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ID Consult: National immunization coverage and measles
August was National Immunization Awareness Month. For most pediatricians, it is also a very busy month as patients prepare for the start of the new school year. So how are we doing?
On August 28, 2013, vaccination coverage of U.S. children aged 19-35 months was published in Morbidity and Mortality Weekly Review (2014; 63:741-8) based on results from the National Information Survey (NIS), which provides national, regional, state, and selected local area vaccination coverage estimates. NIS has monitored vaccination coverage since 1994 for all 50 states and assists in tracking the progress of achieving our national goals. It also can identify problem areas that may require special interventions. Survey data was obtained by a random telephone survey using both landline and cellular phones to households that have children born between January 2010 and May 2012. The verbal interview was followed by a survey mailed to the vaccine provider to confirm the verbal vaccine history.

Highlights
Vaccination coverage of at least 90 %, a goal of Healthy People 2020, was achieved for receipt of one or more dose of MMR (91.9%); three or more doses of hepatitis B vaccine (HepB) (90.8 %); three or more doses of poliovirus vaccine (92.7%) and one or more doses of varicella vaccine (91.2%).
Coverage for the following vaccines failed to meet this goal: four or more doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%); four or more doses of pneumococcal conjugate vaccine (PCV) (82%); and a full series of Haemophilus influenzae type b (Hib) (82%). Coverage for the remaining vaccines also fell short of their respective targeted goals: two or more doses of hepatitis A vaccine (54.7%; target 85%); rotavirus (72.6%; target 80%); and hepatitis B birth dose (74.2%; target 85%).
Compared with 2012, coverage remained stable for the four vaccines that achieved at least 90% coverage. For those that did not, rotavirus was the only vaccine in 2013 that had an increase (4%) in coverage. Of note, there was an increase in the birth dose of 2.6% for Hep B.
Children living at or below the poverty level had lower vaccination coverage, compared with those living at or above this level for several vaccines, including four or more doses of DTaP; full series of Hib vaccine, four or more doses of PCV, and rotavirus vaccine. Coverage was between 8% and 12.6% points lower for these vaccines.

Measles
Let’s take a closer look at measles. Nationally, almost 92 % of children received at least one dose of MMR. However, coverage varied by state – an observation unchanged from 2012. New Hampshire had the highest coverage at 96.3% and three states had coverage of only 86% (Colorado, Ohio, and West Virginia). Overall 17 states had immunization rates less than 90%. Additionally, 1 in 12 children did not receive their first dose of MMR on time. Why the concern? In 2013, there were 187 cases of measles including 11 outbreaks. A total of 82% occurred in unvaccinated individuals, and another 9% were unaware of their immunization status.
As of Aug. 25, 2014, there were 595 cases of measles in the United States in 21 states, according to the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. This is the highest number of cases reported since endemic measles was eliminated in 2000. There were as a result of 18 outbreaks, representing 89% of the reported cases. Cases are occurring even in states where immunization rates are reported to be at least 90% – a reminder that there can be pockets of low or nonimmunizing communities that leave its citizens vulnerable to outbreaks when a highly contagious virus is introduced.
Since endemic measles was eliminated 14 years ago in the United States, many health care providers have never seen a case of measles or may not realize the impact it once had on our public health system. Prior to the initiation of the measles vaccination program in 1963, 3-4 million cases of measles occurred annually in the United States with 400-500 deaths and 48,000 hospitalizations. Approximately another 1,000 individuals were left disabled secondary to measles encephalitis. Once the vaccine was introduced, the incidence of measles declined 98%, according to "Epidemiology and Prevention of Vaccine-Preventable Diseases," 12th ed., second printing. (Washington, D.C: Public Health Foundation, 2012). Between 1989 and 1991, there was a resurgence of measles resulting in approximately 55,000 cases, 11,000 hospitalizations, and 123 deaths. The resurgence was caused primarily by the failure to vaccinate uninsured children at the recommended 12-15 months of age. Children younger than 5 years of age accounted for 45% of all cases. The Vaccines for Children Program was created in 1993 as a direct response to the resurgence of measles. It would ensure that no child would contract a vaccine preventable disease because of inability to pay.
Measles remains endemic in multiple countries worldwide that are travel destinations for many Americans. In 2013, 99% of 159 U.S. cases were import related. An overwhelming majority of infections occurred in unvaccinated individuals. In 2014, this trend continues, with the majority of cases occurring in unvaccinated international travelers who return infected and spread disease to susceptible persons including children in their communities (MMWR 2014:63;496-9). Of the 288 cases reported in by May 23, 2014, 97% were associated with importations from 18 countries.
High immunization coverage must be maintained to prevent and sustain measles elimination in the United States. As a reminder, all children aged 6-11 months should receive one dose of MMR ideally 2 weeks prior to international travel. When the infant is at least 12 months of age, they should receive two additional doses of MMR or MMRV according to the routine immunization schedule. Those children older than 12 months of age should receive two doses of MMR. The second can be administered as soon as 4 weeks after the first dose. It is not uncommon for families to travel internationally and fail to mention it to you. Many have been told their child’s immunizations are up to date, not realizing that international travel may alter that definition. It behooves primary care providers to develop strategies to facilitate discussions regarding sharing international travel plans in a timely manner.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].
August was National Immunization Awareness Month. For most pediatricians, it is also a very busy month as patients prepare for the start of the new school year. So how are we doing?
On August 28, 2013, vaccination coverage of U.S. children aged 19-35 months was published in Morbidity and Mortality Weekly Review (2014; 63:741-8) based on results from the National Information Survey (NIS), which provides national, regional, state, and selected local area vaccination coverage estimates. NIS has monitored vaccination coverage since 1994 for all 50 states and assists in tracking the progress of achieving our national goals. It also can identify problem areas that may require special interventions. Survey data was obtained by a random telephone survey using both landline and cellular phones to households that have children born between January 2010 and May 2012. The verbal interview was followed by a survey mailed to the vaccine provider to confirm the verbal vaccine history.

Highlights
Vaccination coverage of at least 90 %, a goal of Healthy People 2020, was achieved for receipt of one or more dose of MMR (91.9%); three or more doses of hepatitis B vaccine (HepB) (90.8 %); three or more doses of poliovirus vaccine (92.7%) and one or more doses of varicella vaccine (91.2%).
Coverage for the following vaccines failed to meet this goal: four or more doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%); four or more doses of pneumococcal conjugate vaccine (PCV) (82%); and a full series of Haemophilus influenzae type b (Hib) (82%). Coverage for the remaining vaccines also fell short of their respective targeted goals: two or more doses of hepatitis A vaccine (54.7%; target 85%); rotavirus (72.6%; target 80%); and hepatitis B birth dose (74.2%; target 85%).
Compared with 2012, coverage remained stable for the four vaccines that achieved at least 90% coverage. For those that did not, rotavirus was the only vaccine in 2013 that had an increase (4%) in coverage. Of note, there was an increase in the birth dose of 2.6% for Hep B.
Children living at or below the poverty level had lower vaccination coverage, compared with those living at or above this level for several vaccines, including four or more doses of DTaP; full series of Hib vaccine, four or more doses of PCV, and rotavirus vaccine. Coverage was between 8% and 12.6% points lower for these vaccines.

Measles
Let’s take a closer look at measles. Nationally, almost 92 % of children received at least one dose of MMR. However, coverage varied by state – an observation unchanged from 2012. New Hampshire had the highest coverage at 96.3% and three states had coverage of only 86% (Colorado, Ohio, and West Virginia). Overall 17 states had immunization rates less than 90%. Additionally, 1 in 12 children did not receive their first dose of MMR on time. Why the concern? In 2013, there were 187 cases of measles including 11 outbreaks. A total of 82% occurred in unvaccinated individuals, and another 9% were unaware of their immunization status.
As of Aug. 25, 2014, there were 595 cases of measles in the United States in 21 states, according to the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. This is the highest number of cases reported since endemic measles was eliminated in 2000. There were as a result of 18 outbreaks, representing 89% of the reported cases. Cases are occurring even in states where immunization rates are reported to be at least 90% – a reminder that there can be pockets of low or nonimmunizing communities that leave its citizens vulnerable to outbreaks when a highly contagious virus is introduced.
Since endemic measles was eliminated 14 years ago in the United States, many health care providers have never seen a case of measles or may not realize the impact it once had on our public health system. Prior to the initiation of the measles vaccination program in 1963, 3-4 million cases of measles occurred annually in the United States with 400-500 deaths and 48,000 hospitalizations. Approximately another 1,000 individuals were left disabled secondary to measles encephalitis. Once the vaccine was introduced, the incidence of measles declined 98%, according to "Epidemiology and Prevention of Vaccine-Preventable Diseases," 12th ed., second printing. (Washington, D.C: Public Health Foundation, 2012). Between 1989 and 1991, there was a resurgence of measles resulting in approximately 55,000 cases, 11,000 hospitalizations, and 123 deaths. The resurgence was caused primarily by the failure to vaccinate uninsured children at the recommended 12-15 months of age. Children younger than 5 years of age accounted for 45% of all cases. The Vaccines for Children Program was created in 1993 as a direct response to the resurgence of measles. It would ensure that no child would contract a vaccine preventable disease because of inability to pay.
Measles remains endemic in multiple countries worldwide that are travel destinations for many Americans. In 2013, 99% of 159 U.S. cases were import related. An overwhelming majority of infections occurred in unvaccinated individuals. In 2014, this trend continues, with the majority of cases occurring in unvaccinated international travelers who return infected and spread disease to susceptible persons including children in their communities (MMWR 2014:63;496-9). Of the 288 cases reported in by May 23, 2014, 97% were associated with importations from 18 countries.
High immunization coverage must be maintained to prevent and sustain measles elimination in the United States. As a reminder, all children aged 6-11 months should receive one dose of MMR ideally 2 weeks prior to international travel. When the infant is at least 12 months of age, they should receive two additional doses of MMR or MMRV according to the routine immunization schedule. Those children older than 12 months of age should receive two doses of MMR. The second can be administered as soon as 4 weeks after the first dose. It is not uncommon for families to travel internationally and fail to mention it to you. Many have been told their child’s immunizations are up to date, not realizing that international travel may alter that definition. It behooves primary care providers to develop strategies to facilitate discussions regarding sharing international travel plans in a timely manner.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].
August was National Immunization Awareness Month. For most pediatricians, it is also a very busy month as patients prepare for the start of the new school year. So how are we doing?
On August 28, 2013, vaccination coverage of U.S. children aged 19-35 months was published in Morbidity and Mortality Weekly Review (2014; 63:741-8) based on results from the National Information Survey (NIS), which provides national, regional, state, and selected local area vaccination coverage estimates. NIS has monitored vaccination coverage since 1994 for all 50 states and assists in tracking the progress of achieving our national goals. It also can identify problem areas that may require special interventions. Survey data was obtained by a random telephone survey using both landline and cellular phones to households that have children born between January 2010 and May 2012. The verbal interview was followed by a survey mailed to the vaccine provider to confirm the verbal vaccine history.

Highlights
Vaccination coverage of at least 90 %, a goal of Healthy People 2020, was achieved for receipt of one or more dose of MMR (91.9%); three or more doses of hepatitis B vaccine (HepB) (90.8 %); three or more doses of poliovirus vaccine (92.7%) and one or more doses of varicella vaccine (91.2%).
Coverage for the following vaccines failed to meet this goal: four or more doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%); four or more doses of pneumococcal conjugate vaccine (PCV) (82%); and a full series of Haemophilus influenzae type b (Hib) (82%). Coverage for the remaining vaccines also fell short of their respective targeted goals: two or more doses of hepatitis A vaccine (54.7%; target 85%); rotavirus (72.6%; target 80%); and hepatitis B birth dose (74.2%; target 85%).
Compared with 2012, coverage remained stable for the four vaccines that achieved at least 90% coverage. For those that did not, rotavirus was the only vaccine in 2013 that had an increase (4%) in coverage. Of note, there was an increase in the birth dose of 2.6% for Hep B.
Children living at or below the poverty level had lower vaccination coverage, compared with those living at or above this level for several vaccines, including four or more doses of DTaP; full series of Hib vaccine, four or more doses of PCV, and rotavirus vaccine. Coverage was between 8% and 12.6% points lower for these vaccines.

Measles
Let’s take a closer look at measles. Nationally, almost 92 % of children received at least one dose of MMR. However, coverage varied by state – an observation unchanged from 2012. New Hampshire had the highest coverage at 96.3% and three states had coverage of only 86% (Colorado, Ohio, and West Virginia). Overall 17 states had immunization rates less than 90%. Additionally, 1 in 12 children did not receive their first dose of MMR on time. Why the concern? In 2013, there were 187 cases of measles including 11 outbreaks. A total of 82% occurred in unvaccinated individuals, and another 9% were unaware of their immunization status.
As of Aug. 25, 2014, there were 595 cases of measles in the United States in 21 states, according to the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. This is the highest number of cases reported since endemic measles was eliminated in 2000. There were as a result of 18 outbreaks, representing 89% of the reported cases. Cases are occurring even in states where immunization rates are reported to be at least 90% – a reminder that there can be pockets of low or nonimmunizing communities that leave its citizens vulnerable to outbreaks when a highly contagious virus is introduced.
Since endemic measles was eliminated 14 years ago in the United States, many health care providers have never seen a case of measles or may not realize the impact it once had on our public health system. Prior to the initiation of the measles vaccination program in 1963, 3-4 million cases of measles occurred annually in the United States with 400-500 deaths and 48,000 hospitalizations. Approximately another 1,000 individuals were left disabled secondary to measles encephalitis. Once the vaccine was introduced, the incidence of measles declined 98%, according to "Epidemiology and Prevention of Vaccine-Preventable Diseases," 12th ed., second printing. (Washington, D.C: Public Health Foundation, 2012). Between 1989 and 1991, there was a resurgence of measles resulting in approximately 55,000 cases, 11,000 hospitalizations, and 123 deaths. The resurgence was caused primarily by the failure to vaccinate uninsured children at the recommended 12-15 months of age. Children younger than 5 years of age accounted for 45% of all cases. The Vaccines for Children Program was created in 1993 as a direct response to the resurgence of measles. It would ensure that no child would contract a vaccine preventable disease because of inability to pay.
Measles remains endemic in multiple countries worldwide that are travel destinations for many Americans. In 2013, 99% of 159 U.S. cases were import related. An overwhelming majority of infections occurred in unvaccinated individuals. In 2014, this trend continues, with the majority of cases occurring in unvaccinated international travelers who return infected and spread disease to susceptible persons including children in their communities (MMWR 2014:63;496-9). Of the 288 cases reported in by May 23, 2014, 97% were associated with importations from 18 countries.
High immunization coverage must be maintained to prevent and sustain measles elimination in the United States. As a reminder, all children aged 6-11 months should receive one dose of MMR ideally 2 weeks prior to international travel. When the infant is at least 12 months of age, they should receive two additional doses of MMR or MMRV according to the routine immunization schedule. Those children older than 12 months of age should receive two doses of MMR. The second can be administered as soon as 4 weeks after the first dose. It is not uncommon for families to travel internationally and fail to mention it to you. Many have been told their child’s immunizations are up to date, not realizing that international travel may alter that definition. It behooves primary care providers to develop strategies to facilitate discussions regarding sharing international travel plans in a timely manner.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].
LISTEN NOW: Greg Maynard, MD, SFHM, Chats about SHM's Mentored Implementation Programs
Click here to listen to excerpts of our interview with Dr. Maynard
Click here to listen to excerpts of our interview with Dr. Maynard
Click here to listen to excerpts of our interview with Dr. Maynard
Right-sided living donor kidney transplant found safe
SAN FRANCISCO – The practice of preferentially using left instead of right kidneys in living donor kidney transplantation may no longer be justified in the era of contemporary laparoscopic surgery, suggests a national study reported at the 2014 World Transplant Congress.
"The current approach in many centers is to prefer left living donor nephrectomy due to longer vessel length...Right donor nephrectomy, at least in our center and I think in most centers, has generally been reserved for cases of multiple or complex vessels on the left or incidental anatomical abnormalities on the right like cysts or stones," commented presenting author Dr. Tim E. Taber of Indiana University in Indianapolis.
Only one in seven of the roughly 59,000 living donor kidney transplants studied was performed using a right kidney. However, most short- and long-term outcomes were statistically indistinguishable between recipients of left and right kidneys, and the differences that were significant were small, he reported at the congress sponsored by the American Society of Transplant Surgeons.
"Our [study] is the largest national analysis or most recent large data analysis done on this subject in today’s surgical era of established laparoscopic living donor nephrectomies. There may be a minor risk for slightly inferior outcomes with right versus left kidneys," Dr. Taber concluded.
"Right-donor nephrectomy continues to be performed with great reluctance," he added. Yet, "under the accepted principles of live-donor nephrectomy, with enough surgical expertise, right-donor nephrectomy can be performed successfully. Right kidneys seem to have a very small difference, if any, in outcomes as compared to left kidneys. Surgical expertise and experience should be tailored toward this aspect."
A session attendee from Brazil commented, "We [prefer] to choose the right kidney in situations where we have one artery on the right side and multiple arteries on the left side." In these cases, his group uses an approach to the vasculature adopted from pancreas transplantation. "We have identical results with the right and left side," he reported.
Dr. Lloyd E. Ratner, director of renal and pancreatic transplantation at Columbia University Medical Center in New York, who also attended the session, said, "I feel somewhat responsible for causing this problem with the right kidney because we were the ones that originally described the higher thrombosis rate with the right kidney with the laparoscopic donor nephrectomies. And I think it scared everyone off from this topic."
As several attendees noted, "there are surgical ways of getting around this," he agreed, offering two more options. "The first is that if we get a short vein, we’re not reluctant at all to put a piece of Dacron onto it, so you don’t even need to dig out the saphenous and cause additional time or morbidity to the patient. And the nice thing about the Dacron grafts is that they are corrugated and they don’t collapse. They also stretch, so you don’t need to cut them exactly precisely," he said.
"And number two is when you are stapling ... it’s often useful to be able to staple onto the cava and not get the vein in one staple byte." By using two passes in the appropriate configuration, "you actually get a cuff of cava, then you have plenty of vein," he explained.
In the study, Dr. Taber and colleagues retrospectively analyzed data from 58,599 adult living donor kidney transplants performed during 2000-2009 and captured in the United Network for Organ Sharing (UNOS) database. In 86% of cases, surgeons used the donor’s left kidney.
Recipients of left and right kidneys were statistically indistinguishable with respect to hospital length of stay, treatment for acute rejection within 6 months, acute rejection as a cause of graft failure, inadequate urine production in the first 24 hours, primary graft failure, graft thrombosis or surgical complication as a contributory cause of graft failure, and 1-year graft survival.
Those receiving a right kidney did have significant but small increases in rates of delayed graft function, as defined by the need for dialysis within 7 days of transplantation (5.7% vs. 4.2%), lack of decline in serum creatinine in the first 24 hours (19.7% vs. 16.4%), treatment for acute rejection within 1 year (12.7% vs. 11.8%), and graft thrombosis as the cause of graft failure (1.1% vs. 0.8%).
The Kaplan-Meier cumulative rate of graft survival was better for left kidneys than for right kidneys (P = .006), but "these are essentially superimposed numbers," said Dr. Taber, who disclosed no conflicts of interest related to the research.
The study had limitations, such as its retrospective design, lack of more detailed information about donor and recipient outcomes, and reliance on data as reported by centers, he acknowledged. Also, such large studies may pick up small differences that are not clinically meaningful.
"With ever-increasing demands for living donor transplantation, right-donor nephrectomies are being considered more often. Every effort should be made to leave the donor with the higher-functioning kidney, but at the same time maximizing the living donor pool," Dr. Taber concluded.
Dr. Taber disclosed no relevant conflicts of interest.
SAN FRANCISCO – The practice of preferentially using left instead of right kidneys in living donor kidney transplantation may no longer be justified in the era of contemporary laparoscopic surgery, suggests a national study reported at the 2014 World Transplant Congress.
"The current approach in many centers is to prefer left living donor nephrectomy due to longer vessel length...Right donor nephrectomy, at least in our center and I think in most centers, has generally been reserved for cases of multiple or complex vessels on the left or incidental anatomical abnormalities on the right like cysts or stones," commented presenting author Dr. Tim E. Taber of Indiana University in Indianapolis.
Only one in seven of the roughly 59,000 living donor kidney transplants studied was performed using a right kidney. However, most short- and long-term outcomes were statistically indistinguishable between recipients of left and right kidneys, and the differences that were significant were small, he reported at the congress sponsored by the American Society of Transplant Surgeons.
"Our [study] is the largest national analysis or most recent large data analysis done on this subject in today’s surgical era of established laparoscopic living donor nephrectomies. There may be a minor risk for slightly inferior outcomes with right versus left kidneys," Dr. Taber concluded.
"Right-donor nephrectomy continues to be performed with great reluctance," he added. Yet, "under the accepted principles of live-donor nephrectomy, with enough surgical expertise, right-donor nephrectomy can be performed successfully. Right kidneys seem to have a very small difference, if any, in outcomes as compared to left kidneys. Surgical expertise and experience should be tailored toward this aspect."
A session attendee from Brazil commented, "We [prefer] to choose the right kidney in situations where we have one artery on the right side and multiple arteries on the left side." In these cases, his group uses an approach to the vasculature adopted from pancreas transplantation. "We have identical results with the right and left side," he reported.
Dr. Lloyd E. Ratner, director of renal and pancreatic transplantation at Columbia University Medical Center in New York, who also attended the session, said, "I feel somewhat responsible for causing this problem with the right kidney because we were the ones that originally described the higher thrombosis rate with the right kidney with the laparoscopic donor nephrectomies. And I think it scared everyone off from this topic."
As several attendees noted, "there are surgical ways of getting around this," he agreed, offering two more options. "The first is that if we get a short vein, we’re not reluctant at all to put a piece of Dacron onto it, so you don’t even need to dig out the saphenous and cause additional time or morbidity to the patient. And the nice thing about the Dacron grafts is that they are corrugated and they don’t collapse. They also stretch, so you don’t need to cut them exactly precisely," he said.
"And number two is when you are stapling ... it’s often useful to be able to staple onto the cava and not get the vein in one staple byte." By using two passes in the appropriate configuration, "you actually get a cuff of cava, then you have plenty of vein," he explained.
In the study, Dr. Taber and colleagues retrospectively analyzed data from 58,599 adult living donor kidney transplants performed during 2000-2009 and captured in the United Network for Organ Sharing (UNOS) database. In 86% of cases, surgeons used the donor’s left kidney.
Recipients of left and right kidneys were statistically indistinguishable with respect to hospital length of stay, treatment for acute rejection within 6 months, acute rejection as a cause of graft failure, inadequate urine production in the first 24 hours, primary graft failure, graft thrombosis or surgical complication as a contributory cause of graft failure, and 1-year graft survival.
Those receiving a right kidney did have significant but small increases in rates of delayed graft function, as defined by the need for dialysis within 7 days of transplantation (5.7% vs. 4.2%), lack of decline in serum creatinine in the first 24 hours (19.7% vs. 16.4%), treatment for acute rejection within 1 year (12.7% vs. 11.8%), and graft thrombosis as the cause of graft failure (1.1% vs. 0.8%).
The Kaplan-Meier cumulative rate of graft survival was better for left kidneys than for right kidneys (P = .006), but "these are essentially superimposed numbers," said Dr. Taber, who disclosed no conflicts of interest related to the research.
The study had limitations, such as its retrospective design, lack of more detailed information about donor and recipient outcomes, and reliance on data as reported by centers, he acknowledged. Also, such large studies may pick up small differences that are not clinically meaningful.
"With ever-increasing demands for living donor transplantation, right-donor nephrectomies are being considered more often. Every effort should be made to leave the donor with the higher-functioning kidney, but at the same time maximizing the living donor pool," Dr. Taber concluded.
Dr. Taber disclosed no relevant conflicts of interest.
SAN FRANCISCO – The practice of preferentially using left instead of right kidneys in living donor kidney transplantation may no longer be justified in the era of contemporary laparoscopic surgery, suggests a national study reported at the 2014 World Transplant Congress.
"The current approach in many centers is to prefer left living donor nephrectomy due to longer vessel length...Right donor nephrectomy, at least in our center and I think in most centers, has generally been reserved for cases of multiple or complex vessels on the left or incidental anatomical abnormalities on the right like cysts or stones," commented presenting author Dr. Tim E. Taber of Indiana University in Indianapolis.
Only one in seven of the roughly 59,000 living donor kidney transplants studied was performed using a right kidney. However, most short- and long-term outcomes were statistically indistinguishable between recipients of left and right kidneys, and the differences that were significant were small, he reported at the congress sponsored by the American Society of Transplant Surgeons.
"Our [study] is the largest national analysis or most recent large data analysis done on this subject in today’s surgical era of established laparoscopic living donor nephrectomies. There may be a minor risk for slightly inferior outcomes with right versus left kidneys," Dr. Taber concluded.
"Right-donor nephrectomy continues to be performed with great reluctance," he added. Yet, "under the accepted principles of live-donor nephrectomy, with enough surgical expertise, right-donor nephrectomy can be performed successfully. Right kidneys seem to have a very small difference, if any, in outcomes as compared to left kidneys. Surgical expertise and experience should be tailored toward this aspect."
A session attendee from Brazil commented, "We [prefer] to choose the right kidney in situations where we have one artery on the right side and multiple arteries on the left side." In these cases, his group uses an approach to the vasculature adopted from pancreas transplantation. "We have identical results with the right and left side," he reported.
Dr. Lloyd E. Ratner, director of renal and pancreatic transplantation at Columbia University Medical Center in New York, who also attended the session, said, "I feel somewhat responsible for causing this problem with the right kidney because we were the ones that originally described the higher thrombosis rate with the right kidney with the laparoscopic donor nephrectomies. And I think it scared everyone off from this topic."
As several attendees noted, "there are surgical ways of getting around this," he agreed, offering two more options. "The first is that if we get a short vein, we’re not reluctant at all to put a piece of Dacron onto it, so you don’t even need to dig out the saphenous and cause additional time or morbidity to the patient. And the nice thing about the Dacron grafts is that they are corrugated and they don’t collapse. They also stretch, so you don’t need to cut them exactly precisely," he said.
"And number two is when you are stapling ... it’s often useful to be able to staple onto the cava and not get the vein in one staple byte." By using two passes in the appropriate configuration, "you actually get a cuff of cava, then you have plenty of vein," he explained.
In the study, Dr. Taber and colleagues retrospectively analyzed data from 58,599 adult living donor kidney transplants performed during 2000-2009 and captured in the United Network for Organ Sharing (UNOS) database. In 86% of cases, surgeons used the donor’s left kidney.
Recipients of left and right kidneys were statistically indistinguishable with respect to hospital length of stay, treatment for acute rejection within 6 months, acute rejection as a cause of graft failure, inadequate urine production in the first 24 hours, primary graft failure, graft thrombosis or surgical complication as a contributory cause of graft failure, and 1-year graft survival.
Those receiving a right kidney did have significant but small increases in rates of delayed graft function, as defined by the need for dialysis within 7 days of transplantation (5.7% vs. 4.2%), lack of decline in serum creatinine in the first 24 hours (19.7% vs. 16.4%), treatment for acute rejection within 1 year (12.7% vs. 11.8%), and graft thrombosis as the cause of graft failure (1.1% vs. 0.8%).
The Kaplan-Meier cumulative rate of graft survival was better for left kidneys than for right kidneys (P = .006), but "these are essentially superimposed numbers," said Dr. Taber, who disclosed no conflicts of interest related to the research.
The study had limitations, such as its retrospective design, lack of more detailed information about donor and recipient outcomes, and reliance on data as reported by centers, he acknowledged. Also, such large studies may pick up small differences that are not clinically meaningful.
"With ever-increasing demands for living donor transplantation, right-donor nephrectomies are being considered more often. Every effort should be made to leave the donor with the higher-functioning kidney, but at the same time maximizing the living donor pool," Dr. Taber concluded.
Dr. Taber disclosed no relevant conflicts of interest.
FROM THE 2014 WORLD TRANSPLANT CONGRESS
Key clinical point: Choices of kidney to transplant may not need to hinge on left or right donor organ as a deciding factor.
Major Finding: Recipients of left and right kidneys were statistically indistinguishable with respect to hospital length of stay, treatment for acute rejection within 6 months, acute rejection as a cause of graft failure, inadequate urine production in the first 24 hours, and primary graft failure for acute rejection.
Data Source: A national retrospective cohort study of 58,599 adult living donor kidney transplants done during 2000-2009
Disclosures: Dr. Taber disclosed no relevant conflicts of interest.
Abstracts Presented at the 2014 AVAHO Annual Meeting
A new treatment strategy for high-risk MDS/AML
Credit: Rhoda Baer
Preclinical research has revealed a potential therapeutic strategy for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
In experiments with human cells and mouse models of del(5q) AML/MDS, researchers found that an NF-κB signaling network fueled the survival and growth of leukemic cells.
But the team could inhibit this network by targeting p62, thereby impeding leukemic cell expansion and inducing apoptosis.
Daniel Starczynowski PhD, of Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues described this work in Cell Reports.
“Unfortunately, a large portion of del(5q) AML and MDS patients have an increased number of bone marrow blasts and additional chromosomal mutations,” Dr Starczynowski said.
“These patients have very poor prognosis because the disease is very resistant to available treatments such as chemotherapy and radiation. Finding new therapies is important, and this study identifies new therapeutic possibilities.”
Dr Starczynowski and his colleagues began this research by focusing on miR-146a, a microRNA previously shown to be involved in the pathogenesis of del(5q) MDS/AML.
The team found the loss of miR-146a in leukemic cells results in derepression of TRAF6, a mediator of NF-κB activation, which implicates this molecular complex in the aggressive nature of del(5q) MDS/AML.
So the researchers theorized that inhibiting the TRAF6/NF-κB axis might help treat aggressive forms of del(5q) MDS/AML with low miR-146a expression. The problem was that past attempts to directly inhibit NF-κB had not exactly proven successful.
Fortunately, chromosome deletions that target tumor suppressor genes also involve multiple neighboring genes. So the team examined the expression of all genes residing within chromosome 5q from del(5q) and control CD34+ cells, with the goal of finding a more suitable therapeutic target.
To determine which of the genes they identified are necessary for del(5q) leukemic cell function, the researchers knocked down each gene and examined leukemic progenitor function. They found that only knockdown of SQSTM1/p62 resulted in reduced colony formation.
So the team tested inhibition/knockdown of p62 as an experimental treatment strategy in miR-146alow MDS/AML cell lines, primary del(5q) AML samples, and mouse models of AML/MDS.
They found that targeting p62 reduced the number of leukemic cell colonies by 80% in human AML/MDS cells. And in mice, targeting p62 prevented the expansion of leukemic cells and significantly delayed mortality.
These results suggest that interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
However, Dr Starczynowski noted that additional research is needed to further verify these findings and learn more about the molecular processes involved.
Credit: Rhoda Baer
Preclinical research has revealed a potential therapeutic strategy for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
In experiments with human cells and mouse models of del(5q) AML/MDS, researchers found that an NF-κB signaling network fueled the survival and growth of leukemic cells.
But the team could inhibit this network by targeting p62, thereby impeding leukemic cell expansion and inducing apoptosis.
Daniel Starczynowski PhD, of Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues described this work in Cell Reports.
“Unfortunately, a large portion of del(5q) AML and MDS patients have an increased number of bone marrow blasts and additional chromosomal mutations,” Dr Starczynowski said.
“These patients have very poor prognosis because the disease is very resistant to available treatments such as chemotherapy and radiation. Finding new therapies is important, and this study identifies new therapeutic possibilities.”
Dr Starczynowski and his colleagues began this research by focusing on miR-146a, a microRNA previously shown to be involved in the pathogenesis of del(5q) MDS/AML.
The team found the loss of miR-146a in leukemic cells results in derepression of TRAF6, a mediator of NF-κB activation, which implicates this molecular complex in the aggressive nature of del(5q) MDS/AML.
So the researchers theorized that inhibiting the TRAF6/NF-κB axis might help treat aggressive forms of del(5q) MDS/AML with low miR-146a expression. The problem was that past attempts to directly inhibit NF-κB had not exactly proven successful.
Fortunately, chromosome deletions that target tumor suppressor genes also involve multiple neighboring genes. So the team examined the expression of all genes residing within chromosome 5q from del(5q) and control CD34+ cells, with the goal of finding a more suitable therapeutic target.
To determine which of the genes they identified are necessary for del(5q) leukemic cell function, the researchers knocked down each gene and examined leukemic progenitor function. They found that only knockdown of SQSTM1/p62 resulted in reduced colony formation.
So the team tested inhibition/knockdown of p62 as an experimental treatment strategy in miR-146alow MDS/AML cell lines, primary del(5q) AML samples, and mouse models of AML/MDS.
They found that targeting p62 reduced the number of leukemic cell colonies by 80% in human AML/MDS cells. And in mice, targeting p62 prevented the expansion of leukemic cells and significantly delayed mortality.
These results suggest that interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
However, Dr Starczynowski noted that additional research is needed to further verify these findings and learn more about the molecular processes involved.
Credit: Rhoda Baer
Preclinical research has revealed a potential therapeutic strategy for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
In experiments with human cells and mouse models of del(5q) AML/MDS, researchers found that an NF-κB signaling network fueled the survival and growth of leukemic cells.
But the team could inhibit this network by targeting p62, thereby impeding leukemic cell expansion and inducing apoptosis.
Daniel Starczynowski PhD, of Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues described this work in Cell Reports.
“Unfortunately, a large portion of del(5q) AML and MDS patients have an increased number of bone marrow blasts and additional chromosomal mutations,” Dr Starczynowski said.
“These patients have very poor prognosis because the disease is very resistant to available treatments such as chemotherapy and radiation. Finding new therapies is important, and this study identifies new therapeutic possibilities.”
Dr Starczynowski and his colleagues began this research by focusing on miR-146a, a microRNA previously shown to be involved in the pathogenesis of del(5q) MDS/AML.
The team found the loss of miR-146a in leukemic cells results in derepression of TRAF6, a mediator of NF-κB activation, which implicates this molecular complex in the aggressive nature of del(5q) MDS/AML.
So the researchers theorized that inhibiting the TRAF6/NF-κB axis might help treat aggressive forms of del(5q) MDS/AML with low miR-146a expression. The problem was that past attempts to directly inhibit NF-κB had not exactly proven successful.
Fortunately, chromosome deletions that target tumor suppressor genes also involve multiple neighboring genes. So the team examined the expression of all genes residing within chromosome 5q from del(5q) and control CD34+ cells, with the goal of finding a more suitable therapeutic target.
To determine which of the genes they identified are necessary for del(5q) leukemic cell function, the researchers knocked down each gene and examined leukemic progenitor function. They found that only knockdown of SQSTM1/p62 resulted in reduced colony formation.
So the team tested inhibition/knockdown of p62 as an experimental treatment strategy in miR-146alow MDS/AML cell lines, primary del(5q) AML samples, and mouse models of AML/MDS.
They found that targeting p62 reduced the number of leukemic cell colonies by 80% in human AML/MDS cells. And in mice, targeting p62 prevented the expansion of leukemic cells and significantly delayed mortality.
These results suggest that interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
However, Dr Starczynowski noted that additional research is needed to further verify these findings and learn more about the molecular processes involved.
Regimen confers PFS benefit in newly diagnosed MM
Credit: CDC
In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).
Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.
Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.
Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.
Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.
The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).
The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).
The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).
The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).
At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.
Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).
Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.
The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.
Credit: CDC
In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).
Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.
Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.
Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.
Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.
The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).
The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).
The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).
The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).
At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.
Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).
Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.
The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.
Credit: CDC
In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).
Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.
Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.
Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.
Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.
The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).
The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).
The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).
The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).
At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.
Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).
Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.
The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.
Deaths from childhood cancer on decline in UK
Credit: Logan Tuttle
The rate of children dying from cancer in the UK has dropped 22% in the last decade, according to new figures published by Cancer Research UK.
From 2001 to 2003, 328 children died from cancer each year. But from 2010 to 2012, the annual death toll from childhood cancers decreased to 258.
The steepest decline in mortality was among leukemia patients. Death rates across all forms of leukemia combined dropped by 47%, from 102 to 53 deaths each year.
For acute lymphoblastic leukemia, the annual mortality rate decreased by 52%, falling from 63 to 29 deaths per year. For acute myeloid leukemia, the death rate fell by 33%, from 30 to 20 deaths per year. And for chronic myeloid leukemia, the death rate decreased by 74%, from 2 deaths per year to 1.
Annual mortality rates decreased for lymphoma patients as well. For all lymphomas, the death rate decreased by 31%, falling from 15 to 11 deaths per year. And for non-Hodgkin lymphomas, the rate dropped 35%, from 14 to 10 deaths per year.
Much of this success is due to new combinations of chemotherapy drugs, but efforts to improve imaging and radiotherapy techniques has also played a part, according to Cancer Research UK.
“It’s very encouraging to see that fewer children are dying of cancer, but a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
“Many children who survive cancer will live with the long-term side effects of their treatment that can have an impact throughout their adult lives, so it’s vital that we find kinder and even more effective treatments for them.”
Around 1600 children are diagnosed with cancer every year in the UK. Overall survival for childhood cancer has tripled since the 1960s. The proportion of children surviving their cancer for at least 10 years increased from 24% in 1966-1970 to 76% in 2001-2005.
Note: The above figures are age-standardized mortality rates, which take the age and size of the population into account, providing a figure for the number of children who die from cancer per million individuals. Looking at the numbers of children dying from the disease does not adjust for the increasing size of the UK population over the last 10 years, so changes in the numbers of deaths will not match the changes in rates.
Credit: Logan Tuttle
The rate of children dying from cancer in the UK has dropped 22% in the last decade, according to new figures published by Cancer Research UK.
From 2001 to 2003, 328 children died from cancer each year. But from 2010 to 2012, the annual death toll from childhood cancers decreased to 258.
The steepest decline in mortality was among leukemia patients. Death rates across all forms of leukemia combined dropped by 47%, from 102 to 53 deaths each year.
For acute lymphoblastic leukemia, the annual mortality rate decreased by 52%, falling from 63 to 29 deaths per year. For acute myeloid leukemia, the death rate fell by 33%, from 30 to 20 deaths per year. And for chronic myeloid leukemia, the death rate decreased by 74%, from 2 deaths per year to 1.
Annual mortality rates decreased for lymphoma patients as well. For all lymphomas, the death rate decreased by 31%, falling from 15 to 11 deaths per year. And for non-Hodgkin lymphomas, the rate dropped 35%, from 14 to 10 deaths per year.
Much of this success is due to new combinations of chemotherapy drugs, but efforts to improve imaging and radiotherapy techniques has also played a part, according to Cancer Research UK.
“It’s very encouraging to see that fewer children are dying of cancer, but a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
“Many children who survive cancer will live with the long-term side effects of their treatment that can have an impact throughout their adult lives, so it’s vital that we find kinder and even more effective treatments for them.”
Around 1600 children are diagnosed with cancer every year in the UK. Overall survival for childhood cancer has tripled since the 1960s. The proportion of children surviving their cancer for at least 10 years increased from 24% in 1966-1970 to 76% in 2001-2005.
Note: The above figures are age-standardized mortality rates, which take the age and size of the population into account, providing a figure for the number of children who die from cancer per million individuals. Looking at the numbers of children dying from the disease does not adjust for the increasing size of the UK population over the last 10 years, so changes in the numbers of deaths will not match the changes in rates.
Credit: Logan Tuttle
The rate of children dying from cancer in the UK has dropped 22% in the last decade, according to new figures published by Cancer Research UK.
From 2001 to 2003, 328 children died from cancer each year. But from 2010 to 2012, the annual death toll from childhood cancers decreased to 258.
The steepest decline in mortality was among leukemia patients. Death rates across all forms of leukemia combined dropped by 47%, from 102 to 53 deaths each year.
For acute lymphoblastic leukemia, the annual mortality rate decreased by 52%, falling from 63 to 29 deaths per year. For acute myeloid leukemia, the death rate fell by 33%, from 30 to 20 deaths per year. And for chronic myeloid leukemia, the death rate decreased by 74%, from 2 deaths per year to 1.
Annual mortality rates decreased for lymphoma patients as well. For all lymphomas, the death rate decreased by 31%, falling from 15 to 11 deaths per year. And for non-Hodgkin lymphomas, the rate dropped 35%, from 14 to 10 deaths per year.
Much of this success is due to new combinations of chemotherapy drugs, but efforts to improve imaging and radiotherapy techniques has also played a part, according to Cancer Research UK.
“It’s very encouraging to see that fewer children are dying of cancer, but a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
“Many children who survive cancer will live with the long-term side effects of their treatment that can have an impact throughout their adult lives, so it’s vital that we find kinder and even more effective treatments for them.”
Around 1600 children are diagnosed with cancer every year in the UK. Overall survival for childhood cancer has tripled since the 1960s. The proportion of children surviving their cancer for at least 10 years increased from 24% in 1966-1970 to 76% in 2001-2005.
Note: The above figures are age-standardized mortality rates, which take the age and size of the population into account, providing a figure for the number of children who die from cancer per million individuals. Looking at the numbers of children dying from the disease does not adjust for the increasing size of the UK population over the last 10 years, so changes in the numbers of deaths will not match the changes in rates.
A step toward safer, effective malaria treatment
Walter and Eliza Hall Institute
In uncovering how an antibiotic fights malaria, investigators may have enabled the development of safer and more effective antimalarial drugs.
The group has determined how the antibiotic emetine blocks the molecular machinery that produces the proteins required for malaria parasite survival.
Although emetine is known to be effective against malaria, the drug is not used for this purpose because it confers significant side effects.
By gaining new insight into how emetine works, the investigators have forged the way ahead for designing drugs that can provide the efficacy of emetine without the adverse effects.
Wilson Wong, PhD, of the Walter and Eliza Hall Institute in Victoria, Australia, and his colleagues described this research in eLife.
For this work, the team used Cryo-EM, a technique that allows researchers to visualize the structure of protein complexes from cellular material without having to crystallize them. This method revealed how emetine binds to the ribosome of the malaria parasite Plasmodium falciparum.
“The ribosome is responsible for constructing all proteins inside the cell, based on the DNA ‘blueprint,’” Dr Wong said. “Antibiotics such as emetine kill the malaria parasite by binding to its ribosome and preventing the parasite from building the proteins it needs to produce energy, grow, reproduce, and evade the immune system.”
The investigators discovered that emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin. And emetine delivers its antimalaria effect by blocking mRNA/tRNA translocation.
“Our structure is an exciting discovery, as it gives a clear path forward in developing new drugs to tackle this deadly disease,” Dr Wong said. “We have found features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features in order to specifically target the production of proteins within the malaria parasite.”
“We are now working with our colleagues from the institute’s ACRF Chemical Biology division to develop new molecules based on emetine and pactamycin. Knowing exactly how these antibiotics work will enable development of new antimalarial drugs that replicate the active component of these antibiotics, while changing the parts that make it toxic to patients.”
Walter and Eliza Hall Institute
In uncovering how an antibiotic fights malaria, investigators may have enabled the development of safer and more effective antimalarial drugs.
The group has determined how the antibiotic emetine blocks the molecular machinery that produces the proteins required for malaria parasite survival.
Although emetine is known to be effective against malaria, the drug is not used for this purpose because it confers significant side effects.
By gaining new insight into how emetine works, the investigators have forged the way ahead for designing drugs that can provide the efficacy of emetine without the adverse effects.
Wilson Wong, PhD, of the Walter and Eliza Hall Institute in Victoria, Australia, and his colleagues described this research in eLife.
For this work, the team used Cryo-EM, a technique that allows researchers to visualize the structure of protein complexes from cellular material without having to crystallize them. This method revealed how emetine binds to the ribosome of the malaria parasite Plasmodium falciparum.
“The ribosome is responsible for constructing all proteins inside the cell, based on the DNA ‘blueprint,’” Dr Wong said. “Antibiotics such as emetine kill the malaria parasite by binding to its ribosome and preventing the parasite from building the proteins it needs to produce energy, grow, reproduce, and evade the immune system.”
The investigators discovered that emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin. And emetine delivers its antimalaria effect by blocking mRNA/tRNA translocation.
“Our structure is an exciting discovery, as it gives a clear path forward in developing new drugs to tackle this deadly disease,” Dr Wong said. “We have found features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features in order to specifically target the production of proteins within the malaria parasite.”
“We are now working with our colleagues from the institute’s ACRF Chemical Biology division to develop new molecules based on emetine and pactamycin. Knowing exactly how these antibiotics work will enable development of new antimalarial drugs that replicate the active component of these antibiotics, while changing the parts that make it toxic to patients.”
Walter and Eliza Hall Institute
In uncovering how an antibiotic fights malaria, investigators may have enabled the development of safer and more effective antimalarial drugs.
The group has determined how the antibiotic emetine blocks the molecular machinery that produces the proteins required for malaria parasite survival.
Although emetine is known to be effective against malaria, the drug is not used for this purpose because it confers significant side effects.
By gaining new insight into how emetine works, the investigators have forged the way ahead for designing drugs that can provide the efficacy of emetine without the adverse effects.
Wilson Wong, PhD, of the Walter and Eliza Hall Institute in Victoria, Australia, and his colleagues described this research in eLife.
For this work, the team used Cryo-EM, a technique that allows researchers to visualize the structure of protein complexes from cellular material without having to crystallize them. This method revealed how emetine binds to the ribosome of the malaria parasite Plasmodium falciparum.
“The ribosome is responsible for constructing all proteins inside the cell, based on the DNA ‘blueprint,’” Dr Wong said. “Antibiotics such as emetine kill the malaria parasite by binding to its ribosome and preventing the parasite from building the proteins it needs to produce energy, grow, reproduce, and evade the immune system.”
The investigators discovered that emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin. And emetine delivers its antimalaria effect by blocking mRNA/tRNA translocation.
“Our structure is an exciting discovery, as it gives a clear path forward in developing new drugs to tackle this deadly disease,” Dr Wong said. “We have found features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features in order to specifically target the production of proteins within the malaria parasite.”
“We are now working with our colleagues from the institute’s ACRF Chemical Biology division to develop new molecules based on emetine and pactamycin. Knowing exactly how these antibiotics work will enable development of new antimalarial drugs that replicate the active component of these antibiotics, while changing the parts that make it toxic to patients.”
Getting Hip to Vitamin D
Hip fracture is a common clinical problem, with an incidence of 957 cases/100,000 adults in the United States.[1] Studies have found a high prevalence of vitamin D deficiency among elderly patients with fragility fractures, though many of these studies were performed in high latitude regions.[2, 3, 4, 5, 6, 7, 8, 9, 10] Endocrine Society clinical practice guidelines recommend screening patients with fragility fractures for vitamin D deficiency.[11]
Our hospitalist group practices in an academic tertiary care facility in the southeastern United States. Beginning in June 2010, all patients with acute hip fracture were admitted to our service with consultative comanagement from orthopedics. Our group did not have a standardized approach for the assessment or treatment of vitamin D deficiency in this population. Preliminary analysis of a subgroup of our patients with acute hip fracture revealed that only 29% had been screened for vitamin D deficiency. Of these patients, 68% were deficient or insufficient, yet less than half had been discharged on an appropriate dose of vitamin D. We concluded that our group practice was both varied and substandard.
In this report we describe the creation and implementation of a process for improving the assessment and treatment of vitamin D deficiency in elderly patients with fragility hip fracture. We evaluated the effect of our process on the percentages of patients screened and treated appropriately for vitamin D deficiency.
METHODS
Creation of Intervention
We assembled a task force, consisting of 4 hospitalist physicians. The task force reviewed available literature on the prevalence of vitamin D deficiency in elderly patients with fragility fracture and major practice guidelines related to vitamin D. We utilized Endocrine Society clinical practice guidelines to define vitamin D deficiency, insufficiency, and recommended treatment dosing for each condition[11] (Table 1).
Vitamin D Level (25‐OH) | Vitamin D Status | Treatment Dose Recommendation |
---|---|---|
019 ng/mL | Deficient | 50,000 IU/week for 68 weeks |
2029 ng/mL | Insufficient | 1,000 to 2,000 IU/day or 50,000 IU/month |
We developed 2 processes for improving group practice. First, we presented a review of evidence and preliminary data from our group practice at a meeting of hospitalist staff. Second, we revised the computerized physician order entry (CPOE) set for patients with hip fractures to include 2 new orders: (1) an automatic order for 25‐OH vitamin D level to be drawn the morning after admission and (2) an order for initiation of 1000 IU daily of vitamin D at admission.
The reasons for starting empiric vitamin D supplementation were 2fold. First was to prompt dosing of vitamin D at the time of discharge by already having it on the patient's medication list. Second was to conform to US Preventive Services Task Force guidelines for fall prevention.[12] The dose of 1000 IU was selected due to its being adequate treatment for insufficient (though not deficient) patients, and yet a low enough dose to minimize risk of toxicity.
Providers
Our hospitalist group includes 21 physicians and 3 physician extenders. Two nocturnist positions were added to our group in July 2013, part way through our intervention. There were no other additions or subtractions to the staff during the study period.
Patients
Patients were identified by search of University of North Carolina (UNC) Hospitals' database using International Classification of Diseases, 9th Revision codes for femoral neck fracture (821.x) and femur fracture NOS (820.x), linked to hospital services covered by our group. Exclusion criteria included age 50 years, fracture due to high‐speed trauma, fracture due to malignancy, end‐stage renal disease, and death or transition to comfort care during the index hospitalization.
Outcome Measures
Primary outcome measures were the percentage of patients with acute hip fracture with vitamin D level checked during hospitalization and the percentage of deficient patients discharged on the recommended dose of vitamin D. Outcomes were measured for the 28 months before intervention (when our group assumed direct care for hip fracture patients) and were compared with the 12 months after intervention. We also report the prevalence of vitamin D deficiency in our population.
Laboratory Methodology
25‐OH vitamin D assays were performed by UNC Hospitals' core laboratories. Assays were performed using liquid chromatography tandem mass spectroscopy technique. Methodology remained constant through the study period.
During implementation of the project, we identified slow turnaround time in reporting of the vitamin D assays as an issue. We subsequently plotted the percentage of assays returned within 48 hours for each month of the study period on a run chart.
Analysis
Primary outcome measures and demographic data were tested for statistical significance with the 2 test. As a separate means of analysis, we plotted a control chart for the percentage of patients with vitamin D level checked and a run chart for the percentage of deficient or insufficient patients discharged on the recommended dose of vitamin D. To ensure a constant sample size, consecutive samples of patients were plotted in chronologic order. Results were interpreted with standard Shewhart rules.[13] 2 testing and plotting of control and run charts were performed using Microsoft Excel (Microsoft Corp., Redmond, WA) and QI Charts (Process Improvement Products, Austin, TX).
Implementation
In October 2012, we presented the review of evidence and preliminary data to the hospitalist group and made the new CPOE hip fracture order set available. Implementation was monitored by solicitation of qualitative feedback from group physicians and analysis of outcome data every 6 months. Issues that arose during implementation are described in a project timeline (Figure 1) and discussed in detail in manuscript discussion. We received institutional review board approval to study the project's implementation.

RESULTS
Patients
There were 220 patients identified in the 28 months before implementation. Twenty‐four were excluded by criteria, leaving 196 for analysis. One hundred thirteen patients were identified after implementation. Six patients were excluded by criteria, leaving 107 for analysis.
The mean patient age was 80 years, and the median age was 83 years. Seventy‐five percent were female. Race categories were 85% Caucasian, 8% African American, 3% Asian, 1% Native American, 1% Hispanic, and 3% other.
The preintervention group had mean and median ages of 80 and 82 years, respectively, compared with 81 and 84 years, respectively, in the postintervention group. Seventy‐five percent of the preintervention group was female, compared with 74% postintervention. The only statistically significant difference was in the percentage of Caucasian patients81% of preintervention group compared with 91% of the postintervention group (P = 0.028).
Primary Outcomes
The percentage of patients with acute hip fracture with vitamin D level checked before project implementation was 37.2% (n = 196). After implementation, the percentage improved to 93.5% (n = 107, P < 0.001).
The proportion chart plot of the same data (Figure 2) shows evidence of a fundamental change after intervention. Data points showing the proportion of consecutive samples of 15 patients were plotted chronologically. All points after implementation were above the upper control limit, meeting Shewhart control chart rules for special cause variation.[13]

The percentage of vitamin D deficient/emnsufficient patients discharged on the recommended dose of vitamin D also improved, rising from 40.9% (n = 44) before to 68.0% (n = 50) after implementation (P = 0.008). Because there were fewer candidates for this outcome, we plotted samples of 10 patients consecutively on a run chart (Figure 3). Although there were insufficient data to establish a trend by run chart rules, the last 4 consecutive data points showed sequential improvement.

Prevalence of Vitamin D Insufficiency and Deficiency
Before implementation, 44 of the 73 patients (60.3%) with vitamin D levels checked were deficient or insufficient (25‐OH vitamin D <30 ng/mL); of those 44 patients, 21 (28.8% of total checked) had 25‐OH vitamin D levels <20 ng/mL. After implementation, 50 of 100 patients with levels checked were identified as deficient or insufficient (50%); of those 50 patients, 23 (23% of total) had 25‐OH vitamin D levels <20 ng/mL.
DISCUSSION
Our interventions correlated with significant improvements in the assessment and treatment of vitamin D deficiency in elderly patients with fragility hip fractures. Our study demonstrates a systematic method groups may use to adopt and reliably implement practice guidelines. Moreover, we report several steps to implementation that enhanced our ability to standardize clinical care.
The prevalence of vitamin D deficiency and insufficiency we identified50.0% after change implementationis within the range reported in prior studies, though our result is notable for being in a southern region of the United States. The prevalence we found before implementation (60.3%) may have been subject to selection bias in screening, so 50.0% is likely the more correct prevalence. Other US studies of vitamin D deficiency prevalence in hip fracture patients report rates from 50% to 65.8%.[2, 8, 10]
The percentage of hip fracture patients screened for vitamin D deficiency showed significant improvement after our interventions, rising to 93.5%. As a comparison with our results, a 2008 study after implementation of a hip fracture pathway reported only screening 37% of patients for vitamin D deficiency.[14] The main barrier we identified was occasional failure to use the electronic order set. This was in large part due to moonlighting physicians, who occasionally cover hospitalist shifts. They accounted for 5 of the 7 missed patients. The other 2 misses were due to group physicians not using the order set. These findings were first identified after 6 months of data were analyzed. These data were presented to the hospitalist group, with reminders to reinforce order set use with moonlighters and to manually order levels after admission if the order set was not utilized.
We found more difficulty with discharging deficient patients on the recommended dose of vitamin D. Our low level at the time of implementation40.9%was actually higher than a recent Swiss study, which found that only 27% of patients with acute hip fracture were discharged on any vitamin D, despite 91% of patients having 25‐OH vitamin D levels <30 ng/mL.[15] However, our proportion of deficient patients discharged on the recommended vitamin D dose only improved to 68.0% during our interventions. This is similar to Glowacki et al., who reported discharging 76% of hip fracture patients on vitamin D and/or calcium through utilization of a discharge pathway, though they did not differentiate vitamin D from calcium in results or attempt to identify patient‐specific vitamin D dosing based on serum levels.[14]
We did identify and address several barriers to discharging patients on the recommended dose. First, we experienced slow turnaround time in measurement of 25‐OH vitamin D. Early into the project, we received several reports of patients being discharged before vitamin D levels had returned. We communicated with the director of UNC Hospitals' core laboratories. A major issue was that the special chemistry section of the core laboratory did not report results directly into the hospital's main electronic reporting system, so that the results had to be hand entered. Over several months, the laboratory worked to improve turnaround times. A run chart plot of the percentage of assays reported within 48 hours for each month showed significant improvement with these efforts (see Supporting Information, Figure 1, in the online version of this article). All 9 data points after our initial discussion with the laboratory director were above the mean established during the prior 4 months, meeting run chart rules for a fundamental change in the system.[13]
The second issue identified was that the ranges for deficiency and insufficiency recommended by Endocrine Society guidelines did not match the reference ranges provided by UNC Hospitals. UNC Hospitals reported levels of 25‐OH vitamin D as normal if above 24, whereas the Endocrine Society defined normal as above 29. When analyzing data after 6 months, we found several patients who had been screened appropriately with results available and noted by the discharging physician, but with results in the normal range per our laboratory. Several of these patients, though low in vitamin D by Endocrine Society standards, were not treated. The laboratory director was again contacted, who noted that the UNC reference ranges had been formed before the Endocrine Society guidelines had been published. We elected to continue with the more conservative ranges recommended by the Endocrine Society. We presented results to the group after 6 months of data had been collected and emphasized our recommended reference ranges and vitamin D dosing (Table 1). We also created reference charts with this information and hung them by all computer workstations in the hospitalist office. With this continued assessment of data and provider education, we did note further improvement through the implementation period, with 90.0% of the last sample of deficient/emnsufficient patients discharged on the recommended dose of vitamin D (Figure 3).
We debated whether to include calcium supplementation as part of our intervention, but given known potential harms from calcium supplementation, including nephrolithiasis and possible increased cardiovascular risk,[16] we elected to focus exclusively on vitamin D. Although studies of primary and secondary fragility fracture prevention with vitamin D have not demonstrated consistently positive results, the studies were not specifically targeted to vitamin D‐deficient patients.[17, 18] Even in the absence of definitively proven secondary fracture prevention, given the multiple health issues associated with vitamin D deficiency, we believe that screening high prevalence populations and treating appropriately is best practice. With minimal patient costs (our institution charges $93 per assay) and a high prevalence (50% in our population), we believe universal screening of elderly patients with hip fracture for vitamin D deficiency is also cost‐effective.
Our project was specifically designed to address the issue of vitamin D deficiency in elderly hip fracture patients, but most of these patients also have osteoporosis. Although vitamin D deficiency contributes to osteoporosis, it is certainly not the only factor. It is also recognized that a minority of patients with fragility fractures receives subsequent evaluation and treatment for osteoporosis, <20% in a recent large population‐based study.[19] The American Orthopedic Association has recently launched a website and campaign entitled Own the Bone to improve the quality of care for patients after osteoporotic fracture.[20] A number of measures have been studied to improve the deficit in care, often termed the osteoporosis treatment gap. Edwards and colleagues recently described an intervention based on their institutional electronic medical record.[21] The intervention included order sets for diagnosing osteoporosis and educational materials for patients and providers, but did not demonstrate any change in percentage of patients evaluated for osteoporosis after fragility fracture. Successful randomized controlled trials have been reported using mail notification of physicians and patients after osteoporotic fracture[22]; multifaceted telephone, education and mail notification interventions after wrist fracture[23]; and through the use of a central osteoporosis coordinator to coordinate osteoporosis treatment after a fragility fracture.[24] These successful trials were broad in scope and yet reported modest (10%20%) gains in improvement.
Although bisphophonate therapy is of proven benefit in secondary fracture prevention, there are a number of barriers to initiating it in the acute setting after fragility fracture, as the difficulty in getting large improvement during the above trials suggests. These include recommendations from some experts for bone density testing before starting treatment and theoretic concerns of impairing fracture healing in the initial weeks after acute fracture. Both of these concerns make a hospitalist‐based intervention for osteoporosis evaluation and treatment challenging and beyond the scope of our project's quality improvement efforts.
Our study has some limitations. It was conducted in a single institution and electronic order entry system, which could limit the ability to generalize the results. We did not assess vitamin D compliance or follow‐up after hospitalization, so we are unable to determine if patients successfully completed treatment after it was prescribed. We also found slight differences in race between the pre‐ and postintervention groups. Although we did not perform multivariable regression to account for these differences, we feel such analyses would be unlikely to alter our results. Last, it should be noted that there may be unintended consequences from preselected orders, such as the ones we utilized for vitamin D assays and empiric supplementation. For example, patients with a recently checked vitamin D assay would have duplication of that lab. Similarly, patients who were already taking vitamin D could theoretically be placed on double therapy at admission. With safeguards in the electronic system to flag duplicate medications, low toxicity of standard doses of vitamin D, and minimal economic harm with duplicate laboratory therapy in the context of a hospitalization for hip fracture, we believe the risks are outweighed by the benefits of screening.
In summary, with review of evidence, modification of a computerized physician order set, provider education and feedback, and collaboration with our clinical laboratory, we were able to standardize and improve group practice for the assessment and treatment of vitamin D deficiency in elderly patients with hip fracture. We believe that our model could be applied to other institutions to further improve patient care. Given the extremely high incidence of hip fracture and consistently high prevalence of vitamin D deficiency in this population across studies, these findings have important implications for the care of this commonly encountered and vulnerable group of patients.
Disclosures: Data from this project were presented in abstract form at the Society of Hospital Medicine Annual Meetings in 2013 and 2014 and as an abstract at the Society of General Internal Medicine Annual Meeting in 2014. Dr. Catherine Hammett‐Stabler, Director of UNC Hospitals McLendon Core Laboratories, provided data on vitamin D assay turnaround times. The authors report no conflicts of interest.
- Incidence and mortality of hip fractures in the United States. JAMA. 2009;302(14):1573–1579. , , , .
- Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281(16):1505–1511. , , , , , .
- Prevalence of vitamin D inadequacy in Scottish adults with non‐vertebral fragility fractures. Curr Med Res Opin. 2005;21(9):1355–1361. , , , , , .
- Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London. Curr Med Res Opin. 2005;21(12):1891–1894. , , .
- Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland. Osteoporos Int. 2005;16(12):2018–2024. , , , et al.
- Prevalence of vitamin D inadequacy in Belfast following fragility fracture. Curr Med Res Opin. 2006;22(1):101–105. , , , et al.
- High prevalence of hypovitaminosis D and K in patients with hip fracture. Asia Pac J Clin Nutr. 2011;20(1):56–61. , , , , , .
- Vitamin D insufficiency in patients with acute hip fractures of all ages and both sexes in a sunny climate. J Orthop Trauma. 2013;27(12):e275–e280. , , , .
- Vitamin D and intact PTH status in patients with hip fracture. Osteoporos Int. 2006;17(11):1608–1614. , , , et al.
- Distribution and correlates of serum 25‐hydroxyvitamin D levels in a sample of patients with hip fracture. Am J Geriatr Pharmacother. 2007;5(4):335–340. , , , et al.
- Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930. , , , et al.
- Prevention of falls in community‐dwelling older adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(3):197–204. , .
- The Health Care Data Guide: Learning From Data for Improvement. 1st ed. San Francisco, CA: Jossey‐Bass; 2011. , .
- Importance of vitamin D in hospital‐based fracture care pathways. J Nutr Health Aging. 2008;12(5):291–293. , , , , .
- Before and after hip fracture, vitamin D deficiency may not be treated sufficiently. Osteoporos Int. 2013;24(11):2765–2773. , , , et al.
- Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta‐analysis. BMJ. 2010;341:c3691. , , , et al.
- A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–49. , , , et al.
- Oral vitamin D3 and calcium for secondary prevention of low‐trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo‐controlled trial. Lancet. 2005;365(9471):1621–1628. , , , et al.
- A population‐based analysis of the post‐fracture care gap 1996–2008: the situation is not improving. Osteoporos Int. 2012;23(5):1623–1629. , , , et al.
- American Orthopedic Association. Own the Bone website. 2011. Available at: http://www.ownthebone.org. Accessed August 1, 2014.
- Development of an electronic medical record based intervention to improve medical care of osteoporosis. Osteoporos Int. 2012;23(10):2489–2498. , , , et al.
- Closing the gap in postfracture care at the population level: a randomized controlled trial. CMAJ. 2012;184(3):290–296. , , , , .
- Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial. CMAJ. 2008;178(5):569–575. , , , et al.
- Impact of a centralized osteoporosis coordinator on post‐fracture osteoporosis management: a cluster randomized trial. Osteoporos Int. 2012;23(1):87–95. , , , et al.
Hip fracture is a common clinical problem, with an incidence of 957 cases/100,000 adults in the United States.[1] Studies have found a high prevalence of vitamin D deficiency among elderly patients with fragility fractures, though many of these studies were performed in high latitude regions.[2, 3, 4, 5, 6, 7, 8, 9, 10] Endocrine Society clinical practice guidelines recommend screening patients with fragility fractures for vitamin D deficiency.[11]
Our hospitalist group practices in an academic tertiary care facility in the southeastern United States. Beginning in June 2010, all patients with acute hip fracture were admitted to our service with consultative comanagement from orthopedics. Our group did not have a standardized approach for the assessment or treatment of vitamin D deficiency in this population. Preliminary analysis of a subgroup of our patients with acute hip fracture revealed that only 29% had been screened for vitamin D deficiency. Of these patients, 68% were deficient or insufficient, yet less than half had been discharged on an appropriate dose of vitamin D. We concluded that our group practice was both varied and substandard.
In this report we describe the creation and implementation of a process for improving the assessment and treatment of vitamin D deficiency in elderly patients with fragility hip fracture. We evaluated the effect of our process on the percentages of patients screened and treated appropriately for vitamin D deficiency.
METHODS
Creation of Intervention
We assembled a task force, consisting of 4 hospitalist physicians. The task force reviewed available literature on the prevalence of vitamin D deficiency in elderly patients with fragility fracture and major practice guidelines related to vitamin D. We utilized Endocrine Society clinical practice guidelines to define vitamin D deficiency, insufficiency, and recommended treatment dosing for each condition[11] (Table 1).
Vitamin D Level (25‐OH) | Vitamin D Status | Treatment Dose Recommendation |
---|---|---|
019 ng/mL | Deficient | 50,000 IU/week for 68 weeks |
2029 ng/mL | Insufficient | 1,000 to 2,000 IU/day or 50,000 IU/month |
We developed 2 processes for improving group practice. First, we presented a review of evidence and preliminary data from our group practice at a meeting of hospitalist staff. Second, we revised the computerized physician order entry (CPOE) set for patients with hip fractures to include 2 new orders: (1) an automatic order for 25‐OH vitamin D level to be drawn the morning after admission and (2) an order for initiation of 1000 IU daily of vitamin D at admission.
The reasons for starting empiric vitamin D supplementation were 2fold. First was to prompt dosing of vitamin D at the time of discharge by already having it on the patient's medication list. Second was to conform to US Preventive Services Task Force guidelines for fall prevention.[12] The dose of 1000 IU was selected due to its being adequate treatment for insufficient (though not deficient) patients, and yet a low enough dose to minimize risk of toxicity.
Providers
Our hospitalist group includes 21 physicians and 3 physician extenders. Two nocturnist positions were added to our group in July 2013, part way through our intervention. There were no other additions or subtractions to the staff during the study period.
Patients
Patients were identified by search of University of North Carolina (UNC) Hospitals' database using International Classification of Diseases, 9th Revision codes for femoral neck fracture (821.x) and femur fracture NOS (820.x), linked to hospital services covered by our group. Exclusion criteria included age 50 years, fracture due to high‐speed trauma, fracture due to malignancy, end‐stage renal disease, and death or transition to comfort care during the index hospitalization.
Outcome Measures
Primary outcome measures were the percentage of patients with acute hip fracture with vitamin D level checked during hospitalization and the percentage of deficient patients discharged on the recommended dose of vitamin D. Outcomes were measured for the 28 months before intervention (when our group assumed direct care for hip fracture patients) and were compared with the 12 months after intervention. We also report the prevalence of vitamin D deficiency in our population.
Laboratory Methodology
25‐OH vitamin D assays were performed by UNC Hospitals' core laboratories. Assays were performed using liquid chromatography tandem mass spectroscopy technique. Methodology remained constant through the study period.
During implementation of the project, we identified slow turnaround time in reporting of the vitamin D assays as an issue. We subsequently plotted the percentage of assays returned within 48 hours for each month of the study period on a run chart.
Analysis
Primary outcome measures and demographic data were tested for statistical significance with the 2 test. As a separate means of analysis, we plotted a control chart for the percentage of patients with vitamin D level checked and a run chart for the percentage of deficient or insufficient patients discharged on the recommended dose of vitamin D. To ensure a constant sample size, consecutive samples of patients were plotted in chronologic order. Results were interpreted with standard Shewhart rules.[13] 2 testing and plotting of control and run charts were performed using Microsoft Excel (Microsoft Corp., Redmond, WA) and QI Charts (Process Improvement Products, Austin, TX).
Implementation
In October 2012, we presented the review of evidence and preliminary data to the hospitalist group and made the new CPOE hip fracture order set available. Implementation was monitored by solicitation of qualitative feedback from group physicians and analysis of outcome data every 6 months. Issues that arose during implementation are described in a project timeline (Figure 1) and discussed in detail in manuscript discussion. We received institutional review board approval to study the project's implementation.

RESULTS
Patients
There were 220 patients identified in the 28 months before implementation. Twenty‐four were excluded by criteria, leaving 196 for analysis. One hundred thirteen patients were identified after implementation. Six patients were excluded by criteria, leaving 107 for analysis.
The mean patient age was 80 years, and the median age was 83 years. Seventy‐five percent were female. Race categories were 85% Caucasian, 8% African American, 3% Asian, 1% Native American, 1% Hispanic, and 3% other.
The preintervention group had mean and median ages of 80 and 82 years, respectively, compared with 81 and 84 years, respectively, in the postintervention group. Seventy‐five percent of the preintervention group was female, compared with 74% postintervention. The only statistically significant difference was in the percentage of Caucasian patients81% of preintervention group compared with 91% of the postintervention group (P = 0.028).
Primary Outcomes
The percentage of patients with acute hip fracture with vitamin D level checked before project implementation was 37.2% (n = 196). After implementation, the percentage improved to 93.5% (n = 107, P < 0.001).
The proportion chart plot of the same data (Figure 2) shows evidence of a fundamental change after intervention. Data points showing the proportion of consecutive samples of 15 patients were plotted chronologically. All points after implementation were above the upper control limit, meeting Shewhart control chart rules for special cause variation.[13]

The percentage of vitamin D deficient/emnsufficient patients discharged on the recommended dose of vitamin D also improved, rising from 40.9% (n = 44) before to 68.0% (n = 50) after implementation (P = 0.008). Because there were fewer candidates for this outcome, we plotted samples of 10 patients consecutively on a run chart (Figure 3). Although there were insufficient data to establish a trend by run chart rules, the last 4 consecutive data points showed sequential improvement.

Prevalence of Vitamin D Insufficiency and Deficiency
Before implementation, 44 of the 73 patients (60.3%) with vitamin D levels checked were deficient or insufficient (25‐OH vitamin D <30 ng/mL); of those 44 patients, 21 (28.8% of total checked) had 25‐OH vitamin D levels <20 ng/mL. After implementation, 50 of 100 patients with levels checked were identified as deficient or insufficient (50%); of those 50 patients, 23 (23% of total) had 25‐OH vitamin D levels <20 ng/mL.
DISCUSSION
Our interventions correlated with significant improvements in the assessment and treatment of vitamin D deficiency in elderly patients with fragility hip fractures. Our study demonstrates a systematic method groups may use to adopt and reliably implement practice guidelines. Moreover, we report several steps to implementation that enhanced our ability to standardize clinical care.
The prevalence of vitamin D deficiency and insufficiency we identified50.0% after change implementationis within the range reported in prior studies, though our result is notable for being in a southern region of the United States. The prevalence we found before implementation (60.3%) may have been subject to selection bias in screening, so 50.0% is likely the more correct prevalence. Other US studies of vitamin D deficiency prevalence in hip fracture patients report rates from 50% to 65.8%.[2, 8, 10]
The percentage of hip fracture patients screened for vitamin D deficiency showed significant improvement after our interventions, rising to 93.5%. As a comparison with our results, a 2008 study after implementation of a hip fracture pathway reported only screening 37% of patients for vitamin D deficiency.[14] The main barrier we identified was occasional failure to use the electronic order set. This was in large part due to moonlighting physicians, who occasionally cover hospitalist shifts. They accounted for 5 of the 7 missed patients. The other 2 misses were due to group physicians not using the order set. These findings were first identified after 6 months of data were analyzed. These data were presented to the hospitalist group, with reminders to reinforce order set use with moonlighters and to manually order levels after admission if the order set was not utilized.
We found more difficulty with discharging deficient patients on the recommended dose of vitamin D. Our low level at the time of implementation40.9%was actually higher than a recent Swiss study, which found that only 27% of patients with acute hip fracture were discharged on any vitamin D, despite 91% of patients having 25‐OH vitamin D levels <30 ng/mL.[15] However, our proportion of deficient patients discharged on the recommended vitamin D dose only improved to 68.0% during our interventions. This is similar to Glowacki et al., who reported discharging 76% of hip fracture patients on vitamin D and/or calcium through utilization of a discharge pathway, though they did not differentiate vitamin D from calcium in results or attempt to identify patient‐specific vitamin D dosing based on serum levels.[14]
We did identify and address several barriers to discharging patients on the recommended dose. First, we experienced slow turnaround time in measurement of 25‐OH vitamin D. Early into the project, we received several reports of patients being discharged before vitamin D levels had returned. We communicated with the director of UNC Hospitals' core laboratories. A major issue was that the special chemistry section of the core laboratory did not report results directly into the hospital's main electronic reporting system, so that the results had to be hand entered. Over several months, the laboratory worked to improve turnaround times. A run chart plot of the percentage of assays reported within 48 hours for each month showed significant improvement with these efforts (see Supporting Information, Figure 1, in the online version of this article). All 9 data points after our initial discussion with the laboratory director were above the mean established during the prior 4 months, meeting run chart rules for a fundamental change in the system.[13]
The second issue identified was that the ranges for deficiency and insufficiency recommended by Endocrine Society guidelines did not match the reference ranges provided by UNC Hospitals. UNC Hospitals reported levels of 25‐OH vitamin D as normal if above 24, whereas the Endocrine Society defined normal as above 29. When analyzing data after 6 months, we found several patients who had been screened appropriately with results available and noted by the discharging physician, but with results in the normal range per our laboratory. Several of these patients, though low in vitamin D by Endocrine Society standards, were not treated. The laboratory director was again contacted, who noted that the UNC reference ranges had been formed before the Endocrine Society guidelines had been published. We elected to continue with the more conservative ranges recommended by the Endocrine Society. We presented results to the group after 6 months of data had been collected and emphasized our recommended reference ranges and vitamin D dosing (Table 1). We also created reference charts with this information and hung them by all computer workstations in the hospitalist office. With this continued assessment of data and provider education, we did note further improvement through the implementation period, with 90.0% of the last sample of deficient/emnsufficient patients discharged on the recommended dose of vitamin D (Figure 3).
We debated whether to include calcium supplementation as part of our intervention, but given known potential harms from calcium supplementation, including nephrolithiasis and possible increased cardiovascular risk,[16] we elected to focus exclusively on vitamin D. Although studies of primary and secondary fragility fracture prevention with vitamin D have not demonstrated consistently positive results, the studies were not specifically targeted to vitamin D‐deficient patients.[17, 18] Even in the absence of definitively proven secondary fracture prevention, given the multiple health issues associated with vitamin D deficiency, we believe that screening high prevalence populations and treating appropriately is best practice. With minimal patient costs (our institution charges $93 per assay) and a high prevalence (50% in our population), we believe universal screening of elderly patients with hip fracture for vitamin D deficiency is also cost‐effective.
Our project was specifically designed to address the issue of vitamin D deficiency in elderly hip fracture patients, but most of these patients also have osteoporosis. Although vitamin D deficiency contributes to osteoporosis, it is certainly not the only factor. It is also recognized that a minority of patients with fragility fractures receives subsequent evaluation and treatment for osteoporosis, <20% in a recent large population‐based study.[19] The American Orthopedic Association has recently launched a website and campaign entitled Own the Bone to improve the quality of care for patients after osteoporotic fracture.[20] A number of measures have been studied to improve the deficit in care, often termed the osteoporosis treatment gap. Edwards and colleagues recently described an intervention based on their institutional electronic medical record.[21] The intervention included order sets for diagnosing osteoporosis and educational materials for patients and providers, but did not demonstrate any change in percentage of patients evaluated for osteoporosis after fragility fracture. Successful randomized controlled trials have been reported using mail notification of physicians and patients after osteoporotic fracture[22]; multifaceted telephone, education and mail notification interventions after wrist fracture[23]; and through the use of a central osteoporosis coordinator to coordinate osteoporosis treatment after a fragility fracture.[24] These successful trials were broad in scope and yet reported modest (10%20%) gains in improvement.
Although bisphophonate therapy is of proven benefit in secondary fracture prevention, there are a number of barriers to initiating it in the acute setting after fragility fracture, as the difficulty in getting large improvement during the above trials suggests. These include recommendations from some experts for bone density testing before starting treatment and theoretic concerns of impairing fracture healing in the initial weeks after acute fracture. Both of these concerns make a hospitalist‐based intervention for osteoporosis evaluation and treatment challenging and beyond the scope of our project's quality improvement efforts.
Our study has some limitations. It was conducted in a single institution and electronic order entry system, which could limit the ability to generalize the results. We did not assess vitamin D compliance or follow‐up after hospitalization, so we are unable to determine if patients successfully completed treatment after it was prescribed. We also found slight differences in race between the pre‐ and postintervention groups. Although we did not perform multivariable regression to account for these differences, we feel such analyses would be unlikely to alter our results. Last, it should be noted that there may be unintended consequences from preselected orders, such as the ones we utilized for vitamin D assays and empiric supplementation. For example, patients with a recently checked vitamin D assay would have duplication of that lab. Similarly, patients who were already taking vitamin D could theoretically be placed on double therapy at admission. With safeguards in the electronic system to flag duplicate medications, low toxicity of standard doses of vitamin D, and minimal economic harm with duplicate laboratory therapy in the context of a hospitalization for hip fracture, we believe the risks are outweighed by the benefits of screening.
In summary, with review of evidence, modification of a computerized physician order set, provider education and feedback, and collaboration with our clinical laboratory, we were able to standardize and improve group practice for the assessment and treatment of vitamin D deficiency in elderly patients with hip fracture. We believe that our model could be applied to other institutions to further improve patient care. Given the extremely high incidence of hip fracture and consistently high prevalence of vitamin D deficiency in this population across studies, these findings have important implications for the care of this commonly encountered and vulnerable group of patients.
Disclosures: Data from this project were presented in abstract form at the Society of Hospital Medicine Annual Meetings in 2013 and 2014 and as an abstract at the Society of General Internal Medicine Annual Meeting in 2014. Dr. Catherine Hammett‐Stabler, Director of UNC Hospitals McLendon Core Laboratories, provided data on vitamin D assay turnaround times. The authors report no conflicts of interest.
Hip fracture is a common clinical problem, with an incidence of 957 cases/100,000 adults in the United States.[1] Studies have found a high prevalence of vitamin D deficiency among elderly patients with fragility fractures, though many of these studies were performed in high latitude regions.[2, 3, 4, 5, 6, 7, 8, 9, 10] Endocrine Society clinical practice guidelines recommend screening patients with fragility fractures for vitamin D deficiency.[11]
Our hospitalist group practices in an academic tertiary care facility in the southeastern United States. Beginning in June 2010, all patients with acute hip fracture were admitted to our service with consultative comanagement from orthopedics. Our group did not have a standardized approach for the assessment or treatment of vitamin D deficiency in this population. Preliminary analysis of a subgroup of our patients with acute hip fracture revealed that only 29% had been screened for vitamin D deficiency. Of these patients, 68% were deficient or insufficient, yet less than half had been discharged on an appropriate dose of vitamin D. We concluded that our group practice was both varied and substandard.
In this report we describe the creation and implementation of a process for improving the assessment and treatment of vitamin D deficiency in elderly patients with fragility hip fracture. We evaluated the effect of our process on the percentages of patients screened and treated appropriately for vitamin D deficiency.
METHODS
Creation of Intervention
We assembled a task force, consisting of 4 hospitalist physicians. The task force reviewed available literature on the prevalence of vitamin D deficiency in elderly patients with fragility fracture and major practice guidelines related to vitamin D. We utilized Endocrine Society clinical practice guidelines to define vitamin D deficiency, insufficiency, and recommended treatment dosing for each condition[11] (Table 1).
Vitamin D Level (25‐OH) | Vitamin D Status | Treatment Dose Recommendation |
---|---|---|
019 ng/mL | Deficient | 50,000 IU/week for 68 weeks |
2029 ng/mL | Insufficient | 1,000 to 2,000 IU/day or 50,000 IU/month |
We developed 2 processes for improving group practice. First, we presented a review of evidence and preliminary data from our group practice at a meeting of hospitalist staff. Second, we revised the computerized physician order entry (CPOE) set for patients with hip fractures to include 2 new orders: (1) an automatic order for 25‐OH vitamin D level to be drawn the morning after admission and (2) an order for initiation of 1000 IU daily of vitamin D at admission.
The reasons for starting empiric vitamin D supplementation were 2fold. First was to prompt dosing of vitamin D at the time of discharge by already having it on the patient's medication list. Second was to conform to US Preventive Services Task Force guidelines for fall prevention.[12] The dose of 1000 IU was selected due to its being adequate treatment for insufficient (though not deficient) patients, and yet a low enough dose to minimize risk of toxicity.
Providers
Our hospitalist group includes 21 physicians and 3 physician extenders. Two nocturnist positions were added to our group in July 2013, part way through our intervention. There were no other additions or subtractions to the staff during the study period.
Patients
Patients were identified by search of University of North Carolina (UNC) Hospitals' database using International Classification of Diseases, 9th Revision codes for femoral neck fracture (821.x) and femur fracture NOS (820.x), linked to hospital services covered by our group. Exclusion criteria included age 50 years, fracture due to high‐speed trauma, fracture due to malignancy, end‐stage renal disease, and death or transition to comfort care during the index hospitalization.
Outcome Measures
Primary outcome measures were the percentage of patients with acute hip fracture with vitamin D level checked during hospitalization and the percentage of deficient patients discharged on the recommended dose of vitamin D. Outcomes were measured for the 28 months before intervention (when our group assumed direct care for hip fracture patients) and were compared with the 12 months after intervention. We also report the prevalence of vitamin D deficiency in our population.
Laboratory Methodology
25‐OH vitamin D assays were performed by UNC Hospitals' core laboratories. Assays were performed using liquid chromatography tandem mass spectroscopy technique. Methodology remained constant through the study period.
During implementation of the project, we identified slow turnaround time in reporting of the vitamin D assays as an issue. We subsequently plotted the percentage of assays returned within 48 hours for each month of the study period on a run chart.
Analysis
Primary outcome measures and demographic data were tested for statistical significance with the 2 test. As a separate means of analysis, we plotted a control chart for the percentage of patients with vitamin D level checked and a run chart for the percentage of deficient or insufficient patients discharged on the recommended dose of vitamin D. To ensure a constant sample size, consecutive samples of patients were plotted in chronologic order. Results were interpreted with standard Shewhart rules.[13] 2 testing and plotting of control and run charts were performed using Microsoft Excel (Microsoft Corp., Redmond, WA) and QI Charts (Process Improvement Products, Austin, TX).
Implementation
In October 2012, we presented the review of evidence and preliminary data to the hospitalist group and made the new CPOE hip fracture order set available. Implementation was monitored by solicitation of qualitative feedback from group physicians and analysis of outcome data every 6 months. Issues that arose during implementation are described in a project timeline (Figure 1) and discussed in detail in manuscript discussion. We received institutional review board approval to study the project's implementation.

RESULTS
Patients
There were 220 patients identified in the 28 months before implementation. Twenty‐four were excluded by criteria, leaving 196 for analysis. One hundred thirteen patients were identified after implementation. Six patients were excluded by criteria, leaving 107 for analysis.
The mean patient age was 80 years, and the median age was 83 years. Seventy‐five percent were female. Race categories were 85% Caucasian, 8% African American, 3% Asian, 1% Native American, 1% Hispanic, and 3% other.
The preintervention group had mean and median ages of 80 and 82 years, respectively, compared with 81 and 84 years, respectively, in the postintervention group. Seventy‐five percent of the preintervention group was female, compared with 74% postintervention. The only statistically significant difference was in the percentage of Caucasian patients81% of preintervention group compared with 91% of the postintervention group (P = 0.028).
Primary Outcomes
The percentage of patients with acute hip fracture with vitamin D level checked before project implementation was 37.2% (n = 196). After implementation, the percentage improved to 93.5% (n = 107, P < 0.001).
The proportion chart plot of the same data (Figure 2) shows evidence of a fundamental change after intervention. Data points showing the proportion of consecutive samples of 15 patients were plotted chronologically. All points after implementation were above the upper control limit, meeting Shewhart control chart rules for special cause variation.[13]

The percentage of vitamin D deficient/emnsufficient patients discharged on the recommended dose of vitamin D also improved, rising from 40.9% (n = 44) before to 68.0% (n = 50) after implementation (P = 0.008). Because there were fewer candidates for this outcome, we plotted samples of 10 patients consecutively on a run chart (Figure 3). Although there were insufficient data to establish a trend by run chart rules, the last 4 consecutive data points showed sequential improvement.

Prevalence of Vitamin D Insufficiency and Deficiency
Before implementation, 44 of the 73 patients (60.3%) with vitamin D levels checked were deficient or insufficient (25‐OH vitamin D <30 ng/mL); of those 44 patients, 21 (28.8% of total checked) had 25‐OH vitamin D levels <20 ng/mL. After implementation, 50 of 100 patients with levels checked were identified as deficient or insufficient (50%); of those 50 patients, 23 (23% of total) had 25‐OH vitamin D levels <20 ng/mL.
DISCUSSION
Our interventions correlated with significant improvements in the assessment and treatment of vitamin D deficiency in elderly patients with fragility hip fractures. Our study demonstrates a systematic method groups may use to adopt and reliably implement practice guidelines. Moreover, we report several steps to implementation that enhanced our ability to standardize clinical care.
The prevalence of vitamin D deficiency and insufficiency we identified50.0% after change implementationis within the range reported in prior studies, though our result is notable for being in a southern region of the United States. The prevalence we found before implementation (60.3%) may have been subject to selection bias in screening, so 50.0% is likely the more correct prevalence. Other US studies of vitamin D deficiency prevalence in hip fracture patients report rates from 50% to 65.8%.[2, 8, 10]
The percentage of hip fracture patients screened for vitamin D deficiency showed significant improvement after our interventions, rising to 93.5%. As a comparison with our results, a 2008 study after implementation of a hip fracture pathway reported only screening 37% of patients for vitamin D deficiency.[14] The main barrier we identified was occasional failure to use the electronic order set. This was in large part due to moonlighting physicians, who occasionally cover hospitalist shifts. They accounted for 5 of the 7 missed patients. The other 2 misses were due to group physicians not using the order set. These findings were first identified after 6 months of data were analyzed. These data were presented to the hospitalist group, with reminders to reinforce order set use with moonlighters and to manually order levels after admission if the order set was not utilized.
We found more difficulty with discharging deficient patients on the recommended dose of vitamin D. Our low level at the time of implementation40.9%was actually higher than a recent Swiss study, which found that only 27% of patients with acute hip fracture were discharged on any vitamin D, despite 91% of patients having 25‐OH vitamin D levels <30 ng/mL.[15] However, our proportion of deficient patients discharged on the recommended vitamin D dose only improved to 68.0% during our interventions. This is similar to Glowacki et al., who reported discharging 76% of hip fracture patients on vitamin D and/or calcium through utilization of a discharge pathway, though they did not differentiate vitamin D from calcium in results or attempt to identify patient‐specific vitamin D dosing based on serum levels.[14]
We did identify and address several barriers to discharging patients on the recommended dose. First, we experienced slow turnaround time in measurement of 25‐OH vitamin D. Early into the project, we received several reports of patients being discharged before vitamin D levels had returned. We communicated with the director of UNC Hospitals' core laboratories. A major issue was that the special chemistry section of the core laboratory did not report results directly into the hospital's main electronic reporting system, so that the results had to be hand entered. Over several months, the laboratory worked to improve turnaround times. A run chart plot of the percentage of assays reported within 48 hours for each month showed significant improvement with these efforts (see Supporting Information, Figure 1, in the online version of this article). All 9 data points after our initial discussion with the laboratory director were above the mean established during the prior 4 months, meeting run chart rules for a fundamental change in the system.[13]
The second issue identified was that the ranges for deficiency and insufficiency recommended by Endocrine Society guidelines did not match the reference ranges provided by UNC Hospitals. UNC Hospitals reported levels of 25‐OH vitamin D as normal if above 24, whereas the Endocrine Society defined normal as above 29. When analyzing data after 6 months, we found several patients who had been screened appropriately with results available and noted by the discharging physician, but with results in the normal range per our laboratory. Several of these patients, though low in vitamin D by Endocrine Society standards, were not treated. The laboratory director was again contacted, who noted that the UNC reference ranges had been formed before the Endocrine Society guidelines had been published. We elected to continue with the more conservative ranges recommended by the Endocrine Society. We presented results to the group after 6 months of data had been collected and emphasized our recommended reference ranges and vitamin D dosing (Table 1). We also created reference charts with this information and hung them by all computer workstations in the hospitalist office. With this continued assessment of data and provider education, we did note further improvement through the implementation period, with 90.0% of the last sample of deficient/emnsufficient patients discharged on the recommended dose of vitamin D (Figure 3).
We debated whether to include calcium supplementation as part of our intervention, but given known potential harms from calcium supplementation, including nephrolithiasis and possible increased cardiovascular risk,[16] we elected to focus exclusively on vitamin D. Although studies of primary and secondary fragility fracture prevention with vitamin D have not demonstrated consistently positive results, the studies were not specifically targeted to vitamin D‐deficient patients.[17, 18] Even in the absence of definitively proven secondary fracture prevention, given the multiple health issues associated with vitamin D deficiency, we believe that screening high prevalence populations and treating appropriately is best practice. With minimal patient costs (our institution charges $93 per assay) and a high prevalence (50% in our population), we believe universal screening of elderly patients with hip fracture for vitamin D deficiency is also cost‐effective.
Our project was specifically designed to address the issue of vitamin D deficiency in elderly hip fracture patients, but most of these patients also have osteoporosis. Although vitamin D deficiency contributes to osteoporosis, it is certainly not the only factor. It is also recognized that a minority of patients with fragility fractures receives subsequent evaluation and treatment for osteoporosis, <20% in a recent large population‐based study.[19] The American Orthopedic Association has recently launched a website and campaign entitled Own the Bone to improve the quality of care for patients after osteoporotic fracture.[20] A number of measures have been studied to improve the deficit in care, often termed the osteoporosis treatment gap. Edwards and colleagues recently described an intervention based on their institutional electronic medical record.[21] The intervention included order sets for diagnosing osteoporosis and educational materials for patients and providers, but did not demonstrate any change in percentage of patients evaluated for osteoporosis after fragility fracture. Successful randomized controlled trials have been reported using mail notification of physicians and patients after osteoporotic fracture[22]; multifaceted telephone, education and mail notification interventions after wrist fracture[23]; and through the use of a central osteoporosis coordinator to coordinate osteoporosis treatment after a fragility fracture.[24] These successful trials were broad in scope and yet reported modest (10%20%) gains in improvement.
Although bisphophonate therapy is of proven benefit in secondary fracture prevention, there are a number of barriers to initiating it in the acute setting after fragility fracture, as the difficulty in getting large improvement during the above trials suggests. These include recommendations from some experts for bone density testing before starting treatment and theoretic concerns of impairing fracture healing in the initial weeks after acute fracture. Both of these concerns make a hospitalist‐based intervention for osteoporosis evaluation and treatment challenging and beyond the scope of our project's quality improvement efforts.
Our study has some limitations. It was conducted in a single institution and electronic order entry system, which could limit the ability to generalize the results. We did not assess vitamin D compliance or follow‐up after hospitalization, so we are unable to determine if patients successfully completed treatment after it was prescribed. We also found slight differences in race between the pre‐ and postintervention groups. Although we did not perform multivariable regression to account for these differences, we feel such analyses would be unlikely to alter our results. Last, it should be noted that there may be unintended consequences from preselected orders, such as the ones we utilized for vitamin D assays and empiric supplementation. For example, patients with a recently checked vitamin D assay would have duplication of that lab. Similarly, patients who were already taking vitamin D could theoretically be placed on double therapy at admission. With safeguards in the electronic system to flag duplicate medications, low toxicity of standard doses of vitamin D, and minimal economic harm with duplicate laboratory therapy in the context of a hospitalization for hip fracture, we believe the risks are outweighed by the benefits of screening.
In summary, with review of evidence, modification of a computerized physician order set, provider education and feedback, and collaboration with our clinical laboratory, we were able to standardize and improve group practice for the assessment and treatment of vitamin D deficiency in elderly patients with hip fracture. We believe that our model could be applied to other institutions to further improve patient care. Given the extremely high incidence of hip fracture and consistently high prevalence of vitamin D deficiency in this population across studies, these findings have important implications for the care of this commonly encountered and vulnerable group of patients.
Disclosures: Data from this project were presented in abstract form at the Society of Hospital Medicine Annual Meetings in 2013 and 2014 and as an abstract at the Society of General Internal Medicine Annual Meeting in 2014. Dr. Catherine Hammett‐Stabler, Director of UNC Hospitals McLendon Core Laboratories, provided data on vitamin D assay turnaround times. The authors report no conflicts of interest.
- Incidence and mortality of hip fractures in the United States. JAMA. 2009;302(14):1573–1579. , , , .
- Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281(16):1505–1511. , , , , , .
- Prevalence of vitamin D inadequacy in Scottish adults with non‐vertebral fragility fractures. Curr Med Res Opin. 2005;21(9):1355–1361. , , , , , .
- Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London. Curr Med Res Opin. 2005;21(12):1891–1894. , , .
- Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland. Osteoporos Int. 2005;16(12):2018–2024. , , , et al.
- Prevalence of vitamin D inadequacy in Belfast following fragility fracture. Curr Med Res Opin. 2006;22(1):101–105. , , , et al.
- High prevalence of hypovitaminosis D and K in patients with hip fracture. Asia Pac J Clin Nutr. 2011;20(1):56–61. , , , , , .
- Vitamin D insufficiency in patients with acute hip fractures of all ages and both sexes in a sunny climate. J Orthop Trauma. 2013;27(12):e275–e280. , , , .
- Vitamin D and intact PTH status in patients with hip fracture. Osteoporos Int. 2006;17(11):1608–1614. , , , et al.
- Distribution and correlates of serum 25‐hydroxyvitamin D levels in a sample of patients with hip fracture. Am J Geriatr Pharmacother. 2007;5(4):335–340. , , , et al.
- Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930. , , , et al.
- Prevention of falls in community‐dwelling older adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(3):197–204. , .
- The Health Care Data Guide: Learning From Data for Improvement. 1st ed. San Francisco, CA: Jossey‐Bass; 2011. , .
- Importance of vitamin D in hospital‐based fracture care pathways. J Nutr Health Aging. 2008;12(5):291–293. , , , , .
- Before and after hip fracture, vitamin D deficiency may not be treated sufficiently. Osteoporos Int. 2013;24(11):2765–2773. , , , et al.
- Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta‐analysis. BMJ. 2010;341:c3691. , , , et al.
- A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–49. , , , et al.
- Oral vitamin D3 and calcium for secondary prevention of low‐trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo‐controlled trial. Lancet. 2005;365(9471):1621–1628. , , , et al.
- A population‐based analysis of the post‐fracture care gap 1996–2008: the situation is not improving. Osteoporos Int. 2012;23(5):1623–1629. , , , et al.
- American Orthopedic Association. Own the Bone website. 2011. Available at: http://www.ownthebone.org. Accessed August 1, 2014.
- Development of an electronic medical record based intervention to improve medical care of osteoporosis. Osteoporos Int. 2012;23(10):2489–2498. , , , et al.
- Closing the gap in postfracture care at the population level: a randomized controlled trial. CMAJ. 2012;184(3):290–296. , , , , .
- Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial. CMAJ. 2008;178(5):569–575. , , , et al.
- Impact of a centralized osteoporosis coordinator on post‐fracture osteoporosis management: a cluster randomized trial. Osteoporos Int. 2012;23(1):87–95. , , , et al.
- Incidence and mortality of hip fractures in the United States. JAMA. 2009;302(14):1573–1579. , , , .
- Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281(16):1505–1511. , , , , , .
- Prevalence of vitamin D inadequacy in Scottish adults with non‐vertebral fragility fractures. Curr Med Res Opin. 2005;21(9):1355–1361. , , , , , .
- Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London. Curr Med Res Opin. 2005;21(12):1891–1894. , , .
- Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland. Osteoporos Int. 2005;16(12):2018–2024. , , , et al.
- Prevalence of vitamin D inadequacy in Belfast following fragility fracture. Curr Med Res Opin. 2006;22(1):101–105. , , , et al.
- High prevalence of hypovitaminosis D and K in patients with hip fracture. Asia Pac J Clin Nutr. 2011;20(1):56–61. , , , , , .
- Vitamin D insufficiency in patients with acute hip fractures of all ages and both sexes in a sunny climate. J Orthop Trauma. 2013;27(12):e275–e280. , , , .
- Vitamin D and intact PTH status in patients with hip fracture. Osteoporos Int. 2006;17(11):1608–1614. , , , et al.
- Distribution and correlates of serum 25‐hydroxyvitamin D levels in a sample of patients with hip fracture. Am J Geriatr Pharmacother. 2007;5(4):335–340. , , , et al.
- Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930. , , , et al.
- Prevention of falls in community‐dwelling older adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(3):197–204. , .
- The Health Care Data Guide: Learning From Data for Improvement. 1st ed. San Francisco, CA: Jossey‐Bass; 2011. , .
- Importance of vitamin D in hospital‐based fracture care pathways. J Nutr Health Aging. 2008;12(5):291–293. , , , , .
- Before and after hip fracture, vitamin D deficiency may not be treated sufficiently. Osteoporos Int. 2013;24(11):2765–2773. , , , et al.
- Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta‐analysis. BMJ. 2010;341:c3691. , , , et al.
- A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–49. , , , et al.
- Oral vitamin D3 and calcium for secondary prevention of low‐trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo‐controlled trial. Lancet. 2005;365(9471):1621–1628. , , , et al.
- A population‐based analysis of the post‐fracture care gap 1996–2008: the situation is not improving. Osteoporos Int. 2012;23(5):1623–1629. , , , et al.
- American Orthopedic Association. Own the Bone website. 2011. Available at: http://www.ownthebone.org. Accessed August 1, 2014.
- Development of an electronic medical record based intervention to improve medical care of osteoporosis. Osteoporos Int. 2012;23(10):2489–2498. , , , et al.
- Closing the gap in postfracture care at the population level: a randomized controlled trial. CMAJ. 2012;184(3):290–296. , , , , .
- Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial. CMAJ. 2008;178(5):569–575. , , , et al.
- Impact of a centralized osteoporosis coordinator on post‐fracture osteoporosis management: a cluster randomized trial. Osteoporos Int. 2012;23(1):87–95. , , , et al.
© 2014 Society of Hospital Medicine
Systems Automation for Cancer Surveillance: A Useful Tool for Tracking the Care of Head and Neck Cancer Patients in the Ear, Nose, and Throat Clinic
Purpose: About 400,000 new cases of Head and Neck Cancer (HNC) are diagnosed and reported each year. HNC patients require frequent follow-up care and additional interventions due to the potential for disease recurrence and second primaries. A robust and automated HNC identification and surveillance program can aid in case identification and can track appointments and required care, using the guidelines of the National Comprehensive Cancer Network (NCCN). An automated tool would provide for optimal treatment interventions while preventing any patients from being inadvertently lost to follow-up, enhancing veteran centered care.
Methods: The ear, nose, and throat (ENT) Cancer Tracking System (CTS) queries the VA Corporate Data Warehouse each night to identify all patients recently diagnosed with a HNC. All patients residing in the Albuquerque, New Mexico, and Big Spring, Texas, catchment areas are included in the capture pool. Cases are identified by examining outpatient visits and inpatient discharge diagnosis International Classification of Diseases (ICD) codes, surgical pathology Systematized Nomenclature of Medicine—Clinical Terms (SNOMED codes), and VistA problem list diagnoses. Patients identified as having cancer are presented, using an interactive report hosted on a secure SharePoint site. Newly identified patients are automatically assigned to “active” management status, minimizing the risk of missing a new patient. The coordinator can toggle a patient’s status between “inactive” and “active” at any time, but can never delete a patient from the CTS. Inactive patients with a new cancer diagnosis are automatically toggled to active status. The CTS report tracks and presents a number of pertinent medical indicators, including patient identifiers and residence location, most recent diagnosis date, days since last diagnosis, diagnosis ICD code, date captured on the CTS, most recent ear, nose, and throat (ENT) visit, most recent ENT appointment, days since last visit, date of last thyroid-stimulating hormone (TSH) test, and date of last PET scan. Cancellations, no-shows, and patients overdue for TSH testing are highlighted.
Results: Baseline data obtained in 2012 prior to the activation of the CTS revealed that about 31.1% of diagnosed HNC patients in the ENT clinic experienced delays in care or were lost to follow-up care through cancellations, no shows, and nonrescheduled appointments. A dedicated cancer care coordinator (CCC) was assigned to the ENT clinic to record, monitor, and track HNC patients manually using an Excel spreadsheet. Although cancer surveillance reports proved that launching a cancer surveillance program prevented patients with cancer from being lost to follow-up care, the manual tracking system was time consuming and labor intensive. The automated CTS has optimized cancer surveillance by providing the CCC with immediate identification of new HNC diagnoses, appointment tracking, alerts for HNC patients that have not been scheduled, alerts of overdue required lab tests, tracking of completed PET CT imaging, and improved timeliness in obtaining quality improvement data; all were accomplished without the CCC manually tracking anything.
Conclusions: During the first 4 months of operation (February to May 2014), 14 new HNC patients were identified automatically—patients that manual tracking might have missed or incurred delays in care. The CTS has proved to be a vital tool to the CCC and will continue to assist in the identification of new HNC patients, provide access to patient information on follow-up care, and improve access to recommended diagnostic procedures from NCCN guidelines. Other benefits of an electronic tracking system are optimized time, improved workflows, and improvements to patient safety by providing timely access to care and treatment.
Purpose: About 400,000 new cases of Head and Neck Cancer (HNC) are diagnosed and reported each year. HNC patients require frequent follow-up care and additional interventions due to the potential for disease recurrence and second primaries. A robust and automated HNC identification and surveillance program can aid in case identification and can track appointments and required care, using the guidelines of the National Comprehensive Cancer Network (NCCN). An automated tool would provide for optimal treatment interventions while preventing any patients from being inadvertently lost to follow-up, enhancing veteran centered care.
Methods: The ear, nose, and throat (ENT) Cancer Tracking System (CTS) queries the VA Corporate Data Warehouse each night to identify all patients recently diagnosed with a HNC. All patients residing in the Albuquerque, New Mexico, and Big Spring, Texas, catchment areas are included in the capture pool. Cases are identified by examining outpatient visits and inpatient discharge diagnosis International Classification of Diseases (ICD) codes, surgical pathology Systematized Nomenclature of Medicine—Clinical Terms (SNOMED codes), and VistA problem list diagnoses. Patients identified as having cancer are presented, using an interactive report hosted on a secure SharePoint site. Newly identified patients are automatically assigned to “active” management status, minimizing the risk of missing a new patient. The coordinator can toggle a patient’s status between “inactive” and “active” at any time, but can never delete a patient from the CTS. Inactive patients with a new cancer diagnosis are automatically toggled to active status. The CTS report tracks and presents a number of pertinent medical indicators, including patient identifiers and residence location, most recent diagnosis date, days since last diagnosis, diagnosis ICD code, date captured on the CTS, most recent ear, nose, and throat (ENT) visit, most recent ENT appointment, days since last visit, date of last thyroid-stimulating hormone (TSH) test, and date of last PET scan. Cancellations, no-shows, and patients overdue for TSH testing are highlighted.
Results: Baseline data obtained in 2012 prior to the activation of the CTS revealed that about 31.1% of diagnosed HNC patients in the ENT clinic experienced delays in care or were lost to follow-up care through cancellations, no shows, and nonrescheduled appointments. A dedicated cancer care coordinator (CCC) was assigned to the ENT clinic to record, monitor, and track HNC patients manually using an Excel spreadsheet. Although cancer surveillance reports proved that launching a cancer surveillance program prevented patients with cancer from being lost to follow-up care, the manual tracking system was time consuming and labor intensive. The automated CTS has optimized cancer surveillance by providing the CCC with immediate identification of new HNC diagnoses, appointment tracking, alerts for HNC patients that have not been scheduled, alerts of overdue required lab tests, tracking of completed PET CT imaging, and improved timeliness in obtaining quality improvement data; all were accomplished without the CCC manually tracking anything.
Conclusions: During the first 4 months of operation (February to May 2014), 14 new HNC patients were identified automatically—patients that manual tracking might have missed or incurred delays in care. The CTS has proved to be a vital tool to the CCC and will continue to assist in the identification of new HNC patients, provide access to patient information on follow-up care, and improve access to recommended diagnostic procedures from NCCN guidelines. Other benefits of an electronic tracking system are optimized time, improved workflows, and improvements to patient safety by providing timely access to care and treatment.
Purpose: About 400,000 new cases of Head and Neck Cancer (HNC) are diagnosed and reported each year. HNC patients require frequent follow-up care and additional interventions due to the potential for disease recurrence and second primaries. A robust and automated HNC identification and surveillance program can aid in case identification and can track appointments and required care, using the guidelines of the National Comprehensive Cancer Network (NCCN). An automated tool would provide for optimal treatment interventions while preventing any patients from being inadvertently lost to follow-up, enhancing veteran centered care.
Methods: The ear, nose, and throat (ENT) Cancer Tracking System (CTS) queries the VA Corporate Data Warehouse each night to identify all patients recently diagnosed with a HNC. All patients residing in the Albuquerque, New Mexico, and Big Spring, Texas, catchment areas are included in the capture pool. Cases are identified by examining outpatient visits and inpatient discharge diagnosis International Classification of Diseases (ICD) codes, surgical pathology Systematized Nomenclature of Medicine—Clinical Terms (SNOMED codes), and VistA problem list diagnoses. Patients identified as having cancer are presented, using an interactive report hosted on a secure SharePoint site. Newly identified patients are automatically assigned to “active” management status, minimizing the risk of missing a new patient. The coordinator can toggle a patient’s status between “inactive” and “active” at any time, but can never delete a patient from the CTS. Inactive patients with a new cancer diagnosis are automatically toggled to active status. The CTS report tracks and presents a number of pertinent medical indicators, including patient identifiers and residence location, most recent diagnosis date, days since last diagnosis, diagnosis ICD code, date captured on the CTS, most recent ear, nose, and throat (ENT) visit, most recent ENT appointment, days since last visit, date of last thyroid-stimulating hormone (TSH) test, and date of last PET scan. Cancellations, no-shows, and patients overdue for TSH testing are highlighted.
Results: Baseline data obtained in 2012 prior to the activation of the CTS revealed that about 31.1% of diagnosed HNC patients in the ENT clinic experienced delays in care or were lost to follow-up care through cancellations, no shows, and nonrescheduled appointments. A dedicated cancer care coordinator (CCC) was assigned to the ENT clinic to record, monitor, and track HNC patients manually using an Excel spreadsheet. Although cancer surveillance reports proved that launching a cancer surveillance program prevented patients with cancer from being lost to follow-up care, the manual tracking system was time consuming and labor intensive. The automated CTS has optimized cancer surveillance by providing the CCC with immediate identification of new HNC diagnoses, appointment tracking, alerts for HNC patients that have not been scheduled, alerts of overdue required lab tests, tracking of completed PET CT imaging, and improved timeliness in obtaining quality improvement data; all were accomplished without the CCC manually tracking anything.
Conclusions: During the first 4 months of operation (February to May 2014), 14 new HNC patients were identified automatically—patients that manual tracking might have missed or incurred delays in care. The CTS has proved to be a vital tool to the CCC and will continue to assist in the identification of new HNC patients, provide access to patient information on follow-up care, and improve access to recommended diagnostic procedures from NCCN guidelines. Other benefits of an electronic tracking system are optimized time, improved workflows, and improvements to patient safety by providing timely access to care and treatment.