Brian F. Mandell, MD, PhD

Angioedema associated with insufficient activity of circulating complement component 1 (C1) inhibitor is a rare condition that can be hereditary or acquired. The clinical characteristics of this disorder are nicely reviewed by Drs. Tse and Zuraw in this issue of the Journal. Despite the rarity of this condition, there are good reasons to spend a few minutes with this article.

Angioedema and the urticarias differ in their clinical manifestations and diagnostic and therapeutic implications. Patients who have recurrent urticaria, no matter the severity, need not be evaluated for C1 inhibitor deficiency. Some patients who have recurrent angioedema without urticaria may respond well to antiallergic therapies (eg, antihistamines, corticosteroids), and these patients also are unlikely to have C1 inhibitor deficiency. Other patients who have intermittent localized peripheral swelling (or visceral edema manifest as abdominal pain) without urticaria may not respond, and it is in these patients that a pathophysiologic mechanism other than typical allergy should be considered.

In some patients, bradykinin-mediated angioedema is due to deficient C1 inhibitor activity, in others, to angiotensin-converting enzyme (ACE) inhibition. Although the biochemical site of action is different, both of these conditions result from an imbalance of protease activation and inhibition. If there is not enough C1 inhibition, there is too much kallikrein activity, which leads to excess proteolytic generation of the peptide bradykinin from kininogen. In contrast, ACE inhibitors occasionally cause angioedema by decreasing catabolism of bradykinin. In either case, bradykinin-mediated angioedema is generally clinically resistant to antiallergic therapy.

Thinking about these mechanisms reminds us of the complexity and overlap of many physiologic proteolytic cascades. Although C1 inhibitor is known as an inhibitor of C1 esterase and C4 levels are almost always low when C1 inhibitor activity is depressed, the angioedema in C1-inhibitor-deficiency states is more a result of decreased inhibition of enzymes in the coagulation cascade than in the complement cascade. Similarly, ACE-inhibitor-associated angioedema has little to do with the decreased generation of angiotensin that accounts for these drugs’ antihypertensive effect.

Generalizing these principles should make us vigilant for unpredicted adverse reactions to other newer drugs such as protease and kinase inhibitors, which may variably affect multiple biochemical pathways.

Angioedema associated with insufficient activity of circulating complement component 1 (C1) inhibitor is a rare condition that can be hereditary or acquired. The clinical characteristics of this disorder are nicely reviewed by Drs. Tse and Zuraw in this issue of the Journal. Despite the rarity of this condition, there are good reasons to spend a few minutes with this article.

Angioedema and the urticarias differ in their clinical manifestations and diagnostic and therapeutic implications. Patients who have recurrent urticaria, no matter the severity, need not be evaluated for C1 inhibitor deficiency. Some patients who have recurrent angioedema without urticaria may respond well to antiallergic therapies (eg, antihistamines, corticosteroids), and these patients also are unlikely to have C1 inhibitor deficiency. Other patients who have intermittent localized peripheral swelling (or visceral edema manifest as abdominal pain) without urticaria may not respond, and it is in these patients that a pathophysiologic mechanism other than typical allergy should be considered.

In some patients, bradykinin-mediated angioedema is due to deficient C1 inhibitor activity, in others, to angiotensin-converting enzyme (ACE) inhibition. Although the biochemical site of action is different, both of these conditions result from an imbalance of protease activation and inhibition. If there is not enough C1 inhibition, there is too much kallikrein activity, which leads to excess proteolytic generation of the peptide bradykinin from kininogen. In contrast, ACE inhibitors occasionally cause angioedema by decreasing catabolism of bradykinin. In either case, bradykinin-mediated angioedema is generally clinically resistant to antiallergic therapy.

Thinking about these mechanisms reminds us of the complexity and overlap of many physiologic proteolytic cascades. Although C1 inhibitor is known as an inhibitor of C1 esterase and C4 levels are almost always low when C1 inhibitor activity is depressed, the angioedema in C1-inhibitor-deficiency states is more a result of decreased inhibition of enzymes in the coagulation cascade than in the complement cascade. Similarly, ACE-inhibitor-associated angioedema has little to do with the decreased generation of angiotensin that accounts for these drugs’ antihypertensive effect.

Generalizing these principles should make us vigilant for unpredicted adverse reactions to other newer drugs such as protease and kinase inhibitors, which may variably affect multiple biochemical pathways.

Angioedema associated with insufficient activity of circulating complement component 1 (C1) inhibitor is a rare condition that can be hereditary or acquired. The clinical characteristics of this disorder are nicely reviewed by Drs. Tse and Zuraw in this issue of the Journal. Despite the rarity of this condition, there are good reasons to spend a few minutes with this article.

Angioedema and the urticarias differ in their clinical manifestations and diagnostic and therapeutic implications. Patients who have recurrent urticaria, no matter the severity, need not be evaluated for C1 inhibitor deficiency. Some patients who have recurrent angioedema without urticaria may respond well to antiallergic therapies (eg, antihistamines, corticosteroids), and these patients also are unlikely to have C1 inhibitor deficiency. Other patients who have intermittent localized peripheral swelling (or visceral edema manifest as abdominal pain) without urticaria may not respond, and it is in these patients that a pathophysiologic mechanism other than typical allergy should be considered.

In some patients, bradykinin-mediated angioedema is due to deficient C1 inhibitor activity, in others, to angiotensin-converting enzyme (ACE) inhibition. Although the biochemical site of action is different, both of these conditions result from an imbalance of protease activation and inhibition. If there is not enough C1 inhibition, there is too much kallikrein activity, which leads to excess proteolytic generation of the peptide bradykinin from kininogen. In contrast, ACE inhibitors occasionally cause angioedema by decreasing catabolism of bradykinin. In either case, bradykinin-mediated angioedema is generally clinically resistant to antiallergic therapy.

Thinking about these mechanisms reminds us of the complexity and overlap of many physiologic proteolytic cascades. Although C1 inhibitor is known as an inhibitor of C1 esterase and C4 levels are almost always low when C1 inhibitor activity is depressed, the angioedema in C1-inhibitor-deficiency states is more a result of decreased inhibition of enzymes in the coagulation cascade than in the complement cascade. Similarly, ACE-inhibitor-associated angioedema has little to do with the decreased generation of angiotensin that accounts for these drugs’ antihypertensive effect.

Generalizing these principles should make us vigilant for unpredicted adverse reactions to other newer drugs such as protease and kinase inhibitors, which may variably affect multiple biochemical pathways.

Why individual clinicians make specific decisions usually can be sorted out. But our behavior as a group is more difficult to understand and, even when there are pressing and convincing reasons to change, behavior is difficult to alter.

In this issue, Drs. Federico Perez and David Van Duin discuss the emergence of carbapenem-resistant bacteria, dubbed “superbugs” by the media. Antibiotic resistance is not new; it was reported in Staphylococcus species within several years of the introduction of penicillin.¹ However, it has been increasing in prevalence and molecular complexity after years of relatively promiscuous antibiotic use. As the percentage of inpatients with immunosuppression and frailty increases in this environment of known antibiotic resistance, initial empiric antibiotic choices will by necessity include drugs likely to further promote development of resistant strains. But why do physicians still prescribe antibiotics for uncomplicated upper respiratory tract infections and asymptomatic bacteriuria, despite numerous studies and guidelines suggesting this practice has little benefit? Is it because patients expect a prescription in return for their copayment? Is it the path of least resistance? Or do physicians not accept the data showing that it is unnecessary?

Dr. Gerald Appel discusses diabetic nephropathy, an area that involves resistance of another kind, ie, the apparent resistance of physicians and patients to achieving evidence-based treatment targets. We hold controlled trials as the Holy Grail of evidence-based medicine, yet we seem to have an aversion to following guidelines based on trial-derived evidence. (I do not refer here to blind guideline adherence, ignoring individual patient characteristics.)

So how can physicians’ behavior be altered and our resistance to change be reduced? Experiments are under way, such as paying physicians based on their performance, linking patients’ insurance rates to achieving selected outcomes, and linking physician practice self-review to certification. Perhaps naively, I continue to believe that the most effective impetus to changing personal practice is the dissemination of data from high-quality trials (tempered by our accumulated experience and keeping our eyes wide open), coupled with our desire to do the best for our patients.

Why individual clinicians make specific decisions usually can be sorted out. But our behavior as a group is more difficult to understand and, even when there are pressing and convincing reasons to change, behavior is difficult to alter.

In this issue, Drs. Federico Perez and David Van Duin discuss the emergence of carbapenem-resistant bacteria, dubbed “superbugs” by the media. Antibiotic resistance is not new; it was reported in Staphylococcus species within several years of the introduction of penicillin.¹ However, it has been increasing in prevalence and molecular complexity after years of relatively promiscuous antibiotic use. As the percentage of inpatients with immunosuppression and frailty increases in this environment of known antibiotic resistance, initial empiric antibiotic choices will by necessity include drugs likely to further promote development of resistant strains. But why do physicians still prescribe antibiotics for uncomplicated upper respiratory tract infections and asymptomatic bacteriuria, despite numerous studies and guidelines suggesting this practice has little benefit? Is it because patients expect a prescription in return for their copayment? Is it the path of least resistance? Or do physicians not accept the data showing that it is unnecessary?

Dr. Gerald Appel discusses diabetic nephropathy, an area that involves resistance of another kind, ie, the apparent resistance of physicians and patients to achieving evidence-based treatment targets. We hold controlled trials as the Holy Grail of evidence-based medicine, yet we seem to have an aversion to following guidelines based on trial-derived evidence. (I do not refer here to blind guideline adherence, ignoring individual patient characteristics.)

So how can physicians’ behavior be altered and our resistance to change be reduced? Experiments are under way, such as paying physicians based on their performance, linking patients’ insurance rates to achieving selected outcomes, and linking physician practice self-review to certification. Perhaps naively, I continue to believe that the most effective impetus to changing personal practice is the dissemination of data from high-quality trials (tempered by our accumulated experience and keeping our eyes wide open), coupled with our desire to do the best for our patients.

Why individual clinicians make specific decisions usually can be sorted out. But our behavior as a group is more difficult to understand and, even when there are pressing and convincing reasons to change, behavior is difficult to alter.

In this issue, Drs. Federico Perez and David Van Duin discuss the emergence of carbapenem-resistant bacteria, dubbed “superbugs” by the media. Antibiotic resistance is not new; it was reported in Staphylococcus species within several years of the introduction of penicillin.¹ However, it has been increasing in prevalence and molecular complexity after years of relatively promiscuous antibiotic use. As the percentage of inpatients with immunosuppression and frailty increases in this environment of known antibiotic resistance, initial empiric antibiotic choices will by necessity include drugs likely to further promote development of resistant strains. But why do physicians still prescribe antibiotics for uncomplicated upper respiratory tract infections and asymptomatic bacteriuria, despite numerous studies and guidelines suggesting this practice has little benefit? Is it because patients expect a prescription in return for their copayment? Is it the path of least resistance? Or do physicians not accept the data showing that it is unnecessary?

Dr. Gerald Appel discusses diabetic nephropathy, an area that involves resistance of another kind, ie, the apparent resistance of physicians and patients to achieving evidence-based treatment targets. We hold controlled trials as the Holy Grail of evidence-based medicine, yet we seem to have an aversion to following guidelines based on trial-derived evidence. (I do not refer here to blind guideline adherence, ignoring individual patient characteristics.)

So how can physicians’ behavior be altered and our resistance to change be reduced? Experiments are under way, such as paying physicians based on their performance, linking patients’ insurance rates to achieving selected outcomes, and linking physician practice self-review to certification. Perhaps naively, I continue to believe that the most effective impetus to changing personal practice is the dissemination of data from high-quality trials (tempered by our accumulated experience and keeping our eyes wide open), coupled with our desire to do the best for our patients.

With great enthusiasm, I introduce our two new deputy editors, and inform you of the career change of our exiting deputy editor, Dr. Tim Gilligan.

Tim, a practicing oncologist and program director of Cleveland Clinic’s hematology-oncology fellowship program, is transitioning from his work at the Journal to further pursue his interest in promoting physician communication skills. He is now co-director of the Clinic’s new Center for Excellence in Health Care Communication. Tim will refine and implement a coaching program for physicians in communication skills and will continue to conduct educational sessions for physicians on communication at institutions around the country. He will also continue his work with the American Society of Clinical Oncology as chair of their measures-of-quality subcommittee and as co-chair of the panel writing guidelines on the management of testicular cancer.

Joining us as deputy editors are Pelin Batur and Jim Pile—two superb clinician-educators who have divergent interests and experience, but who share a genuine passion for creating and delivering high-quality postgraduate and continuing medical education (CME) material and programs.

Pelin is a practicing general internist with additional fellowship training in women’s health. She is a North American Menopause Society-certified menopause practitioner and the Education Director for Primary Care Women’s Health at the Clinic, and she lectures nationally and internationally on women’s health issues. Jim is a practicing hospitalist and consultant in infectious disease at the Clinic. He is the former editor of The Hospitalist, he is current deputy editor of the Journal of Hospital Medicine, and he fulfills various education-focused roles at the Clinic and with the Society of Hospital Medicine.

In addition to our expectation that they will increase the Journal’s offerings within their clinical areas of interest, particularly hospital medicine and women’s health, they both will follow Tim’s lead in enhancing the depth and breadth of our CME activities, as well as expanding our online and digital presence. I am confident their efforts will enable us to even further improve the quality and utility of our practice- and evidencebased papers for you, our clinician readers.

With great enthusiasm, I introduce our two new deputy editors, and inform you of the career change of our exiting deputy editor, Dr. Tim Gilligan.

Tim, a practicing oncologist and program director of Cleveland Clinic’s hematology-oncology fellowship program, is transitioning from his work at the Journal to further pursue his interest in promoting physician communication skills. He is now co-director of the Clinic’s new Center for Excellence in Health Care Communication. Tim will refine and implement a coaching program for physicians in communication skills and will continue to conduct educational sessions for physicians on communication at institutions around the country. He will also continue his work with the American Society of Clinical Oncology as chair of their measures-of-quality subcommittee and as co-chair of the panel writing guidelines on the management of testicular cancer.

Joining us as deputy editors are Pelin Batur and Jim Pile—two superb clinician-educators who have divergent interests and experience, but who share a genuine passion for creating and delivering high-quality postgraduate and continuing medical education (CME) material and programs.

Pelin is a practicing general internist with additional fellowship training in women’s health. She is a North American Menopause Society-certified menopause practitioner and the Education Director for Primary Care Women’s Health at the Clinic, and she lectures nationally and internationally on women’s health issues. Jim is a practicing hospitalist and consultant in infectious disease at the Clinic. He is the former editor of The Hospitalist, he is current deputy editor of the Journal of Hospital Medicine, and he fulfills various education-focused roles at the Clinic and with the Society of Hospital Medicine.

In addition to our expectation that they will increase the Journal’s offerings within their clinical areas of interest, particularly hospital medicine and women’s health, they both will follow Tim’s lead in enhancing the depth and breadth of our CME activities, as well as expanding our online and digital presence. I am confident their efforts will enable us to even further improve the quality and utility of our practice- and evidencebased papers for you, our clinician readers.

With great enthusiasm, I introduce our two new deputy editors, and inform you of the career change of our exiting deputy editor, Dr. Tim Gilligan.

Tim, a practicing oncologist and program director of Cleveland Clinic’s hematology-oncology fellowship program, is transitioning from his work at the Journal to further pursue his interest in promoting physician communication skills. He is now co-director of the Clinic’s new Center for Excellence in Health Care Communication. Tim will refine and implement a coaching program for physicians in communication skills and will continue to conduct educational sessions for physicians on communication at institutions around the country. He will also continue his work with the American Society of Clinical Oncology as chair of their measures-of-quality subcommittee and as co-chair of the panel writing guidelines on the management of testicular cancer.

Joining us as deputy editors are Pelin Batur and Jim Pile—two superb clinician-educators who have divergent interests and experience, but who share a genuine passion for creating and delivering high-quality postgraduate and continuing medical education (CME) material and programs.

Pelin is a practicing general internist with additional fellowship training in women’s health. She is a North American Menopause Society-certified menopause practitioner and the Education Director for Primary Care Women’s Health at the Clinic, and she lectures nationally and internationally on women’s health issues. Jim is a practicing hospitalist and consultant in infectious disease at the Clinic. He is the former editor of The Hospitalist, he is current deputy editor of the Journal of Hospital Medicine, and he fulfills various education-focused roles at the Clinic and with the Society of Hospital Medicine.

In addition to our expectation that they will increase the Journal’s offerings within their clinical areas of interest, particularly hospital medicine and women’s health, they both will follow Tim’s lead in enhancing the depth and breadth of our CME activities, as well as expanding our online and digital presence. I am confident their efforts will enable us to even further improve the quality and utility of our practice- and evidencebased papers for you, our clinician readers.

At first, the idea of collecting feces, putting it in a blender, and then transferring it into the gastrointestinal (GI) tract of another person might seem to be the creation of a third-grade boy writing a composition on the grossest thing he could think of. And yet, as Agito et al describe in this issue, this very procedure may hold promise for some patients suffering from recurrent and recalcitrant Clostridium difficile infection—and may help open the book on a new area of clinical biology.

The complete story on the biology of primary and recurrent C difficile infection has yet to be fully elaborated. For most patients, the plotline involves an alteration of their resident bacteria by an antibiotic that permits the overgrowth of C difficile, including spore-forming strains that can generate a significant amount of toxin. If the depletion of competitive intestinal bacteria allows for unfettered growth of this toxic bacterium, then it is predictable that replenishing the intestinal microbiome will permit balanced bacterial growth and control of C difficile multiplication.

But the C difficile story is only part of a biologic anthology that is still being written. The microbial biome accounts for probably 90% of the DNA that each of us carries. This microbial DNA, although diverse since it represents nuclear material from many species of bacteria, is not distributed randomly among individuals. There are at least several enterotypes (patterns of gut bacterial ecosystems) that can be identified by molecular techniques. The GI microbiome patterns of couples and household contacts are more similar than would be expected by chance alone, and patterns are seemingly influenced by dietary intake (carnivores differ from vegans) and perhaps by the host’s unique immune responsiveness. Our intestinal microbiome may exert a greater influence on our overall health than we previously thought.

The gut microbiome not only participates in digestion of what we eat and synthesizes some necessary nutritional factors, it also generates small molecules capable of regulating aspects of our systemic immune response. Altering the microbiome, by fecal transplantation or other means, may well contribute to the development or suppression of inflammatory disorders as diverse as spondylitis, atherosclerosis, immune thrombocytopenia, and allergies.

Soon, peptic ulcer disease may not be the only condition treated by therapies directed at bacteria within our GI tract. This is an evolving story that may seem weird but is worth following.

At first, the idea of collecting feces, putting it in a blender, and then transferring it into the gastrointestinal (GI) tract of another person might seem to be the creation of a third-grade boy writing a composition on the grossest thing he could think of. And yet, as Agito et al describe in this issue, this very procedure may hold promise for some patients suffering from recurrent and recalcitrant Clostridium difficile infection—and may help open the book on a new area of clinical biology.

The complete story on the biology of primary and recurrent C difficile infection has yet to be fully elaborated. For most patients, the plotline involves an alteration of their resident bacteria by an antibiotic that permits the overgrowth of C difficile, including spore-forming strains that can generate a significant amount of toxin. If the depletion of competitive intestinal bacteria allows for unfettered growth of this toxic bacterium, then it is predictable that replenishing the intestinal microbiome will permit balanced bacterial growth and control of C difficile multiplication.

But the C difficile story is only part of a biologic anthology that is still being written. The microbial biome accounts for probably 90% of the DNA that each of us carries. This microbial DNA, although diverse since it represents nuclear material from many species of bacteria, is not distributed randomly among individuals. There are at least several enterotypes (patterns of gut bacterial ecosystems) that can be identified by molecular techniques. The GI microbiome patterns of couples and household contacts are more similar than would be expected by chance alone, and patterns are seemingly influenced by dietary intake (carnivores differ from vegans) and perhaps by the host’s unique immune responsiveness. Our intestinal microbiome may exert a greater influence on our overall health than we previously thought.

The gut microbiome not only participates in digestion of what we eat and synthesizes some necessary nutritional factors, it also generates small molecules capable of regulating aspects of our systemic immune response. Altering the microbiome, by fecal transplantation or other means, may well contribute to the development or suppression of inflammatory disorders as diverse as spondylitis, atherosclerosis, immune thrombocytopenia, and allergies.

Soon, peptic ulcer disease may not be the only condition treated by therapies directed at bacteria within our GI tract. This is an evolving story that may seem weird but is worth following.

At first, the idea of collecting feces, putting it in a blender, and then transferring it into the gastrointestinal (GI) tract of another person might seem to be the creation of a third-grade boy writing a composition on the grossest thing he could think of. And yet, as Agito et al describe in this issue, this very procedure may hold promise for some patients suffering from recurrent and recalcitrant Clostridium difficile infection—and may help open the book on a new area of clinical biology.

The complete story on the biology of primary and recurrent C difficile infection has yet to be fully elaborated. For most patients, the plotline involves an alteration of their resident bacteria by an antibiotic that permits the overgrowth of C difficile, including spore-forming strains that can generate a significant amount of toxin. If the depletion of competitive intestinal bacteria allows for unfettered growth of this toxic bacterium, then it is predictable that replenishing the intestinal microbiome will permit balanced bacterial growth and control of C difficile multiplication.

But the C difficile story is only part of a biologic anthology that is still being written. The microbial biome accounts for probably 90% of the DNA that each of us carries. This microbial DNA, although diverse since it represents nuclear material from many species of bacteria, is not distributed randomly among individuals. There are at least several enterotypes (patterns of gut bacterial ecosystems) that can be identified by molecular techniques. The GI microbiome patterns of couples and household contacts are more similar than would be expected by chance alone, and patterns are seemingly influenced by dietary intake (carnivores differ from vegans) and perhaps by the host’s unique immune responsiveness. Our intestinal microbiome may exert a greater influence on our overall health than we previously thought.

The gut microbiome not only participates in digestion of what we eat and synthesizes some necessary nutritional factors, it also generates small molecules capable of regulating aspects of our systemic immune response. Altering the microbiome, by fecal transplantation or other means, may well contribute to the development or suppression of inflammatory disorders as diverse as spondylitis, atherosclerosis, immune thrombocytopenia, and allergies.

Soon, peptic ulcer disease may not be the only condition treated by therapies directed at bacteria within our GI tract. This is an evolving story that may seem weird but is worth following.

Before we write a prescription, we review the patient’s diagnosis, the known evidence, and our own experience. Then we discuss the risks and benefits with the patient. If he or she chooses to fill the prescription, we are responsible for the outcome. But patients may choose to not take the medication, feeling that the accumulated evidence does not apply to them or not fully understanding the balance of potential benefit and harm.

When a group of expert physicians writes practice guidelines, they review the literature and their own experience and then summarize key practices that they believe should be followed or avoided. These guidelines are offered to practicing physicians to accept or reject. Unlike the physician writing an individual prescription, the authors of the guidelines are not held directly responsible for the outcome in a specific patient.

Guidelines seem to be accepted on an academic level, not as a prescriptive approach to care but as a way of evaluating the relevant evidence and its practical application. But many practicing clinicians fear that guidelines are leading to the algorithmic practice of medicine and to reimbursement according to adherence to the guidelines, regardless of patient outcomes.

In this issue, Roland Moskowitz, an expert in osteoarthritis, comments on the 2012 American College of Rheumatology “recommendations” for the treatment of this disease.¹ He notes that these recommendations are not a cookbook, points out areas in which his own practices differ from them, and emphasizes the need to individualize our recommendations. For instance, he notes that some of his patients have relief of pain after hyaluronan injections into their osteoarthritic knees, even though the guidelines do not recommend this therapy¹ and structured reviews suggest it has little benefit (in groups of patients) beyond that of placebo injections. This apparent paradox suggests that this therapy is not appropriate for everyone, but also that it should not be removed from our toolkit. Certainly, the patient’s response to an injection (outcome) should be evaluated before repeating this therapy.

We should not worship the idol of guidelines alone, but neither should we ignore them and make decisions only on the basis of anecdote and experience. When making individual treatment decisions, we must assess external validity before applying pooled trial data. And administrators need to understand that clinicians may choose to not follow practice guidelines in individual patients for very valid reasons.

Most studies of the impact of guidelines have focused on how well physicians comply with them, not on patient outcomes. Compliance—of patients with physicians’ advice and of physicians with guidelines—is a complicated process. Compliance should not be considered a cookbook expectation—for patients or for doctors.

Before we write a prescription, we review the patient’s diagnosis, the known evidence, and our own experience. Then we discuss the risks and benefits with the patient. If he or she chooses to fill the prescription, we are responsible for the outcome. But patients may choose to not take the medication, feeling that the accumulated evidence does not apply to them or not fully understanding the balance of potential benefit and harm.

When a group of expert physicians writes practice guidelines, they review the literature and their own experience and then summarize key practices that they believe should be followed or avoided. These guidelines are offered to practicing physicians to accept or reject. Unlike the physician writing an individual prescription, the authors of the guidelines are not held directly responsible for the outcome in a specific patient.

Guidelines seem to be accepted on an academic level, not as a prescriptive approach to care but as a way of evaluating the relevant evidence and its practical application. But many practicing clinicians fear that guidelines are leading to the algorithmic practice of medicine and to reimbursement according to adherence to the guidelines, regardless of patient outcomes.

In this issue, Roland Moskowitz, an expert in osteoarthritis, comments on the 2012 American College of Rheumatology “recommendations” for the treatment of this disease.¹ He notes that these recommendations are not a cookbook, points out areas in which his own practices differ from them, and emphasizes the need to individualize our recommendations. For instance, he notes that some of his patients have relief of pain after hyaluronan injections into their osteoarthritic knees, even though the guidelines do not recommend this therapy¹ and structured reviews suggest it has little benefit (in groups of patients) beyond that of placebo injections. This apparent paradox suggests that this therapy is not appropriate for everyone, but also that it should not be removed from our toolkit. Certainly, the patient’s response to an injection (outcome) should be evaluated before repeating this therapy.

We should not worship the idol of guidelines alone, but neither should we ignore them and make decisions only on the basis of anecdote and experience. When making individual treatment decisions, we must assess external validity before applying pooled trial data. And administrators need to understand that clinicians may choose to not follow practice guidelines in individual patients for very valid reasons.

Most studies of the impact of guidelines have focused on how well physicians comply with them, not on patient outcomes. Compliance—of patients with physicians’ advice and of physicians with guidelines—is a complicated process. Compliance should not be considered a cookbook expectation—for patients or for doctors.

Before we write a prescription, we review the patient’s diagnosis, the known evidence, and our own experience. Then we discuss the risks and benefits with the patient. If he or she chooses to fill the prescription, we are responsible for the outcome. But patients may choose to not take the medication, feeling that the accumulated evidence does not apply to them or not fully understanding the balance of potential benefit and harm.

When a group of expert physicians writes practice guidelines, they review the literature and their own experience and then summarize key practices that they believe should be followed or avoided. These guidelines are offered to practicing physicians to accept or reject. Unlike the physician writing an individual prescription, the authors of the guidelines are not held directly responsible for the outcome in a specific patient.

Guidelines seem to be accepted on an academic level, not as a prescriptive approach to care but as a way of evaluating the relevant evidence and its practical application. But many practicing clinicians fear that guidelines are leading to the algorithmic practice of medicine and to reimbursement according to adherence to the guidelines, regardless of patient outcomes.

In this issue, Roland Moskowitz, an expert in osteoarthritis, comments on the 2012 American College of Rheumatology “recommendations” for the treatment of this disease.¹ He notes that these recommendations are not a cookbook, points out areas in which his own practices differ from them, and emphasizes the need to individualize our recommendations. For instance, he notes that some of his patients have relief of pain after hyaluronan injections into their osteoarthritic knees, even though the guidelines do not recommend this therapy¹ and structured reviews suggest it has little benefit (in groups of patients) beyond that of placebo injections. This apparent paradox suggests that this therapy is not appropriate for everyone, but also that it should not be removed from our toolkit. Certainly, the patient’s response to an injection (outcome) should be evaluated before repeating this therapy.

We should not worship the idol of guidelines alone, but neither should we ignore them and make decisions only on the basis of anecdote and experience. When making individual treatment decisions, we must assess external validity before applying pooled trial data. And administrators need to understand that clinicians may choose to not follow practice guidelines in individual patients for very valid reasons.

Most studies of the impact of guidelines have focused on how well physicians comply with them, not on patient outcomes. Compliance—of patients with physicians’ advice and of physicians with guidelines—is a complicated process. Compliance should not be considered a cookbook expectation—for patients or for doctors.

The numbers are striking: about 1% of 8-year-old children will receive a diagnosis of an autism spectrum disorder. We still have much to learn about autism, and many factors make study difficult. Reliable older data are scarce, and the diagnostic criteria change—for instance, the currently distinct diagnosis of Asperger syndrome will soon be redefined.

To many, the image of autism is of a cute sandy-haired boy, perhaps staring thoughtfully into space, perhaps reciting the batting averages of individual New York Yankees over the past 10 years—a kid stuck behind a wax-paper wall that blocks the full development of emotional connectivity and complex communication.

The autism spectrum is wide. Those diagnosed carry various features of social impairment, such as a limited ability to recognize and respond to social cues, language and communication challenges, and tendencies to get stuck on the literal. Some show severe social withdrawal and heightened sensitivity to sensory stimuli. Others perseverate on concepts, numbers, ritual behaviors, and repetitive movements.

Special schools and programs can offer a haven. They can buffer children from the unkindness of other children and from the unrealistic expectations of well-meaning but unaware adults; they can protect the more severely affected from self-destructive behaviors, and perhaps they can even decrease some distracting behaviors while promoting communication skills and reducing anxiety. But schools can’t provide forever-care.

Eight-year-olds have a way of growing into adults; nearly half a million autistic children will enter adulthood over the next 10 years. Many will need lifelong comprehensive care and support, others can function well in the workplace but are challenged in social interactions. Perhaps 25% of children diagnosed with an autism spectrum disorder will be high-functioning—with traits displayed graphically (but a little over-the-top) by Dustin Hoffman in the film Rain Man and by Christian Clemenson as the hopping, popping, brilliant attorney Jerry Espenson in the television series Boston Legal. But these are caricatures, and although they heighten our awareness they are limited in perspective.

The patients we see with Asperger syndrome or high-functioning autism do not always wear their diagnosis on their sleeve. Our office staff may recognize them as being a bit quirky. Most first come to our attention for common, unrelated diseases such as diabetes, abdominal pain, and cancer, needing extensive patient education as part of their disease management, but with whom we struggle to make our message clear. Our skills in recognizing these patients need to be refined in order to understand and respond to their unique needs.

At times, we are all challenged in communicating with some patients, even those not perceiving the emotional world through that wall of wax paper. In this issue of the Journal, Prayson and Franco and Shane offer practical advice in interacting with patients with Asperger syndrome. We need to pay attention. In fact, we would do well to follow many of their suggestions with all of our patients.

The numbers are striking: about 1% of 8-year-old children will receive a diagnosis of an autism spectrum disorder. We still have much to learn about autism, and many factors make study difficult. Reliable older data are scarce, and the diagnostic criteria change—for instance, the currently distinct diagnosis of Asperger syndrome will soon be redefined.

To many, the image of autism is of a cute sandy-haired boy, perhaps staring thoughtfully into space, perhaps reciting the batting averages of individual New York Yankees over the past 10 years—a kid stuck behind a wax-paper wall that blocks the full development of emotional connectivity and complex communication.

The autism spectrum is wide. Those diagnosed carry various features of social impairment, such as a limited ability to recognize and respond to social cues, language and communication challenges, and tendencies to get stuck on the literal. Some show severe social withdrawal and heightened sensitivity to sensory stimuli. Others perseverate on concepts, numbers, ritual behaviors, and repetitive movements.

Special schools and programs can offer a haven. They can buffer children from the unkindness of other children and from the unrealistic expectations of well-meaning but unaware adults; they can protect the more severely affected from self-destructive behaviors, and perhaps they can even decrease some distracting behaviors while promoting communication skills and reducing anxiety. But schools can’t provide forever-care.

Eight-year-olds have a way of growing into adults; nearly half a million autistic children will enter adulthood over the next 10 years. Many will need lifelong comprehensive care and support, others can function well in the workplace but are challenged in social interactions. Perhaps 25% of children diagnosed with an autism spectrum disorder will be high-functioning—with traits displayed graphically (but a little over-the-top) by Dustin Hoffman in the film Rain Man and by Christian Clemenson as the hopping, popping, brilliant attorney Jerry Espenson in the television series Boston Legal. But these are caricatures, and although they heighten our awareness they are limited in perspective.

The patients we see with Asperger syndrome or high-functioning autism do not always wear their diagnosis on their sleeve. Our office staff may recognize them as being a bit quirky. Most first come to our attention for common, unrelated diseases such as diabetes, abdominal pain, and cancer, needing extensive patient education as part of their disease management, but with whom we struggle to make our message clear. Our skills in recognizing these patients need to be refined in order to understand and respond to their unique needs.

At times, we are all challenged in communicating with some patients, even those not perceiving the emotional world through that wall of wax paper. In this issue of the Journal, Prayson and Franco and Shane offer practical advice in interacting with patients with Asperger syndrome. We need to pay attention. In fact, we would do well to follow many of their suggestions with all of our patients.

The numbers are striking: about 1% of 8-year-old children will receive a diagnosis of an autism spectrum disorder. We still have much to learn about autism, and many factors make study difficult. Reliable older data are scarce, and the diagnostic criteria change—for instance, the currently distinct diagnosis of Asperger syndrome will soon be redefined.

To many, the image of autism is of a cute sandy-haired boy, perhaps staring thoughtfully into space, perhaps reciting the batting averages of individual New York Yankees over the past 10 years—a kid stuck behind a wax-paper wall that blocks the full development of emotional connectivity and complex communication.

The autism spectrum is wide. Those diagnosed carry various features of social impairment, such as a limited ability to recognize and respond to social cues, language and communication challenges, and tendencies to get stuck on the literal. Some show severe social withdrawal and heightened sensitivity to sensory stimuli. Others perseverate on concepts, numbers, ritual behaviors, and repetitive movements.

Special schools and programs can offer a haven. They can buffer children from the unkindness of other children and from the unrealistic expectations of well-meaning but unaware adults; they can protect the more severely affected from self-destructive behaviors, and perhaps they can even decrease some distracting behaviors while promoting communication skills and reducing anxiety. But schools can’t provide forever-care.

Eight-year-olds have a way of growing into adults; nearly half a million autistic children will enter adulthood over the next 10 years. Many will need lifelong comprehensive care and support, others can function well in the workplace but are challenged in social interactions. Perhaps 25% of children diagnosed with an autism spectrum disorder will be high-functioning—with traits displayed graphically (but a little over-the-top) by Dustin Hoffman in the film Rain Man and by Christian Clemenson as the hopping, popping, brilliant attorney Jerry Espenson in the television series Boston Legal. But these are caricatures, and although they heighten our awareness they are limited in perspective.

The patients we see with Asperger syndrome or high-functioning autism do not always wear their diagnosis on their sleeve. Our office staff may recognize them as being a bit quirky. Most first come to our attention for common, unrelated diseases such as diabetes, abdominal pain, and cancer, needing extensive patient education as part of their disease management, but with whom we struggle to make our message clear. Our skills in recognizing these patients need to be refined in order to understand and respond to their unique needs.

At times, we are all challenged in communicating with some patients, even those not perceiving the emotional world through that wall of wax paper. In this issue of the Journal, Prayson and Franco and Shane offer practical advice in interacting with patients with Asperger syndrome. We need to pay attention. In fact, we would do well to follow many of their suggestions with all of our patients.

As autumn arrives and thoughts turn to pumpkins, football, and Thanks-giving dinner, it is time for health systems and physicians to prepare for the upcoming influenza season. In this issue of the Journal, Drs. Jin and Mossad review some practical virology and remind us why we must continue to encourage our patients and staff to be immunized against the flu.

Last year the flu season was surprisingly mild. The infection incidence seemed to peak late in the season, a reasonable number of people got vaccinated, and the level of viral antigenic drift was low. New hybrid viral strains did appear, but apparently with low prevalence, and the avian strains did not mutate to permit efficient human-to-human infection. But the relatively benign 2011–2012 flu season should not lull us into a lackadaisical approach to offering vaccination to all of our patients.

Ever since my own encounter with the flu a number of years ago, I have been pushing the vaccine with the zeal of a telemarketer. I was pleased that the vaccine arrived early this time, but continue to be surprised by the reasons patients offer for not receiving it—some strike me as akin to “the dog ate my homework.” For example: “I got the vaccine once and I got walking pneumonia.” And the always-popular “I got the vaccine and I got the flu.” Many patients don’t think they need the vaccine because they have never gotten the flu. (To them, I relate my tale of spending a weekend lying curled up on the floor of my bedroom having chills despite a sweatsuit and blanket). Some voice the scientifically irrational but common concern that since their immune system has been weakened by medications, they don’t want to get sick from the shot. And creatively, this year several patients have told me that they heard it is too early to get the vaccine—the effect won’t last all season.

Whatever our patients’ reason for recalcitrance, we should persevere and follow the national recommendation to vaccinate all persons over the age of 6 months. The vaccine may not be perfect, but with an estimated success rate of about 60%, it is better than any alternative approach. Plus, as Drs. Jin and Mossad note in their article, there is concern about emerging strains that are resistant to available antiviral therapies—0.5 mL of prevention trumps a pound of ineffective treatment.

As autumn arrives and thoughts turn to pumpkins, football, and Thanks-giving dinner, it is time for health systems and physicians to prepare for the upcoming influenza season. In this issue of the Journal, Drs. Jin and Mossad review some practical virology and remind us why we must continue to encourage our patients and staff to be immunized against the flu.

Last year the flu season was surprisingly mild. The infection incidence seemed to peak late in the season, a reasonable number of people got vaccinated, and the level of viral antigenic drift was low. New hybrid viral strains did appear, but apparently with low prevalence, and the avian strains did not mutate to permit efficient human-to-human infection. But the relatively benign 2011–2012 flu season should not lull us into a lackadaisical approach to offering vaccination to all of our patients.

Ever since my own encounter with the flu a number of years ago, I have been pushing the vaccine with the zeal of a telemarketer. I was pleased that the vaccine arrived early this time, but continue to be surprised by the reasons patients offer for not receiving it—some strike me as akin to “the dog ate my homework.” For example: “I got the vaccine once and I got walking pneumonia.” And the always-popular “I got the vaccine and I got the flu.” Many patients don’t think they need the vaccine because they have never gotten the flu. (To them, I relate my tale of spending a weekend lying curled up on the floor of my bedroom having chills despite a sweatsuit and blanket). Some voice the scientifically irrational but common concern that since their immune system has been weakened by medications, they don’t want to get sick from the shot. And creatively, this year several patients have told me that they heard it is too early to get the vaccine—the effect won’t last all season.

Whatever our patients’ reason for recalcitrance, we should persevere and follow the national recommendation to vaccinate all persons over the age of 6 months. The vaccine may not be perfect, but with an estimated success rate of about 60%, it is better than any alternative approach. Plus, as Drs. Jin and Mossad note in their article, there is concern about emerging strains that are resistant to available antiviral therapies—0.5 mL of prevention trumps a pound of ineffective treatment.

As autumn arrives and thoughts turn to pumpkins, football, and Thanks-giving dinner, it is time for health systems and physicians to prepare for the upcoming influenza season. In this issue of the Journal, Drs. Jin and Mossad review some practical virology and remind us why we must continue to encourage our patients and staff to be immunized against the flu.

Last year the flu season was surprisingly mild. The infection incidence seemed to peak late in the season, a reasonable number of people got vaccinated, and the level of viral antigenic drift was low. New hybrid viral strains did appear, but apparently with low prevalence, and the avian strains did not mutate to permit efficient human-to-human infection. But the relatively benign 2011–2012 flu season should not lull us into a lackadaisical approach to offering vaccination to all of our patients.

Ever since my own encounter with the flu a number of years ago, I have been pushing the vaccine with the zeal of a telemarketer. I was pleased that the vaccine arrived early this time, but continue to be surprised by the reasons patients offer for not receiving it—some strike me as akin to “the dog ate my homework.” For example: “I got the vaccine once and I got walking pneumonia.” And the always-popular “I got the vaccine and I got the flu.” Many patients don’t think they need the vaccine because they have never gotten the flu. (To them, I relate my tale of spending a weekend lying curled up on the floor of my bedroom having chills despite a sweatsuit and blanket). Some voice the scientifically irrational but common concern that since their immune system has been weakened by medications, they don’t want to get sick from the shot. And creatively, this year several patients have told me that they heard it is too early to get the vaccine—the effect won’t last all season.

Whatever our patients’ reason for recalcitrance, we should persevere and follow the national recommendation to vaccinate all persons over the age of 6 months. The vaccine may not be perfect, but with an estimated success rate of about 60%, it is better than any alternative approach. Plus, as Drs. Jin and Mossad note in their article, there is concern about emerging strains that are resistant to available antiviral therapies—0.5 mL of prevention trumps a pound of ineffective treatment.

Most of us have not spent the past 25 years on the front line continuously managing HIV-infected patients, but I am sure that at various points in our lives we all have been touched by the AIDS epidemic. Whether comforting a woman with knee pain in the office who is crying over the impending death of her son who lives in a group home for men with AIDS, diagnosing immune thrombocytopenia in a college student only to realize it is the seminal manifestation of his HIV infection, pleading unsuccessfully with several neurosurgeons to get one to perform a brain biopsy on an “enhancing ring lesion” in a young gay opera singer, or being part of a team caring for a gouty patient with AIDS and hepatitis C who had just undergone a successful liver transplantation, we all have our stories with resultant reflections on the era of medicine in which we practice.

In July 2012, the New York Times described the new home test for HIV infection as part of “the normalization of a disease once seen as a mark of shame.”¹ As with home pregnancy testing, people can now self-manage their need to know about what is going on in their body. But HIV goes so much deeper than this: it has been and remains a metaphor for and a reflection of many of the social issues that permeate our current political and social environment.

The politics and the social reactions to testing for HIV over the years since the virus was recognized in 1983–1984 is stuff for sociopsychologic treatises. Antibody testing was available in 1985, but in the absence of treatment, to test was simply to deliver a death sentence. Plus, with a diagnosis of AIDS, there would be no dental care, no insurance, no renting of an apartment, and perhaps no job. For some, family ties would be broken as closet doors would be thrown open, revealing a now unrecognized visage wearing the “mark of shame.” Some gay advocates rallied hard against testing, since anonymity and social protection for the infected could not be assured, a pragmatic response to blatant discrimination. In 1987, the first home test for HIV was in development, but—no surprise—there was no need for it.

As early treatments such as zidovudine (AZT) appeared and the value of specific antibiotic prophylaxis was demonstrated, there was some initial hope for treatment, and thus testing made medical sense. The size of the population infected (we were looking at the tip of the iceberg) was also being realized, so testing appealed to the social consciousness—try to limit infection. But discrimination wasn’t gone, and the politics of the time couldn’t quite handle all of the implications of a rapidly growing epidemic. America wasn’t ready for clean-needle-exchange programs, promotion of condom use, or open discussion of gay lifestyles. The Reagan White House was initially dead silent, except for proposing to limit entrance of potentially infected immigrants and promoting abstinence as the ideal protective approach.

Social righteousness took some hold, and protection of patient anonymity and autonomy became of paramount importance. But unintended consequences turned out to include limitation of testing: laws were written to require that HIV testing be accompanied by “appropriate,” stringently defined counseling, something that wasn’t always feasible. Patients needed to sign a release to be tested (“opt in”); many just said no. This tied the hands of physicians, so we developed work-arounds: we checked lymphocyte counts and CD4 counts to help us take care of patients too afraid to let us test for HIV directly.

Finally, in 2006, as therapies began to become increasingly effective and more data started to accumulate regarding the benefits of early antiretroviral therapy, the US Centers for Disease Control and Prevention recommended routine testing for all patients entering most acute health care facilities, unless they would actively decline (“opt out”). We have still not hit full stride in implementing universal testing for HIV. Nor have we hit our stride on fully accepting all demographic segments of the population. In some communities, HIV infection is still equivalent to the scarlet letter of Hester Prynne, not just because of the disease itself but because of the lifestyle it implies. Legislating laboratory testing practices cannot change all social attitudes. But maybe, hopefully, it is another step.

Dr. Christine Koval in this issue of the Journal discusses the practical use of the newly approved home HIV test. It is a short article, but it took a very, very long time for social and political forces to be modestly aligned sufficiently for there to be anything to write about. Since perhaps 18% of HIV-infected Americans are unaware of their infection, maybe some TV ads for this test, wedged between the ads for treating erectile dysfunction, can indeed bring (as the New York Times described) further “normalization” to the approach to managing HIV-infected patients.

Most of us have not spent the past 25 years on the front line continuously managing HIV-infected patients, but I am sure that at various points in our lives we all have been touched by the AIDS epidemic. Whether comforting a woman with knee pain in the office who is crying over the impending death of her son who lives in a group home for men with AIDS, diagnosing immune thrombocytopenia in a college student only to realize it is the seminal manifestation of his HIV infection, pleading unsuccessfully with several neurosurgeons to get one to perform a brain biopsy on an “enhancing ring lesion” in a young gay opera singer, or being part of a team caring for a gouty patient with AIDS and hepatitis C who had just undergone a successful liver transplantation, we all have our stories with resultant reflections on the era of medicine in which we practice.

In July 2012, the New York Times described the new home test for HIV infection as part of “the normalization of a disease once seen as a mark of shame.”¹ As with home pregnancy testing, people can now self-manage their need to know about what is going on in their body. But HIV goes so much deeper than this: it has been and remains a metaphor for and a reflection of many of the social issues that permeate our current political and social environment.

The politics and the social reactions to testing for HIV over the years since the virus was recognized in 1983–1984 is stuff for sociopsychologic treatises. Antibody testing was available in 1985, but in the absence of treatment, to test was simply to deliver a death sentence. Plus, with a diagnosis of AIDS, there would be no dental care, no insurance, no renting of an apartment, and perhaps no job. For some, family ties would be broken as closet doors would be thrown open, revealing a now unrecognized visage wearing the “mark of shame.” Some gay advocates rallied hard against testing, since anonymity and social protection for the infected could not be assured, a pragmatic response to blatant discrimination. In 1987, the first home test for HIV was in development, but—no surprise—there was no need for it.

As early treatments such as zidovudine (AZT) appeared and the value of specific antibiotic prophylaxis was demonstrated, there was some initial hope for treatment, and thus testing made medical sense. The size of the population infected (we were looking at the tip of the iceberg) was also being realized, so testing appealed to the social consciousness—try to limit infection. But discrimination wasn’t gone, and the politics of the time couldn’t quite handle all of the implications of a rapidly growing epidemic. America wasn’t ready for clean-needle-exchange programs, promotion of condom use, or open discussion of gay lifestyles. The Reagan White House was initially dead silent, except for proposing to limit entrance of potentially infected immigrants and promoting abstinence as the ideal protective approach.

Social righteousness took some hold, and protection of patient anonymity and autonomy became of paramount importance. But unintended consequences turned out to include limitation of testing: laws were written to require that HIV testing be accompanied by “appropriate,” stringently defined counseling, something that wasn’t always feasible. Patients needed to sign a release to be tested (“opt in”); many just said no. This tied the hands of physicians, so we developed work-arounds: we checked lymphocyte counts and CD4 counts to help us take care of patients too afraid to let us test for HIV directly.

Finally, in 2006, as therapies began to become increasingly effective and more data started to accumulate regarding the benefits of early antiretroviral therapy, the US Centers for Disease Control and Prevention recommended routine testing for all patients entering most acute health care facilities, unless they would actively decline (“opt out”). We have still not hit full stride in implementing universal testing for HIV. Nor have we hit our stride on fully accepting all demographic segments of the population. In some communities, HIV infection is still equivalent to the scarlet letter of Hester Prynne, not just because of the disease itself but because of the lifestyle it implies. Legislating laboratory testing practices cannot change all social attitudes. But maybe, hopefully, it is another step.

Dr. Christine Koval in this issue of the Journal discusses the practical use of the newly approved home HIV test. It is a short article, but it took a very, very long time for social and political forces to be modestly aligned sufficiently for there to be anything to write about. Since perhaps 18% of HIV-infected Americans are unaware of their infection, maybe some TV ads for this test, wedged between the ads for treating erectile dysfunction, can indeed bring (as the New York Times described) further “normalization” to the approach to managing HIV-infected patients.

Most of us have not spent the past 25 years on the front line continuously managing HIV-infected patients, but I am sure that at various points in our lives we all have been touched by the AIDS epidemic. Whether comforting a woman with knee pain in the office who is crying over the impending death of her son who lives in a group home for men with AIDS, diagnosing immune thrombocytopenia in a college student only to realize it is the seminal manifestation of his HIV infection, pleading unsuccessfully with several neurosurgeons to get one to perform a brain biopsy on an “enhancing ring lesion” in a young gay opera singer, or being part of a team caring for a gouty patient with AIDS and hepatitis C who had just undergone a successful liver transplantation, we all have our stories with resultant reflections on the era of medicine in which we practice.

In July 2012, the New York Times described the new home test for HIV infection as part of “the normalization of a disease once seen as a mark of shame.”¹ As with home pregnancy testing, people can now self-manage their need to know about what is going on in their body. But HIV goes so much deeper than this: it has been and remains a metaphor for and a reflection of many of the social issues that permeate our current political and social environment.

The politics and the social reactions to testing for HIV over the years since the virus was recognized in 1983–1984 is stuff for sociopsychologic treatises. Antibody testing was available in 1985, but in the absence of treatment, to test was simply to deliver a death sentence. Plus, with a diagnosis of AIDS, there would be no dental care, no insurance, no renting of an apartment, and perhaps no job. For some, family ties would be broken as closet doors would be thrown open, revealing a now unrecognized visage wearing the “mark of shame.” Some gay advocates rallied hard against testing, since anonymity and social protection for the infected could not be assured, a pragmatic response to blatant discrimination. In 1987, the first home test for HIV was in development, but—no surprise—there was no need for it.

As early treatments such as zidovudine (AZT) appeared and the value of specific antibiotic prophylaxis was demonstrated, there was some initial hope for treatment, and thus testing made medical sense. The size of the population infected (we were looking at the tip of the iceberg) was also being realized, so testing appealed to the social consciousness—try to limit infection. But discrimination wasn’t gone, and the politics of the time couldn’t quite handle all of the implications of a rapidly growing epidemic. America wasn’t ready for clean-needle-exchange programs, promotion of condom use, or open discussion of gay lifestyles. The Reagan White House was initially dead silent, except for proposing to limit entrance of potentially infected immigrants and promoting abstinence as the ideal protective approach.

Social righteousness took some hold, and protection of patient anonymity and autonomy became of paramount importance. But unintended consequences turned out to include limitation of testing: laws were written to require that HIV testing be accompanied by “appropriate,” stringently defined counseling, something that wasn’t always feasible. Patients needed to sign a release to be tested (“opt in”); many just said no. This tied the hands of physicians, so we developed work-arounds: we checked lymphocyte counts and CD4 counts to help us take care of patients too afraid to let us test for HIV directly.

Finally, in 2006, as therapies began to become increasingly effective and more data started to accumulate regarding the benefits of early antiretroviral therapy, the US Centers for Disease Control and Prevention recommended routine testing for all patients entering most acute health care facilities, unless they would actively decline (“opt out”). We have still not hit full stride in implementing universal testing for HIV. Nor have we hit our stride on fully accepting all demographic segments of the population. In some communities, HIV infection is still equivalent to the scarlet letter of Hester Prynne, not just because of the disease itself but because of the lifestyle it implies. Legislating laboratory testing practices cannot change all social attitudes. But maybe, hopefully, it is another step.

Dr. Christine Koval in this issue of the Journal discusses the practical use of the newly approved home HIV test. It is a short article, but it took a very, very long time for social and political forces to be modestly aligned sufficiently for there to be anything to write about. Since perhaps 18% of HIV-infected Americans are unaware of their infection, maybe some TV ads for this test, wedged between the ads for treating erectile dysfunction, can indeed bring (as the New York Times described) further “normalization” to the approach to managing HIV-infected patients.

The “I” has changed its meaning, the “P” is not necessary to make the diagnosis, and the syndrome is not strikingly common in adults. But the disease formerly known as idiopathic thrombocytopenic purpura (ITP) remains important for internists to diagnose because thrombocytopenia is extremely common.

ITP has long been recognized in children (in whom it is often self-limited but severe) and in adults (in whom it is often more insidious and chronic, with a wider differential diagnosis).

The “I” used to stand for “idiopathic” but now it stands for “immune,” following a half decade of work by many investigators. The seminal experimental work of Dr. William J. Harrington and others while the former was a hematology fellow with Carl Moore at Washington University is the stuff of legend and ethical debate. Harrington had himself injected with a pint of serum from a patient with ITP and nearly died, demonstrating that the patient’s blood contained a substance or substances capable of inducing reversible profound thrombocytopenia in the recipient.¹ Today, this classic experiment would probably not be performed, nor would the many more infusions that Harrington subsequently gave himself, other physicians, and support staff.²

Understanding the immunologic basis for ITP has led to treatments that are usually but not uniformly successful. Prednisone remains the main initial therapy, but its myriad side effects have led to the strategy of turning sooner to other therapies, such as intravenous immunoglobulin, splenectomy, rituximab (Rituxan), and, most recently, thrombopoietin agonists, in order to control the disease or even put it into remission.

Treatment decisions are often assigned to the hematologist or rheumatologist, but recognizing ITP and distinguishing it from other causes of thrombocytopenia remain the province of primary care providers, as discussed by Thota et al in this issue of the Journal.³ The diagnosis of ITP does not require the presence of purpura, which most adults ITP patients probably do not have, nor does it always require a bone marrow biopsy. It is important that ITP be distinguished from thrombocytopenia that is induced by drugs (particularly heparin) and myelodysplastic and other marrow processes (potential clues being other cytopenias, an unexplained elevated mean corpuscular volume, or constitutional symptoms). Undiagnosed thyroid disease and HIV infection should be tested for routinely, once drug-associated and other obvious causes are excluded.

The “I” has changed its meaning, the “P” is not necessary to make the diagnosis, and the syndrome is not strikingly common in adults. But the disease formerly known as idiopathic thrombocytopenic purpura (ITP) remains important for internists to diagnose because thrombocytopenia is extremely common.

ITP has long been recognized in children (in whom it is often self-limited but severe) and in adults (in whom it is often more insidious and chronic, with a wider differential diagnosis).

The “I” used to stand for “idiopathic” but now it stands for “immune,” following a half decade of work by many investigators. The seminal experimental work of Dr. William J. Harrington and others while the former was a hematology fellow with Carl Moore at Washington University is the stuff of legend and ethical debate. Harrington had himself injected with a pint of serum from a patient with ITP and nearly died, demonstrating that the patient’s blood contained a substance or substances capable of inducing reversible profound thrombocytopenia in the recipient.¹ Today, this classic experiment would probably not be performed, nor would the many more infusions that Harrington subsequently gave himself, other physicians, and support staff.²

Understanding the immunologic basis for ITP has led to treatments that are usually but not uniformly successful. Prednisone remains the main initial therapy, but its myriad side effects have led to the strategy of turning sooner to other therapies, such as intravenous immunoglobulin, splenectomy, rituximab (Rituxan), and, most recently, thrombopoietin agonists, in order to control the disease or even put it into remission.

Treatment decisions are often assigned to the hematologist or rheumatologist, but recognizing ITP and distinguishing it from other causes of thrombocytopenia remain the province of primary care providers, as discussed by Thota et al in this issue of the Journal.³ The diagnosis of ITP does not require the presence of purpura, which most adults ITP patients probably do not have, nor does it always require a bone marrow biopsy. It is important that ITP be distinguished from thrombocytopenia that is induced by drugs (particularly heparin) and myelodysplastic and other marrow processes (potential clues being other cytopenias, an unexplained elevated mean corpuscular volume, or constitutional symptoms). Undiagnosed thyroid disease and HIV infection should be tested for routinely, once drug-associated and other obvious causes are excluded.

The “I” has changed its meaning, the “P” is not necessary to make the diagnosis, and the syndrome is not strikingly common in adults. But the disease formerly known as idiopathic thrombocytopenic purpura (ITP) remains important for internists to diagnose because thrombocytopenia is extremely common.

ITP has long been recognized in children (in whom it is often self-limited but severe) and in adults (in whom it is often more insidious and chronic, with a wider differential diagnosis).

The “I” used to stand for “idiopathic” but now it stands for “immune,” following a half decade of work by many investigators. The seminal experimental work of Dr. William J. Harrington and others while the former was a hematology fellow with Carl Moore at Washington University is the stuff of legend and ethical debate. Harrington had himself injected with a pint of serum from a patient with ITP and nearly died, demonstrating that the patient’s blood contained a substance or substances capable of inducing reversible profound thrombocytopenia in the recipient.¹ Today, this classic experiment would probably not be performed, nor would the many more infusions that Harrington subsequently gave himself, other physicians, and support staff.²

Understanding the immunologic basis for ITP has led to treatments that are usually but not uniformly successful. Prednisone remains the main initial therapy, but its myriad side effects have led to the strategy of turning sooner to other therapies, such as intravenous immunoglobulin, splenectomy, rituximab (Rituxan), and, most recently, thrombopoietin agonists, in order to control the disease or even put it into remission.

Treatment decisions are often assigned to the hematologist or rheumatologist, but recognizing ITP and distinguishing it from other causes of thrombocytopenia remain the province of primary care providers, as discussed by Thota et al in this issue of the Journal.³ The diagnosis of ITP does not require the presence of purpura, which most adults ITP patients probably do not have, nor does it always require a bone marrow biopsy. It is important that ITP be distinguished from thrombocytopenia that is induced by drugs (particularly heparin) and myelodysplastic and other marrow processes (potential clues being other cytopenias, an unexplained elevated mean corpuscular volume, or constitutional symptoms). Undiagnosed thyroid disease and HIV infection should be tested for routinely, once drug-associated and other obvious causes are excluded.

Atrial fibrillation is the most common chronic rapid arrhythmia requiring the attention of internists and cardiologists. Patients with this arrhythmia have higher rates of morbidity and death than similar patients with normal sinus rhythm, and they do so for a number of reasons.

Patients with atrial fibrillation have a slew of comorbidities, including hypertensive and ischemic heart disease. Patients undergoing cardiac surgery have a dramatically higher risk of a postoperative bout of atrial fibrillation. The main concerns are the risk of stroke and the symptoms of heart failure and fatigue (often with exercise intolerance).

Information from registries of patients with atrial fibrillation has permitted the development of prognosticators of stroke risk. The CHADS₂ score (congestive heart failure, hypertension, age > 75, diabetes, and prior stroke or transient ischemic attack) is an amazingly simple way to identify patients with atrial fibrillation who are at highest risk of stroke. This in turn has allowed stratification of patients for entrance into various anticoagulation studies. And perhaps surprisingly, when many factors are considered, nothing turns out to be dramatically better than warfarin (Coumadin)—if the international normalized ratio (INR) can be appropriately controlled.

Not many options are available to prevent atrial fibrillation. Postoperative atrial fibrillation may be prevented with high-dose steroids or colchicine (Colcrys), but this is often a self-limited, situational event. Chronic or recurrent intermittent atrial fibrillation is not readily prevented in most patients, and many symptomatic patients, as discussed by Dr. Bruce Lindsay in this issue, may benefit from drug therapy or radiofrequency ablation.

Studies suggest that trying to convert atrial fibrillation to normal sinus rhythm (vs controlling the rate) may not be worth the effort and the risk in many patients with asymptomatic atrial fibrillation. Furthermore, in patients with symptomatic atrial fibrillation, determining the cause of symptoms is difficult. For example, it may not always be easily determined if fatigue in an elderly patient with chronic atrial fibrillation is due to mild rate-related congestive heart failure, decreased left ventricular output due to the loss of the atrial “kick,” chronic ischemia, or the sedating effect of a beta-blocker given in an effort to control the tachycardia.

Despite many large, well-done studies comparing antiarrhythmic drugs, ablation techniques, and anticoagulants, patients will still benefit most from an experienced clinician’s reflective, individualized assessment before embarking on algorithm-driven long-term therapy. We have more choices, more data, and more management algorithms, but there is still no panacea for patients with atrial fibrillation.

Atrial fibrillation is the most common chronic rapid arrhythmia requiring the attention of internists and cardiologists. Patients with this arrhythmia have higher rates of morbidity and death than similar patients with normal sinus rhythm, and they do so for a number of reasons.

Patients with atrial fibrillation have a slew of comorbidities, including hypertensive and ischemic heart disease. Patients undergoing cardiac surgery have a dramatically higher risk of a postoperative bout of atrial fibrillation. The main concerns are the risk of stroke and the symptoms of heart failure and fatigue (often with exercise intolerance).

Information from registries of patients with atrial fibrillation has permitted the development of prognosticators of stroke risk. The CHADS₂ score (congestive heart failure, hypertension, age > 75, diabetes, and prior stroke or transient ischemic attack) is an amazingly simple way to identify patients with atrial fibrillation who are at highest risk of stroke. This in turn has allowed stratification of patients for entrance into various anticoagulation studies. And perhaps surprisingly, when many factors are considered, nothing turns out to be dramatically better than warfarin (Coumadin)—if the international normalized ratio (INR) can be appropriately controlled.

Not many options are available to prevent atrial fibrillation. Postoperative atrial fibrillation may be prevented with high-dose steroids or colchicine (Colcrys), but this is often a self-limited, situational event. Chronic or recurrent intermittent atrial fibrillation is not readily prevented in most patients, and many symptomatic patients, as discussed by Dr. Bruce Lindsay in this issue, may benefit from drug therapy or radiofrequency ablation.

Studies suggest that trying to convert atrial fibrillation to normal sinus rhythm (vs controlling the rate) may not be worth the effort and the risk in many patients with asymptomatic atrial fibrillation. Furthermore, in patients with symptomatic atrial fibrillation, determining the cause of symptoms is difficult. For example, it may not always be easily determined if fatigue in an elderly patient with chronic atrial fibrillation is due to mild rate-related congestive heart failure, decreased left ventricular output due to the loss of the atrial “kick,” chronic ischemia, or the sedating effect of a beta-blocker given in an effort to control the tachycardia.

Despite many large, well-done studies comparing antiarrhythmic drugs, ablation techniques, and anticoagulants, patients will still benefit most from an experienced clinician’s reflective, individualized assessment before embarking on algorithm-driven long-term therapy. We have more choices, more data, and more management algorithms, but there is still no panacea for patients with atrial fibrillation.

Atrial fibrillation is the most common chronic rapid arrhythmia requiring the attention of internists and cardiologists. Patients with this arrhythmia have higher rates of morbidity and death than similar patients with normal sinus rhythm, and they do so for a number of reasons.

Patients with atrial fibrillation have a slew of comorbidities, including hypertensive and ischemic heart disease. Patients undergoing cardiac surgery have a dramatically higher risk of a postoperative bout of atrial fibrillation. The main concerns are the risk of stroke and the symptoms of heart failure and fatigue (often with exercise intolerance).

Information from registries of patients with atrial fibrillation has permitted the development of prognosticators of stroke risk. The CHADS₂ score (congestive heart failure, hypertension, age > 75, diabetes, and prior stroke or transient ischemic attack) is an amazingly simple way to identify patients with atrial fibrillation who are at highest risk of stroke. This in turn has allowed stratification of patients for entrance into various anticoagulation studies. And perhaps surprisingly, when many factors are considered, nothing turns out to be dramatically better than warfarin (Coumadin)—if the international normalized ratio (INR) can be appropriately controlled.

Not many options are available to prevent atrial fibrillation. Postoperative atrial fibrillation may be prevented with high-dose steroids or colchicine (Colcrys), but this is often a self-limited, situational event. Chronic or recurrent intermittent atrial fibrillation is not readily prevented in most patients, and many symptomatic patients, as discussed by Dr. Bruce Lindsay in this issue, may benefit from drug therapy or radiofrequency ablation.

Studies suggest that trying to convert atrial fibrillation to normal sinus rhythm (vs controlling the rate) may not be worth the effort and the risk in many patients with asymptomatic atrial fibrillation. Furthermore, in patients with symptomatic atrial fibrillation, determining the cause of symptoms is difficult. For example, it may not always be easily determined if fatigue in an elderly patient with chronic atrial fibrillation is due to mild rate-related congestive heart failure, decreased left ventricular output due to the loss of the atrial “kick,” chronic ischemia, or the sedating effect of a beta-blocker given in an effort to control the tachycardia.

Despite many large, well-done studies comparing antiarrhythmic drugs, ablation techniques, and anticoagulants, patients will still benefit most from an experienced clinician’s reflective, individualized assessment before embarking on algorithm-driven long-term therapy. We have more choices, more data, and more management algorithms, but there is still no panacea for patients with atrial fibrillation.