From the Editor

In the past decade, it has been increasingly recognized that these clonally produced proteins—entire immunoglobulins or free light chains—may be directly pathogenic, independent of any pathologic effect of cellular clonal expansion and infiltration. Brouet class 1 cryoglobulinemia (in which a monoclonal paraprotein precipitates in cooler temperatures and acts as a source of complement, activating the immune complex) and light chain (usually lambda)-related amyloidosis have been recognized for much longer. But a newer concept, monoclonal gammopathy of renal significance (MGRS), has attracted significant attention and to some extent has modified our approach to patients with either known MGUS or unexplained chronic kidney disease.

Finding MGUS still warrants a parsimonious evaluation for possible progression to myeloma or other proliferative disorder, as discussed by Khouri et al in this issue of the Journal. But it should also prompt a thoughtful assessment of renal function, including estimating the glomerular filtration rate and looking for proteinuria, hematuria, and unexplained glucosuria or inappropriate urine pH. While typical light chain-induced renal tubular injury is usually associated with high levels of proteins such as those seen with myeloma, other patterns of glomerular, vascular, and mixed renal disease are associated with deposition of proteins that, once considered in the differential diagnosis, warrant renal biopsy to diagnose and direct appropriate therapy. That MGUS and MGRS occur more frequently in older patients, who are already at greater risk of multiple common causes of kidney disease, complicates clinical decision-making.1 Some of these disorders are associated with other initially subtle or seemingly disconnected clinical symptoms such as polyneuropathy, rash, and carpal tunnel syndrome, but many are at least initially limited to the kidneys.

As we enter a new calendar year, we at the Journal send our best wishes to all of our readers, authors, and peer reviewers, and we thank you for sharing in our medical education ventures. I personally hope that we have added some joy, enthusiasm—and some knowledge—to your professional activities, and I hope that we all can participate in some way to refashion a more civil and peaceful world in 2019.

In the past decade, it has been increasingly recognized that these clonally produced proteins—entire immunoglobulins or free light chains—may be directly pathogenic, independent of any pathologic effect of cellular clonal expansion and infiltration. Brouet class 1 cryoglobulinemia (in which a monoclonal paraprotein precipitates in cooler temperatures and acts as a source of complement, activating the immune complex) and light chain (usually lambda)-related amyloidosis have been recognized for much longer. But a newer concept, monoclonal gammopathy of renal significance (MGRS), has attracted significant attention and to some extent has modified our approach to patients with either known MGUS or unexplained chronic kidney disease.

Finding MGUS still warrants a parsimonious evaluation for possible progression to myeloma or other proliferative disorder, as discussed by Khouri et al in this issue of the Journal. But it should also prompt a thoughtful assessment of renal function, including estimating the glomerular filtration rate and looking for proteinuria, hematuria, and unexplained glucosuria or inappropriate urine pH. While typical light chain-induced renal tubular injury is usually associated with high levels of proteins such as those seen with myeloma, other patterns of glomerular, vascular, and mixed renal disease are associated with deposition of proteins that, once considered in the differential diagnosis, warrant renal biopsy to diagnose and direct appropriate therapy. That MGUS and MGRS occur more frequently in older patients, who are already at greater risk of multiple common causes of kidney disease, complicates clinical decision-making.1 Some of these disorders are associated with other initially subtle or seemingly disconnected clinical symptoms such as polyneuropathy, rash, and carpal tunnel syndrome, but many are at least initially limited to the kidneys.

As we enter a new calendar year, we at the Journal send our best wishes to all of our readers, authors, and peer reviewers, and we thank you for sharing in our medical education ventures. I personally hope that we have added some joy, enthusiasm—and some knowledge—to your professional activities, and I hope that we all can participate in some way to refashion a more civil and peaceful world in 2019.

In the past decade, it has been increasingly recognized that these clonally produced proteins—entire immunoglobulins or free light chains—may be directly pathogenic, independent of any pathologic effect of cellular clonal expansion and infiltration. Brouet class 1 cryoglobulinemia (in which a monoclonal paraprotein precipitates in cooler temperatures and acts as a source of complement, activating the immune complex) and light chain (usually lambda)-related amyloidosis have been recognized for much longer. But a newer concept, monoclonal gammopathy of renal significance (MGRS), has attracted significant attention and to some extent has modified our approach to patients with either known MGUS or unexplained chronic kidney disease.

Finding MGUS still warrants a parsimonious evaluation for possible progression to myeloma or other proliferative disorder, as discussed by Khouri et al in this issue of the Journal. But it should also prompt a thoughtful assessment of renal function, including estimating the glomerular filtration rate and looking for proteinuria, hematuria, and unexplained glucosuria or inappropriate urine pH. While typical light chain-induced renal tubular injury is usually associated with high levels of proteins such as those seen with myeloma, other patterns of glomerular, vascular, and mixed renal disease are associated with deposition of proteins that, once considered in the differential diagnosis, warrant renal biopsy to diagnose and direct appropriate therapy. That MGUS and MGRS occur more frequently in older patients, who are already at greater risk of multiple common causes of kidney disease, complicates clinical decision-making.1 Some of these disorders are associated with other initially subtle or seemingly disconnected clinical symptoms such as polyneuropathy, rash, and carpal tunnel syndrome, but many are at least initially limited to the kidneys.

As we enter a new calendar year, we at the Journal send our best wishes to all of our readers, authors, and peer reviewers, and we thank you for sharing in our medical education ventures. I personally hope that we have added some joy, enthusiasm—and some knowledge—to your professional activities, and I hope that we all can participate in some way to refashion a more civil and peaceful world in 2019.

My father was a general surgeon in a very small town in West Virginia. He was very successful and his patients loved him. He loved them, too, and chose to practice well into his 70s. In retrospect, he should not have.

Perhaps brilliant in his day, he was less so at the end of his career. I realized his deficiencies when I was in residency. I wondered if, despite his undeniable experience, his age was compromising his clinical acumen.

There are data available that support my suspicions. Investigators from the Department of Health Policy and Management at Harvard T.H. Chan School of Public Health reviewed a random sample of Medicare beneficiaries admitted to a hospital between 2011 and 2014. They hypothesized that physician age may affect outcomes such as 30-day mortality, readmissions, and cost of care. Among the more than 700,000 admissions by more than 18,000 hospitalists, the 30-day mortality rates were significantly higher for physicians aged 60 years and older, compared with younger physicians. Importantly though, there was no difference in mortality for older, but high-volume, physicians, compared with younger ones.

These results were published in the BMJ (2017 May 16;357:j1797. doi: 10.1136/bmj.j1797) by the same group that described a similar reduction in mortality among female versus male internists (JAMA Intern Med. 2017 Feb 1;177[2]:206-13). Both studies attracted widespread media attention.

The BMJ study analyzed outcomes among hospitalists who exclusively manage inpatients. Hematologists, in contrast, are largely based in the outpatient setting or in a lab. Yet, hematologists are often called upon to cover inpatient units of very sick patients. We care for patients with acute leukemia, thrombotic thrombocytopenic purpura, and graft versus host disease, among other debilitating diseases. In that sense, I believe data generated from hospitalists probably apply to inpatient hematology as well.

Having just been the attending on one of these services, I am uncomfortably certain that they apply. I proudly boast that I once attended for 6 months in a year. I was good at it and enjoyed it. With time, though, we hired additional staff and I acquired administrative duties that decreased my attending service time. I now attend for 2 weeks, twice a year.

During the last one of these service times, I began to suspect that I was not as sharp as I once was. I don’t think I missed anything, I just didn’t seem to catch changes in clinical status as quickly as I once did. I was less comfortable with the new medications I was prescribing. I was depending more on the clinical pharmacist and the hematology fellow to keep track of side effects and dose adjustments. I was worried – more than ever – that I would make a mistake. The last thing I want to be is dangerous.


As department chairman, though, it is part of my job to ensure that no one else is dangerous either. The Joint Commission mandates Ongoing Professional Practice Evaluation (OPPE), which is intended to help assess a practitioner’s clinical competence. Yet, the commission recognizes that “Cognitive specialties (internal medicine, family practice, psychiatry, med specialties ...) are very difficult” in terms of identifying meaningful data that can be evaluated.

We do not have adequate tools to assess clinical competency. As a result, we are generally aware that physicians do a poor job of policing our own, in no small part because of a reluctance to identify and confront less competent physicians. Where police departments are accused of hiding behind a blue wall of silence, are physicians guilty of maintaining a white wall of silence?

Of course we are. How many clinically shaky fellows do we graduate into our profession every year? How many of us are aware of colleagues who are unskilled, but are reluctant to speak up about them? Our sins are documented in books such as “Wall of Silence: The Untold Story of the Medical Mistakes that Kill and Injure Millions of Americans” by Rosemary Gibson and Janardan Prasad Singh and “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care,” by Marty Makary.

Concern for my own competence notwithstanding, medicine as a profession requires reflection on its role in allowing substandard patient care to continue.

Punishment doesn’t seem to be the best way to right wrongs. The punished may not learn the lesson and the unpunished will be less forthcoming with their own errors.

Taking a lesson from highly reliable industries such as airlines, the medical profession is addressing medical errors better. For example, my institution has mandated thorough checklists before any and all invasive procedures, including bone marrow biopsies. Through a morbidity and mortality review of a case of hepatitis, we developed an automatic method of ordering hepatitis panels in every patient treated with monoclonal antibodies. Making systemic changes to prevent error avoids having to punish those who make errors, while holding accountable those who skirt the built-in safeguards.

We are less successful at applying similar error mitigation techniques to individual physicians who may not be clinically excellent. Examples abound of physicians who provide substandard care, but are allowed to continue. The repercussions continue at Wake Forest Baptist Medical Center, where a pathologist misdiagnosed some cancer cases over at least a 2-year period of time. Physicians, as a group, are not as good at certifying competency as are nurses, advanced practice providers, and pharmacists.

With many academic hematologists having relatively small practices, getting older, and getting burned out, the potential for patient harm as a result of medical error increases. Further, these physicians may not realize their increased risk and may be indignant when confronted.

I am interested in best practices that address this difficult and contentious issue. I hope our readers will offer their policies and procedures so that we can learn from each other. Patients should not have to worry about their doctors’ competency and doctors should be able to hold each other accountable by removing the white wall of silence.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

My father was a general surgeon in a very small town in West Virginia. He was very successful and his patients loved him. He loved them, too, and chose to practice well into his 70s. In retrospect, he should not have.

Perhaps brilliant in his day, he was less so at the end of his career. I realized his deficiencies when I was in residency. I wondered if, despite his undeniable experience, his age was compromising his clinical acumen.

There are data available that support my suspicions. Investigators from the Department of Health Policy and Management at Harvard T.H. Chan School of Public Health reviewed a random sample of Medicare beneficiaries admitted to a hospital between 2011 and 2014. They hypothesized that physician age may affect outcomes such as 30-day mortality, readmissions, and cost of care. Among the more than 700,000 admissions by more than 18,000 hospitalists, the 30-day mortality rates were significantly higher for physicians aged 60 years and older, compared with younger physicians. Importantly though, there was no difference in mortality for older, but high-volume, physicians, compared with younger ones.

These results were published in the BMJ (2017 May 16;357:j1797. doi: 10.1136/bmj.j1797) by the same group that described a similar reduction in mortality among female versus male internists (JAMA Intern Med. 2017 Feb 1;177[2]:206-13). Both studies attracted widespread media attention.

The BMJ study analyzed outcomes among hospitalists who exclusively manage inpatients. Hematologists, in contrast, are largely based in the outpatient setting or in a lab. Yet, hematologists are often called upon to cover inpatient units of very sick patients. We care for patients with acute leukemia, thrombotic thrombocytopenic purpura, and graft versus host disease, among other debilitating diseases. In that sense, I believe data generated from hospitalists probably apply to inpatient hematology as well.

Having just been the attending on one of these services, I am uncomfortably certain that they apply. I proudly boast that I once attended for 6 months in a year. I was good at it and enjoyed it. With time, though, we hired additional staff and I acquired administrative duties that decreased my attending service time. I now attend for 2 weeks, twice a year.

During the last one of these service times, I began to suspect that I was not as sharp as I once was. I don’t think I missed anything, I just didn’t seem to catch changes in clinical status as quickly as I once did. I was less comfortable with the new medications I was prescribing. I was depending more on the clinical pharmacist and the hematology fellow to keep track of side effects and dose adjustments. I was worried – more than ever – that I would make a mistake. The last thing I want to be is dangerous.


As department chairman, though, it is part of my job to ensure that no one else is dangerous either. The Joint Commission mandates Ongoing Professional Practice Evaluation (OPPE), which is intended to help assess a practitioner’s clinical competence. Yet, the commission recognizes that “Cognitive specialties (internal medicine, family practice, psychiatry, med specialties ...) are very difficult” in terms of identifying meaningful data that can be evaluated.

We do not have adequate tools to assess clinical competency. As a result, we are generally aware that physicians do a poor job of policing our own, in no small part because of a reluctance to identify and confront less competent physicians. Where police departments are accused of hiding behind a blue wall of silence, are physicians guilty of maintaining a white wall of silence?

Of course we are. How many clinically shaky fellows do we graduate into our profession every year? How many of us are aware of colleagues who are unskilled, but are reluctant to speak up about them? Our sins are documented in books such as “Wall of Silence: The Untold Story of the Medical Mistakes that Kill and Injure Millions of Americans” by Rosemary Gibson and Janardan Prasad Singh and “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care,” by Marty Makary.

Concern for my own competence notwithstanding, medicine as a profession requires reflection on its role in allowing substandard patient care to continue.

Punishment doesn’t seem to be the best way to right wrongs. The punished may not learn the lesson and the unpunished will be less forthcoming with their own errors.

Taking a lesson from highly reliable industries such as airlines, the medical profession is addressing medical errors better. For example, my institution has mandated thorough checklists before any and all invasive procedures, including bone marrow biopsies. Through a morbidity and mortality review of a case of hepatitis, we developed an automatic method of ordering hepatitis panels in every patient treated with monoclonal antibodies. Making systemic changes to prevent error avoids having to punish those who make errors, while holding accountable those who skirt the built-in safeguards.

We are less successful at applying similar error mitigation techniques to individual physicians who may not be clinically excellent. Examples abound of physicians who provide substandard care, but are allowed to continue. The repercussions continue at Wake Forest Baptist Medical Center, where a pathologist misdiagnosed some cancer cases over at least a 2-year period of time. Physicians, as a group, are not as good at certifying competency as are nurses, advanced practice providers, and pharmacists.

With many academic hematologists having relatively small practices, getting older, and getting burned out, the potential for patient harm as a result of medical error increases. Further, these physicians may not realize their increased risk and may be indignant when confronted.

I am interested in best practices that address this difficult and contentious issue. I hope our readers will offer their policies and procedures so that we can learn from each other. Patients should not have to worry about their doctors’ competency and doctors should be able to hold each other accountable by removing the white wall of silence.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

My father was a general surgeon in a very small town in West Virginia. He was very successful and his patients loved him. He loved them, too, and chose to practice well into his 70s. In retrospect, he should not have.

Perhaps brilliant in his day, he was less so at the end of his career. I realized his deficiencies when I was in residency. I wondered if, despite his undeniable experience, his age was compromising his clinical acumen.

There are data available that support my suspicions. Investigators from the Department of Health Policy and Management at Harvard T.H. Chan School of Public Health reviewed a random sample of Medicare beneficiaries admitted to a hospital between 2011 and 2014. They hypothesized that physician age may affect outcomes such as 30-day mortality, readmissions, and cost of care. Among the more than 700,000 admissions by more than 18,000 hospitalists, the 30-day mortality rates were significantly higher for physicians aged 60 years and older, compared with younger physicians. Importantly though, there was no difference in mortality for older, but high-volume, physicians, compared with younger ones.

These results were published in the BMJ (2017 May 16;357:j1797. doi: 10.1136/bmj.j1797) by the same group that described a similar reduction in mortality among female versus male internists (JAMA Intern Med. 2017 Feb 1;177[2]:206-13). Both studies attracted widespread media attention.

The BMJ study analyzed outcomes among hospitalists who exclusively manage inpatients. Hematologists, in contrast, are largely based in the outpatient setting or in a lab. Yet, hematologists are often called upon to cover inpatient units of very sick patients. We care for patients with acute leukemia, thrombotic thrombocytopenic purpura, and graft versus host disease, among other debilitating diseases. In that sense, I believe data generated from hospitalists probably apply to inpatient hematology as well.

Having just been the attending on one of these services, I am uncomfortably certain that they apply. I proudly boast that I once attended for 6 months in a year. I was good at it and enjoyed it. With time, though, we hired additional staff and I acquired administrative duties that decreased my attending service time. I now attend for 2 weeks, twice a year.

During the last one of these service times, I began to suspect that I was not as sharp as I once was. I don’t think I missed anything, I just didn’t seem to catch changes in clinical status as quickly as I once did. I was less comfortable with the new medications I was prescribing. I was depending more on the clinical pharmacist and the hematology fellow to keep track of side effects and dose adjustments. I was worried – more than ever – that I would make a mistake. The last thing I want to be is dangerous.


As department chairman, though, it is part of my job to ensure that no one else is dangerous either. The Joint Commission mandates Ongoing Professional Practice Evaluation (OPPE), which is intended to help assess a practitioner’s clinical competence. Yet, the commission recognizes that “Cognitive specialties (internal medicine, family practice, psychiatry, med specialties ...) are very difficult” in terms of identifying meaningful data that can be evaluated.

We do not have adequate tools to assess clinical competency. As a result, we are generally aware that physicians do a poor job of policing our own, in no small part because of a reluctance to identify and confront less competent physicians. Where police departments are accused of hiding behind a blue wall of silence, are physicians guilty of maintaining a white wall of silence?

Of course we are. How many clinically shaky fellows do we graduate into our profession every year? How many of us are aware of colleagues who are unskilled, but are reluctant to speak up about them? Our sins are documented in books such as “Wall of Silence: The Untold Story of the Medical Mistakes that Kill and Injure Millions of Americans” by Rosemary Gibson and Janardan Prasad Singh and “Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care,” by Marty Makary.

Concern for my own competence notwithstanding, medicine as a profession requires reflection on its role in allowing substandard patient care to continue.

Punishment doesn’t seem to be the best way to right wrongs. The punished may not learn the lesson and the unpunished will be less forthcoming with their own errors.

Taking a lesson from highly reliable industries such as airlines, the medical profession is addressing medical errors better. For example, my institution has mandated thorough checklists before any and all invasive procedures, including bone marrow biopsies. Through a morbidity and mortality review of a case of hepatitis, we developed an automatic method of ordering hepatitis panels in every patient treated with monoclonal antibodies. Making systemic changes to prevent error avoids having to punish those who make errors, while holding accountable those who skirt the built-in safeguards.

We are less successful at applying similar error mitigation techniques to individual physicians who may not be clinically excellent. Examples abound of physicians who provide substandard care, but are allowed to continue. The repercussions continue at Wake Forest Baptist Medical Center, where a pathologist misdiagnosed some cancer cases over at least a 2-year period of time. Physicians, as a group, are not as good at certifying competency as are nurses, advanced practice providers, and pharmacists.

With many academic hematologists having relatively small practices, getting older, and getting burned out, the potential for patient harm as a result of medical error increases. Further, these physicians may not realize their increased risk and may be indignant when confronted.

I am interested in best practices that address this difficult and contentious issue. I hope our readers will offer their policies and procedures so that we can learn from each other. Patients should not have to worry about their doctors’ competency and doctors should be able to hold each other accountable by removing the white wall of silence.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

“To every thing there is a season, and a time to every purpose under the heaven.”

— Ecclesiastes

The month of birth is not just relevant to one’s astrological sign. It may have medical consequences. An impressive number of published studies have found that the month and season of birth may be related to a higher risk of various medical and psychiatric disorders.

For decades, it has been reported in more than 250 studies¹ that a disproportionate number of individuals with schizophrenia are born during the winter months (January/February/March in the Northern Hemisphere and July/August/September in the Southern Hemisphere). This seasonal pattern was eventually linked to the lack of sunlight during winter months and a deficiency of vitamin D, a hormone that is critical for normal brain development. Recent studies have reported that very low serum levels of vitamin D during pregnancy significantly increase the risk of schizophrenia in offspring.²

But the plot thickens. Numerous studies over the past 20 to 30 years have reported an association between month or season of birth with sundry general medical and psychiatric conditions. Even longevity has been reported to vary with season of birth, with a longer life span for people born in autumn (October to December), compared with those born in spring (April to June).³ Of note, a longer life span for an individual born in autumn has been attributed to a higher birth weight during that season compared with those born in other seasons. In addition, the shorter life span of those with spring births has been attributed to factors during fetal life that increase the susceptibility to disease later in life (after age 50).

The following studies have reported an association between month/season of birth and general medical disorders:

• Higher rate of myopia for summer births⁴
• Tenfold higher risk of respiratory syntactical virus in babies born in January compared with October, and a 2 to 3 times higher risk of hospitalization⁵
• Higher rates of asthma during childhood for March and April births⁶
• Lower rate of lung cancer for winter births compared with all other seasons⁷
• An excess of colon and rectal cancer for people born in September, and the lowest rate for spring births⁸
• Lowest diabetes risk for summer births⁹
• For males: Cardiac mortality is 11% less likely for 4th-quarter births compared with 1st-quarter births. For females: Cancer mortality is lowest in 3rd-quarter vs 1st-quarter births¹⁰
• The peak risk for both Hodgkin and non-Hodgkin lymphoma is for April births compared with other months¹¹
• A strong trend for malignant neoplasm in males was reported for births during the 1st trimester of the year (January through April) compared with the rest of the year¹²
• Higher rate of spring births among patients who have insulin-dependent diabetes¹³
• Breast cancer is 5% higher for June births compared with December births¹⁴
• Higher risk of developing an allergy later in life for those born approximately 3 months before the main allergy season.¹⁵

The above studies may imply that birth seasonality is medical destiny. However, most such reports need further replication, or may be due to chance findings in various databases. However, they are worth considering as hypothesis-generating signals.

Continue to: And now for the risk of psychiatric disorders...

And now for the risk of psychi­atric disorders and month or season of birth. Here, too, there are multiple published reports:

• Higher social anhedonia and schizoid features among persons born in June and July¹⁶
• Higher autism rates for children conceived in December to March compared with those conceived during summer months¹⁷
• In contrast to the above report, the risk of autism spectrum disorders in the United Kingdom was higher for those born in summer¹⁸
• Another study labeled seasonality of birth in autism as “fiction”!¹⁹
• Significant spring births for persons with anxiety²⁰
• Highest occurrence of postpartum depression in December²¹
• High prepartum depression in winter and postpartum depression in fall²²
• Lower performance IQ among spring births²³
• Disproportionate excess of births in April, May, and June for those who die by suicide²⁴
• Suicide by burning oneself is higher among individuals born in January compared with any other month²⁵
• Relative increase in March and August births among patients with anorexia²⁶
• Season of birth is a predictor of emotional and behavioral regulation²⁷
• Serotonin metabolites show a peak in spring and a trough in fall²⁸
• Increase of spring births in individuals with Down syndrome²⁹
• Excess of spring births among patients with Alzheimer’s disease.³⁰

As with the seasonality of medical illness risk, the association of the month or season of birth with psychiatric disorders may be based on skewed samples or simply a chance finding. However, there may be some seasonal environmental factors that could increase the risk for disorders of the body or the brain/mind. The most plausible factors may be season-related fetal developmental disruptions caused by maternal infection, diet, lack of sunlight, temperature, substance use, or immune dysregulation from comorbid medical conditions during pregnancy. Some researchers have speculated that fluctuations in the availability of various fresh fruits and vegetables during certain seasons of the year may influence fetal development or increase the susceptibility to some medical disorders. This may be at the time of conception or during the 2nd trimester of pregnancy, when the brain develops.

On the other hand, those studies, published in peer-reviewed journals, may constitute a sophisticated form of “psychiatric astrology” whose credibility could be as suspect as the imaginative predictions of one’s horoscope in the daily newspaper…

To comment on this editorial or other topics of interest: [email protected].

“To every thing there is a season, and a time to every purpose under the heaven.”

— Ecclesiastes

The month of birth is not just relevant to one’s astrological sign. It may have medical consequences. An impressive number of published studies have found that the month and season of birth may be related to a higher risk of various medical and psychiatric disorders.

For decades, it has been reported in more than 250 studies¹ that a disproportionate number of individuals with schizophrenia are born during the winter months (January/February/March in the Northern Hemisphere and July/August/September in the Southern Hemisphere). This seasonal pattern was eventually linked to the lack of sunlight during winter months and a deficiency of vitamin D, a hormone that is critical for normal brain development. Recent studies have reported that very low serum levels of vitamin D during pregnancy significantly increase the risk of schizophrenia in offspring.²

But the plot thickens. Numerous studies over the past 20 to 30 years have reported an association between month or season of birth with sundry general medical and psychiatric conditions. Even longevity has been reported to vary with season of birth, with a longer life span for people born in autumn (October to December), compared with those born in spring (April to June).³ Of note, a longer life span for an individual born in autumn has been attributed to a higher birth weight during that season compared with those born in other seasons. In addition, the shorter life span of those with spring births has been attributed to factors during fetal life that increase the susceptibility to disease later in life (after age 50).

The following studies have reported an association between month/season of birth and general medical disorders:

• Higher rate of myopia for summer births⁴
• Tenfold higher risk of respiratory syntactical virus in babies born in January compared with October, and a 2 to 3 times higher risk of hospitalization⁵
• Higher rates of asthma during childhood for March and April births⁶
• Lower rate of lung cancer for winter births compared with all other seasons⁷
• An excess of colon and rectal cancer for people born in September, and the lowest rate for spring births⁸
• Lowest diabetes risk for summer births⁹
• For males: Cardiac mortality is 11% less likely for 4th-quarter births compared with 1st-quarter births. For females: Cancer mortality is lowest in 3rd-quarter vs 1st-quarter births¹⁰
• The peak risk for both Hodgkin and non-Hodgkin lymphoma is for April births compared with other months¹¹
• A strong trend for malignant neoplasm in males was reported for births during the 1st trimester of the year (January through April) compared with the rest of the year¹²
• Higher rate of spring births among patients who have insulin-dependent diabetes¹³
• Breast cancer is 5% higher for June births compared with December births¹⁴
• Higher risk of developing an allergy later in life for those born approximately 3 months before the main allergy season.¹⁵

The above studies may imply that birth seasonality is medical destiny. However, most such reports need further replication, or may be due to chance findings in various databases. However, they are worth considering as hypothesis-generating signals.

Continue to: And now for the risk of psychiatric disorders...

And now for the risk of psychi­atric disorders and month or season of birth. Here, too, there are multiple published reports:

• Higher social anhedonia and schizoid features among persons born in June and July¹⁶
• Higher autism rates for children conceived in December to March compared with those conceived during summer months¹⁷
• In contrast to the above report, the risk of autism spectrum disorders in the United Kingdom was higher for those born in summer¹⁸
• Another study labeled seasonality of birth in autism as “fiction”!¹⁹
• Significant spring births for persons with anxiety²⁰
• Highest occurrence of postpartum depression in December²¹
• High prepartum depression in winter and postpartum depression in fall²²
• Lower performance IQ among spring births²³
• Disproportionate excess of births in April, May, and June for those who die by suicide²⁴
• Suicide by burning oneself is higher among individuals born in January compared with any other month²⁵
• Relative increase in March and August births among patients with anorexia²⁶
• Season of birth is a predictor of emotional and behavioral regulation²⁷
• Serotonin metabolites show a peak in spring and a trough in fall²⁸
• Increase of spring births in individuals with Down syndrome²⁹
• Excess of spring births among patients with Alzheimer’s disease.³⁰

As with the seasonality of medical illness risk, the association of the month or season of birth with psychiatric disorders may be based on skewed samples or simply a chance finding. However, there may be some seasonal environmental factors that could increase the risk for disorders of the body or the brain/mind. The most plausible factors may be season-related fetal developmental disruptions caused by maternal infection, diet, lack of sunlight, temperature, substance use, or immune dysregulation from comorbid medical conditions during pregnancy. Some researchers have speculated that fluctuations in the availability of various fresh fruits and vegetables during certain seasons of the year may influence fetal development or increase the susceptibility to some medical disorders. This may be at the time of conception or during the 2nd trimester of pregnancy, when the brain develops.

On the other hand, those studies, published in peer-reviewed journals, may constitute a sophisticated form of “psychiatric astrology” whose credibility could be as suspect as the imaginative predictions of one’s horoscope in the daily newspaper…

To comment on this editorial or other topics of interest: [email protected].

“To every thing there is a season, and a time to every purpose under the heaven.”

— Ecclesiastes

The month of birth is not just relevant to one’s astrological sign. It may have medical consequences. An impressive number of published studies have found that the month and season of birth may be related to a higher risk of various medical and psychiatric disorders.

For decades, it has been reported in more than 250 studies¹ that a disproportionate number of individuals with schizophrenia are born during the winter months (January/February/March in the Northern Hemisphere and July/August/September in the Southern Hemisphere). This seasonal pattern was eventually linked to the lack of sunlight during winter months and a deficiency of vitamin D, a hormone that is critical for normal brain development. Recent studies have reported that very low serum levels of vitamin D during pregnancy significantly increase the risk of schizophrenia in offspring.²

But the plot thickens. Numerous studies over the past 20 to 30 years have reported an association between month or season of birth with sundry general medical and psychiatric conditions. Even longevity has been reported to vary with season of birth, with a longer life span for people born in autumn (October to December), compared with those born in spring (April to June).³ Of note, a longer life span for an individual born in autumn has been attributed to a higher birth weight during that season compared with those born in other seasons. In addition, the shorter life span of those with spring births has been attributed to factors during fetal life that increase the susceptibility to disease later in life (after age 50).

The following studies have reported an association between month/season of birth and general medical disorders:

• Higher rate of myopia for summer births⁴
• Tenfold higher risk of respiratory syntactical virus in babies born in January compared with October, and a 2 to 3 times higher risk of hospitalization⁵
• Higher rates of asthma during childhood for March and April births⁶
• Lower rate of lung cancer for winter births compared with all other seasons⁷
• An excess of colon and rectal cancer for people born in September, and the lowest rate for spring births⁸
• Lowest diabetes risk for summer births⁹
• For males: Cardiac mortality is 11% less likely for 4th-quarter births compared with 1st-quarter births. For females: Cancer mortality is lowest in 3rd-quarter vs 1st-quarter births¹⁰
• The peak risk for both Hodgkin and non-Hodgkin lymphoma is for April births compared with other months¹¹
• A strong trend for malignant neoplasm in males was reported for births during the 1st trimester of the year (January through April) compared with the rest of the year¹²
• Higher rate of spring births among patients who have insulin-dependent diabetes¹³
• Breast cancer is 5% higher for June births compared with December births¹⁴
• Higher risk of developing an allergy later in life for those born approximately 3 months before the main allergy season.¹⁵

The above studies may imply that birth seasonality is medical destiny. However, most such reports need further replication, or may be due to chance findings in various databases. However, they are worth considering as hypothesis-generating signals.

Continue to: And now for the risk of psychiatric disorders...

And now for the risk of psychi­atric disorders and month or season of birth. Here, too, there are multiple published reports:

• Higher social anhedonia and schizoid features among persons born in June and July¹⁶
• Higher autism rates for children conceived in December to March compared with those conceived during summer months¹⁷
• In contrast to the above report, the risk of autism spectrum disorders in the United Kingdom was higher for those born in summer¹⁸
• Another study labeled seasonality of birth in autism as “fiction”!¹⁹
• Significant spring births for persons with anxiety²⁰
• Highest occurrence of postpartum depression in December²¹
• High prepartum depression in winter and postpartum depression in fall²²
• Lower performance IQ among spring births²³
• Disproportionate excess of births in April, May, and June for those who die by suicide²⁴
• Suicide by burning oneself is higher among individuals born in January compared with any other month²⁵
• Relative increase in March and August births among patients with anorexia²⁶
• Season of birth is a predictor of emotional and behavioral regulation²⁷
• Serotonin metabolites show a peak in spring and a trough in fall²⁸
• Increase of spring births in individuals with Down syndrome²⁹
• Excess of spring births among patients with Alzheimer’s disease.³⁰

As with the seasonality of medical illness risk, the association of the month or season of birth with psychiatric disorders may be based on skewed samples or simply a chance finding. However, there may be some seasonal environmental factors that could increase the risk for disorders of the body or the brain/mind. The most plausible factors may be season-related fetal developmental disruptions caused by maternal infection, diet, lack of sunlight, temperature, substance use, or immune dysregulation from comorbid medical conditions during pregnancy. Some researchers have speculated that fluctuations in the availability of various fresh fruits and vegetables during certain seasons of the year may influence fetal development or increase the susceptibility to some medical disorders. This may be at the time of conception or during the 2nd trimester of pregnancy, when the brain develops.

On the other hand, those studies, published in peer-reviewed journals, may constitute a sophisticated form of “psychiatric astrology” whose credibility could be as suspect as the imaginative predictions of one’s horoscope in the daily newspaper…

To comment on this editorial or other topics of interest: [email protected].

The last few years have flown by for us as coeditors of the ACS Surgery News. It is often said that the perceived acceleration of time is a phenomenon of age as each year that goes by represents an ever decreasing percentage of one’s remaining time on earth.

As we age, we may come to feel that we have outlived our time and culture. What was certain yesterday is indeterminate today and likely completely wrong tomorrow. Among those things is the economic viability of print media. Some of you may remember the line from the old movie “Ghostbusters” (old: 1984!) in which Egon makes the statement, “Print is dead.” He was a few decades off, but even Gutenberg would have to admit that technology trumps almost everything when it comes to the written word.

So, ACS Surgery News comes to an end with this issue. We would like to believe that the editors past and present – Lazar Greenfield, Bing Rikkers, Karen Deveney, and Tyler Hughes – all aided you as surgeons in some small way. Our intent was always to inform and occasionally to entertain lightly.

The fact that the “Official Newspaper of the American College of Surgeons” is passing from the scene is, we hope, a reflection of technology and economics and not that our efforts were in vain. Behind the scenes were dozens of skilled reporters who did interviews and summarized papers. Our managing editor during our time as coeditors has been Therese Borden, who has been largely responsible for the quality and integrity of what was reported herein. If you have learned something unexpectedly in our newspaper, Therese has actually been the one behind the scenes making that accessible to you. Both of us are deeply grateful for her superb expertise and eternally positive attitude.

Of course, the American College of Surgeons was always the moving force behind this paper. We like to think that the value of the newspaper was largely because the college, with its dedication to surgery with skill and fidelity to all, gave us the credibility other such newspapers just don’t have. As editors, our primary goal has always been to report without concern for anything other than what is useful to the surgeon.

Although ACS has many other publications and products that serve the practicing surgeon, we do feel that ACS Surgery News provided seamless access for surgeons to learn about emerging techniques and ideas. The ACS leadership agrees. After considerable thought and discussion about possible digital replacements, we have agreed to use a platform that is already available to us and easy to use: the ACS Communities. A new Community, named the ACS Emerging News Community, is born.

We will continue as coeditors and offer a commentary every other month. The Editorial Board, the invaluable consultants to ACS Surgery News, will contribute short articles describing the best presentation that they have heard at a recent major surgical meeting and describe why it is important or summarize an article of importance from a recent major journal. Surgeons already on the General Surgery Community will receive the new community monthly unless they choose to unsubscribe. Community members can also respond to or query the authors of the articles and commentaries if they so desire. The ACS Emerging News Community will commence early in 2019, so look for it in your inbox then.

Many thanks to all of you for reading the ACS Surgery News when you had the time and special thanks to those who wrote in the paper or wrote to the paper to tell us how we were doing. As ACS Surgery News sunsets, we have no final words of great import that you can laminate and put in your wallets, purses, or on your computers. Whatever transpires in that as-yet-undiscovered country (the future), surgery will always boil down to those willing to care for a patient enough to cut to the cure with compassion, regardless of all other considerations. Good luck to you all. We’ll see you in the cloud.

Dr. Deveney is professor of surgery emerita in the department of surgery at Oregon Health & Science University, Portland. She is the coeditor of ACS Surgery News. Dr. Hughes is a clinical professor in the department of surgery and the director of medical education at the University of Kansas, Salina, and coeditor of ACS Surgery News.

The last few years have flown by for us as coeditors of the ACS Surgery News. It is often said that the perceived acceleration of time is a phenomenon of age as each year that goes by represents an ever decreasing percentage of one’s remaining time on earth.

As we age, we may come to feel that we have outlived our time and culture. What was certain yesterday is indeterminate today and likely completely wrong tomorrow. Among those things is the economic viability of print media. Some of you may remember the line from the old movie “Ghostbusters” (old: 1984!) in which Egon makes the statement, “Print is dead.” He was a few decades off, but even Gutenberg would have to admit that technology trumps almost everything when it comes to the written word.

So, ACS Surgery News comes to an end with this issue. We would like to believe that the editors past and present – Lazar Greenfield, Bing Rikkers, Karen Deveney, and Tyler Hughes – all aided you as surgeons in some small way. Our intent was always to inform and occasionally to entertain lightly.

The fact that the “Official Newspaper of the American College of Surgeons” is passing from the scene is, we hope, a reflection of technology and economics and not that our efforts were in vain. Behind the scenes were dozens of skilled reporters who did interviews and summarized papers. Our managing editor during our time as coeditors has been Therese Borden, who has been largely responsible for the quality and integrity of what was reported herein. If you have learned something unexpectedly in our newspaper, Therese has actually been the one behind the scenes making that accessible to you. Both of us are deeply grateful for her superb expertise and eternally positive attitude.

Of course, the American College of Surgeons was always the moving force behind this paper. We like to think that the value of the newspaper was largely because the college, with its dedication to surgery with skill and fidelity to all, gave us the credibility other such newspapers just don’t have. As editors, our primary goal has always been to report without concern for anything other than what is useful to the surgeon.

Although ACS has many other publications and products that serve the practicing surgeon, we do feel that ACS Surgery News provided seamless access for surgeons to learn about emerging techniques and ideas. The ACS leadership agrees. After considerable thought and discussion about possible digital replacements, we have agreed to use a platform that is already available to us and easy to use: the ACS Communities. A new Community, named the ACS Emerging News Community, is born.

We will continue as coeditors and offer a commentary every other month. The Editorial Board, the invaluable consultants to ACS Surgery News, will contribute short articles describing the best presentation that they have heard at a recent major surgical meeting and describe why it is important or summarize an article of importance from a recent major journal. Surgeons already on the General Surgery Community will receive the new community monthly unless they choose to unsubscribe. Community members can also respond to or query the authors of the articles and commentaries if they so desire. The ACS Emerging News Community will commence early in 2019, so look for it in your inbox then.

Many thanks to all of you for reading the ACS Surgery News when you had the time and special thanks to those who wrote in the paper or wrote to the paper to tell us how we were doing. As ACS Surgery News sunsets, we have no final words of great import that you can laminate and put in your wallets, purses, or on your computers. Whatever transpires in that as-yet-undiscovered country (the future), surgery will always boil down to those willing to care for a patient enough to cut to the cure with compassion, regardless of all other considerations. Good luck to you all. We’ll see you in the cloud.

Dr. Deveney is professor of surgery emerita in the department of surgery at Oregon Health & Science University, Portland. She is the coeditor of ACS Surgery News. Dr. Hughes is a clinical professor in the department of surgery and the director of medical education at the University of Kansas, Salina, and coeditor of ACS Surgery News.

The last few years have flown by for us as coeditors of the ACS Surgery News. It is often said that the perceived acceleration of time is a phenomenon of age as each year that goes by represents an ever decreasing percentage of one’s remaining time on earth.

As we age, we may come to feel that we have outlived our time and culture. What was certain yesterday is indeterminate today and likely completely wrong tomorrow. Among those things is the economic viability of print media. Some of you may remember the line from the old movie “Ghostbusters” (old: 1984!) in which Egon makes the statement, “Print is dead.” He was a few decades off, but even Gutenberg would have to admit that technology trumps almost everything when it comes to the written word.

So, ACS Surgery News comes to an end with this issue. We would like to believe that the editors past and present – Lazar Greenfield, Bing Rikkers, Karen Deveney, and Tyler Hughes – all aided you as surgeons in some small way. Our intent was always to inform and occasionally to entertain lightly.

The fact that the “Official Newspaper of the American College of Surgeons” is passing from the scene is, we hope, a reflection of technology and economics and not that our efforts were in vain. Behind the scenes were dozens of skilled reporters who did interviews and summarized papers. Our managing editor during our time as coeditors has been Therese Borden, who has been largely responsible for the quality and integrity of what was reported herein. If you have learned something unexpectedly in our newspaper, Therese has actually been the one behind the scenes making that accessible to you. Both of us are deeply grateful for her superb expertise and eternally positive attitude.

Of course, the American College of Surgeons was always the moving force behind this paper. We like to think that the value of the newspaper was largely because the college, with its dedication to surgery with skill and fidelity to all, gave us the credibility other such newspapers just don’t have. As editors, our primary goal has always been to report without concern for anything other than what is useful to the surgeon.

Although ACS has many other publications and products that serve the practicing surgeon, we do feel that ACS Surgery News provided seamless access for surgeons to learn about emerging techniques and ideas. The ACS leadership agrees. After considerable thought and discussion about possible digital replacements, we have agreed to use a platform that is already available to us and easy to use: the ACS Communities. A new Community, named the ACS Emerging News Community, is born.

We will continue as coeditors and offer a commentary every other month. The Editorial Board, the invaluable consultants to ACS Surgery News, will contribute short articles describing the best presentation that they have heard at a recent major surgical meeting and describe why it is important or summarize an article of importance from a recent major journal. Surgeons already on the General Surgery Community will receive the new community monthly unless they choose to unsubscribe. Community members can also respond to or query the authors of the articles and commentaries if they so desire. The ACS Emerging News Community will commence early in 2019, so look for it in your inbox then.

Many thanks to all of you for reading the ACS Surgery News when you had the time and special thanks to those who wrote in the paper or wrote to the paper to tell us how we were doing. As ACS Surgery News sunsets, we have no final words of great import that you can laminate and put in your wallets, purses, or on your computers. Whatever transpires in that as-yet-undiscovered country (the future), surgery will always boil down to those willing to care for a patient enough to cut to the cure with compassion, regardless of all other considerations. Good luck to you all. We’ll see you in the cloud.

Dr. Deveney is professor of surgery emerita in the department of surgery at Oregon Health & Science University, Portland. She is the coeditor of ACS Surgery News. Dr. Hughes is a clinical professor in the department of surgery and the director of medical education at the University of Kansas, Salina, and coeditor of ACS Surgery News.

This is the final issue of The Journal of Community and Supportive Oncology. Since our launch – separately as the Journal of Supportive Oncology in 2003 and Community Oncology in 2004 – and through the 2014 merger to form JCSO, our purpose has always been to connect with practice-based caregivers and to provide them with carefully selected, peer-reviewed information that could easily be incorporated into daily practice. Our overarching goal was to help ensure the delivery of the best-possible care and outcomes for our patients. We hope we achieved that, and the results of a 2016 readership survey seemed to confirm as much. But from a business perspective, and especially with the transition to online publishing and intensely competitive advertising landscape, economic survival became increasingly elusive, and management decided to close the journal.

Looking ahead

From January 2019, JCSO’s sister publications, Hematology News and Oncology Practice, will reside on a shared digital platform, MDedge Oncology, that will focus on news and conference coverage. Archives for JCSO, JSO, and Community Oncology will be available on this new platform at www.mdedge.com/oncology after the launch. In addition, I will host a weekly podcast focusing on current trends and advances in clinical and supportive care. It will include a long-form interview with an expert in oncology, along the lines of the former JCSO Interview, and with short end-segments on patient care, translating new research to daily practice, and a monthly journal round-up. You'll be able to subscribe to and download it at Apple podcasts, using the search terms HemOnc and MDedge.
 

In this issue

We end with a bumper crop of articles, beginning with a report by Hedden and colleagues on page e234 describing how they developed, implemented, and evaluated a supportive care program for patients with prostate cancer. That is followed by a literature-based review article by Ibrahim colleagues detailing the effectiveness of duloxetine in the treatment of painful chemotherapy-induced peripheral neuropathy (p. e243). In the original research section, on page e250, Palmisiano and colleagues report on mortality outcomes in hospitalized patients with cancer after rapid response team activation; Jeurkar and colleagues compare risk models guiding growth factor use in chemotherapy (p. e256); and Chao and colleagues describe the symptom burdens associated with chemotherapy-induced anemia in patients with late-stage cancer (e260).

Challenging and elusive are the key words in this issue's Case Reports in which Pollock and colleagues describe the difficulties in managing a cetuximab rash (p. e272), Roberts and colleagues write about elevated liver function tests in a patient on palbociclib and fulvestrant (p. e277), and Mukherjee and colleagues describe a patient with intravascular large B-cell lymphoma, who presented both a diagnostic and management challenge for the care team (p. e280). Turn to page e283, where our regular contributor, Jane de Lartigue, has written an in-depth review on everything you need to know about biosimilars. Susan London follows up on page e290 with an article on findings from studies on biosimilars for 3 oncology drugs that were reported at this year’s annual meeting of the American Society of Clinical Oncology. Dr de Lartigue also reports on the approval of dabrafenib and trametinib for BRAF-mutant melanoma (e228) and osimertinib for advanced non–small-cell lung cancer (p. e231).

And finally…

I wish you and your colleagues and families all good things for the coming year. Thank you and goodbye – and stay in touch by downloading my podcast!

This is the final issue of The Journal of Community and Supportive Oncology. Since our launch – separately as the Journal of Supportive Oncology in 2003 and Community Oncology in 2004 – and through the 2014 merger to form JCSO, our purpose has always been to connect with practice-based caregivers and to provide them with carefully selected, peer-reviewed information that could easily be incorporated into daily practice. Our overarching goal was to help ensure the delivery of the best-possible care and outcomes for our patients. We hope we achieved that, and the results of a 2016 readership survey seemed to confirm as much. But from a business perspective, and especially with the transition to online publishing and intensely competitive advertising landscape, economic survival became increasingly elusive, and management decided to close the journal.

Looking ahead

From January 2019, JCSO’s sister publications, Hematology News and Oncology Practice, will reside on a shared digital platform, MDedge Oncology, that will focus on news and conference coverage. Archives for JCSO, JSO, and Community Oncology will be available on this new platform at www.mdedge.com/oncology after the launch. In addition, I will host a weekly podcast focusing on current trends and advances in clinical and supportive care. It will include a long-form interview with an expert in oncology, along the lines of the former JCSO Interview, and with short end-segments on patient care, translating new research to daily practice, and a monthly journal round-up. You'll be able to subscribe to and download it at Apple podcasts, using the search terms HemOnc and MDedge.
 

In this issue

We end with a bumper crop of articles, beginning with a report by Hedden and colleagues on page e234 describing how they developed, implemented, and evaluated a supportive care program for patients with prostate cancer. That is followed by a literature-based review article by Ibrahim colleagues detailing the effectiveness of duloxetine in the treatment of painful chemotherapy-induced peripheral neuropathy (p. e243). In the original research section, on page e250, Palmisiano and colleagues report on mortality outcomes in hospitalized patients with cancer after rapid response team activation; Jeurkar and colleagues compare risk models guiding growth factor use in chemotherapy (p. e256); and Chao and colleagues describe the symptom burdens associated with chemotherapy-induced anemia in patients with late-stage cancer (e260).

Challenging and elusive are the key words in this issue's Case Reports in which Pollock and colleagues describe the difficulties in managing a cetuximab rash (p. e272), Roberts and colleagues write about elevated liver function tests in a patient on palbociclib and fulvestrant (p. e277), and Mukherjee and colleagues describe a patient with intravascular large B-cell lymphoma, who presented both a diagnostic and management challenge for the care team (p. e280). Turn to page e283, where our regular contributor, Jane de Lartigue, has written an in-depth review on everything you need to know about biosimilars. Susan London follows up on page e290 with an article on findings from studies on biosimilars for 3 oncology drugs that were reported at this year’s annual meeting of the American Society of Clinical Oncology. Dr de Lartigue also reports on the approval of dabrafenib and trametinib for BRAF-mutant melanoma (e228) and osimertinib for advanced non–small-cell lung cancer (p. e231).

And finally…

I wish you and your colleagues and families all good things for the coming year. Thank you and goodbye – and stay in touch by downloading my podcast!

This is the final issue of The Journal of Community and Supportive Oncology. Since our launch – separately as the Journal of Supportive Oncology in 2003 and Community Oncology in 2004 – and through the 2014 merger to form JCSO, our purpose has always been to connect with practice-based caregivers and to provide them with carefully selected, peer-reviewed information that could easily be incorporated into daily practice. Our overarching goal was to help ensure the delivery of the best-possible care and outcomes for our patients. We hope we achieved that, and the results of a 2016 readership survey seemed to confirm as much. But from a business perspective, and especially with the transition to online publishing and intensely competitive advertising landscape, economic survival became increasingly elusive, and management decided to close the journal.

Looking ahead

From January 2019, JCSO’s sister publications, Hematology News and Oncology Practice, will reside on a shared digital platform, MDedge Oncology, that will focus on news and conference coverage. Archives for JCSO, JSO, and Community Oncology will be available on this new platform at www.mdedge.com/oncology after the launch. In addition, I will host a weekly podcast focusing on current trends and advances in clinical and supportive care. It will include a long-form interview with an expert in oncology, along the lines of the former JCSO Interview, and with short end-segments on patient care, translating new research to daily practice, and a monthly journal round-up. You'll be able to subscribe to and download it at Apple podcasts, using the search terms HemOnc and MDedge.
 

In this issue

We end with a bumper crop of articles, beginning with a report by Hedden and colleagues on page e234 describing how they developed, implemented, and evaluated a supportive care program for patients with prostate cancer. That is followed by a literature-based review article by Ibrahim colleagues detailing the effectiveness of duloxetine in the treatment of painful chemotherapy-induced peripheral neuropathy (p. e243). In the original research section, on page e250, Palmisiano and colleagues report on mortality outcomes in hospitalized patients with cancer after rapid response team activation; Jeurkar and colleagues compare risk models guiding growth factor use in chemotherapy (p. e256); and Chao and colleagues describe the symptom burdens associated with chemotherapy-induced anemia in patients with late-stage cancer (e260).

Challenging and elusive are the key words in this issue's Case Reports in which Pollock and colleagues describe the difficulties in managing a cetuximab rash (p. e272), Roberts and colleagues write about elevated liver function tests in a patient on palbociclib and fulvestrant (p. e277), and Mukherjee and colleagues describe a patient with intravascular large B-cell lymphoma, who presented both a diagnostic and management challenge for the care team (p. e280). Turn to page e283, where our regular contributor, Jane de Lartigue, has written an in-depth review on everything you need to know about biosimilars. Susan London follows up on page e290 with an article on findings from studies on biosimilars for 3 oncology drugs that were reported at this year’s annual meeting of the American Society of Clinical Oncology. Dr de Lartigue also reports on the approval of dabrafenib and trametinib for BRAF-mutant melanoma (e228) and osimertinib for advanced non–small-cell lung cancer (p. e231).

And finally…

I wish you and your colleagues and families all good things for the coming year. Thank you and goodbye – and stay in touch by downloading my podcast!

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

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Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

But, after the results of many recent studies, it turns out I should not have been so comfortable after all. This should not be a surprise. We should never be overly confident with our understanding of anything in clinical practice.

In this issue, Dr. Martin Blaser discusses his work, which supports the hypothesis that the currently increased prevalence of obesity and diabetes is at least in part due to reduced diversity in the gut microbiome. The increased exposure to antibiotics through prescriptions for women before and during pregnancy, as well as perhaps their exposure to antibiotics in the environment, results in changes to the gut and vaginal flora that influence the developing gut and likely other anatomic microbiomes in the neonate and infant. Fascinating research done in mice, utilizing fecal transfer experiments, is building an evidence trail to support the concept that the microbiome plays a major role in the development of childhood and adult obesity, and the gut microbiome is influenced by its exposure to antibiotics, perhaps given years earlier.

Knowledge of the gastrointestinal and other human microbiomes is exploding. I now wonder how many seemingly random clinical events associated with antibiotic use that were not understood and were easily dismissed as stochastic warrant formal study. Some of my patients with rheumatoid arthritis have described flares after eating certain foods and transient remissions or exacerbations after treatment with antibiotics. An epidemiologic study has linked the likelihood of developing childhood inflammatory bowel disease with exposure to antibiotics. Even more fascinating are observations that the microbiota composition (influenced by antibiotics) can influence the outcome of cardiac allografts in a murine model and the response of certain tumors to immune checkpoint inhibitors in murine and human studies. The mechanism may relate to the effects of the microbiome on immune cell activation and migration. Several disorders have been linked to specific bacteria in the gut microbiome, and others as diverse as cardiovascular events and the acute inflammatory response to monosodium urate crystals (gout) are affected by metabolites generated by bacteria in the gut.

The use of germ-free and antibiotic-treated mice in the laboratory, with selective repopulation of their gut microbiome with flora harvested from other strains of mice or selected humans, will continue to teach us much about the role that these microbes and other inhabitants play in controlling normal and disease-disrupted homeostasis. C difficile overgrowth after antibiotic exposure, and the successful treatment of refractory C difficile with fecal transplantation,¹ was just the beginning.

The simple writing of a prescription for an antibiotic is a far more complicated and long-lasting affair than most of us have thought.

But, after the results of many recent studies, it turns out I should not have been so comfortable after all. This should not be a surprise. We should never be overly confident with our understanding of anything in clinical practice.

In this issue, Dr. Martin Blaser discusses his work, which supports the hypothesis that the currently increased prevalence of obesity and diabetes is at least in part due to reduced diversity in the gut microbiome. The increased exposure to antibiotics through prescriptions for women before and during pregnancy, as well as perhaps their exposure to antibiotics in the environment, results in changes to the gut and vaginal flora that influence the developing gut and likely other anatomic microbiomes in the neonate and infant. Fascinating research done in mice, utilizing fecal transfer experiments, is building an evidence trail to support the concept that the microbiome plays a major role in the development of childhood and adult obesity, and the gut microbiome is influenced by its exposure to antibiotics, perhaps given years earlier.

Knowledge of the gastrointestinal and other human microbiomes is exploding. I now wonder how many seemingly random clinical events associated with antibiotic use that were not understood and were easily dismissed as stochastic warrant formal study. Some of my patients with rheumatoid arthritis have described flares after eating certain foods and transient remissions or exacerbations after treatment with antibiotics. An epidemiologic study has linked the likelihood of developing childhood inflammatory bowel disease with exposure to antibiotics. Even more fascinating are observations that the microbiota composition (influenced by antibiotics) can influence the outcome of cardiac allografts in a murine model and the response of certain tumors to immune checkpoint inhibitors in murine and human studies. The mechanism may relate to the effects of the microbiome on immune cell activation and migration. Several disorders have been linked to specific bacteria in the gut microbiome, and others as diverse as cardiovascular events and the acute inflammatory response to monosodium urate crystals (gout) are affected by metabolites generated by bacteria in the gut.

The use of germ-free and antibiotic-treated mice in the laboratory, with selective repopulation of their gut microbiome with flora harvested from other strains of mice or selected humans, will continue to teach us much about the role that these microbes and other inhabitants play in controlling normal and disease-disrupted homeostasis. C difficile overgrowth after antibiotic exposure, and the successful treatment of refractory C difficile with fecal transplantation,¹ was just the beginning.

The simple writing of a prescription for an antibiotic is a far more complicated and long-lasting affair than most of us have thought.

But, after the results of many recent studies, it turns out I should not have been so comfortable after all. This should not be a surprise. We should never be overly confident with our understanding of anything in clinical practice.

In this issue, Dr. Martin Blaser discusses his work, which supports the hypothesis that the currently increased prevalence of obesity and diabetes is at least in part due to reduced diversity in the gut microbiome. The increased exposure to antibiotics through prescriptions for women before and during pregnancy, as well as perhaps their exposure to antibiotics in the environment, results in changes to the gut and vaginal flora that influence the developing gut and likely other anatomic microbiomes in the neonate and infant. Fascinating research done in mice, utilizing fecal transfer experiments, is building an evidence trail to support the concept that the microbiome plays a major role in the development of childhood and adult obesity, and the gut microbiome is influenced by its exposure to antibiotics, perhaps given years earlier.

Knowledge of the gastrointestinal and other human microbiomes is exploding. I now wonder how many seemingly random clinical events associated with antibiotic use that were not understood and were easily dismissed as stochastic warrant formal study. Some of my patients with rheumatoid arthritis have described flares after eating certain foods and transient remissions or exacerbations after treatment with antibiotics. An epidemiologic study has linked the likelihood of developing childhood inflammatory bowel disease with exposure to antibiotics. Even more fascinating are observations that the microbiota composition (influenced by antibiotics) can influence the outcome of cardiac allografts in a murine model and the response of certain tumors to immune checkpoint inhibitors in murine and human studies. The mechanism may relate to the effects of the microbiome on immune cell activation and migration. Several disorders have been linked to specific bacteria in the gut microbiome, and others as diverse as cardiovascular events and the acute inflammatory response to monosodium urate crystals (gout) are affected by metabolites generated by bacteria in the gut.

The use of germ-free and antibiotic-treated mice in the laboratory, with selective repopulation of their gut microbiome with flora harvested from other strains of mice or selected humans, will continue to teach us much about the role that these microbes and other inhabitants play in controlling normal and disease-disrupted homeostasis. C difficile overgrowth after antibiotic exposure, and the successful treatment of refractory C difficile with fecal transplantation,¹ was just the beginning.

The simple writing of a prescription for an antibiotic is a far more complicated and long-lasting affair than most of us have thought.