7%. Over the same period, non–obesity-related cancers declined, according to C. Brooke Steele, DO, of the CDC’s Division of Cancer Prevention and Control, and her associates.

The researchers examined the United States Cancer Statistics data set, which includes data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program.

They found that 631,604 people were diagnosed with an overweight- or obesity-related cancer, 40% of nearly 1.6 million of all cancer diagnoses in 2014. The effect was more pronounced in older people (age at least 50 years), compared with younger people, with two-thirds of cases occurring in the 50- to 74-year-old age range.

Women were much more likely to have overweight- and obesity-related cancers, with higher incidence rates (218.1 per 100,000 population) than those of men (115.0 per 100,000). A contributing factor for this difference between men and women was female-specific cancers such as endometrial, ovarian, and postmenopausal breast cancers, which accounted for 42% (268,091) of overweight- and obesity-related cancers.

Researchers found that, between 2005 and 2014, the overall incidence of overweight- and obesity-related cancers (including colorectal cancer) decreased by 2%, colorectal cancer decreased by 23%, and cancers unrelated to body weight decreased by 13%. A contributing factor to the decrease in colorectal cancer was most likely cancer screening tests, which can detect and lead to the removal of precancerous polyps.

“A majority of American adults weigh more than recommended – and being overweight or obese puts people at higher risk for a number of cancers – so these findings are a cause for concern,” CDC Director Brenda Fitzgerald, MD, said in a statement. “By getting to and keeping a healthy weight, we all can play a role in cancer prevention.”

FDA approves triple-therapy inhaler for COPD

The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.

Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.

The most common adverse events associated with Trelegy Ellipta include headache, back pain, dysgeusia, diarrhea, cough, oropharyngeal pain, and gastroenteritis, and the inhaler is contraindicated for people with “severe hypersensitivity to milk proteins.” Trelegy Ellipta is not indicated for people with asthma or acute bronchospasm.

“This approval represents a significant therapeutic convenience for those appropriate patients already on Breo Ellipta, that require additional bronchodilation or for those patients already on a combination of Breo Ellipta and Incruse Ellipta,” Mike Aguiar, CEO of Innoviva said in the press release.

In results supporting the FDA approval, the IMPACT study, a 52-week phase 3 clinical trial including 10,355 COPD patients sponsored by GSK, found that patients receiving Trelegy Ellipta experienced a 25% reduction in moderate to severe exacerbations compared to patients receiving Anoro Ellipta, and a 15% reduction in moderate to severe exacerbations, compared with patients receiving Relvar/Breo Ellipta. Change from baseline FEV1, change from baseline scores on the St George’s Respiratory Questionnaire, and time to first moderate/severe COPD exacerbation also were improved in the Trelegy Ellipta study group compared to the others.

“This is the first study to report a comparison of a single inhaler triple therapy with two dual therapies, providing much needed clinical evidence about the ability of a single inhaler triple therapy to reduce exacerbations,” Patrick Vallance, President of R&D at GSK, noted in a press release announcing the results of the IMPACT study.

Early cognitive impairment associated with later Parkinson’s disease

Adults with early cognitive impairment are at greater risk for developing parkinsonism than those without cognitive impairment, based on data from 7,386 adults participating in the ongoing Rotterdam Study. The findings were published online Sept. 25 in JAMA Neurology.

“Between 15% and 43% of patients with newly diagnosed Parkinson disease (PD) are cognitively impaired,” wrote Sirwan K. L. Darweesh, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues. However, data on the predictive value of cognitive impairment for parkinsonism has not been well studied.

The researchers reviewed data from participants in the Rotterdam Study with an average age of 65 years; 57% were women. Dementia was assessed using either the Mini-Mental State Examination or the Geriatric Mental State Schedule organic level, followed by the Cambridge Examination for Mental Disorders of the Elderly.

Over approximately 8 years’ follow-up, 1% of the participants were diagnosed with incident parkinsonism.

“Poor global cognition at baseline was associated with a higher risk of incident parkinsonism” with a hazard ratio of 1.79, the researchers said.

“To enable translation of our findings to clinical practice, we present likelihood ratios (LRs) for the baseline presence of isolated or combined cognitive dysfunction and subtle motor features for incident parkinsonism during follow-up,” they noted.

Approximately half of participants diagnosed with incident parkinsonism during the study period had subtle motor features, cognitive dysfunction, or both, at baseline. Baseline cognitive impairment alone showed a likelihood ratio of 1.76 for development of parkinsonism, but the likelihood ratio was greater when both cognitive impairment and subtle motor findings were present (2.66).

“In individuals who received a diagnosis of both incident dementia and incident parkinsonism, baseline cognitive dysfunction was not associated with incident dementia,” the researchers noted.

The researchers determined that the most likely explanation for the association between cognitive decline and increased Parkinson’s risk was that “low baseline cognitive scores may indicate ongoing cognitive decline in prediagnostic patients who probably will develop parkinsonism, most of whom have prediagnostic PD,” they said.

The study findings were limited by several factors including the potential misclassification of parkinsonism diagnosis, the researchers noted. However, the association between poor cognitive function and the risk of parkinsonism and probably Parkinson’s disease remained for the executive, attention, cognitive speed, and memory domains of cognition, they said. “Our findings suggest that poor cognitive functioning can be considered a prodromal sign of PD,” they concluded.

This study was supported in part by Stichting ParkinsonFonds. The researchers had no financial conflicts to disclose.

Poor Sleep Increases Risk of Heart Disease, Stroke

A new study has found that poor sleep quality, long sleep latency, low sleep efficiency, and the use of sleeping pills are associated with ischemic heart disease and stroke, while difficulty maintaining sleep, short sleep duration, and daytime dysfunction are associated only with ischemic heart disease.

Findings were presented by Dr Nobuo Sasaki on August 29, 2017, at the European Society of Cardiology Congress in Barcelona, Spain.

It is well known that poor sleep is associated with cardiovascular (CV) diseases like ischemic heart disease and stroke. However, little data exists about which types of sleep disturbances affect this risk the most.

In order to further explore the factors that impact this risk, Dr Sasaki and colleagues assessed 12,876 residents of Hiroshima, Japan, who were scheduled for an annual health check-up. Of these patients, 773 had a history of ischemic heart disease in the form of myocardial infarction (MI) or angina, 560 had a history of stroke in the form of intracranial hemorrhagic and/or cerebral infarction, and 11,543 had no history of CV disease.

The Pittsburgh Sleep Quality Index (PSQI) was used to assess self-reported sleep habits. The questionnaire evaluated 7 components of sleep habits: subjective poor sleep quality, long sleep latency, short sleep duration, low sleep efficiency, difficulty maintaining sleep, the use of sleeping pills, and daytime dysfunction.

Results indicated that 52% of patients with ischemic heart disease had poor sleep, compared with 48% of patients with a history of stroke and 37% of patients with no CV disease.

Ultimately, the researchers found that poor sleep was significantly associated with ischemic heart disease and stroke. The incidence of sleep disturbances was found to be 1.5 times higher in patients with a history of ischemic heart disease or stroke vs those with no history of CV disease. Specifically, subjective poor sleep quality, long sleep latency, low sleep efficiency, and the use of sleeping pills were significantly associated with ischemic heart disease and stroke, while difficulty maintaining sleep, short sleep duration, and daytime dysfunction were associated only with ischemic heart disease.

“Our results support the hypothesis that sleep deterioration may lead to cardiovascular disease,” the researchers concluded. “Poor sleep in patients with ischemic heart disease may be characterized by shorter sleep and brief moments of waking up.”

Contact Arlington Heights physician to reduce your risk of stroke and cardiovascular disease.

Heart failure guidelines update – 2017

New evidence is available to guide heart failure (HF) management.

Beta-natriuretic peptide (BNP) is recommended to screen at risk patients (IIaB), on admission (IA), and prior to discharge (IIaB).

The combination of ARB and neprilysin inhibitor (ARB-NI) is recommended in symptomatic patients with HF with reduced ejection fraction (HFrEF) who are tolerant of ACE inhibition (IB). For these patients, transitioning from ACE-inhibitor to the ARB-NI combination, valsartan-sacubitril significantly reduced hospitalization and mortality. Optimal dose and titration strategies remain unclear. ARB-NIs should not be used in patients with a history of angioedema (IIIC) or within 36 hours of receiving ACE-inhibitors (IIIB).

Ivabradine, a selective inhibitor of the HCN channel (mixed sodium and potassium channel that carries the If current) in the sinoatrial node, is recommended to reduce hospitalizations for patients with HFrEF with stable symptoms with resting sinus heart rate greater than or equal to 70 despite maximally-tolerated beta-blockade (IIaB).

Intravenous iron replacement is recommended to improve function and quality of life for patients with symptomatic HF and iron deficiency (IIbB).

HF optimization is a collaborative venture between patient and physician. The medical regimen requires periodic adjustments and careful monitoring. Unfortunately this is not achieved in many cases, leading to symptoms exacerbation and ultimately hospital admissions. Partner with an experienced Arlington Heights physician to optimize your HF management.

CDC 2017-18 Influenza Vaccine Recommendations

The Centers for Disease Control and Prevention (CDC) has issued the recommendations of the Advisory Committee on Immunization Practices (ACIP) for the 2017-18 influenza season. The CDC continues to recommend routine annual influenza vaccination for all persons aged ≥6 months who do not have contraindications. Standard dose or high dose vaccine is acceptable for adults aged ≥65 years. Among the changes from last year:

  • Vaccine viruses included in the 2017–18 US trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these 3 viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage).
  • Afluria Quadrivalent and Flublok Quadrivalent are now available for patients aged ≥18 years, and there is an expansion of the age indication for FluLaval Quadrivalent, previously licensed for ≥3 years, to ≥6 months.
  • Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine.
  • FluMist Quadrivalent should not be used during the 2017–18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the US during the 2013–14 and 2015–16 influenza seasons.

Even Short-Term Steroids Have Complications

Clinical Question: What is the frequency of short-term corticosteroid prescriptions and adverse events associated with their use?


Background: Long-term corticosteroid use is usually plagued by complications (ie weight gain, glucose intolerance/diabetes, adrenal suppression, hypertension, skin changes etc), therefore is avoided when possible. Less is known about the risk and frequency of short-term steroid use.

Study Design: Retrospective cohort study and self-controlled case series.

Setting: National U.S. dataset of private insurance claims.

Data from 1,548,945 adults (aged 18-64 years) showed that 21.1% of adults received a prescription for short-term corticosteroids. Within 30 days of filling corticosteroids, incident rate ratios (IRR) were increased for sepsis (5.3; 95% confidence interval, 3.8-7.4), venous thromboembolism (3.3; 95% CI, 2.78-3.99), and fracture (1.87; 95% CI, 1.69-2.07).

Short-term corticosteroids were frequently prescribed for indications with little evidence of benefit, such as upper respiratory conditions, spinal conditions, and allergies. For these conditions, patients should be educated about the risks of short-term corticosteroid use and alternative treatments should be considered. This study only evaluated for these three adverse reactions and excluded the elderly, so these findings likely underestimate the adverse effects of short-term corticosteroids.

Bottom Line:  Corticosteroids are much of the time recommended for short courses and were related with higher rates of sepsis, venous thromboembolism, and fracture.

Related article: Sleeping Patient

Undiagnosed Atrial Fibrillation and Stroke

Over an 18-month period, small, insertable cardiac monitors detected atrial fibrillation in 29% of previously undiagnosed patients who were at high risk of both AF and stroke, and in 40% of patients over 30 months, according to investigators. The study was presented at the annual congress of the European Society of Cardiology and simultaneously published in JAMA Cardiology.

“The incidence of previously undiagnosed atrial fibrillation may be substantial in patients with risk factors for AF and stroke,” they concluded. “Atrial fibrillation would have gone undetected in most patients had monitoring been limited to 30 days. Further trials regarding the value of detecting subclinical AF and of prophylactic therapies are warranted.”

atrial fibrillation tracing
atrial fibrillation tracing

Atrial fibrillation affects millions worldwide and is associated with older age, hypertension, diabetes, and heart failure, all of which also independently increase the risk of stroke. Minimally invasive prolonged electrocardiographic monitoring with insertable cardiac monitors might help hasten detection and treatment of AF, but diagnostic yield in high-risk patients has been unclear.

In this single-arm, multicenter, prospective study, researchers inserted Reveal XT or Reveal LINQ (Medtronic) cardiac monitors in 385 adults who had either CHAD2 scores of 3, or CHAD2 scores of 2 and one additional risk factor for AF, such as coronary artery disease, sleep apnea, chronic obstructive pulmonary disease, or renal insufficiency. The primary endpoint was AF lasting at least 6 minutes (JAMA Cardiol. 2017 Aug 26. doi: 10.1001/jamacardio.2017.3180). Median follow-up time was 22.5 months. Rates of detecting AF were 6% at 30 days compared with 20% at 6 months, 27% at 12 months, 34% at 24 months, and 40% at 30 months. Patients typically had their first AF episode about 4 months (median, 123 days) after the device was inserted. Among patients who had experienced AF by 18 months, 10% had one or more episodes lasting at least 24 hours, and 72 (56%) were prescribed oral anticoagulation therapy.

The recent PREDATE AF and ASSERT-II studies also found that previously undiagnosed AF was common among high-risk patients, the researchers noted. However, whether anticoagulating patients who have only brief episodes of AF significantly reduces their risk of stroke remains unclear, they added. Three trials (ARTESiA, NOAH, and LOOP) are underway to assess whether oral anticoagulation therapy improves outcomes in patients with device-detected AF.

Medtronic funded the study.

If you are located in the Northwest Suburbs and would like to discuss atrial fibrillation diagnosis and treatment contact Dr. Ivan, in Arlington Heights.

Simplified Diagnostic Management of Suspected Pulmonary Embolism

Patients with suspected pulmonary embolism (PE), including those in Arlington Heights, often undergo computed tomography pulmonary angiography (CTPA) to confirm or exclude the diagnosis. However, CTPA exposes them to radiation, the risk of contrast-induced nephropathy, and increases health care costs. Therefore ways to reduce the use of CTPA in this setting are required.

pulmonary embolism
pulmonary embolism

Findings presented at ESC Congress 2016, suggest a simple diagnostic algorithm can be used to rule out PE in a significant number of these patients, eliminating their need for CTPA.

The advantage of the YEARS algorithm over existing algorithms is a 14% reduction in the need for CTPA imaging and with that, reduced potential for radiation-induced harm and overdiagnosis.

Unlike other, multi-item, sequential algorithms used to assess PE risk, the YEARS clinical decision rule consists of one blood test and 3 items of the original Wells rule.

Patients presenting to the emergency department can be evaluated based on:

  • clinical signs of deep vein thrombosis (e.g., swelling, edema);
  •  hemoptysis (coughing up blood);
  •  and whether the clinician considers PE to be “the most likely diagnosis”

Using this information combined with results of a blood test measuring D-dimer – a protein produced by blood clots –  clinicians can either exclude PE,  or recommend a CTPA for definitive diagnosis.

The YEARS study prospectively evaluated this algorithm in 3,465 patients (mean age 53 years), 88% of whom were outpatients.

Based on the algorithm, PE was excluded and CPTA was withheld in 1,651 patients who either had: no YEARS items and a D-dimer level <1000 ng/mL; or one or more YEARS items and a D-dimer level <500 ng/mL.

All other patients were referred for CTPA.

Patients in whom PE was excluded were left untreated and followed for 3 months, while those diagnosed with PE were treated with anticoagulants.

The primary outcome of the study was the 3-month incidence of symptomatic venous thromboembolism (VTE), which occurred in  0.43% of patients who had PE excluded based on the YEARS algorithm alone and 0.84% of the patients who had PE excluded based on CTPA.

Using the YEARS algorithm, CTPA was not indicated in 48% of  patients at baseline, but this would have been only 34% of patients using the traditional algorithm. This shows that the YEARS algorithm can safely exclude PE and resulted in an absolute reduction of required CPTA of 14%.”