AMDA Long Term Care Medicine 2012

March 8-11, 2012; San Antonio, TX

Optimal Influenza Immunization Reduces Serious Flu-Related Consequences in Older Adults

Immunizing persons 65 years and older against influenza remains a national health priority, as this group is at highest risk of influenza-related complications, which can lead to hospitalization and death. A high-dose influenza virus vaccine, designed to improve immune responses in the vulnerable population of persons 65 years and older, is a recent innovation to achieve optimal immunization in this group, said Charles A. Cefalu, MD, professor and chief of geriatrics, Louisiana State University (LSU) Health Sciences Center, and medical director, LSU Affiliated Nursing Homes, New Orleans, at an AMDA Long Term Care Medicine 2012 product theater.

Although older adults represent only about 15% of the US population, they account for 63% of influenza-related hospitalizations, more than 90% of influenza-related deaths, and 64% of the economic burden of influenza, highlighting the need for effective influenza prevention in this group, said Cefalu. In the United States, influenza and pneumonia combined are the seventh leading cause of death among individuals 65 years and older, and the eighth leading cause of death among Americans overall. Vaccination has been shown not only to prevent mortality from pneumonia and other acute respiratory diseases, but also cardiovascular disease, stroke, renal disease, diabetes, and chronic obstructive pulmonary disease.

According to Cefalu, no age group reached the goals of Healthy People 2020— a 10-year federally supported agenda to improve Americans’ health—for influenza vaccination coverage during the 2009-2010 influenza season, although at 69.6% coverage, the 65 and older age group was the most vaccinated. Despite this high vaccination rate in elders, older adults have what is known as immunosenescence, which limits the success of the vaccine.

“The elderly have a blunted antibody response…their antibody response is only about 40% to 60%,” said Cefalu, leaving them more vulnerable to influenza infection and severe complications. A hemagglutination inhibition (HAI) titer of 1:32 to 1:40 is often referred to as a protective titer, and one-third or fewer vaccine recipients with HAI titers in this range become infected with influenza virus, he noted.

Post-influenza vaccination geometric mean titers (GMT) are much lower in older adults (≥65 years) compared with those 18 to 64 years old, which may explain the reduced effectiveness of influenza vaccination against influenza-like illness with increasing age. In clinical studies performed over seven influenza seasons, the range of vaccine effectiveness was 26% to 52% in those 65 years and older, compared with 62% to 76% in those 18 to 64 years old.

One potential solution to the reduced vaccination immunogenicity in older patients is the use of a high-dose influenza vaccine, which is indicated for active immunization of persons 65 years and older. Efficacy of this vaccine was established in a phase 3 clinical trial that compared the standard-dose (15 µg HA per strain) and high-dose (60 µg HA per strain) versions in community-dwelling medically stable persons 65 years and older.

“There was a significantly higher antibody titer in two of the three influenza strains [H1N1 and H3N2] in recipients of the high-dose versus the standard-dose vaccine,” said Cefalu. When stratified by age (65-74 years, 75-84 years, and ≥85 years), postvaccination GMT were significantly higher in all age groups receiving the high-dose vaccine versus the standard-dose vaccine. Seroconversion rates were also superior for H1N1 and H3N2, with noninferiority for influenza B, in the group receiving the high-dose vaccine.

Individuals receiving the high-dose vaccine experienced slightly more mild injection-site reactions, including pain, which was probably due to the higher potency, said Cefalu. Rates of serious adverse events were comparable between the two groups, and no deaths occurred between day 0 and day 28 postvaccination.

The potential clinical benefit of the high-dose vaccine, although as yet unproved (a postlicensure efficacy trial is ongoing), outweighs any risk, said Cefalu.

A new intradermal influenza virus vaccine has been approved for use in 18- to 64-year olds for immunization against influenza disease caused by subtypes B and A. Immune responses were noninferior to those obtained with the intramuscular route of administration, and a lower dose of antigen was required.—Wayne Kuznar

Rational Polypharmacy is Key to Managing Pain in Long-Term Care Residents

Polypharmacy and pain are commonly encountered in long-term care (LTC) residents, with about 60% to 70% of individuals reporting the latter. Uncontrolled pain can significantly affect residents’ physical function and quality of life. A rational approach to polypharmacy includes management of pain to improve functional capacity while avoiding drug–drug interactions or adverse drug events. This approach is a key component of quality drug prescribing, said Todd Berner, MD, Health Outcomes and Pharmacoeconomics, Research and Development, and field scientist, Endo Pharmaceuticals, at an AMDA Long Term Care Medicine 2012 product theater.

Low-quality prescribing is costlier prescribing because it is associated with more adverse drug events that may require additional expense to treat, such as emergency department visits and hospital admissions, said Berner. Incentives by the Centers for Medicare & Medicaid Services (CMS) for accountable care organizations to achieve financial bonuses may be impacted by elements of pain management pathways and their clinical performance measures, especially within transitions of care, he said. One such measure may be the ability of LTC residents to participate in rehabilitative sessions.

“Patients’ ability to participate in their rehabilitation because their pain is well controlled, compared to not being able to participate in their rehabilitation, can affect their length of stay and the facility’s level of reimbursement,” he said. “It starts from the point of recognizing pain, and you end up being four square in the center of healthcare reform.”

Recognition, evaluation, and management of pain in LTC residents are components of F-Tag 309 quality of care requirements. In 2009, CMS released revised guidance and investigative protocols for F-Tag 309, stating that “each resident must receive and the facility must provide the necessary care and services to attain or maintain the highest practicable physical, mental, and psychosocial well-being in accordance with the comprehensive assessment and plan of care.” A facility is in compliance if each resident has his or her pain managed in alignment with these goals. The protocol determines whether the facility has provided and the resident has received care and services to address and manage pain. It applies to residents who state that they have pain, who display indicators of pain (that cannot be attributed to another cause), are found to have pain, and receive pain treatment.

In addition to evaluating residents with pain, each facility under F-Tag 309 must develop and implement interventions consistent with current standards of practice and recognize or provide measures to minimize or prevent pain when pain is anticipated. The goals of clinical assessment of pain are to identify and characterize the pain by type, quality, location, intensity, and etiology. “The single most reliable indicator of the existence and intensity of pain is the individual’s self report,” said Berner.

“We found that’s it’s very difficult to make correlations between pain scales from one observer to another, from one patient’s self report to another,” he said. “What we determined was functional capacity and quality of life were much more reliable measures of response to pain therapy. Functional end points—observing and speaking to a nursing home resident who says, ‘Today, I could take my meals in a chair, but yesterday I couldn’t get out of bed.’—enable one to correlate that level of function with response to the pain therapy.”

An analgesic should be selected and titrated on an individual basis.  Considering that most older patients use multiple drugs (about 60% use five or more medications weekly), polypharmacy should be rational. The incidence of adverse drug reactions increases significantly when patients take four or more drugs. The most common interactions involve the CYP450 metabolic enzyme system.

Topical treament is often overlooked in pain therapy, said Berner. “Topical therapy is not for everybody; a certain percentage can’t tolerate it but on the other hand, for those who do, it’s one less pill to take,” he said. “With topical therapy, therapy can be interrupted immediately by removing the patch. There are no gastrointestinal issues and there are fewer drug–drug interactions.”—Wayne Kuznar

Long-Term Care is a Challenge for Huntington’s Patients with Chorea

Chorea (abnormal involuntary movements) may be the first presenting symptom of Huntington’s Disease (HD). Although chorea may be minimal at the outset, affecting only the face or distal portions of the limbs, the degenerative nature of HD is such that chorea becomes generalized, interfering with voluntary movements, said Victor Sung, MD, assistant professor, Department of Neurology, University of Alabama-Birmingham (UAB), and clinical director, UAB/HDSA [Huntington Disease Society of America] Huntington’s Disease Center of Excellence, at an AMDA Long Term Care Medicine 2012 product theater.

Chorea affects 90% of patients with HD at some stage in their illness, said Sung. Identifying a long-term care (LTC) facility that meets the needs of patients with HD is an important hurdle for many families because the degenerative nature of HD can require 24-hour supervision of those affected.

Patients with HD differ from the average LTC resident in that they are younger, often lack serious comorbid medical diagnoses on admission, and can have severe movement, psychiatric, and behavioral disorders. The motor, psychiatric, and cognitive symptoms are referred to as the “HD triad,” said Sung.

Currently, the only FDA-approved treatment for chorea associated with HD is tetrabenazine. This agent is thought to work by reversibly depleting monoamines, such as dopamine, serotonin, norepinephrine, and histamine, from nerve terminals by inhibiting vesicular monoamine transporter subtype 2 (VMAT2), decreasing uptake of monoamines into synaptic vesicles and depleting monoamine stores.

The effects of tetrabenazine on monoamine depletion are due primarily to the actions of alpha-HTBZ and beta-HTBZ, two metabolites that are metabolized through the CYP2D6 enzyme. As such, tetrabenazine has significant interactions with some antidepressants, including paroxetine. CYP2D6 testing is offered through Lundbeck, the drug’s manufacturer, said Sung.

In the pivotal trial of tetrabenazine, the mean reduction in the total chorea score on the Unified HD Rating Scale (UHDRS) from baseline exceeded five unit in patients assigned to tetrabenazine, whereas those randomly assigned to received the placebo had a mean reduction of only one unit (P<.0001). On the UHDRS, chorea for each body part (face, bucco-oral-lingual, trunk, right upper extremity, left upper extremity, right lower extremity, left lower extremity) is scored on a 0 to 4 scale; the total score ranges from 0 to 28.  A reduction of three or more units was defined as clinically meaningful in the pivotal trial. By week 3 of treatment, significant efficacy was observed with tetrabenazine, and after the washout period, the total chorea score returned to baseline levels.

Dosing of tetrabenazine should be individualized, said Sung, who advised “start low and go slow.” The starting dosage in the pivotal trial was 12.5 mg on day 1 and 12.5 mg twice daily on days 2 to 7. The dosage was then increased weekly by 12.5 mg. Of the patients, 56% required more than 50 mg per day. The maximum daily dosage is 100 mg. Lundbeck recommends genotyping for CYP2D6 in patients who require dosages of more than 50 mg per day.

Tetrabenazine is not stocked in retail pharmacies. It is distributed directly to LTC facilities through an LTC specialized pharmacy. Patient assistance programs and refills are available through the LTC specialty pharmacy. —Wayne Kuznar

Treating Inappropriate Laughing and Crying Can Prevent Isolation of Long-Term Care Residents

Pseudobulbar affect (PBA), a disorder characterized by involuntary and inappropriate outbursts of laughing or crying, occurs secondary to other unrelated neurologic conditions, and can lead to social isolation when it occurs in long-term care (LTC) residents. In a typical 120-bed facility, the number of PBA cases can range from 6 to 27 in the population with Alzheimer’s disease or dementia, 1 to 13 in those with stroke, and 1 to 3 in those with Parkinson’s disease.

First described in the literature 130 years ago, PBA has had multiple terms applied to it throughout the literature, including affective instability, emotional dyscontrol, emotional/affective lability, said Manuel A. Suarez-Barcelo, MD, CMD, internist, Partners in Internal Medicine, North Miami Beach, FL, at an AMDA Long Term Care Medicine 2012 product theater.

The criteria for a PBA diagnosis require the presence of episodic (sudden and intense), brief (lasting seconds to minutes), frequent, stereotypical outbursts of crying, laughing, or both. The disorder is differentiated from depression by the episodes being incongruent or exaggerated relative to the patient’s mood and the patient’s inability to control his or her emotions. “Depressed patients can sometimes mask their depression, whereas the behavior is involuntary in PBA,” said Suarez-Barcelo. “There may be coexisting depression, but [with PBA] the patients usually can’t tell you why they’re doing what they’re doing,” he noted. Identification of PBA requires a team approach between the front-line observers, who should document the inappropriate crying or laughing episodes, and the prescribers (physician, nurse practitioner, physician assistant).

Social phobia, withdrawal, and isolation can result from PBA, and those affected often cannot participate in their prescribed rehabilitative therapy as a result of the episodes. “PBA can lead to social isolation because you’re disruptive to others,” said Suarez-Barcelo.

Disruption of the neural network controlling emotional motor expression is thought to be responsible for PBA. “It’s believed to result from a loss of frontal voluntary control or lesions in the cortico-ponto-cerebellar pathways,” said Suarez-Barcelo.

Dextromorphan HBr and quinidine sulfate (Nuedexta) is FDA-approved as a therapy for PBA; the dextromorphan is the active ingredient that acts on the central nervous system and the quinidine is a metabolic inhibitor that enables achievement of therapeutic dextromorphan concentration. The drug is covered under Medicare Part D.

Studies supporting the efficacy of dextromorphan HBr/quinidine sulfate in PBA were conducted in patients with amyotrophic lateral sclerosis and multiple sclerosis. A decrease in manifestations of PBA occured at week 1 of therapy and were sustained. Half of all patients treated with dextromorphan HBr/quinidine sulfate achieved remission (episode-free) over the final 14 days of the study.

The amount of quinidine (10 mg) in the tablet is .05% of the lowest commercially available dosage, contributing to the cardiovascular safety profile of dextromorphan HBr/quinidine sulfate, including a lack of reported torsades de pointes, said Suarez-Barcelo. Nevertheless, he noted that a baseline electrocardiogram “might be a good idea in some patients,” such as those taking drugs that prolong the QT interval or inhibit CYP3A4, and those with left ventricular hypertrophy or dysfunction.

Although the pharmacokinetics of dextromorphan HBr/quinidine sulfate are similar in adult and geriatric patients, there were too few patients 65 years and older enrolled in clinical trials to determine whether this age group responds differently than younger patients. However, the drug should be used with caution in patients prone to falls.

Dextromorphan HBr/quinidine sulfate should be started at one capsule daily for 7 days, followed by one capsule every 12 hours thereafter. The maximum dosage is two capsules in a 24-hour period. “You can periodically reassess the need for the medication after the patient goes into remission,” said Suarez-Barcelo.—Wayne Kuznar

High Index of Suspicion for Norovirus Can Contain Potential Outbreaks

Prevention of norovirus outbreaks in long-term care (LTC) settings is difficult because of prodromal shedding and continued shedding after symptoms resolve. Knowing how to contain an outbreak is crucial because of the substantial morbidity and mortality it can cause, and the financial implications of an uncontrolled norovirus outbreak to a facility can be significant, said a panel of speakers at the AMDA Long Term Care Medicine 2012 meeting.

“Keep norovirus on top of your differential diagnosis,” advised Tae Joon Lee, MD, CMD, clinical assistant professor, department of family medicine, geriatric division, East Carolina University, Greenville, NC, whose facility had to temporarily ban admissions after a December 2008 outbreak.

Because norovirus is not a reportable illness in the United States, precise estimates of the incidence of outbreaks are not available; however, it is the leading cause of acute gastroenteritis in older nursing home residents. Although norovirus is more common in the winter, “it’s here year round,” warned David A. Nace, MD, MPH, CMD, director, LTC & Flu Programs, University of Pittsburgh, and chief of medical affairs, University of Pittsburgh Medical Center Senior Communities, PA.

Norovirus can be spread by person-to-person contact, excretions (feces, vomitus), contaminated surfaces, aerosolized particles, and contaminated food. In addition, because the norovirus genome undergoes frequent change, the ability for a person to maintain immunity is lost. “You can get it more than once,” said Nace.

Although the acute symptoms resolve within 3 to 4 days, the nonspecific symptoms (ie, lethargy) can last up to 19 days. Relapses between 3 and 8 days occur in 60% of patients.

A norovirus outbreak can be detected by applying the following four Kaplan criteria: mean or median illness duration of 12 to 60 hours; mean or median incubation period of 24 to 48 hours; vomiting in more than 50% of people; and no bacterial agent found. “When all four criteria are present, there’s a high likelihood that the outbreak is norovirus,” said Nace.

The difficulty in controlling norovirus outbreaks in healthcare settings is attributable to several factors, including a low infectious dose of the virus; environmental stability of the virus; a large human reservoir of infection; ability of the virus to be transferred by a variety of routes; substantial strain diversity; and prodromal viral shedding, which occurs at least 24 hours before symptoms manifest and continues after symptoms resolve, noted Nace, whose facility had a 6-week shutdown after failure to control an outbreak.

An outbreak can cause “lots of chaos in the facility,” said Lee. Dining rooms and other gathering areas may need to be temporarily closed, some patients may need to be quarantined, a substantial proportion of staff will miss work while others will need to work overtime, and temporary workers not familiar with the facility may need to be called in, he noted. An outbreak of 24 cases at his facility resulted in a median of 2.5 days of missed work, required a ban on new admissions, and restricted visitation. Ill staff were quarantined at home until 48 hours after their gastrointestinal symptoms resolved. The outbreak cost the facility $34,000 from the ban on admissions and additional staffing and patient care expenses. Factoring in emergency department visits and hospitalizations, the total cost to the system was estimated to be $49,000.

In 2011, the Centers for Disease Control and Prevention (CDC) issued healthcare facility guidelines that contain recommendations on preventing and containing norovirus outbreaks in healthcare settings. Because most household disinfectants have little or no activity against norovirus, preventing outbreaks is a challenge, said Taranisia MacCannell, PhD, MSc, epidemiologist, Division of Healthcare Quality Promotion, CDC. The evidence for hand hygiene in preventing transmission is inconclusive, but the CDC recommends soap and water after having contact with patients and use of an ethanol-based hand sanitizer before contact with patients who have norovirus.

If a resident has symptoms consistent with norovirus gastroenteritis, the CDC recommends placing him or her on contact precautions in a single-occupancy room (evidence: category 1B). Specimens for norovirus should be taken during the acute phase of the patient’s illness, or 3 or more days after onset, said MacCannell.

The full CDC guidelines can be found at https://1.usa.gov/NorovirusManagement.

—Wayne Kuznar