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Pandemic Influenza and the Hospitalist
Background
Influenza viruses are among the most common respiratory viral infections in humans. There are two major types of human influenza viruses, A and B, with influenza A strains responsible for seasonal or pandemic influenza. Influenza illness is characterized by fever, lower respiratory and often upper respiratory symptoms, myalgia, and malaise and occurs seasonally in temperate climates between late fall and early spring. The average flu season in the United States is marked by 30,000‐40,000 deaths, primarily in elderly patients with significant comorbidity and in the very young. Many of these deaths are caused by secondary bacterial pneumonias. Long interpandemic periods, including the current one of almost 40 years, involve minor mutations of the predominant influenza strain from year to year. Typically, adequate time exists to predict the prevailing strain with reasonable accuracy and to tailor a vaccine accordingly. Periodically an influenza pandemic involving a novel influenza strain emerges, attended by greater‐than‐expected morbidity and mortality.
All influenza viruses are subtyped on the basis of two surface glycoproteins. One of these, hemagglutinin (H), is responsible for viral cell entry; whereas the other, neuraminidase (N), facilitates release of the virus from infected cells, thus allowing perpetuation and amplification of infection. Antigenic drift is the ongoing process of genetic mutations that lead to new strains demonstrating variable change in antigenicity and is the basis for the annual updating of vaccine strains. Antigenic shift is the emergence of a novel influenza A subtype among humans, usually as the result of a recombination event. This radical change is necessary but not sufficient to initiate pandemic influenza, with efficient transmission from person to person also a critical feature. Pandemic influenza strains arise in 1 of 2 fashions. Genetic reassortment may occur when a mammalian host (human or porcine) is infected with both an avian and a human influenza virus, with subsequent dramatic movement into human populations, the source of the 1957 and 1968 pandemics. Alternatively, a novel virus may, after sufficient mutation, move directly from the avian population to humans, as appears to have occurred in 1918.
The 1918‐19 Pandemic
Abruptly in 1918, an influenza pandemic of seemingly unprecedented severity swept the world. Although disagreement remains regarding the source of the outbreak (China, the front lines of World War I, and even the United States have all been suggested), within 6‐9 months essentially the entire globe had been affected. Unlike more typical influenza seasons, the virus preferentially infected previously healthy young individuals, with those aged 15‐40 bearing the brunt of the illness. US military training installations, overcrowded with troops staging for service on the European front, played a particularly ill‐fated role in the pandemic as it swept through the United States.
Estimates of the pandemic's worldwide impact on mortality are sketchy at best, but many authorities believe that at least 50 million deaths resulted, with some suggesting a figure as high as 100 million. In the United States the virus was responsible for an estimated 700,000 deaths, with an untold burden of morbidity. Economic and social disruption was the norm in many areas, with widespread closure of businesses and schools and suspension of public gatherings of any kind. Many communities were simply overwhelmed by the sheer numbers of dying individuals. In Philadelphia, steam shovels were used to dig mass graves for influenza victims.1 The pandemic's effect on the health care system was likewise profound. Most hospitals counted their own physicians and nurses among those who died during the pandemic, and many of the health care workers who succumbed were infected in the course of caring for influenza patients. Overall, an estimated 2%‐3% of those infected with the virus died, a far higher percentage than is seen during interpandemic seasons. Strikingly, the vast majority of deaths do not appear to have resulted from secondary bacterial pneumonias, but rather to have been directly virally mediated through ARDS, a necrotizing viral pneumonia, or both.
The mystery of the 1918 pandemic has recently been partially unlocked, with the successful sequencing of the entire RNA genome of strains recovered from pathology tissue of two soldiers, as well as from lung tissue of a victim frozen in Alaskan permafrost since 1918.2, 3 The data suggest that the 1918 virus was derived from an avian source. Notably, some of the same changes in the polymerase proteins have been found in the highly pathogenic H5N1 viruses.
Avian Influenza Viruses
Influenza viruses that primarily infect birds are characterized as avian influenza viruses. These are always type A and are classified as either of low or high pathogenicity on the basis of the severity of the illness they cause in birds. The currently circulating H5N1 avian viruses are highly pathogenic.
Avian influenza viruses do not usually infect humans; however, several instances of human infections have been reported since 1997. The 1997 Hong Kong outbreak of avian (H5N1) influenza in 18 humans resulted in 6 deaths and was a seminal event that provided evidence that avian influenza viruses can infect people. It also provided the epidemiologic link between avian influenza infection in poultry with disease in humans and was proclaimed as a pandemic warning. These sentinel human infections led to the culling of the entire Hong Kong poultry population, with no subsequent human infection reported at that time. In 2003, more than 80 cases of avian influenza A (H7N7) illness occurred in the Netherlands among persons who handled infected poultry. Sustained human‐to‐human transmission did not occur in this or other outbreaks of avian influenza to date.
Since 2003, sporadic human cases of H5N1 have occurred, most recently reported from Turkey and Iraq. Human cases have also occurred in Vietnam, China, Cambodia, Thailand, and Indonesia, with a total of 173 reported cases and a case fatality rate exceeding 50% as of this writing.4 This mortality rate may be artificially inflated, as less severe cases have certainly gone unreported. All countries reporting human avian influenza diseases since 2003 have had concurrent epizoonotics in birds (both poultry and migratory birds).
Human cases of H5N1 influenza illness have been characterized by high fever and symptoms in the lower respiratory tract, as would be expected. Less predictable has been the presence of watery diarrhea in many patients and of abdominal and pleuritic pain and bleeding from the nose and gums in some. Sputum production has been variably present, and hemoptysis has been seen in some individuals. Most patients have had clinical and radiological evidence of pneumonia at the time they sought medical care, and progression to ARDS and multiorgan failure has been common. The majority of patients to date have required the initiation of mechanical ventilation early in their hospital course. Laboratory studies have typically shown lymphopenia, thrombocytopenia, and, in many cases, modestly elevated transaminase levels.5 Notably, the currently predominant strain of H5N1 (Z strain) is resistant to the M2 ion channel inhibitors amantadine and rimantadine but is susceptible to the newer class of neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu). Neuraminidase inhibitors and corticosteroids have been used to treat patients, although their efficacy in this setting is unclear. To date, virtually all cases appear to have been transmitted directly from poultry, although person‐to‐person transmission appears likely to have occurred in at least one family in Thailand.6 A recent study of the 14 clusters of avian influenza among humans emphasized the lack of sustained person‐to‐person transmission of H5N1 to date.7
Three factors are necessary for the emergence of a pandemic influenza strain: the ability to infect humans, a novel genetic makeup, and the ability for sustained transmission between people. A virus that in addition proves highly virulent, as did the 1918‐19 H1N1 strain, essentially creates the perfect storm. H5N1 influenza has currently fulfilled 2 of these 3 criteria. The virus is highly pathogenic, although how much of this fitness would be sacrificed with mutation to a more transmissible strain is uncertain. As many have observed, whether there will be another influenza pandemic does not seem in doubt; rather, it is when such a pandemic will occur and whether the pandemic will be caused by H5N1 or another influenza virus, that are the questions.
Potential Effects of the Next Pandemic
The global and national effects of an influenza pandemic will vary in direct proportion to the virulence of the circulating viral strain, but if such a virus is highly virulent, significant and perhaps severe economic and social disruption are likely.
The global economic impact has been estimated to be $800 billion with anticipated quarantines and interruption in global trade. On a national level, it has been estimated that in the United States a pandemic virus whose severity is comparable to that of the 1968 Hong Kong influenza pandemic would lead to approximately 200,000 deaths and 700,000 hospitalizations, of which roughly 100,000 would require treatment in intensive care unit settings. A more virulent strain, similar to that of the 1918‐19 pandemic, might easily result in 1 million deaths; with the number of patients hospitalized approaching 10 million, well over 1 million of which would require ICU‐level care. As an estimated 75% of the 105,000 ventilators in this country are in use at any given time under normal circumstances, the potential for demand to greatly outstrip supply is evident.8 Depending on the severity of a pandemic, suspension or curtailment of international trade and travel could be reasonably likely. Although the World Health Organization has recommended against closing borders or quarantining countries even in the throes of a pandemic, the prospect of this occurring does not seem implausible. In a worst‐case scenario, even the type of national and international chaos envisioned in the Dark Winter smallpox planning exercise might occur.9
Fortress America Versus Containment Strategies
Although the pandemic influenza plan calls for stockpiling antiviral drugs and increasing vaccine production capabilities, the most effective plan for pandemic preparedness may involve a surveillance and containment strategy. No country has enough medicines or vaccines to control a widespread outbreak of pandemic avian influenza. The best solution to prevention of a pandemic is stopping any virus from spreading in the first place. Increased surveillance for avian influenza among poultry and migratory birds in key Asian countries, along with provision of funds to compensate farmers for culling of potentially infected flocks, would align incentives for early detection and eradication. Containing an initial outbreak wherever it occurs is the best defense against a pandemic. Notably, China is thought to be a potential hot zone for emergence of pandemic avian influenza. China is not only the most populous nation in the world but has one quarter of the world's chickens, two thirds of the world's domesticated ducks, and 90% of the world's domesticated geese.
The challenges of biosecurity (protecting humans against animal‐borne diseases such as bird flu) in developing countries include the reality that populations living in close proximity to poultry are also the most illiterate and impoverished, with the most limited access to health care. The recent introduction of H5N1 into Europe has heightened surveillance efforts in the United States. The introduction of H5N1 into the United States may occur through movement of migratory birds and/or importation of exotic birds. The surveillance system has been expanded to include sampling for the influenza virus not only in poultry but also in bodies of water, as the virus is shed in bird feces.
Pandemic Planning
In the setting of a severe pandemic, hospitals will face an enormous burden of patients, with a huge influx of individuals requiring both intensive care unit as well as regular nursing floor care. At the local height of such a pandemic, the ability to successfully discharge every patient whose condition will permit this to the community or elsewhere will be critical, and almost certainly hospitals will need to expand to accept more patients than they are normally configured to hold. Hospitals staffs, particularly nurses and physicians, will be required to handle very large patient censuses. Among medical staffs, emergency physicians, hospitalists, critical care specialists, and infectious disease specialists will certainly be called on to play leading roles, much as they were during and in the aftermath of Hurricane Katrina recently. Despite all of the above, the ability of existing hospitals to accommodate all gravely ill patients may be outstripped, and auxiliary hospitals in schools and other public edifices may need to be established. Hospitalists are likely to be called on to play a major role in such temporary hospitals. The frustration and anguish of not being able to provide a standard level of care to patients (for example, being forced to triage which patients are most deserving of mechanical ventilation) should not be underestimated.
Although characterized by a relatively limited number of patients, the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, Canada, presented some of the same challenges that will be encountered in a virulent influenza pandemic. These include the need to quickly and drastically modify the usual emergency department and inpatient procedures, as hospitals initially serve to amplify the epidemic, as well as the additional stressor of health care workers becoming ill as a result of work‐related exposure. That fewer than 400 cases of SARS pushed the medical system of one of North America's largest cities nearly to its breaking point is both sobering and instructive.10, 11 Interested readers are directed to an excellent summary of lessons learned from the SARS outbreak, most of which are widely applicable to preparations for future infectious epidemics.12
Infection Control
Although the CDC and other Web sites currently recommend airborne isolation (respiratory personal protection) for avian influenza in humans, there is not strong epidemiologic evidence of transmission other than via droplets (the transmission mode of human influenza). The emergence of a limited number of cases of avian influenza in the United States would allow employment of airborne isolation measures; but in the event of a larger outbreak, the use of surgical masks and the practice of good hand hygiene would be sufficient by health care workers caring for persons with suspected or proven disease.
The CDC recently released proposed changes to help prevent disease outbreaks from contacts of those exposed to ill persons on airplanes. Proposed guidelines would require airlines to maintain computerized lists of passengers taken at point of departure in order to facilitate tracking of contacts and implementation of quarantine if necessary. These measures are part of pandemic planning and result from problems in tracking passengers on planes with SARS cases. By executive order, imposition of quarantine is limited to 9 diseases: cholera, diphtheria, smallpox, yellow fever, viral hemorrhagic fevers (eg, Ebola), plague, infectious tuberculosis, SARS and influenza caused by new strains with pandemic potential.
What Can Be Done?
Although valuable time has elapsed to prepare for the possibility of an H5N1 influenza pandemic, the US and global communities are presently taking the threat seriously and are engaging in a variety of activities to prepare for such an eventuality. Although currently available influenza vaccines do not provide any appreciable protection against H5N1, significant work is under way to develop an effective vaccine; with Chiron and sanofi pasteur preparing vaccine trials in association with the National Institute of Allergy and Infectious Diseases. Current influenza vaccine production is hampered by use of obsolete egg‐based manufacturing processes requiring 6 months, along with a limited capacity to manufacture adequate vaccine supplies even in many usual influenza seasons. The herculean task of providing hundreds of millions of doses of vaccine as soon as possible after the emergence of a pandemic strain, as daunting as it is, is further complicated by the fact that a successful H5N1 vaccine would not necessarily be effective against a strain that mutated sufficiently to move efficiently from person to person. Nonetheless, even partially solving these problems will pay dividends, whether or not H5N1 proves to be responsible for the next pandemic.
Given these difficulties with vaccine development and production, the backbone of any successful early response to a pandemic in the near future will be development of an adequate stockpile of antiviral medication, accompanied by a successful plan to distribute the drug when and where disease erupts. Despite uncertainties regarding their effectiveness as well as questions regarding optimal dose and duration in the setting of avian influenza, the neuraminidase inhibitors are the current drugs of choice. Of the 2 currently available agents, oseltamivir is the preferred drug for pandemic use, given its oral administration,. Unfortunately, the ability to manufacture the drug in sufficient quantities to stockpile has thus far proved problematic. Roche, the manufacturer of Tamiflu, has recently opened a new manufacturing plant and has stated that it can increase its current production of 55 million doses per year to 300 million doses by 2007. We do not recommend a role for personal stockpiling of neuraminidase inhibitors. Concerns include a shortage of the drug for seasonal influenza, absence of a pandemic at present, ignorance regarding the efficacy and optimal dose for H5N1, inappropriate use by individuals, and inequitable distribution. Recent case reports of oseltamivir resistance emerging during prophylaxis13 and treatment14 are of potential concern but do not alter current recommendations.
What can be done locally and specifically, and what can hospitalists do to prepare? First, although we are not sure that Dr Michael Osterholm's goal that planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor8 is entirely realistic, every hospital clearly needs to include pandemic influenza as a significant part of its disaster preparedness plan. Such planning will have broad overlap with planning for other potential disasters, including bioterrorist attacks, SARS outbreaks, and others. Hospitals must develop a plan for surge capacity, and such a plan should include not only coordination with other local hospitals, but also planning with local communities to identify sites where temporary flu hospitals can be established. Within hospital medicine groups, emergency staffing plans should be established before pandemic influenza (or another disaster) strikes. Such staffing plans need to include the ability to care for a much higher than normal number of patients for an extended period. Conceivably, a large number of patients will need to be manually ventilated for prolonged periods, which of course will tax the resources of any institution. Prompt discharge of all patients stable enough to leave the hospital will be critical, and given the investment of most hospital medicine groups in hospital throughput issues under normal conditions, much of the responsibility for helping to create beds during a crisis will inevitably fall on the shoulders of hospitalists.
Experiences during and shortly after Hurricane Katrina served to underscore that issues such as physical and mental fatigue, concern for the safety of family members, lack of supplies, communication difficulties, and absenteeism all add additional layers of complexity to the task of providing hospital care under extraordinary conditions such as during a natural disaster. These lessons can and should be extended to a major epidemic. This disaster also showed the importance of military involvement in the response to disasters that exceed local and state capabilities. The primary objective of the federal government in responding to disaster is to maintain security and essential services while preventing chaos. A pandemic of virulent influenza will raise the stakes still further, as physicians and nurses become casualties themselves. Despite these challenges, we are confident that the vast majority of hospitalists and other health care workers will rise to the occasion, and just as during the peri‐Katrina period, stories of selflessness and heroism will be de rigueur. Appropriate advance planning on all levels will serve to reduce the morbidity and mortality associated with the next pandemic and will help to ensure that health care workers do not sacrifice needlessly.0
1. World Health Organization (WHO) Website: |
2. Centers for Disease Control and Prevention (CDC): |
3. U.S. Government Avian Influenza Website: |
4. U.S. Department of Health and Human Services Pandemic Influenza Plan: |
5. Infectious Diseases Society of America (IDSA) Website: |
- The Great Influenza.New York, NY:Viking Penguin,2004. .
- Characterization of the 1918 influenza virus polymerase genes.Nature.2005;437:889–893. , , , , , .
- Characterization of the reconstructed 1918 Spanish influenza pandemic virus.Science.2005;310:77–80. , , , et al.
- WHO Epidemic and Pandemic Alert and Response. Confirmed cases of avian influenza A (H5N1). Available at http://www.who.int/csr/disease/avian_influenza/country/en/index.html. Accessed on February 28,2006.
- Writing Committee of the WHO Consultation on Human Influenza A/H5.Avian influenza A (H5N1) infection in humans.N Engl J Med.2005;353:1374–1385.
- Probable person‐to‐person transmission of avian influenza A (H5N1).N Engl J Med.2005;352:333–40. , , , et al.
- Family clustering of avian influenza A (H5N1).EID.2005;11:1799–1801. , , , et al.
- Preparing for the next pandemic.N Engl J Med.2005;352:1839–1842. .
- Center for Biosecurity. Dark Winter overview. Available at http://www.upmc‐biosecurity.org/pages/events/dark_winter/dark_winter.html. Accessed November 28,2005.
- SARS outbreak in the Greater Toronto Area: the emergency department experience.CMAJ.2004;171:1342–1344. , , , et al.
- Severe acute respiratory syndrome and critical care medicine: The Toronto experience.Crit Care Med.2005;33(suppl):S53–S60. , .
- Learning from SARS in Hong Kong and Toronto.JAMA.2004;291:2483–2487. , , .
- Avian flu: Isolation of drug‐resistant H5N1 virus.Nature.2005;438:754. , , , et al.
- Oseltamivir resistance during treatment of influenza A (H5N1) infection.N Engl J Med.2005;353:2667–2672. , , , et al.
Background
Influenza viruses are among the most common respiratory viral infections in humans. There are two major types of human influenza viruses, A and B, with influenza A strains responsible for seasonal or pandemic influenza. Influenza illness is characterized by fever, lower respiratory and often upper respiratory symptoms, myalgia, and malaise and occurs seasonally in temperate climates between late fall and early spring. The average flu season in the United States is marked by 30,000‐40,000 deaths, primarily in elderly patients with significant comorbidity and in the very young. Many of these deaths are caused by secondary bacterial pneumonias. Long interpandemic periods, including the current one of almost 40 years, involve minor mutations of the predominant influenza strain from year to year. Typically, adequate time exists to predict the prevailing strain with reasonable accuracy and to tailor a vaccine accordingly. Periodically an influenza pandemic involving a novel influenza strain emerges, attended by greater‐than‐expected morbidity and mortality.
All influenza viruses are subtyped on the basis of two surface glycoproteins. One of these, hemagglutinin (H), is responsible for viral cell entry; whereas the other, neuraminidase (N), facilitates release of the virus from infected cells, thus allowing perpetuation and amplification of infection. Antigenic drift is the ongoing process of genetic mutations that lead to new strains demonstrating variable change in antigenicity and is the basis for the annual updating of vaccine strains. Antigenic shift is the emergence of a novel influenza A subtype among humans, usually as the result of a recombination event. This radical change is necessary but not sufficient to initiate pandemic influenza, with efficient transmission from person to person also a critical feature. Pandemic influenza strains arise in 1 of 2 fashions. Genetic reassortment may occur when a mammalian host (human or porcine) is infected with both an avian and a human influenza virus, with subsequent dramatic movement into human populations, the source of the 1957 and 1968 pandemics. Alternatively, a novel virus may, after sufficient mutation, move directly from the avian population to humans, as appears to have occurred in 1918.
The 1918‐19 Pandemic
Abruptly in 1918, an influenza pandemic of seemingly unprecedented severity swept the world. Although disagreement remains regarding the source of the outbreak (China, the front lines of World War I, and even the United States have all been suggested), within 6‐9 months essentially the entire globe had been affected. Unlike more typical influenza seasons, the virus preferentially infected previously healthy young individuals, with those aged 15‐40 bearing the brunt of the illness. US military training installations, overcrowded with troops staging for service on the European front, played a particularly ill‐fated role in the pandemic as it swept through the United States.
Estimates of the pandemic's worldwide impact on mortality are sketchy at best, but many authorities believe that at least 50 million deaths resulted, with some suggesting a figure as high as 100 million. In the United States the virus was responsible for an estimated 700,000 deaths, with an untold burden of morbidity. Economic and social disruption was the norm in many areas, with widespread closure of businesses and schools and suspension of public gatherings of any kind. Many communities were simply overwhelmed by the sheer numbers of dying individuals. In Philadelphia, steam shovels were used to dig mass graves for influenza victims.1 The pandemic's effect on the health care system was likewise profound. Most hospitals counted their own physicians and nurses among those who died during the pandemic, and many of the health care workers who succumbed were infected in the course of caring for influenza patients. Overall, an estimated 2%‐3% of those infected with the virus died, a far higher percentage than is seen during interpandemic seasons. Strikingly, the vast majority of deaths do not appear to have resulted from secondary bacterial pneumonias, but rather to have been directly virally mediated through ARDS, a necrotizing viral pneumonia, or both.
The mystery of the 1918 pandemic has recently been partially unlocked, with the successful sequencing of the entire RNA genome of strains recovered from pathology tissue of two soldiers, as well as from lung tissue of a victim frozen in Alaskan permafrost since 1918.2, 3 The data suggest that the 1918 virus was derived from an avian source. Notably, some of the same changes in the polymerase proteins have been found in the highly pathogenic H5N1 viruses.
Avian Influenza Viruses
Influenza viruses that primarily infect birds are characterized as avian influenza viruses. These are always type A and are classified as either of low or high pathogenicity on the basis of the severity of the illness they cause in birds. The currently circulating H5N1 avian viruses are highly pathogenic.
Avian influenza viruses do not usually infect humans; however, several instances of human infections have been reported since 1997. The 1997 Hong Kong outbreak of avian (H5N1) influenza in 18 humans resulted in 6 deaths and was a seminal event that provided evidence that avian influenza viruses can infect people. It also provided the epidemiologic link between avian influenza infection in poultry with disease in humans and was proclaimed as a pandemic warning. These sentinel human infections led to the culling of the entire Hong Kong poultry population, with no subsequent human infection reported at that time. In 2003, more than 80 cases of avian influenza A (H7N7) illness occurred in the Netherlands among persons who handled infected poultry. Sustained human‐to‐human transmission did not occur in this or other outbreaks of avian influenza to date.
Since 2003, sporadic human cases of H5N1 have occurred, most recently reported from Turkey and Iraq. Human cases have also occurred in Vietnam, China, Cambodia, Thailand, and Indonesia, with a total of 173 reported cases and a case fatality rate exceeding 50% as of this writing.4 This mortality rate may be artificially inflated, as less severe cases have certainly gone unreported. All countries reporting human avian influenza diseases since 2003 have had concurrent epizoonotics in birds (both poultry and migratory birds).
Human cases of H5N1 influenza illness have been characterized by high fever and symptoms in the lower respiratory tract, as would be expected. Less predictable has been the presence of watery diarrhea in many patients and of abdominal and pleuritic pain and bleeding from the nose and gums in some. Sputum production has been variably present, and hemoptysis has been seen in some individuals. Most patients have had clinical and radiological evidence of pneumonia at the time they sought medical care, and progression to ARDS and multiorgan failure has been common. The majority of patients to date have required the initiation of mechanical ventilation early in their hospital course. Laboratory studies have typically shown lymphopenia, thrombocytopenia, and, in many cases, modestly elevated transaminase levels.5 Notably, the currently predominant strain of H5N1 (Z strain) is resistant to the M2 ion channel inhibitors amantadine and rimantadine but is susceptible to the newer class of neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu). Neuraminidase inhibitors and corticosteroids have been used to treat patients, although their efficacy in this setting is unclear. To date, virtually all cases appear to have been transmitted directly from poultry, although person‐to‐person transmission appears likely to have occurred in at least one family in Thailand.6 A recent study of the 14 clusters of avian influenza among humans emphasized the lack of sustained person‐to‐person transmission of H5N1 to date.7
Three factors are necessary for the emergence of a pandemic influenza strain: the ability to infect humans, a novel genetic makeup, and the ability for sustained transmission between people. A virus that in addition proves highly virulent, as did the 1918‐19 H1N1 strain, essentially creates the perfect storm. H5N1 influenza has currently fulfilled 2 of these 3 criteria. The virus is highly pathogenic, although how much of this fitness would be sacrificed with mutation to a more transmissible strain is uncertain. As many have observed, whether there will be another influenza pandemic does not seem in doubt; rather, it is when such a pandemic will occur and whether the pandemic will be caused by H5N1 or another influenza virus, that are the questions.
Potential Effects of the Next Pandemic
The global and national effects of an influenza pandemic will vary in direct proportion to the virulence of the circulating viral strain, but if such a virus is highly virulent, significant and perhaps severe economic and social disruption are likely.
The global economic impact has been estimated to be $800 billion with anticipated quarantines and interruption in global trade. On a national level, it has been estimated that in the United States a pandemic virus whose severity is comparable to that of the 1968 Hong Kong influenza pandemic would lead to approximately 200,000 deaths and 700,000 hospitalizations, of which roughly 100,000 would require treatment in intensive care unit settings. A more virulent strain, similar to that of the 1918‐19 pandemic, might easily result in 1 million deaths; with the number of patients hospitalized approaching 10 million, well over 1 million of which would require ICU‐level care. As an estimated 75% of the 105,000 ventilators in this country are in use at any given time under normal circumstances, the potential for demand to greatly outstrip supply is evident.8 Depending on the severity of a pandemic, suspension or curtailment of international trade and travel could be reasonably likely. Although the World Health Organization has recommended against closing borders or quarantining countries even in the throes of a pandemic, the prospect of this occurring does not seem implausible. In a worst‐case scenario, even the type of national and international chaos envisioned in the Dark Winter smallpox planning exercise might occur.9
Fortress America Versus Containment Strategies
Although the pandemic influenza plan calls for stockpiling antiviral drugs and increasing vaccine production capabilities, the most effective plan for pandemic preparedness may involve a surveillance and containment strategy. No country has enough medicines or vaccines to control a widespread outbreak of pandemic avian influenza. The best solution to prevention of a pandemic is stopping any virus from spreading in the first place. Increased surveillance for avian influenza among poultry and migratory birds in key Asian countries, along with provision of funds to compensate farmers for culling of potentially infected flocks, would align incentives for early detection and eradication. Containing an initial outbreak wherever it occurs is the best defense against a pandemic. Notably, China is thought to be a potential hot zone for emergence of pandemic avian influenza. China is not only the most populous nation in the world but has one quarter of the world's chickens, two thirds of the world's domesticated ducks, and 90% of the world's domesticated geese.
The challenges of biosecurity (protecting humans against animal‐borne diseases such as bird flu) in developing countries include the reality that populations living in close proximity to poultry are also the most illiterate and impoverished, with the most limited access to health care. The recent introduction of H5N1 into Europe has heightened surveillance efforts in the United States. The introduction of H5N1 into the United States may occur through movement of migratory birds and/or importation of exotic birds. The surveillance system has been expanded to include sampling for the influenza virus not only in poultry but also in bodies of water, as the virus is shed in bird feces.
Pandemic Planning
In the setting of a severe pandemic, hospitals will face an enormous burden of patients, with a huge influx of individuals requiring both intensive care unit as well as regular nursing floor care. At the local height of such a pandemic, the ability to successfully discharge every patient whose condition will permit this to the community or elsewhere will be critical, and almost certainly hospitals will need to expand to accept more patients than they are normally configured to hold. Hospitals staffs, particularly nurses and physicians, will be required to handle very large patient censuses. Among medical staffs, emergency physicians, hospitalists, critical care specialists, and infectious disease specialists will certainly be called on to play leading roles, much as they were during and in the aftermath of Hurricane Katrina recently. Despite all of the above, the ability of existing hospitals to accommodate all gravely ill patients may be outstripped, and auxiliary hospitals in schools and other public edifices may need to be established. Hospitalists are likely to be called on to play a major role in such temporary hospitals. The frustration and anguish of not being able to provide a standard level of care to patients (for example, being forced to triage which patients are most deserving of mechanical ventilation) should not be underestimated.
Although characterized by a relatively limited number of patients, the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, Canada, presented some of the same challenges that will be encountered in a virulent influenza pandemic. These include the need to quickly and drastically modify the usual emergency department and inpatient procedures, as hospitals initially serve to amplify the epidemic, as well as the additional stressor of health care workers becoming ill as a result of work‐related exposure. That fewer than 400 cases of SARS pushed the medical system of one of North America's largest cities nearly to its breaking point is both sobering and instructive.10, 11 Interested readers are directed to an excellent summary of lessons learned from the SARS outbreak, most of which are widely applicable to preparations for future infectious epidemics.12
Infection Control
Although the CDC and other Web sites currently recommend airborne isolation (respiratory personal protection) for avian influenza in humans, there is not strong epidemiologic evidence of transmission other than via droplets (the transmission mode of human influenza). The emergence of a limited number of cases of avian influenza in the United States would allow employment of airborne isolation measures; but in the event of a larger outbreak, the use of surgical masks and the practice of good hand hygiene would be sufficient by health care workers caring for persons with suspected or proven disease.
The CDC recently released proposed changes to help prevent disease outbreaks from contacts of those exposed to ill persons on airplanes. Proposed guidelines would require airlines to maintain computerized lists of passengers taken at point of departure in order to facilitate tracking of contacts and implementation of quarantine if necessary. These measures are part of pandemic planning and result from problems in tracking passengers on planes with SARS cases. By executive order, imposition of quarantine is limited to 9 diseases: cholera, diphtheria, smallpox, yellow fever, viral hemorrhagic fevers (eg, Ebola), plague, infectious tuberculosis, SARS and influenza caused by new strains with pandemic potential.
What Can Be Done?
Although valuable time has elapsed to prepare for the possibility of an H5N1 influenza pandemic, the US and global communities are presently taking the threat seriously and are engaging in a variety of activities to prepare for such an eventuality. Although currently available influenza vaccines do not provide any appreciable protection against H5N1, significant work is under way to develop an effective vaccine; with Chiron and sanofi pasteur preparing vaccine trials in association with the National Institute of Allergy and Infectious Diseases. Current influenza vaccine production is hampered by use of obsolete egg‐based manufacturing processes requiring 6 months, along with a limited capacity to manufacture adequate vaccine supplies even in many usual influenza seasons. The herculean task of providing hundreds of millions of doses of vaccine as soon as possible after the emergence of a pandemic strain, as daunting as it is, is further complicated by the fact that a successful H5N1 vaccine would not necessarily be effective against a strain that mutated sufficiently to move efficiently from person to person. Nonetheless, even partially solving these problems will pay dividends, whether or not H5N1 proves to be responsible for the next pandemic.
Given these difficulties with vaccine development and production, the backbone of any successful early response to a pandemic in the near future will be development of an adequate stockpile of antiviral medication, accompanied by a successful plan to distribute the drug when and where disease erupts. Despite uncertainties regarding their effectiveness as well as questions regarding optimal dose and duration in the setting of avian influenza, the neuraminidase inhibitors are the current drugs of choice. Of the 2 currently available agents, oseltamivir is the preferred drug for pandemic use, given its oral administration,. Unfortunately, the ability to manufacture the drug in sufficient quantities to stockpile has thus far proved problematic. Roche, the manufacturer of Tamiflu, has recently opened a new manufacturing plant and has stated that it can increase its current production of 55 million doses per year to 300 million doses by 2007. We do not recommend a role for personal stockpiling of neuraminidase inhibitors. Concerns include a shortage of the drug for seasonal influenza, absence of a pandemic at present, ignorance regarding the efficacy and optimal dose for H5N1, inappropriate use by individuals, and inequitable distribution. Recent case reports of oseltamivir resistance emerging during prophylaxis13 and treatment14 are of potential concern but do not alter current recommendations.
What can be done locally and specifically, and what can hospitalists do to prepare? First, although we are not sure that Dr Michael Osterholm's goal that planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor8 is entirely realistic, every hospital clearly needs to include pandemic influenza as a significant part of its disaster preparedness plan. Such planning will have broad overlap with planning for other potential disasters, including bioterrorist attacks, SARS outbreaks, and others. Hospitals must develop a plan for surge capacity, and such a plan should include not only coordination with other local hospitals, but also planning with local communities to identify sites where temporary flu hospitals can be established. Within hospital medicine groups, emergency staffing plans should be established before pandemic influenza (or another disaster) strikes. Such staffing plans need to include the ability to care for a much higher than normal number of patients for an extended period. Conceivably, a large number of patients will need to be manually ventilated for prolonged periods, which of course will tax the resources of any institution. Prompt discharge of all patients stable enough to leave the hospital will be critical, and given the investment of most hospital medicine groups in hospital throughput issues under normal conditions, much of the responsibility for helping to create beds during a crisis will inevitably fall on the shoulders of hospitalists.
Experiences during and shortly after Hurricane Katrina served to underscore that issues such as physical and mental fatigue, concern for the safety of family members, lack of supplies, communication difficulties, and absenteeism all add additional layers of complexity to the task of providing hospital care under extraordinary conditions such as during a natural disaster. These lessons can and should be extended to a major epidemic. This disaster also showed the importance of military involvement in the response to disasters that exceed local and state capabilities. The primary objective of the federal government in responding to disaster is to maintain security and essential services while preventing chaos. A pandemic of virulent influenza will raise the stakes still further, as physicians and nurses become casualties themselves. Despite these challenges, we are confident that the vast majority of hospitalists and other health care workers will rise to the occasion, and just as during the peri‐Katrina period, stories of selflessness and heroism will be de rigueur. Appropriate advance planning on all levels will serve to reduce the morbidity and mortality associated with the next pandemic and will help to ensure that health care workers do not sacrifice needlessly.0
1. World Health Organization (WHO) Website: |
2. Centers for Disease Control and Prevention (CDC): |
3. U.S. Government Avian Influenza Website: |
4. U.S. Department of Health and Human Services Pandemic Influenza Plan: |
5. Infectious Diseases Society of America (IDSA) Website: |
Background
Influenza viruses are among the most common respiratory viral infections in humans. There are two major types of human influenza viruses, A and B, with influenza A strains responsible for seasonal or pandemic influenza. Influenza illness is characterized by fever, lower respiratory and often upper respiratory symptoms, myalgia, and malaise and occurs seasonally in temperate climates between late fall and early spring. The average flu season in the United States is marked by 30,000‐40,000 deaths, primarily in elderly patients with significant comorbidity and in the very young. Many of these deaths are caused by secondary bacterial pneumonias. Long interpandemic periods, including the current one of almost 40 years, involve minor mutations of the predominant influenza strain from year to year. Typically, adequate time exists to predict the prevailing strain with reasonable accuracy and to tailor a vaccine accordingly. Periodically an influenza pandemic involving a novel influenza strain emerges, attended by greater‐than‐expected morbidity and mortality.
All influenza viruses are subtyped on the basis of two surface glycoproteins. One of these, hemagglutinin (H), is responsible for viral cell entry; whereas the other, neuraminidase (N), facilitates release of the virus from infected cells, thus allowing perpetuation and amplification of infection. Antigenic drift is the ongoing process of genetic mutations that lead to new strains demonstrating variable change in antigenicity and is the basis for the annual updating of vaccine strains. Antigenic shift is the emergence of a novel influenza A subtype among humans, usually as the result of a recombination event. This radical change is necessary but not sufficient to initiate pandemic influenza, with efficient transmission from person to person also a critical feature. Pandemic influenza strains arise in 1 of 2 fashions. Genetic reassortment may occur when a mammalian host (human or porcine) is infected with both an avian and a human influenza virus, with subsequent dramatic movement into human populations, the source of the 1957 and 1968 pandemics. Alternatively, a novel virus may, after sufficient mutation, move directly from the avian population to humans, as appears to have occurred in 1918.
The 1918‐19 Pandemic
Abruptly in 1918, an influenza pandemic of seemingly unprecedented severity swept the world. Although disagreement remains regarding the source of the outbreak (China, the front lines of World War I, and even the United States have all been suggested), within 6‐9 months essentially the entire globe had been affected. Unlike more typical influenza seasons, the virus preferentially infected previously healthy young individuals, with those aged 15‐40 bearing the brunt of the illness. US military training installations, overcrowded with troops staging for service on the European front, played a particularly ill‐fated role in the pandemic as it swept through the United States.
Estimates of the pandemic's worldwide impact on mortality are sketchy at best, but many authorities believe that at least 50 million deaths resulted, with some suggesting a figure as high as 100 million. In the United States the virus was responsible for an estimated 700,000 deaths, with an untold burden of morbidity. Economic and social disruption was the norm in many areas, with widespread closure of businesses and schools and suspension of public gatherings of any kind. Many communities were simply overwhelmed by the sheer numbers of dying individuals. In Philadelphia, steam shovels were used to dig mass graves for influenza victims.1 The pandemic's effect on the health care system was likewise profound. Most hospitals counted their own physicians and nurses among those who died during the pandemic, and many of the health care workers who succumbed were infected in the course of caring for influenza patients. Overall, an estimated 2%‐3% of those infected with the virus died, a far higher percentage than is seen during interpandemic seasons. Strikingly, the vast majority of deaths do not appear to have resulted from secondary bacterial pneumonias, but rather to have been directly virally mediated through ARDS, a necrotizing viral pneumonia, or both.
The mystery of the 1918 pandemic has recently been partially unlocked, with the successful sequencing of the entire RNA genome of strains recovered from pathology tissue of two soldiers, as well as from lung tissue of a victim frozen in Alaskan permafrost since 1918.2, 3 The data suggest that the 1918 virus was derived from an avian source. Notably, some of the same changes in the polymerase proteins have been found in the highly pathogenic H5N1 viruses.
Avian Influenza Viruses
Influenza viruses that primarily infect birds are characterized as avian influenza viruses. These are always type A and are classified as either of low or high pathogenicity on the basis of the severity of the illness they cause in birds. The currently circulating H5N1 avian viruses are highly pathogenic.
Avian influenza viruses do not usually infect humans; however, several instances of human infections have been reported since 1997. The 1997 Hong Kong outbreak of avian (H5N1) influenza in 18 humans resulted in 6 deaths and was a seminal event that provided evidence that avian influenza viruses can infect people. It also provided the epidemiologic link between avian influenza infection in poultry with disease in humans and was proclaimed as a pandemic warning. These sentinel human infections led to the culling of the entire Hong Kong poultry population, with no subsequent human infection reported at that time. In 2003, more than 80 cases of avian influenza A (H7N7) illness occurred in the Netherlands among persons who handled infected poultry. Sustained human‐to‐human transmission did not occur in this or other outbreaks of avian influenza to date.
Since 2003, sporadic human cases of H5N1 have occurred, most recently reported from Turkey and Iraq. Human cases have also occurred in Vietnam, China, Cambodia, Thailand, and Indonesia, with a total of 173 reported cases and a case fatality rate exceeding 50% as of this writing.4 This mortality rate may be artificially inflated, as less severe cases have certainly gone unreported. All countries reporting human avian influenza diseases since 2003 have had concurrent epizoonotics in birds (both poultry and migratory birds).
Human cases of H5N1 influenza illness have been characterized by high fever and symptoms in the lower respiratory tract, as would be expected. Less predictable has been the presence of watery diarrhea in many patients and of abdominal and pleuritic pain and bleeding from the nose and gums in some. Sputum production has been variably present, and hemoptysis has been seen in some individuals. Most patients have had clinical and radiological evidence of pneumonia at the time they sought medical care, and progression to ARDS and multiorgan failure has been common. The majority of patients to date have required the initiation of mechanical ventilation early in their hospital course. Laboratory studies have typically shown lymphopenia, thrombocytopenia, and, in many cases, modestly elevated transaminase levels.5 Notably, the currently predominant strain of H5N1 (Z strain) is resistant to the M2 ion channel inhibitors amantadine and rimantadine but is susceptible to the newer class of neuraminidase inhibitors, zanamivir (Relenza) and oseltamivir (Tamiflu). Neuraminidase inhibitors and corticosteroids have been used to treat patients, although their efficacy in this setting is unclear. To date, virtually all cases appear to have been transmitted directly from poultry, although person‐to‐person transmission appears likely to have occurred in at least one family in Thailand.6 A recent study of the 14 clusters of avian influenza among humans emphasized the lack of sustained person‐to‐person transmission of H5N1 to date.7
Three factors are necessary for the emergence of a pandemic influenza strain: the ability to infect humans, a novel genetic makeup, and the ability for sustained transmission between people. A virus that in addition proves highly virulent, as did the 1918‐19 H1N1 strain, essentially creates the perfect storm. H5N1 influenza has currently fulfilled 2 of these 3 criteria. The virus is highly pathogenic, although how much of this fitness would be sacrificed with mutation to a more transmissible strain is uncertain. As many have observed, whether there will be another influenza pandemic does not seem in doubt; rather, it is when such a pandemic will occur and whether the pandemic will be caused by H5N1 or another influenza virus, that are the questions.
Potential Effects of the Next Pandemic
The global and national effects of an influenza pandemic will vary in direct proportion to the virulence of the circulating viral strain, but if such a virus is highly virulent, significant and perhaps severe economic and social disruption are likely.
The global economic impact has been estimated to be $800 billion with anticipated quarantines and interruption in global trade. On a national level, it has been estimated that in the United States a pandemic virus whose severity is comparable to that of the 1968 Hong Kong influenza pandemic would lead to approximately 200,000 deaths and 700,000 hospitalizations, of which roughly 100,000 would require treatment in intensive care unit settings. A more virulent strain, similar to that of the 1918‐19 pandemic, might easily result in 1 million deaths; with the number of patients hospitalized approaching 10 million, well over 1 million of which would require ICU‐level care. As an estimated 75% of the 105,000 ventilators in this country are in use at any given time under normal circumstances, the potential for demand to greatly outstrip supply is evident.8 Depending on the severity of a pandemic, suspension or curtailment of international trade and travel could be reasonably likely. Although the World Health Organization has recommended against closing borders or quarantining countries even in the throes of a pandemic, the prospect of this occurring does not seem implausible. In a worst‐case scenario, even the type of national and international chaos envisioned in the Dark Winter smallpox planning exercise might occur.9
Fortress America Versus Containment Strategies
Although the pandemic influenza plan calls for stockpiling antiviral drugs and increasing vaccine production capabilities, the most effective plan for pandemic preparedness may involve a surveillance and containment strategy. No country has enough medicines or vaccines to control a widespread outbreak of pandemic avian influenza. The best solution to prevention of a pandemic is stopping any virus from spreading in the first place. Increased surveillance for avian influenza among poultry and migratory birds in key Asian countries, along with provision of funds to compensate farmers for culling of potentially infected flocks, would align incentives for early detection and eradication. Containing an initial outbreak wherever it occurs is the best defense against a pandemic. Notably, China is thought to be a potential hot zone for emergence of pandemic avian influenza. China is not only the most populous nation in the world but has one quarter of the world's chickens, two thirds of the world's domesticated ducks, and 90% of the world's domesticated geese.
The challenges of biosecurity (protecting humans against animal‐borne diseases such as bird flu) in developing countries include the reality that populations living in close proximity to poultry are also the most illiterate and impoverished, with the most limited access to health care. The recent introduction of H5N1 into Europe has heightened surveillance efforts in the United States. The introduction of H5N1 into the United States may occur through movement of migratory birds and/or importation of exotic birds. The surveillance system has been expanded to include sampling for the influenza virus not only in poultry but also in bodies of water, as the virus is shed in bird feces.
Pandemic Planning
In the setting of a severe pandemic, hospitals will face an enormous burden of patients, with a huge influx of individuals requiring both intensive care unit as well as regular nursing floor care. At the local height of such a pandemic, the ability to successfully discharge every patient whose condition will permit this to the community or elsewhere will be critical, and almost certainly hospitals will need to expand to accept more patients than they are normally configured to hold. Hospitals staffs, particularly nurses and physicians, will be required to handle very large patient censuses. Among medical staffs, emergency physicians, hospitalists, critical care specialists, and infectious disease specialists will certainly be called on to play leading roles, much as they were during and in the aftermath of Hurricane Katrina recently. Despite all of the above, the ability of existing hospitals to accommodate all gravely ill patients may be outstripped, and auxiliary hospitals in schools and other public edifices may need to be established. Hospitalists are likely to be called on to play a major role in such temporary hospitals. The frustration and anguish of not being able to provide a standard level of care to patients (for example, being forced to triage which patients are most deserving of mechanical ventilation) should not be underestimated.
Although characterized by a relatively limited number of patients, the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, Ontario, Canada, presented some of the same challenges that will be encountered in a virulent influenza pandemic. These include the need to quickly and drastically modify the usual emergency department and inpatient procedures, as hospitals initially serve to amplify the epidemic, as well as the additional stressor of health care workers becoming ill as a result of work‐related exposure. That fewer than 400 cases of SARS pushed the medical system of one of North America's largest cities nearly to its breaking point is both sobering and instructive.10, 11 Interested readers are directed to an excellent summary of lessons learned from the SARS outbreak, most of which are widely applicable to preparations for future infectious epidemics.12
Infection Control
Although the CDC and other Web sites currently recommend airborne isolation (respiratory personal protection) for avian influenza in humans, there is not strong epidemiologic evidence of transmission other than via droplets (the transmission mode of human influenza). The emergence of a limited number of cases of avian influenza in the United States would allow employment of airborne isolation measures; but in the event of a larger outbreak, the use of surgical masks and the practice of good hand hygiene would be sufficient by health care workers caring for persons with suspected or proven disease.
The CDC recently released proposed changes to help prevent disease outbreaks from contacts of those exposed to ill persons on airplanes. Proposed guidelines would require airlines to maintain computerized lists of passengers taken at point of departure in order to facilitate tracking of contacts and implementation of quarantine if necessary. These measures are part of pandemic planning and result from problems in tracking passengers on planes with SARS cases. By executive order, imposition of quarantine is limited to 9 diseases: cholera, diphtheria, smallpox, yellow fever, viral hemorrhagic fevers (eg, Ebola), plague, infectious tuberculosis, SARS and influenza caused by new strains with pandemic potential.
What Can Be Done?
Although valuable time has elapsed to prepare for the possibility of an H5N1 influenza pandemic, the US and global communities are presently taking the threat seriously and are engaging in a variety of activities to prepare for such an eventuality. Although currently available influenza vaccines do not provide any appreciable protection against H5N1, significant work is under way to develop an effective vaccine; with Chiron and sanofi pasteur preparing vaccine trials in association with the National Institute of Allergy and Infectious Diseases. Current influenza vaccine production is hampered by use of obsolete egg‐based manufacturing processes requiring 6 months, along with a limited capacity to manufacture adequate vaccine supplies even in many usual influenza seasons. The herculean task of providing hundreds of millions of doses of vaccine as soon as possible after the emergence of a pandemic strain, as daunting as it is, is further complicated by the fact that a successful H5N1 vaccine would not necessarily be effective against a strain that mutated sufficiently to move efficiently from person to person. Nonetheless, even partially solving these problems will pay dividends, whether or not H5N1 proves to be responsible for the next pandemic.
Given these difficulties with vaccine development and production, the backbone of any successful early response to a pandemic in the near future will be development of an adequate stockpile of antiviral medication, accompanied by a successful plan to distribute the drug when and where disease erupts. Despite uncertainties regarding their effectiveness as well as questions regarding optimal dose and duration in the setting of avian influenza, the neuraminidase inhibitors are the current drugs of choice. Of the 2 currently available agents, oseltamivir is the preferred drug for pandemic use, given its oral administration,. Unfortunately, the ability to manufacture the drug in sufficient quantities to stockpile has thus far proved problematic. Roche, the manufacturer of Tamiflu, has recently opened a new manufacturing plant and has stated that it can increase its current production of 55 million doses per year to 300 million doses by 2007. We do not recommend a role for personal stockpiling of neuraminidase inhibitors. Concerns include a shortage of the drug for seasonal influenza, absence of a pandemic at present, ignorance regarding the efficacy and optimal dose for H5N1, inappropriate use by individuals, and inequitable distribution. Recent case reports of oseltamivir resistance emerging during prophylaxis13 and treatment14 are of potential concern but do not alter current recommendations.
What can be done locally and specifically, and what can hospitalists do to prepare? First, although we are not sure that Dr Michael Osterholm's goal that planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor8 is entirely realistic, every hospital clearly needs to include pandemic influenza as a significant part of its disaster preparedness plan. Such planning will have broad overlap with planning for other potential disasters, including bioterrorist attacks, SARS outbreaks, and others. Hospitals must develop a plan for surge capacity, and such a plan should include not only coordination with other local hospitals, but also planning with local communities to identify sites where temporary flu hospitals can be established. Within hospital medicine groups, emergency staffing plans should be established before pandemic influenza (or another disaster) strikes. Such staffing plans need to include the ability to care for a much higher than normal number of patients for an extended period. Conceivably, a large number of patients will need to be manually ventilated for prolonged periods, which of course will tax the resources of any institution. Prompt discharge of all patients stable enough to leave the hospital will be critical, and given the investment of most hospital medicine groups in hospital throughput issues under normal conditions, much of the responsibility for helping to create beds during a crisis will inevitably fall on the shoulders of hospitalists.
Experiences during and shortly after Hurricane Katrina served to underscore that issues such as physical and mental fatigue, concern for the safety of family members, lack of supplies, communication difficulties, and absenteeism all add additional layers of complexity to the task of providing hospital care under extraordinary conditions such as during a natural disaster. These lessons can and should be extended to a major epidemic. This disaster also showed the importance of military involvement in the response to disasters that exceed local and state capabilities. The primary objective of the federal government in responding to disaster is to maintain security and essential services while preventing chaos. A pandemic of virulent influenza will raise the stakes still further, as physicians and nurses become casualties themselves. Despite these challenges, we are confident that the vast majority of hospitalists and other health care workers will rise to the occasion, and just as during the peri‐Katrina period, stories of selflessness and heroism will be de rigueur. Appropriate advance planning on all levels will serve to reduce the morbidity and mortality associated with the next pandemic and will help to ensure that health care workers do not sacrifice needlessly.0
1. World Health Organization (WHO) Website: |
2. Centers for Disease Control and Prevention (CDC): |
3. U.S. Government Avian Influenza Website: |
4. U.S. Department of Health and Human Services Pandemic Influenza Plan: |
5. Infectious Diseases Society of America (IDSA) Website: |
- The Great Influenza.New York, NY:Viking Penguin,2004. .
- Characterization of the 1918 influenza virus polymerase genes.Nature.2005;437:889–893. , , , , , .
- Characterization of the reconstructed 1918 Spanish influenza pandemic virus.Science.2005;310:77–80. , , , et al.
- WHO Epidemic and Pandemic Alert and Response. Confirmed cases of avian influenza A (H5N1). Available at http://www.who.int/csr/disease/avian_influenza/country/en/index.html. Accessed on February 28,2006.
- Writing Committee of the WHO Consultation on Human Influenza A/H5.Avian influenza A (H5N1) infection in humans.N Engl J Med.2005;353:1374–1385.
- Probable person‐to‐person transmission of avian influenza A (H5N1).N Engl J Med.2005;352:333–40. , , , et al.
- Family clustering of avian influenza A (H5N1).EID.2005;11:1799–1801. , , , et al.
- Preparing for the next pandemic.N Engl J Med.2005;352:1839–1842. .
- Center for Biosecurity. Dark Winter overview. Available at http://www.upmc‐biosecurity.org/pages/events/dark_winter/dark_winter.html. Accessed November 28,2005.
- SARS outbreak in the Greater Toronto Area: the emergency department experience.CMAJ.2004;171:1342–1344. , , , et al.
- Severe acute respiratory syndrome and critical care medicine: The Toronto experience.Crit Care Med.2005;33(suppl):S53–S60. , .
- Learning from SARS in Hong Kong and Toronto.JAMA.2004;291:2483–2487. , , .
- Avian flu: Isolation of drug‐resistant H5N1 virus.Nature.2005;438:754. , , , et al.
- Oseltamivir resistance during treatment of influenza A (H5N1) infection.N Engl J Med.2005;353:2667–2672. , , , et al.
- The Great Influenza.New York, NY:Viking Penguin,2004. .
- Characterization of the 1918 influenza virus polymerase genes.Nature.2005;437:889–893. , , , , , .
- Characterization of the reconstructed 1918 Spanish influenza pandemic virus.Science.2005;310:77–80. , , , et al.
- WHO Epidemic and Pandemic Alert and Response. Confirmed cases of avian influenza A (H5N1). Available at http://www.who.int/csr/disease/avian_influenza/country/en/index.html. Accessed on February 28,2006.
- Writing Committee of the WHO Consultation on Human Influenza A/H5.Avian influenza A (H5N1) infection in humans.N Engl J Med.2005;353:1374–1385.
- Probable person‐to‐person transmission of avian influenza A (H5N1).N Engl J Med.2005;352:333–40. , , , et al.
- Family clustering of avian influenza A (H5N1).EID.2005;11:1799–1801. , , , et al.
- Preparing for the next pandemic.N Engl J Med.2005;352:1839–1842. .
- Center for Biosecurity. Dark Winter overview. Available at http://www.upmc‐biosecurity.org/pages/events/dark_winter/dark_winter.html. Accessed November 28,2005.
- SARS outbreak in the Greater Toronto Area: the emergency department experience.CMAJ.2004;171:1342–1344. , , , et al.
- Severe acute respiratory syndrome and critical care medicine: The Toronto experience.Crit Care Med.2005;33(suppl):S53–S60. , .
- Learning from SARS in Hong Kong and Toronto.JAMA.2004;291:2483–2487. , , .
- Avian flu: Isolation of drug‐resistant H5N1 virus.Nature.2005;438:754. , , , et al.
- Oseltamivir resistance during treatment of influenza A (H5N1) infection.N Engl J Med.2005;353:2667–2672. , , , et al.
Care of Hospitalized Older Patients
An emergency room resident once was instructing a medical student in how to place a nasogastric tube in order to evaluate a patient with melena and postural hypotension. When the tube came to a stop, the student connected a syringe to the tube and aspirated. Then, to the consternation of the resident, the student yanked out the tube as soon as he saw blood flowing into the syringe. Why'd you do that? the surprised resident asked. There's blood down there! came the quick reply.
Like that medical student, hospital‐based physicianshospitalists, geriatricians, and othersmay miss the boat when caring for hospitalized older patients. Hospitals are full, and they're filled largely with older patients. These patients, like those who are younger, generally want to be treated and sent home. Older patients, however, frequently pose specific challenges. They may talk and move more slowly, stay longer, and be more likely to die. They more often need help in caring for themselves, and many have lost the support necessary to remain at home, making it difficult for them to return there. In short, older patients often need more care and more time.
It may be tempting to ignore the challenges that arise in caring for older patients. An avoidance strategy is expedient, at least in the short term. Ultimately, however, ignoring the challenges of caring for older patients will prove no wiser than yanking the nasogastric tube. Instead, we can recognize the challenges and use this opportunity to learn to improve their care.
This article describes the state of the science in hospital care for older patients, opportunities awaiting those who care for these patients, and barriers to seizing those opportunities. I conclude with five recommendations for physicians who care for hospitalized older patients.
STATE OF THE SCIENCE
Older patients shape hospital medicine and will determine its future. In 2002 the 12% of the population age 65 years or older accounted for roughly 50% of all hospitalizations unrelated to childbirth.1, 2 Hospital admissions of older persons will balloon as the number of persons older than age 65 rises by a million a year, increasing from 13% of the population today to 21% by 2030.2
Older persons in hospitals pose substantial clinical challenges. Many have multiple comorbid diseases and virtually all have complex medical regimens.1, 35 Many have cognitive impairment or dementia, often accompanied by delirium, which hinder communication and can lead to behaviors that require extra attention and impede diagnostic tests and treatment.611 Some have difficulty walking and caring for themselves, and a third leave the hospital without having recovered to their baseline level of function, with those age 85 years or older at highest risk for this decline independent of the reason for admission.1215 These characteristics increase the care, resources, and staff time older patients need, prolong their stays, and increase their hospital costs beyond those expected for their diagnosis.16 They also are at higher risk for iatrogenic complications, death, and rehospitalization,1720 and the risk of errors may be increased by frequent transitions in providers and sites of care.2125 Older persons require greater assistance at home, and yet they have often lost much of the support needed to live at home.10, 13, 20
Despite the magnitude of these challenges, we know surprisingly little about how best to care for hospitalized older persons, especially those older than age 75. The evidence base for treatment of specific common diseases is inadequate. The very old are underrepresented in clinical trials,26, 27 and the majority of older patients with common conditions such as heart failure may not meet the enrollment criteria for clinical trials.28 Thus, what is known about treating diseases in younger patients may be extrapolated to determine treatments in older persons based only on a leap of faith, which may be misguided.29, 30 In fact, the efficacy of conventional treatments for common conditions (e.g., acute myocardial infarction and hypertension) may diminish with age,31, 32 indicating that clinical trials targeted specifically to older patients may be necessary.
Despite the dearth of evidence about the management of common diseases in hospitalized older patients, hospital‐based geriatricians have developed substantial high‐grade evidence about the prevention of two geriatric syndromes, functional disability and delirium. The incidence of both syndromes can be reduced (without increasing hospital or health care costs) by multicomponent interventions that include comprehensive assessment, targeted treatment, and environmental modification to promote independence and safety.3, 3335 Moreover, the randomized trials that evaluated these interventions have provided models for how other innovations by hospital‐based physicians can be evaluated. Despite the evidence that these approaches are effective and either cost saving or cost neutral, these models have not been widely adopted.36
Many challenges in the prevention and management of geriatric syndromes in the hospital remain. For example, sophisticated approaches to the management of delirium are disappointingonce delirium has developed, intensive state‐of‐the‐art approaches to its management are no more effective than standard care in shortening its duration or ameliorating its sequelae.37, 38 The indiscriminate use of indwelling urinary catheters is decried, but there is no evidence that their use is declining, even in patients without an indication for catheterization.3942 Malnutrition and falls can be prevented and depression treated in patients outside the hospital,4345 but it is unclear whether these maladies can be prevented or treated effectively in hospitalized elders. Finally, intriguing evidence suggests that geriatric syndromes and their sequelae may be prevented and outcomes improved by caring for patients at home whenever possible, bringing intensive nursing and physician care into the home without some of the adverse effects of hospitalization.46
The physician workforce is not prepared to provide optimal care to hospitalized older persons. Few hospitalists or other hospital‐based physicians have received more than minimal training in geriatric medicine, and few geriatricians practice extensively in the hospital. At the same time that the ranks of physicians who consider themselves hospitalists have been expanding by 1000 or more a year in the United States, the number of certified geriatricians has been decreasing as hundreds decide each year not to renew their certificates.47, 48 Fewer than 300 geriatricians complete training each year and enter the workforce, and most new geriatricians practice in ambulatory or long‐term‐care settings. Wald's study in this issue indicates the paucity of geriatricians in hospital medicine (with the apparently single exception of the Mayo Clinic's Hospital Internal Medicine Group) and a relative lack of interest among hospitalists in developing knowledge about the effective and efficient treatment of older persons, in particular.49
OPPORTUNITIES
Opportunities to improve the care of hospitalized older patients arise from the state of the science in their care and from the common ground that hospitalists and geriatricians share. The older patients of both hospitalists and geriatricians are seriously ill, with annual mortality rates of 20%30% for patients with common conditions such as myocardial infarction or colon cancer and mortality rates of 50% or higher for patients with dementia or severe disability.5, 5053 We should view the care of our patients in the context of their prognoses,5, 54 recognizing that patients' preferences for the goals, style, and site of care vary widely.55, 56 The substantial association of mortality with geriatric syndromes such as disability, dementia, delirium, and depressionan association that is independent of pathophysiologic indicators of disease severitysuggests that substantial benefits may accrue by targeting interventions to the prevention or amelioration of these syndromes.5, 9, 10, 53, 57, 58
Hospitalists and geriatricians also share the perspective of working in complex systems in which the effectiveness, efficiency, and safety of care depend on system functions as well as on their technical expertise as individuals.5961 Together, and with colleagues in other disciplines, they may redesign how hospitals and the systems around them work to reduce errors, increase attention to aspects of care that are easily overlooked, and improve patient outcomes.
BARRIERS
Hospitalists and geriatricians face barriers to improving care for hospitalized older patients. First, gaps in knowledge limit the capacity to provide the care and achieve the outcomes desired. Fundamental discoveries in clinical science are needed to prevent or treat geriatric syndromes, to treat common diseases in the very old, and to put into practice what is known. Addressing these gaps in knowledge will require a sustained effort that spans methods and disciplines.
Second, the dominant reductionist paradigm values discovery of the mechanism of disease over discovery of ways to manage illness effectively and efficiently.6267 Similarly, diagnostic tests and therapies based on beliefs about the mechanism of diseasefor example, PET scans in persons with memory disorders and chemotherapy in persons with refractory cancersare pursued aggressively and paid handsomely, whereas efforts to reduce errors or improve continuity of care receive little attention or reward. The challenges of caring for hospitalized older patients will require advances on both fronts: in our knowledge of the pathogenesis of disorders that have proven resistant to current therapies (such as delirium) and in our knowledge of how to structure clinical care that engages patients and families and achieves desired outcomes effectively, consistently, and efficiently.
The structure and styles of our practices provide the third challenge. Hospitalists pride themselves on their efficient management of patients while maintaining or improving patient outcomes. A focus on efficient management can, however, lead to an assembly‐line approach, turning each patient into a series of do‐order‐call‐check tasks to get the patient out of the hospital as quickly as possible. This approach has advantages but may also blind physicians to the scope and complexity of issues that arise in caring for the very old through the course of an illness that often extends beyond hospitalization.25 Geriatricians pride themselves on their comprehensive management of patients, gathering clinical information from many sources (especially in the many patients with cognitive impairment), exploring and articulating goals of care, and assessing self‐care and neurologic, psychological, and social domains in addition to conventional pathophysiology. Yet too often, geriatricians are not available in hospitals, and as Wald found, they have rarely been integrated into hospitalist groups.
FIVE RECOMMENDATIONS FOR HOSPITALISTS AND GERIATRICIANS
I conclude with five recommendations for hospital‐based physicians who care for older patients and for geriatricians. First, step back, look at your patients, and note their predicament in its full complexity. Once hospitalists start looking for cognitive impairment, weakness, and difficulty walking and the difficulty of finding a good situation after leaving the hospital, it will be easy to see these problems. And once geriatricians start looking at why their patients are going into the hospital and what happens to them, it will be easy to see the need to become engaged. Seeing the full range of patients' problems won't address them, but we certainly won't address them if we don't look.
Second, learn what is known about how best to care for the aged and integrate this learning into your hospital practice. For hospitalists, learning how to identify each patient's goals of care, what works to prevent delirium and promote mobility, which drugs to avoid and which doses to modify, and how to access resources to help patients and families achieve their goals after they leave the hospital will benefit older patients. Pocket and PDA resources to extend learning are readily available.68 For geriatricians, learning how to avoid hospitalization (especially when resources can be mobilized to provide a hospital at home), how to work within the timeframe of hospitalization, and what current disease‐specific management strategies have been shown to be effective in the aged will benefit their patients. Maintaining the distinction between what is believed and what is known on the basis of high‐quality evidence will enhance learning and decrease the risk of stubbornly pursuing harmful or wasteful practices. This is especially important in situations where the evidence is weak and opinions are strong.
Third, to provide the best care for our older patients, we must embrace aging, not deny it. Most hospitalized older patients, and most patients of geriatricians, will decline and die in a few years. The inevitability of these outcomes may tempt us either to abandon our incurable patients or to focus single‐mindedly on treatable problems one at a time, rather than on the interplay of multiple problems in an individual person. Either choice is mistaken. Although we are powerless to prevent decline and death in the long run, we have a tremendous capacity to delay and ameliorate decline, to enhance comfort and joy, to protect from harm, and, often, to delay death.
Fourth, ask questions about what you do not know or understand. The risk, of course, is that your curiosity will be sparked, possibly slowing you in completing the myriad tasks to be donea risk worth taking. Will ACE inhibitors and beta‐blockers benefit patients with heart failure without systolic dysfunction? Why do so many older patients become delirious, and are features of hospitalization catalyzing the effects of disease in causing delirium? Why do we continue to send cognitively impaired patients home without scheduled follow‐up and with instruction sheets they cannot read, and how can we change the system to prevent this? If you cannot find answers to your questions grounded in strong evidence, maintain your skepticism about answers given easily.
Finally, consider discovering the answers to some of your questions. Part of the excitement of caring for the very old is that we have so much to learn and that what we do learn can be so powerful.
- Hospitalization in the United States, 2002. Publication 05‐056.Washington (DC):AHRQ,2005. , .
- Improving health care for older persons.Ann Intern Med.2003;139:421–424. .
- A controlled trial of inpatient and outpatient geriatric evaluation and management.N Engl J Med.2002;346:905–912. , , , et al.
- Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled.JAMA.1997;277:728–734. , , , et al.
- Development and validation of a prognostic index for 1‐year mortality in older adults after hospitalization.JAMA.2001;285:2987–2994. , , , et al.
- Delirium is independently associated with poor functional recovery after hip fracture.J Am Geriatr Soc.2000;48:618–624. , , , .
- The course of delirium in older medical inpatients: a prospective study.J Gen Intern Med.2003;18:696–704. , , , et al.
- Does delirium increase hospital stay?J Am Geriatr Soc.2003;51:1539–1546. , , , .
- Does delirium contribute to poor hospital outcomes? A three‐site epidemiologic study.J Gen Intern Med.1998;13:234–242. , , , et al.
- A predictive index for functional decline in hospitalized elderly medical patients.J Gen Intern Med.1993;8:645–652. , , , et al.
- A prospective study of delirium in hospitalized elderly.JAMA.1990;263:1097–1101. , , .
- Unsteadiness reported by older hospitalized patients predicts functional decline.J Am Geriatr Soc.2003;51:621–626. , , , et al.
- Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age.J Am Geriatr Soc.2003;51:451–458. , , , et al.
- Functional outcomes of acute medical illness and hospitalization in older persons.Arch Intern Med.1996;156:645–652. , , , et al.
- Functional disability in the hospitalized elderly.JAMA.1982;248:847–850. , , , et al.
- Diagnosis‐related group‐adjusted hospital costs are higher in older medical patients with lower functional status.J Am Geriatr Soc.2003;51:1729–1734. , , , et al.
- Adverse events, negligence in hospitalized patients: results from the Harvard Medical Practice Study.Perspect Healthc Risk Manage.1991;11(2):2–8. , .
- Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I.N Engl J Med.1991;324:370–376. , , , et al.
- The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II.N Engl J Med.1991;324:377–384. , , , et al.
- Effects of functional status changes before and during hospitalization on nursing home admission of older adults.J Gerontol A Biol Sci Med Sci.1999;54:M521–M526. , , , .
- Characterization of geriatric drug‐related hospital readmissions.Med Care.1991;29:989–1003. , , .
- The impact of clinical pharmacists' consultations on physicians' geriatric drug prescribing. A randomized controlled trial.Med Care.1992;30:646–658. , , , .
- Posthospital medication discrepancies: prevalence and contributing factors.Arch Intern Med.2005;165:1842–1847. , , , .
- A new tool for identifying discrepancies in postacute medications for community‐dwelling older adults.Am J Geriatr Pharmacother.2004;2(2):141–147. , , .
- Lost in transition: challenges and opportunities for improving the quality of transitional care.Ann Intern Med.2004;141:533–536. , .
- Enrollment of older persons in cancer trials after the medicare reimbursement policy change.Arch Intern Med.2005;165:1514–1520. , , , et al.
- Underrepresentation of patients 65 years of age or older in cancer‐treatment trials.N Engl J Med.1999;341:2061–2067. , , , et al.
- Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure.Am Heart J.2003;146(2):250–257. , , , et al.
- Problems in the “evidence” of “evidence‐based medicine.”Am J Med.1997;103:529–535. , .
- National initiatives in ageing research in the United Kingdom.Age Ageing.2002;31(2):93–95. .
- Embracing complexity: A consideration of hypertension in the very old.J Gerontol A Biol Sci Med Sci.2003;58:653–658. .
- Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years.Circulation.2000;101:2239–2246. , , , et al.
- A randomized trial of care in a hospital medical unit especially designed to improve the functional outcomes of acutely ill older patients.N Engl J Med.1995;332:1338–1344. , , , et al.
- A multicomponent intervention to prevent delirium in hospitalized older patients.N Engl J Med.1999;340:669–676. , , , et al.
- Reducing delirium after hip fracture: a randomized trial.J Am Geriatr Soc.2001;49:516–522. , , , .
- Dissemination and characteristics of acute care for elders (ACE) units in the United States.Int J Technol Assess Health Care.2003;19(1):220–227. , , , .
- Treatment of delirium in older medical inpatients: a challenge for geriatric specialists.J Am Geriatr Soc.2002;50:2101–2103. , .
- Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial.CMAJ.2002;167:753–759. , , , et al.
- Clinical and economic consequences of nosocomial catheter‐related bacteriuria.Am J Infect Control.2000;28(1):68–75. .
- Preventing catheter‐related bacteriuria: should we? Can we? How?Arch Intern Med.1999;159:800–808. , .
- Indwelling urinary catheters: a one‐point restraint?Ann Intern Med.2002;137(2):125–127. , , .
- Risk factors for indwelling urinary catheterization among older hospitalized patients without a specific medical indication for catheterization.J Patient Saf.2005. In press. , , et al.
- Protein and energy supplementation in elderly people at risk from malnutrition.Cochrane Database Syst Rev.2005(2):CD003288. , , .
- Clinical practice. Preventing falls in elderly persons.N Engl J Med.2003;348(1):42–49. .
- Collaborative care management of late‐life depression in the primary care setting: a randomized controlled trial.JAMA.2002;288:2836–2845. , , , et al.
- Hospital in the home: a randomised controlled trial.Med J Aust.1999;170(4):156–160. , , , , , .
- Hospitalists in the United States—mission accomplished or work in progress?N Engl J Med.2004;350:1935–1936. .
- Academic geriatric programs in US allopathic and osteopathic medical schools.JAMA.2002;288:2313–2319. , , , .
- Is there a geriatrician in the house? Geriatric care approaches in hospitalist programs.J Hosp Med.2006;1:29–35. , , .
- The implications of regional variations in Medicare spending. Part 1: the content, quality, and accessibility of care.Ann Intern Med.2003;138:273–287. , , , et al.
- The implications of regional variations in Medicare spending. Part 2: health outcomes and satisfaction with care.Ann Intern Med.2003;138:288–298. , , , et al.
- Mortality from pneumonia and hip fractures in patients with advanced dementia.JAMA.2000;284:2447–2448. , .
- Survival in end‐stage dementia following acute illness.JAMA.2000;284(1):47–52. , .
- Cancer screening in elderly patients: a framework for individualized decision making.JAMA.2001;285:2750–2756. , .
- Understanding the treatment preferences of seriously ill patients.N Engl J Med.2002;346:1061–1066. , , , .
- Health values of hospitalized patients 80 years or older. HELP Investigators. Hospitalized Elderly Longitudinal Project.JAMA.1998;279:371–375. , , , et al.
- Depressive symptoms and 3‐year mortality in older hospitalized medical patients.Ann Intern Med.1999;130:563–569. , , , et al.
- Relation between symptoms of depression and health status outcomes in acutely ill hospitalized older persons.Ann Intern Med.1997;126:417–425. , , , et al.
- Five system barriers to achieving ultrasafe health care.Ann Intern Med.2005;142:756–764. , , , .
- Specialized care for elderly patients.N Engl J Med.2002;346:874. .
- The end of the beginning: patient safety five years after ‘To Err Is Human.’Health Aff (Millwood).2004;Suppl Web Exclusives:W4–534–545. .
- An additional basic science for clinical medicine: II. The limitations of randomized trials.Ann Intern Med.1983;99:544–550. .
- An additional basic science for clinical medicine: III. The challenges of comparison and measurement.Ann Intern Med.1983;99:705–712. .
- An additional basic science for clinical medicine: IV. The development of clinimetrics.Ann Intern Med.1983;99:843–848. .
- An additional basic science for clinical medicine: I. The constraining fundamental paradigms.Ann Intern Med.1983;99:393–397. .
- The end of the disease era.Am J Med.2004;116(3):179–185. , .
- , Agostini JV. Potential pitfalls of disease‐specific guidelines for patients with multiple conditions.N Engl J Med.2004;351:2870–2874. ,
- Geriatrics at your fingertips: 2005.7th ed.Malden (MA):Blackwell Publishing, for the American Geriatrics Society,2005. , , , et al.
An emergency room resident once was instructing a medical student in how to place a nasogastric tube in order to evaluate a patient with melena and postural hypotension. When the tube came to a stop, the student connected a syringe to the tube and aspirated. Then, to the consternation of the resident, the student yanked out the tube as soon as he saw blood flowing into the syringe. Why'd you do that? the surprised resident asked. There's blood down there! came the quick reply.
Like that medical student, hospital‐based physicianshospitalists, geriatricians, and othersmay miss the boat when caring for hospitalized older patients. Hospitals are full, and they're filled largely with older patients. These patients, like those who are younger, generally want to be treated and sent home. Older patients, however, frequently pose specific challenges. They may talk and move more slowly, stay longer, and be more likely to die. They more often need help in caring for themselves, and many have lost the support necessary to remain at home, making it difficult for them to return there. In short, older patients often need more care and more time.
It may be tempting to ignore the challenges that arise in caring for older patients. An avoidance strategy is expedient, at least in the short term. Ultimately, however, ignoring the challenges of caring for older patients will prove no wiser than yanking the nasogastric tube. Instead, we can recognize the challenges and use this opportunity to learn to improve their care.
This article describes the state of the science in hospital care for older patients, opportunities awaiting those who care for these patients, and barriers to seizing those opportunities. I conclude with five recommendations for physicians who care for hospitalized older patients.
STATE OF THE SCIENCE
Older patients shape hospital medicine and will determine its future. In 2002 the 12% of the population age 65 years or older accounted for roughly 50% of all hospitalizations unrelated to childbirth.1, 2 Hospital admissions of older persons will balloon as the number of persons older than age 65 rises by a million a year, increasing from 13% of the population today to 21% by 2030.2
Older persons in hospitals pose substantial clinical challenges. Many have multiple comorbid diseases and virtually all have complex medical regimens.1, 35 Many have cognitive impairment or dementia, often accompanied by delirium, which hinder communication and can lead to behaviors that require extra attention and impede diagnostic tests and treatment.611 Some have difficulty walking and caring for themselves, and a third leave the hospital without having recovered to their baseline level of function, with those age 85 years or older at highest risk for this decline independent of the reason for admission.1215 These characteristics increase the care, resources, and staff time older patients need, prolong their stays, and increase their hospital costs beyond those expected for their diagnosis.16 They also are at higher risk for iatrogenic complications, death, and rehospitalization,1720 and the risk of errors may be increased by frequent transitions in providers and sites of care.2125 Older persons require greater assistance at home, and yet they have often lost much of the support needed to live at home.10, 13, 20
Despite the magnitude of these challenges, we know surprisingly little about how best to care for hospitalized older persons, especially those older than age 75. The evidence base for treatment of specific common diseases is inadequate. The very old are underrepresented in clinical trials,26, 27 and the majority of older patients with common conditions such as heart failure may not meet the enrollment criteria for clinical trials.28 Thus, what is known about treating diseases in younger patients may be extrapolated to determine treatments in older persons based only on a leap of faith, which may be misguided.29, 30 In fact, the efficacy of conventional treatments for common conditions (e.g., acute myocardial infarction and hypertension) may diminish with age,31, 32 indicating that clinical trials targeted specifically to older patients may be necessary.
Despite the dearth of evidence about the management of common diseases in hospitalized older patients, hospital‐based geriatricians have developed substantial high‐grade evidence about the prevention of two geriatric syndromes, functional disability and delirium. The incidence of both syndromes can be reduced (without increasing hospital or health care costs) by multicomponent interventions that include comprehensive assessment, targeted treatment, and environmental modification to promote independence and safety.3, 3335 Moreover, the randomized trials that evaluated these interventions have provided models for how other innovations by hospital‐based physicians can be evaluated. Despite the evidence that these approaches are effective and either cost saving or cost neutral, these models have not been widely adopted.36
Many challenges in the prevention and management of geriatric syndromes in the hospital remain. For example, sophisticated approaches to the management of delirium are disappointingonce delirium has developed, intensive state‐of‐the‐art approaches to its management are no more effective than standard care in shortening its duration or ameliorating its sequelae.37, 38 The indiscriminate use of indwelling urinary catheters is decried, but there is no evidence that their use is declining, even in patients without an indication for catheterization.3942 Malnutrition and falls can be prevented and depression treated in patients outside the hospital,4345 but it is unclear whether these maladies can be prevented or treated effectively in hospitalized elders. Finally, intriguing evidence suggests that geriatric syndromes and their sequelae may be prevented and outcomes improved by caring for patients at home whenever possible, bringing intensive nursing and physician care into the home without some of the adverse effects of hospitalization.46
The physician workforce is not prepared to provide optimal care to hospitalized older persons. Few hospitalists or other hospital‐based physicians have received more than minimal training in geriatric medicine, and few geriatricians practice extensively in the hospital. At the same time that the ranks of physicians who consider themselves hospitalists have been expanding by 1000 or more a year in the United States, the number of certified geriatricians has been decreasing as hundreds decide each year not to renew their certificates.47, 48 Fewer than 300 geriatricians complete training each year and enter the workforce, and most new geriatricians practice in ambulatory or long‐term‐care settings. Wald's study in this issue indicates the paucity of geriatricians in hospital medicine (with the apparently single exception of the Mayo Clinic's Hospital Internal Medicine Group) and a relative lack of interest among hospitalists in developing knowledge about the effective and efficient treatment of older persons, in particular.49
OPPORTUNITIES
Opportunities to improve the care of hospitalized older patients arise from the state of the science in their care and from the common ground that hospitalists and geriatricians share. The older patients of both hospitalists and geriatricians are seriously ill, with annual mortality rates of 20%30% for patients with common conditions such as myocardial infarction or colon cancer and mortality rates of 50% or higher for patients with dementia or severe disability.5, 5053 We should view the care of our patients in the context of their prognoses,5, 54 recognizing that patients' preferences for the goals, style, and site of care vary widely.55, 56 The substantial association of mortality with geriatric syndromes such as disability, dementia, delirium, and depressionan association that is independent of pathophysiologic indicators of disease severitysuggests that substantial benefits may accrue by targeting interventions to the prevention or amelioration of these syndromes.5, 9, 10, 53, 57, 58
Hospitalists and geriatricians also share the perspective of working in complex systems in which the effectiveness, efficiency, and safety of care depend on system functions as well as on their technical expertise as individuals.5961 Together, and with colleagues in other disciplines, they may redesign how hospitals and the systems around them work to reduce errors, increase attention to aspects of care that are easily overlooked, and improve patient outcomes.
BARRIERS
Hospitalists and geriatricians face barriers to improving care for hospitalized older patients. First, gaps in knowledge limit the capacity to provide the care and achieve the outcomes desired. Fundamental discoveries in clinical science are needed to prevent or treat geriatric syndromes, to treat common diseases in the very old, and to put into practice what is known. Addressing these gaps in knowledge will require a sustained effort that spans methods and disciplines.
Second, the dominant reductionist paradigm values discovery of the mechanism of disease over discovery of ways to manage illness effectively and efficiently.6267 Similarly, diagnostic tests and therapies based on beliefs about the mechanism of diseasefor example, PET scans in persons with memory disorders and chemotherapy in persons with refractory cancersare pursued aggressively and paid handsomely, whereas efforts to reduce errors or improve continuity of care receive little attention or reward. The challenges of caring for hospitalized older patients will require advances on both fronts: in our knowledge of the pathogenesis of disorders that have proven resistant to current therapies (such as delirium) and in our knowledge of how to structure clinical care that engages patients and families and achieves desired outcomes effectively, consistently, and efficiently.
The structure and styles of our practices provide the third challenge. Hospitalists pride themselves on their efficient management of patients while maintaining or improving patient outcomes. A focus on efficient management can, however, lead to an assembly‐line approach, turning each patient into a series of do‐order‐call‐check tasks to get the patient out of the hospital as quickly as possible. This approach has advantages but may also blind physicians to the scope and complexity of issues that arise in caring for the very old through the course of an illness that often extends beyond hospitalization.25 Geriatricians pride themselves on their comprehensive management of patients, gathering clinical information from many sources (especially in the many patients with cognitive impairment), exploring and articulating goals of care, and assessing self‐care and neurologic, psychological, and social domains in addition to conventional pathophysiology. Yet too often, geriatricians are not available in hospitals, and as Wald found, they have rarely been integrated into hospitalist groups.
FIVE RECOMMENDATIONS FOR HOSPITALISTS AND GERIATRICIANS
I conclude with five recommendations for hospital‐based physicians who care for older patients and for geriatricians. First, step back, look at your patients, and note their predicament in its full complexity. Once hospitalists start looking for cognitive impairment, weakness, and difficulty walking and the difficulty of finding a good situation after leaving the hospital, it will be easy to see these problems. And once geriatricians start looking at why their patients are going into the hospital and what happens to them, it will be easy to see the need to become engaged. Seeing the full range of patients' problems won't address them, but we certainly won't address them if we don't look.
Second, learn what is known about how best to care for the aged and integrate this learning into your hospital practice. For hospitalists, learning how to identify each patient's goals of care, what works to prevent delirium and promote mobility, which drugs to avoid and which doses to modify, and how to access resources to help patients and families achieve their goals after they leave the hospital will benefit older patients. Pocket and PDA resources to extend learning are readily available.68 For geriatricians, learning how to avoid hospitalization (especially when resources can be mobilized to provide a hospital at home), how to work within the timeframe of hospitalization, and what current disease‐specific management strategies have been shown to be effective in the aged will benefit their patients. Maintaining the distinction between what is believed and what is known on the basis of high‐quality evidence will enhance learning and decrease the risk of stubbornly pursuing harmful or wasteful practices. This is especially important in situations where the evidence is weak and opinions are strong.
Third, to provide the best care for our older patients, we must embrace aging, not deny it. Most hospitalized older patients, and most patients of geriatricians, will decline and die in a few years. The inevitability of these outcomes may tempt us either to abandon our incurable patients or to focus single‐mindedly on treatable problems one at a time, rather than on the interplay of multiple problems in an individual person. Either choice is mistaken. Although we are powerless to prevent decline and death in the long run, we have a tremendous capacity to delay and ameliorate decline, to enhance comfort and joy, to protect from harm, and, often, to delay death.
Fourth, ask questions about what you do not know or understand. The risk, of course, is that your curiosity will be sparked, possibly slowing you in completing the myriad tasks to be donea risk worth taking. Will ACE inhibitors and beta‐blockers benefit patients with heart failure without systolic dysfunction? Why do so many older patients become delirious, and are features of hospitalization catalyzing the effects of disease in causing delirium? Why do we continue to send cognitively impaired patients home without scheduled follow‐up and with instruction sheets they cannot read, and how can we change the system to prevent this? If you cannot find answers to your questions grounded in strong evidence, maintain your skepticism about answers given easily.
Finally, consider discovering the answers to some of your questions. Part of the excitement of caring for the very old is that we have so much to learn and that what we do learn can be so powerful.
An emergency room resident once was instructing a medical student in how to place a nasogastric tube in order to evaluate a patient with melena and postural hypotension. When the tube came to a stop, the student connected a syringe to the tube and aspirated. Then, to the consternation of the resident, the student yanked out the tube as soon as he saw blood flowing into the syringe. Why'd you do that? the surprised resident asked. There's blood down there! came the quick reply.
Like that medical student, hospital‐based physicianshospitalists, geriatricians, and othersmay miss the boat when caring for hospitalized older patients. Hospitals are full, and they're filled largely with older patients. These patients, like those who are younger, generally want to be treated and sent home. Older patients, however, frequently pose specific challenges. They may talk and move more slowly, stay longer, and be more likely to die. They more often need help in caring for themselves, and many have lost the support necessary to remain at home, making it difficult for them to return there. In short, older patients often need more care and more time.
It may be tempting to ignore the challenges that arise in caring for older patients. An avoidance strategy is expedient, at least in the short term. Ultimately, however, ignoring the challenges of caring for older patients will prove no wiser than yanking the nasogastric tube. Instead, we can recognize the challenges and use this opportunity to learn to improve their care.
This article describes the state of the science in hospital care for older patients, opportunities awaiting those who care for these patients, and barriers to seizing those opportunities. I conclude with five recommendations for physicians who care for hospitalized older patients.
STATE OF THE SCIENCE
Older patients shape hospital medicine and will determine its future. In 2002 the 12% of the population age 65 years or older accounted for roughly 50% of all hospitalizations unrelated to childbirth.1, 2 Hospital admissions of older persons will balloon as the number of persons older than age 65 rises by a million a year, increasing from 13% of the population today to 21% by 2030.2
Older persons in hospitals pose substantial clinical challenges. Many have multiple comorbid diseases and virtually all have complex medical regimens.1, 35 Many have cognitive impairment or dementia, often accompanied by delirium, which hinder communication and can lead to behaviors that require extra attention and impede diagnostic tests and treatment.611 Some have difficulty walking and caring for themselves, and a third leave the hospital without having recovered to their baseline level of function, with those age 85 years or older at highest risk for this decline independent of the reason for admission.1215 These characteristics increase the care, resources, and staff time older patients need, prolong their stays, and increase their hospital costs beyond those expected for their diagnosis.16 They also are at higher risk for iatrogenic complications, death, and rehospitalization,1720 and the risk of errors may be increased by frequent transitions in providers and sites of care.2125 Older persons require greater assistance at home, and yet they have often lost much of the support needed to live at home.10, 13, 20
Despite the magnitude of these challenges, we know surprisingly little about how best to care for hospitalized older persons, especially those older than age 75. The evidence base for treatment of specific common diseases is inadequate. The very old are underrepresented in clinical trials,26, 27 and the majority of older patients with common conditions such as heart failure may not meet the enrollment criteria for clinical trials.28 Thus, what is known about treating diseases in younger patients may be extrapolated to determine treatments in older persons based only on a leap of faith, which may be misguided.29, 30 In fact, the efficacy of conventional treatments for common conditions (e.g., acute myocardial infarction and hypertension) may diminish with age,31, 32 indicating that clinical trials targeted specifically to older patients may be necessary.
Despite the dearth of evidence about the management of common diseases in hospitalized older patients, hospital‐based geriatricians have developed substantial high‐grade evidence about the prevention of two geriatric syndromes, functional disability and delirium. The incidence of both syndromes can be reduced (without increasing hospital or health care costs) by multicomponent interventions that include comprehensive assessment, targeted treatment, and environmental modification to promote independence and safety.3, 3335 Moreover, the randomized trials that evaluated these interventions have provided models for how other innovations by hospital‐based physicians can be evaluated. Despite the evidence that these approaches are effective and either cost saving or cost neutral, these models have not been widely adopted.36
Many challenges in the prevention and management of geriatric syndromes in the hospital remain. For example, sophisticated approaches to the management of delirium are disappointingonce delirium has developed, intensive state‐of‐the‐art approaches to its management are no more effective than standard care in shortening its duration or ameliorating its sequelae.37, 38 The indiscriminate use of indwelling urinary catheters is decried, but there is no evidence that their use is declining, even in patients without an indication for catheterization.3942 Malnutrition and falls can be prevented and depression treated in patients outside the hospital,4345 but it is unclear whether these maladies can be prevented or treated effectively in hospitalized elders. Finally, intriguing evidence suggests that geriatric syndromes and their sequelae may be prevented and outcomes improved by caring for patients at home whenever possible, bringing intensive nursing and physician care into the home without some of the adverse effects of hospitalization.46
The physician workforce is not prepared to provide optimal care to hospitalized older persons. Few hospitalists or other hospital‐based physicians have received more than minimal training in geriatric medicine, and few geriatricians practice extensively in the hospital. At the same time that the ranks of physicians who consider themselves hospitalists have been expanding by 1000 or more a year in the United States, the number of certified geriatricians has been decreasing as hundreds decide each year not to renew their certificates.47, 48 Fewer than 300 geriatricians complete training each year and enter the workforce, and most new geriatricians practice in ambulatory or long‐term‐care settings. Wald's study in this issue indicates the paucity of geriatricians in hospital medicine (with the apparently single exception of the Mayo Clinic's Hospital Internal Medicine Group) and a relative lack of interest among hospitalists in developing knowledge about the effective and efficient treatment of older persons, in particular.49
OPPORTUNITIES
Opportunities to improve the care of hospitalized older patients arise from the state of the science in their care and from the common ground that hospitalists and geriatricians share. The older patients of both hospitalists and geriatricians are seriously ill, with annual mortality rates of 20%30% for patients with common conditions such as myocardial infarction or colon cancer and mortality rates of 50% or higher for patients with dementia or severe disability.5, 5053 We should view the care of our patients in the context of their prognoses,5, 54 recognizing that patients' preferences for the goals, style, and site of care vary widely.55, 56 The substantial association of mortality with geriatric syndromes such as disability, dementia, delirium, and depressionan association that is independent of pathophysiologic indicators of disease severitysuggests that substantial benefits may accrue by targeting interventions to the prevention or amelioration of these syndromes.5, 9, 10, 53, 57, 58
Hospitalists and geriatricians also share the perspective of working in complex systems in which the effectiveness, efficiency, and safety of care depend on system functions as well as on their technical expertise as individuals.5961 Together, and with colleagues in other disciplines, they may redesign how hospitals and the systems around them work to reduce errors, increase attention to aspects of care that are easily overlooked, and improve patient outcomes.
BARRIERS
Hospitalists and geriatricians face barriers to improving care for hospitalized older patients. First, gaps in knowledge limit the capacity to provide the care and achieve the outcomes desired. Fundamental discoveries in clinical science are needed to prevent or treat geriatric syndromes, to treat common diseases in the very old, and to put into practice what is known. Addressing these gaps in knowledge will require a sustained effort that spans methods and disciplines.
Second, the dominant reductionist paradigm values discovery of the mechanism of disease over discovery of ways to manage illness effectively and efficiently.6267 Similarly, diagnostic tests and therapies based on beliefs about the mechanism of diseasefor example, PET scans in persons with memory disorders and chemotherapy in persons with refractory cancersare pursued aggressively and paid handsomely, whereas efforts to reduce errors or improve continuity of care receive little attention or reward. The challenges of caring for hospitalized older patients will require advances on both fronts: in our knowledge of the pathogenesis of disorders that have proven resistant to current therapies (such as delirium) and in our knowledge of how to structure clinical care that engages patients and families and achieves desired outcomes effectively, consistently, and efficiently.
The structure and styles of our practices provide the third challenge. Hospitalists pride themselves on their efficient management of patients while maintaining or improving patient outcomes. A focus on efficient management can, however, lead to an assembly‐line approach, turning each patient into a series of do‐order‐call‐check tasks to get the patient out of the hospital as quickly as possible. This approach has advantages but may also blind physicians to the scope and complexity of issues that arise in caring for the very old through the course of an illness that often extends beyond hospitalization.25 Geriatricians pride themselves on their comprehensive management of patients, gathering clinical information from many sources (especially in the many patients with cognitive impairment), exploring and articulating goals of care, and assessing self‐care and neurologic, psychological, and social domains in addition to conventional pathophysiology. Yet too often, geriatricians are not available in hospitals, and as Wald found, they have rarely been integrated into hospitalist groups.
FIVE RECOMMENDATIONS FOR HOSPITALISTS AND GERIATRICIANS
I conclude with five recommendations for hospital‐based physicians who care for older patients and for geriatricians. First, step back, look at your patients, and note their predicament in its full complexity. Once hospitalists start looking for cognitive impairment, weakness, and difficulty walking and the difficulty of finding a good situation after leaving the hospital, it will be easy to see these problems. And once geriatricians start looking at why their patients are going into the hospital and what happens to them, it will be easy to see the need to become engaged. Seeing the full range of patients' problems won't address them, but we certainly won't address them if we don't look.
Second, learn what is known about how best to care for the aged and integrate this learning into your hospital practice. For hospitalists, learning how to identify each patient's goals of care, what works to prevent delirium and promote mobility, which drugs to avoid and which doses to modify, and how to access resources to help patients and families achieve their goals after they leave the hospital will benefit older patients. Pocket and PDA resources to extend learning are readily available.68 For geriatricians, learning how to avoid hospitalization (especially when resources can be mobilized to provide a hospital at home), how to work within the timeframe of hospitalization, and what current disease‐specific management strategies have been shown to be effective in the aged will benefit their patients. Maintaining the distinction between what is believed and what is known on the basis of high‐quality evidence will enhance learning and decrease the risk of stubbornly pursuing harmful or wasteful practices. This is especially important in situations where the evidence is weak and opinions are strong.
Third, to provide the best care for our older patients, we must embrace aging, not deny it. Most hospitalized older patients, and most patients of geriatricians, will decline and die in a few years. The inevitability of these outcomes may tempt us either to abandon our incurable patients or to focus single‐mindedly on treatable problems one at a time, rather than on the interplay of multiple problems in an individual person. Either choice is mistaken. Although we are powerless to prevent decline and death in the long run, we have a tremendous capacity to delay and ameliorate decline, to enhance comfort and joy, to protect from harm, and, often, to delay death.
Fourth, ask questions about what you do not know or understand. The risk, of course, is that your curiosity will be sparked, possibly slowing you in completing the myriad tasks to be donea risk worth taking. Will ACE inhibitors and beta‐blockers benefit patients with heart failure without systolic dysfunction? Why do so many older patients become delirious, and are features of hospitalization catalyzing the effects of disease in causing delirium? Why do we continue to send cognitively impaired patients home without scheduled follow‐up and with instruction sheets they cannot read, and how can we change the system to prevent this? If you cannot find answers to your questions grounded in strong evidence, maintain your skepticism about answers given easily.
Finally, consider discovering the answers to some of your questions. Part of the excitement of caring for the very old is that we have so much to learn and that what we do learn can be so powerful.
- Hospitalization in the United States, 2002. Publication 05‐056.Washington (DC):AHRQ,2005. , .
- Improving health care for older persons.Ann Intern Med.2003;139:421–424. .
- A controlled trial of inpatient and outpatient geriatric evaluation and management.N Engl J Med.2002;346:905–912. , , , et al.
- Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled.JAMA.1997;277:728–734. , , , et al.
- Development and validation of a prognostic index for 1‐year mortality in older adults after hospitalization.JAMA.2001;285:2987–2994. , , , et al.
- Delirium is independently associated with poor functional recovery after hip fracture.J Am Geriatr Soc.2000;48:618–624. , , , .
- The course of delirium in older medical inpatients: a prospective study.J Gen Intern Med.2003;18:696–704. , , , et al.
- Does delirium increase hospital stay?J Am Geriatr Soc.2003;51:1539–1546. , , , .
- Does delirium contribute to poor hospital outcomes? A three‐site epidemiologic study.J Gen Intern Med.1998;13:234–242. , , , et al.
- A predictive index for functional decline in hospitalized elderly medical patients.J Gen Intern Med.1993;8:645–652. , , , et al.
- A prospective study of delirium in hospitalized elderly.JAMA.1990;263:1097–1101. , , .
- Unsteadiness reported by older hospitalized patients predicts functional decline.J Am Geriatr Soc.2003;51:621–626. , , , et al.
- Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age.J Am Geriatr Soc.2003;51:451–458. , , , et al.
- Functional outcomes of acute medical illness and hospitalization in older persons.Arch Intern Med.1996;156:645–652. , , , et al.
- Functional disability in the hospitalized elderly.JAMA.1982;248:847–850. , , , et al.
- Diagnosis‐related group‐adjusted hospital costs are higher in older medical patients with lower functional status.J Am Geriatr Soc.2003;51:1729–1734. , , , et al.
- Adverse events, negligence in hospitalized patients: results from the Harvard Medical Practice Study.Perspect Healthc Risk Manage.1991;11(2):2–8. , .
- Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I.N Engl J Med.1991;324:370–376. , , , et al.
- The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II.N Engl J Med.1991;324:377–384. , , , et al.
- Effects of functional status changes before and during hospitalization on nursing home admission of older adults.J Gerontol A Biol Sci Med Sci.1999;54:M521–M526. , , , .
- Characterization of geriatric drug‐related hospital readmissions.Med Care.1991;29:989–1003. , , .
- The impact of clinical pharmacists' consultations on physicians' geriatric drug prescribing. A randomized controlled trial.Med Care.1992;30:646–658. , , , .
- Posthospital medication discrepancies: prevalence and contributing factors.Arch Intern Med.2005;165:1842–1847. , , , .
- A new tool for identifying discrepancies in postacute medications for community‐dwelling older adults.Am J Geriatr Pharmacother.2004;2(2):141–147. , , .
- Lost in transition: challenges and opportunities for improving the quality of transitional care.Ann Intern Med.2004;141:533–536. , .
- Enrollment of older persons in cancer trials after the medicare reimbursement policy change.Arch Intern Med.2005;165:1514–1520. , , , et al.
- Underrepresentation of patients 65 years of age or older in cancer‐treatment trials.N Engl J Med.1999;341:2061–2067. , , , et al.
- Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure.Am Heart J.2003;146(2):250–257. , , , et al.
- Problems in the “evidence” of “evidence‐based medicine.”Am J Med.1997;103:529–535. , .
- National initiatives in ageing research in the United Kingdom.Age Ageing.2002;31(2):93–95. .
- Embracing complexity: A consideration of hypertension in the very old.J Gerontol A Biol Sci Med Sci.2003;58:653–658. .
- Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years.Circulation.2000;101:2239–2246. , , , et al.
- A randomized trial of care in a hospital medical unit especially designed to improve the functional outcomes of acutely ill older patients.N Engl J Med.1995;332:1338–1344. , , , et al.
- A multicomponent intervention to prevent delirium in hospitalized older patients.N Engl J Med.1999;340:669–676. , , , et al.
- Reducing delirium after hip fracture: a randomized trial.J Am Geriatr Soc.2001;49:516–522. , , , .
- Dissemination and characteristics of acute care for elders (ACE) units in the United States.Int J Technol Assess Health Care.2003;19(1):220–227. , , , .
- Treatment of delirium in older medical inpatients: a challenge for geriatric specialists.J Am Geriatr Soc.2002;50:2101–2103. , .
- Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial.CMAJ.2002;167:753–759. , , , et al.
- Clinical and economic consequences of nosocomial catheter‐related bacteriuria.Am J Infect Control.2000;28(1):68–75. .
- Preventing catheter‐related bacteriuria: should we? Can we? How?Arch Intern Med.1999;159:800–808. , .
- Indwelling urinary catheters: a one‐point restraint?Ann Intern Med.2002;137(2):125–127. , , .
- Risk factors for indwelling urinary catheterization among older hospitalized patients without a specific medical indication for catheterization.J Patient Saf.2005. In press. , , et al.
- Protein and energy supplementation in elderly people at risk from malnutrition.Cochrane Database Syst Rev.2005(2):CD003288. , , .
- Clinical practice. Preventing falls in elderly persons.N Engl J Med.2003;348(1):42–49. .
- Collaborative care management of late‐life depression in the primary care setting: a randomized controlled trial.JAMA.2002;288:2836–2845. , , , et al.
- Hospital in the home: a randomised controlled trial.Med J Aust.1999;170(4):156–160. , , , , , .
- Hospitalists in the United States—mission accomplished or work in progress?N Engl J Med.2004;350:1935–1936. .
- Academic geriatric programs in US allopathic and osteopathic medical schools.JAMA.2002;288:2313–2319. , , , .
- Is there a geriatrician in the house? Geriatric care approaches in hospitalist programs.J Hosp Med.2006;1:29–35. , , .
- The implications of regional variations in Medicare spending. Part 1: the content, quality, and accessibility of care.Ann Intern Med.2003;138:273–287. , , , et al.
- The implications of regional variations in Medicare spending. Part 2: health outcomes and satisfaction with care.Ann Intern Med.2003;138:288–298. , , , et al.
- Mortality from pneumonia and hip fractures in patients with advanced dementia.JAMA.2000;284:2447–2448. , .
- Survival in end‐stage dementia following acute illness.JAMA.2000;284(1):47–52. , .
- Cancer screening in elderly patients: a framework for individualized decision making.JAMA.2001;285:2750–2756. , .
- Understanding the treatment preferences of seriously ill patients.N Engl J Med.2002;346:1061–1066. , , , .
- Health values of hospitalized patients 80 years or older. HELP Investigators. Hospitalized Elderly Longitudinal Project.JAMA.1998;279:371–375. , , , et al.
- Depressive symptoms and 3‐year mortality in older hospitalized medical patients.Ann Intern Med.1999;130:563–569. , , , et al.
- Relation between symptoms of depression and health status outcomes in acutely ill hospitalized older persons.Ann Intern Med.1997;126:417–425. , , , et al.
- Five system barriers to achieving ultrasafe health care.Ann Intern Med.2005;142:756–764. , , , .
- Specialized care for elderly patients.N Engl J Med.2002;346:874. .
- The end of the beginning: patient safety five years after ‘To Err Is Human.’Health Aff (Millwood).2004;Suppl Web Exclusives:W4–534–545. .
- An additional basic science for clinical medicine: II. The limitations of randomized trials.Ann Intern Med.1983;99:544–550. .
- An additional basic science for clinical medicine: III. The challenges of comparison and measurement.Ann Intern Med.1983;99:705–712. .
- An additional basic science for clinical medicine: IV. The development of clinimetrics.Ann Intern Med.1983;99:843–848. .
- An additional basic science for clinical medicine: I. The constraining fundamental paradigms.Ann Intern Med.1983;99:393–397. .
- The end of the disease era.Am J Med.2004;116(3):179–185. , .
- , Agostini JV. Potential pitfalls of disease‐specific guidelines for patients with multiple conditions.N Engl J Med.2004;351:2870–2874. ,
- Geriatrics at your fingertips: 2005.7th ed.Malden (MA):Blackwell Publishing, for the American Geriatrics Society,2005. , , , et al.
- Hospitalization in the United States, 2002. Publication 05‐056.Washington (DC):AHRQ,2005. , .
- Improving health care for older persons.Ann Intern Med.2003;139:421–424. .
- A controlled trial of inpatient and outpatient geriatric evaluation and management.N Engl J Med.2002;346:905–912. , , , et al.
- Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled.JAMA.1997;277:728–734. , , , et al.
- Development and validation of a prognostic index for 1‐year mortality in older adults after hospitalization.JAMA.2001;285:2987–2994. , , , et al.
- Delirium is independently associated with poor functional recovery after hip fracture.J Am Geriatr Soc.2000;48:618–624. , , , .
- The course of delirium in older medical inpatients: a prospective study.J Gen Intern Med.2003;18:696–704. , , , et al.
- Does delirium increase hospital stay?J Am Geriatr Soc.2003;51:1539–1546. , , , .
- Does delirium contribute to poor hospital outcomes? A three‐site epidemiologic study.J Gen Intern Med.1998;13:234–242. , , , et al.
- A predictive index for functional decline in hospitalized elderly medical patients.J Gen Intern Med.1993;8:645–652. , , , et al.
- A prospective study of delirium in hospitalized elderly.JAMA.1990;263:1097–1101. , , .
- Unsteadiness reported by older hospitalized patients predicts functional decline.J Am Geriatr Soc.2003;51:621–626. , , , et al.
- Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age.J Am Geriatr Soc.2003;51:451–458. , , , et al.
- Functional outcomes of acute medical illness and hospitalization in older persons.Arch Intern Med.1996;156:645–652. , , , et al.
- Functional disability in the hospitalized elderly.JAMA.1982;248:847–850. , , , et al.
- Diagnosis‐related group‐adjusted hospital costs are higher in older medical patients with lower functional status.J Am Geriatr Soc.2003;51:1729–1734. , , , et al.
- Adverse events, negligence in hospitalized patients: results from the Harvard Medical Practice Study.Perspect Healthc Risk Manage.1991;11(2):2–8. , .
- Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I.N Engl J Med.1991;324:370–376. , , , et al.
- The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II.N Engl J Med.1991;324:377–384. , , , et al.
- Effects of functional status changes before and during hospitalization on nursing home admission of older adults.J Gerontol A Biol Sci Med Sci.1999;54:M521–M526. , , , .
- Characterization of geriatric drug‐related hospital readmissions.Med Care.1991;29:989–1003. , , .
- The impact of clinical pharmacists' consultations on physicians' geriatric drug prescribing. A randomized controlled trial.Med Care.1992;30:646–658. , , , .
- Posthospital medication discrepancies: prevalence and contributing factors.Arch Intern Med.2005;165:1842–1847. , , , .
- A new tool for identifying discrepancies in postacute medications for community‐dwelling older adults.Am J Geriatr Pharmacother.2004;2(2):141–147. , , .
- Lost in transition: challenges and opportunities for improving the quality of transitional care.Ann Intern Med.2004;141:533–536. , .
- Enrollment of older persons in cancer trials after the medicare reimbursement policy change.Arch Intern Med.2005;165:1514–1520. , , , et al.
- Underrepresentation of patients 65 years of age or older in cancer‐treatment trials.N Engl J Med.1999;341:2061–2067. , , , et al.
- Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure.Am Heart J.2003;146(2):250–257. , , , et al.
- Problems in the “evidence” of “evidence‐based medicine.”Am J Med.1997;103:529–535. , .
- National initiatives in ageing research in the United Kingdom.Age Ageing.2002;31(2):93–95. .
- Embracing complexity: A consideration of hypertension in the very old.J Gerontol A Biol Sci Med Sci.2003;58:653–658. .
- Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years.Circulation.2000;101:2239–2246. , , , et al.
- A randomized trial of care in a hospital medical unit especially designed to improve the functional outcomes of acutely ill older patients.N Engl J Med.1995;332:1338–1344. , , , et al.
- A multicomponent intervention to prevent delirium in hospitalized older patients.N Engl J Med.1999;340:669–676. , , , et al.
- Reducing delirium after hip fracture: a randomized trial.J Am Geriatr Soc.2001;49:516–522. , , , .
- Dissemination and characteristics of acute care for elders (ACE) units in the United States.Int J Technol Assess Health Care.2003;19(1):220–227. , , , .
- Treatment of delirium in older medical inpatients: a challenge for geriatric specialists.J Am Geriatr Soc.2002;50:2101–2103. , .
- Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial.CMAJ.2002;167:753–759. , , , et al.
- Clinical and economic consequences of nosocomial catheter‐related bacteriuria.Am J Infect Control.2000;28(1):68–75. .
- Preventing catheter‐related bacteriuria: should we? Can we? How?Arch Intern Med.1999;159:800–808. , .
- Indwelling urinary catheters: a one‐point restraint?Ann Intern Med.2002;137(2):125–127. , , .
- Risk factors for indwelling urinary catheterization among older hospitalized patients without a specific medical indication for catheterization.J Patient Saf.2005. In press. , , et al.
- Protein and energy supplementation in elderly people at risk from malnutrition.Cochrane Database Syst Rev.2005(2):CD003288. , , .
- Clinical practice. Preventing falls in elderly persons.N Engl J Med.2003;348(1):42–49. .
- Collaborative care management of late‐life depression in the primary care setting: a randomized controlled trial.JAMA.2002;288:2836–2845. , , , et al.
- Hospital in the home: a randomised controlled trial.Med J Aust.1999;170(4):156–160. , , , , , .
- Hospitalists in the United States—mission accomplished or work in progress?N Engl J Med.2004;350:1935–1936. .
- Academic geriatric programs in US allopathic and osteopathic medical schools.JAMA.2002;288:2313–2319. , , , .
- Is there a geriatrician in the house? Geriatric care approaches in hospitalist programs.J Hosp Med.2006;1:29–35. , , .
- The implications of regional variations in Medicare spending. Part 1: the content, quality, and accessibility of care.Ann Intern Med.2003;138:273–287. , , , et al.
- The implications of regional variations in Medicare spending. Part 2: health outcomes and satisfaction with care.Ann Intern Med.2003;138:288–298. , , , et al.
- Mortality from pneumonia and hip fractures in patients with advanced dementia.JAMA.2000;284:2447–2448. , .
- Survival in end‐stage dementia following acute illness.JAMA.2000;284(1):47–52. , .
- Cancer screening in elderly patients: a framework for individualized decision making.JAMA.2001;285:2750–2756. , .
- Understanding the treatment preferences of seriously ill patients.N Engl J Med.2002;346:1061–1066. , , , .
- Health values of hospitalized patients 80 years or older. HELP Investigators. Hospitalized Elderly Longitudinal Project.JAMA.1998;279:371–375. , , , et al.
- Depressive symptoms and 3‐year mortality in older hospitalized medical patients.Ann Intern Med.1999;130:563–569. , , , et al.
- Relation between symptoms of depression and health status outcomes in acutely ill hospitalized older persons.Ann Intern Med.1997;126:417–425. , , , et al.
- Five system barriers to achieving ultrasafe health care.Ann Intern Med.2005;142:756–764. , , , .
- Specialized care for elderly patients.N Engl J Med.2002;346:874. .
- The end of the beginning: patient safety five years after ‘To Err Is Human.’Health Aff (Millwood).2004;Suppl Web Exclusives:W4–534–545. .
- An additional basic science for clinical medicine: II. The limitations of randomized trials.Ann Intern Med.1983;99:544–550. .
- An additional basic science for clinical medicine: III. The challenges of comparison and measurement.Ann Intern Med.1983;99:705–712. .
- An additional basic science for clinical medicine: IV. The development of clinimetrics.Ann Intern Med.1983;99:843–848. .
- An additional basic science for clinical medicine: I. The constraining fundamental paradigms.Ann Intern Med.1983;99:393–397. .
- The end of the disease era.Am J Med.2004;116(3):179–185. , .
- , Agostini JV. Potential pitfalls of disease‐specific guidelines for patients with multiple conditions.N Engl J Med.2004;351:2870–2874. ,
- Geriatrics at your fingertips: 2005.7th ed.Malden (MA):Blackwell Publishing, for the American Geriatrics Society,2005. , , , et al.