The best advice Sarah Stella, MD, ever received was simple: “You can’t cure everyone, but you can help everyone.” Why has the adage stuck with her?

Because the advice came from her dad, “and he’s been right about a lot of things before,” she says with a smile.

Dr. Stella got into medicine—clearly with her father’s blessing—to satisfy her “intense curiosity about my fellow human beings and to try to ease suffering.” She has risen to be an academic hospitalist at Denver Health and is one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Tell us about your training. What did you like most/dislike during the process?

Answer: I attended medical school at Michigan State College of Human Medicine. I appreciated their humanistic approach to medical education. I chose the University of Colorado for my internal medicine residency because I love the sunshine and the mountains and because I thought the large academic program would complement my community-based medical school training. I loved being able to easily access nature on my days off.

Q: What do you like most about working as a hospitalist?

A: Spending time with incredible patients and working to solve difficult problems alongside amazing colleagues. I also love the diversity of the work, being involved in direct patient care, teaching students and residents, being a part of committees, performing quality improvement research. I love the flexibility of the job, which allows me to spend time with my family and travel fairly frequently to far-flung places.

Q: Did you have a mentor during your training or early career?

A: My earliest mentor was my father, also a physician [an oncologist]. Some of my earliest medical memories are of going to the hospital with my dad, who also brought home petri dishes from the lab, which my brother and I then used to perform household science experiments. My dad taught me my first lessons about the scientific method and about the importance of a strong work ethic and mentorship. Since then, I have had many outstanding mentors and role models for various aspects of my training/career. During my time at Denver Health, Drs. Richard K. Albert and Marisha Burden have provided me with invaluable mentorship in my scholarly pursuits.

Q: Have you tried to mentor others? Why or why not?

A: I have really loved mentoring students and residents. It is among the most meaningful experiences of my career. Presently, I am a mentor for undergraduate students from underrepresented minority groups. The maturity, passion, and drive these students possess inspires me.

Q: Why is your mentoring focused on minorities? What is the appeal of that to you?

A: I mentor students and residents from all backgrounds. However, mentoring students from underrepresented minority groups is especially important to me. Ethnic minorities continue to have decreased access to healthcare and disproportionately high morbidity and mortality. In order to improve these disparities, we need to have more healthcare providers from these groups. Yet such students, while they may initially be attracted to a career in medicine, are much less likely to maintain their interest. The reasons for this are complicated but may be explained by differences in access to mentors to help guide and inspire them, write letters, etc.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Developing a rapport with patients. I try to use some techniques from social psychology to help me more easily. The hospital is a particularly depersonalizing place, so trying to see the person behind the patient does help.

Q: What aspect of patient care is most rewarding?

A: Really connecting with patients and seeing them thrive. Working at a safety-net hospital, I have the privilege of caring for some of the most underserved but some of the most gracious and beautiful people.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I do enjoy supervising medical students and residents at all levels and attend frequently on the medical wards. I particularly love teaching medical students because of their enthusiasm and curiosity. I love being reminded of basic pathophysiology by a thoughtfully asked question from a medical student. I am a big advocate of bedside rounding. Finding a way to do this efficiently and while teaching to all the levels on the team is challenging. Also, I still enjoy my own direct patient care activities and feel that they challenge me in a different way and make me a better teacher.

Q: Outside of patient care, tell us about your career interests.

A: My research has focused on understanding problems experienced by patients following hospital discharge and designing systems to help ameliorate them. On an institutional level, I serve on several committees, including the Utilization Review Committee, and a group aiming to improve collaboration between hospitalists and primary care physicians and improve discharge transitions. I have participated in several LEAN events aimed at understanding and improving various systems issues.

Q: When you aren’t working, what is important to you?

A: My family and friends, sunshine, and travel. My husband grew up in Papua, New Guinea, and Australia, and both of his parents are physicians, so he is very understanding and not the least bit grossed out when I regale him with stories involving bodily fluids. We have a beautiful, inquisitive 3-year-old daughter and her furry older sister, Ginger Wasabi Ninja. As the oldest of seven, I also love hanging out with my siblings.

Q: What SHM event has made the most lasting impression on you?

A: I really enjoyed HM16, particularly the keynote address by our U.S. Surgeon General and fellow hospitalist, Vivek Murthy, MD, who discussed the role hospitalists can play in public health. His message that we hospitalists should put as much of an effort into trying to improve health outside the walls of the hospital as we do within the walls really resonated with me and has encouraged me to get more involved in the community. TH

Richard Quinn is a freelance writer in New Jersey.

The best advice Sarah Stella, MD, ever received was simple: “You can’t cure everyone, but you can help everyone.” Why has the adage stuck with her?

Because the advice came from her dad, “and he’s been right about a lot of things before,” she says with a smile.

Dr. Stella got into medicine—clearly with her father’s blessing—to satisfy her “intense curiosity about my fellow human beings and to try to ease suffering.” She has risen to be an academic hospitalist at Denver Health and is one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Tell us about your training. What did you like most/dislike during the process?

Answer: I attended medical school at Michigan State College of Human Medicine. I appreciated their humanistic approach to medical education. I chose the University of Colorado for my internal medicine residency because I love the sunshine and the mountains and because I thought the large academic program would complement my community-based medical school training. I loved being able to easily access nature on my days off.

Q: What do you like most about working as a hospitalist?

A: Spending time with incredible patients and working to solve difficult problems alongside amazing colleagues. I also love the diversity of the work, being involved in direct patient care, teaching students and residents, being a part of committees, performing quality improvement research. I love the flexibility of the job, which allows me to spend time with my family and travel fairly frequently to far-flung places.

Q: Did you have a mentor during your training or early career?

A: My earliest mentor was my father, also a physician [an oncologist]. Some of my earliest medical memories are of going to the hospital with my dad, who also brought home petri dishes from the lab, which my brother and I then used to perform household science experiments. My dad taught me my first lessons about the scientific method and about the importance of a strong work ethic and mentorship. Since then, I have had many outstanding mentors and role models for various aspects of my training/career. During my time at Denver Health, Drs. Richard K. Albert and Marisha Burden have provided me with invaluable mentorship in my scholarly pursuits.

Q: Have you tried to mentor others? Why or why not?

A: I have really loved mentoring students and residents. It is among the most meaningful experiences of my career. Presently, I am a mentor for undergraduate students from underrepresented minority groups. The maturity, passion, and drive these students possess inspires me.

Q: Why is your mentoring focused on minorities? What is the appeal of that to you?

A: I mentor students and residents from all backgrounds. However, mentoring students from underrepresented minority groups is especially important to me. Ethnic minorities continue to have decreased access to healthcare and disproportionately high morbidity and mortality. In order to improve these disparities, we need to have more healthcare providers from these groups. Yet such students, while they may initially be attracted to a career in medicine, are much less likely to maintain their interest. The reasons for this are complicated but may be explained by differences in access to mentors to help guide and inspire them, write letters, etc.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Developing a rapport with patients. I try to use some techniques from social psychology to help me more easily. The hospital is a particularly depersonalizing place, so trying to see the person behind the patient does help.

Q: What aspect of patient care is most rewarding?

A: Really connecting with patients and seeing them thrive. Working at a safety-net hospital, I have the privilege of caring for some of the most underserved but some of the most gracious and beautiful people.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I do enjoy supervising medical students and residents at all levels and attend frequently on the medical wards. I particularly love teaching medical students because of their enthusiasm and curiosity. I love being reminded of basic pathophysiology by a thoughtfully asked question from a medical student. I am a big advocate of bedside rounding. Finding a way to do this efficiently and while teaching to all the levels on the team is challenging. Also, I still enjoy my own direct patient care activities and feel that they challenge me in a different way and make me a better teacher.

Q: Outside of patient care, tell us about your career interests.

A: My research has focused on understanding problems experienced by patients following hospital discharge and designing systems to help ameliorate them. On an institutional level, I serve on several committees, including the Utilization Review Committee, and a group aiming to improve collaboration between hospitalists and primary care physicians and improve discharge transitions. I have participated in several LEAN events aimed at understanding and improving various systems issues.

Q: When you aren’t working, what is important to you?

A: My family and friends, sunshine, and travel. My husband grew up in Papua, New Guinea, and Australia, and both of his parents are physicians, so he is very understanding and not the least bit grossed out when I regale him with stories involving bodily fluids. We have a beautiful, inquisitive 3-year-old daughter and her furry older sister, Ginger Wasabi Ninja. As the oldest of seven, I also love hanging out with my siblings.

Q: What SHM event has made the most lasting impression on you?

A: I really enjoyed HM16, particularly the keynote address by our U.S. Surgeon General and fellow hospitalist, Vivek Murthy, MD, who discussed the role hospitalists can play in public health. His message that we hospitalists should put as much of an effort into trying to improve health outside the walls of the hospital as we do within the walls really resonated with me and has encouraged me to get more involved in the community. TH

Richard Quinn is a freelance writer in New Jersey.

The best advice Sarah Stella, MD, ever received was simple: “You can’t cure everyone, but you can help everyone.” Why has the adage stuck with her?

Because the advice came from her dad, “and he’s been right about a lot of things before,” she says with a smile.

Dr. Stella got into medicine—clearly with her father’s blessing—to satisfy her “intense curiosity about my fellow human beings and to try to ease suffering.” She has risen to be an academic hospitalist at Denver Health and is one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Tell us about your training. What did you like most/dislike during the process?

Answer: I attended medical school at Michigan State College of Human Medicine. I appreciated their humanistic approach to medical education. I chose the University of Colorado for my internal medicine residency because I love the sunshine and the mountains and because I thought the large academic program would complement my community-based medical school training. I loved being able to easily access nature on my days off.

Q: What do you like most about working as a hospitalist?

A: Spending time with incredible patients and working to solve difficult problems alongside amazing colleagues. I also love the diversity of the work, being involved in direct patient care, teaching students and residents, being a part of committees, performing quality improvement research. I love the flexibility of the job, which allows me to spend time with my family and travel fairly frequently to far-flung places.

Q: Did you have a mentor during your training or early career?

A: My earliest mentor was my father, also a physician [an oncologist]. Some of my earliest medical memories are of going to the hospital with my dad, who also brought home petri dishes from the lab, which my brother and I then used to perform household science experiments. My dad taught me my first lessons about the scientific method and about the importance of a strong work ethic and mentorship. Since then, I have had many outstanding mentors and role models for various aspects of my training/career. During my time at Denver Health, Drs. Richard K. Albert and Marisha Burden have provided me with invaluable mentorship in my scholarly pursuits.

Q: Have you tried to mentor others? Why or why not?

A: I have really loved mentoring students and residents. It is among the most meaningful experiences of my career. Presently, I am a mentor for undergraduate students from underrepresented minority groups. The maturity, passion, and drive these students possess inspires me.

Q: Why is your mentoring focused on minorities? What is the appeal of that to you?

A: I mentor students and residents from all backgrounds. However, mentoring students from underrepresented minority groups is especially important to me. Ethnic minorities continue to have decreased access to healthcare and disproportionately high morbidity and mortality. In order to improve these disparities, we need to have more healthcare providers from these groups. Yet such students, while they may initially be attracted to a career in medicine, are much less likely to maintain their interest. The reasons for this are complicated but may be explained by differences in access to mentors to help guide and inspire them, write letters, etc.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Developing a rapport with patients. I try to use some techniques from social psychology to help me more easily. The hospital is a particularly depersonalizing place, so trying to see the person behind the patient does help.

Q: What aspect of patient care is most rewarding?

A: Really connecting with patients and seeing them thrive. Working at a safety-net hospital, I have the privilege of caring for some of the most underserved but some of the most gracious and beautiful people.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I do enjoy supervising medical students and residents at all levels and attend frequently on the medical wards. I particularly love teaching medical students because of their enthusiasm and curiosity. I love being reminded of basic pathophysiology by a thoughtfully asked question from a medical student. I am a big advocate of bedside rounding. Finding a way to do this efficiently and while teaching to all the levels on the team is challenging. Also, I still enjoy my own direct patient care activities and feel that they challenge me in a different way and make me a better teacher.

Q: Outside of patient care, tell us about your career interests.

A: My research has focused on understanding problems experienced by patients following hospital discharge and designing systems to help ameliorate them. On an institutional level, I serve on several committees, including the Utilization Review Committee, and a group aiming to improve collaboration between hospitalists and primary care physicians and improve discharge transitions. I have participated in several LEAN events aimed at understanding and improving various systems issues.

Q: When you aren’t working, what is important to you?

A: My family and friends, sunshine, and travel. My husband grew up in Papua, New Guinea, and Australia, and both of his parents are physicians, so he is very understanding and not the least bit grossed out when I regale him with stories involving bodily fluids. We have a beautiful, inquisitive 3-year-old daughter and her furry older sister, Ginger Wasabi Ninja. As the oldest of seven, I also love hanging out with my siblings.

Q: What SHM event has made the most lasting impression on you?

A: I really enjoyed HM16, particularly the keynote address by our U.S. Surgeon General and fellow hospitalist, Vivek Murthy, MD, who discussed the role hospitalists can play in public health. His message that we hospitalists should put as much of an effort into trying to improve health outside the walls of the hospital as we do within the walls really resonated with me and has encouraged me to get more involved in the community. TH

Richard Quinn is a freelance writer in New Jersey.

Monoclonal antibodies

Photo by Linda Bartlett

ORLANDO—Emicizumab, a bispecific monoclonal antibody (mAb), could potentially change the treatment paradigm of hemophilia A, according to a speaker at the World Federation of Hemophilia 2016 World Congress.

Results of a phase 1/2 study suggest that emicizumab can be safe and effective as once-weekly prophylaxis in patients with severe hemophilia A, whether or not they have factor VIII (FVIII) inhibitors.

There were no severe adverse events (AEs) or thromboembolic events associated with the mAb.

None of the patients developed neutralizing anti-drug antibodies, and the annualized bleeding rate (ABR) was low, with 8 of the 18 patients studied having no bleeds.

Keiji Nogami, MD, PhD, of Nara Medical University in Kashihara, Japan, presented these results at the congress.* This research was sponsored by Chugai Pharmaceutical Co., Ltd., which is co-developing emicizumab with Genentech.

The phase 1 part of this study included both healthy subjects and hemophilia A patients. Results in the healthy subjects were published in Blood, and early results in the patients were published in NEJM.

Patients and treatment

The 18 patients in this study had severe hemophilia A, and 11 had FVIII inhibitors. They were 12 to 58 years of age at baseline, and all were Japanese.

The patients received once-weekly subcutaneous injections of emicizumab at one of the following dose levels: 0.3 mg/kg (cohort 1), 1 mg/kg (cohort 2), or 3 mg/kg (cohort 3).

There were 6 patients in each cohort. Cohorts 1 and 2 each had 4 patients with inhibitors, and there were 3 patients with inhibitors in cohort 3.

For the phase 2 extension portion of the study, dose-escalation was allowed in cohorts 1 and 2. A total of 4 patients had their doses increased because of suboptimal bleeding control—3 in cohort 1 and 1 in cohort 2.

The mean follow-up was 32.6 months in cohort 1, 27.0 months in cohort 2, and 21.4 months in cohort 3.

One of the patients with inhibitors in cohort 2 discontinued emicizumab due to injection site erythema of mild intensity during the phase 1 portion of the study. And one of the patients without inhibitors in cohort 3 did not continue on to the phase 2 portion of the study because prior treatment was sufficiently effective.

Safety

The safety analysis included all 18 patients, and all of these patients experienced AEs—a total of 150 events. The most common AEs were nasopharyngitis (n=8), contusion (n=7), and injection site reactions (n=7).

The AEs were largely of mild or moderate intensity. There were 4 severe AEs, but none of them were related to emicizumab.

There were 14 treatment-related AEs in 7 patients, but all were resolved. There were no thromboembolic AEs or clinically significant abnormalities of coagulation tests.

There were no neutralizing anti-drug antibodies. Three patients developed anti-drug antibodies after starting emicizumab, but this did not affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of the mAb.

Efficacy

In cohort 1, the median ABR was 32.5 at baseline, 4.4 at 12 weeks, and 1.4 at last follow-up (median of 32.6 months).

In cohort 2, the median ABR was 18.3 at baseline, 0.0 at 12 weeks, and 0.2 at last follow-up (median of 27.0 months).

In cohort 3, the median ABR was 15.2 at baseline, 0.0 at 12 weeks, and 0.0 at last follow-up (median of 21.4 months).

Eight patients did not experience any bleeds—1 inhibitor patient in cohort 1, 3 inhibitor patients in cohort 2, 2 inhibitor patients in cohort 3, and 2 non-inhibitor patients in cohort 3.

Breakthrough bleeds were successfully treated with standard episodic treatment, FVIII products, or bypassing agents.

Based on these results, Dr Nogami said emicizumab prophylaxis has the potential to change the treatment paradigm of hemophilia A, irrespective of inhibitor status.

*Hanabusa H et al, Updated results of an ongoing long-term phase 1/2 study of emicizumab (ACE910) in hemophilia A patients with or without inhibitors, WFH 2016 World Congress, July 2016.

Monoclonal antibodies

Photo by Linda Bartlett

ORLANDO—Emicizumab, a bispecific monoclonal antibody (mAb), could potentially change the treatment paradigm of hemophilia A, according to a speaker at the World Federation of Hemophilia 2016 World Congress.

Results of a phase 1/2 study suggest that emicizumab can be safe and effective as once-weekly prophylaxis in patients with severe hemophilia A, whether or not they have factor VIII (FVIII) inhibitors.

There were no severe adverse events (AEs) or thromboembolic events associated with the mAb.

None of the patients developed neutralizing anti-drug antibodies, and the annualized bleeding rate (ABR) was low, with 8 of the 18 patients studied having no bleeds.

Keiji Nogami, MD, PhD, of Nara Medical University in Kashihara, Japan, presented these results at the congress.* This research was sponsored by Chugai Pharmaceutical Co., Ltd., which is co-developing emicizumab with Genentech.

The phase 1 part of this study included both healthy subjects and hemophilia A patients. Results in the healthy subjects were published in Blood, and early results in the patients were published in NEJM.

Patients and treatment

The 18 patients in this study had severe hemophilia A, and 11 had FVIII inhibitors. They were 12 to 58 years of age at baseline, and all were Japanese.

The patients received once-weekly subcutaneous injections of emicizumab at one of the following dose levels: 0.3 mg/kg (cohort 1), 1 mg/kg (cohort 2), or 3 mg/kg (cohort 3).

There were 6 patients in each cohort. Cohorts 1 and 2 each had 4 patients with inhibitors, and there were 3 patients with inhibitors in cohort 3.

For the phase 2 extension portion of the study, dose-escalation was allowed in cohorts 1 and 2. A total of 4 patients had their doses increased because of suboptimal bleeding control—3 in cohort 1 and 1 in cohort 2.

The mean follow-up was 32.6 months in cohort 1, 27.0 months in cohort 2, and 21.4 months in cohort 3.

One of the patients with inhibitors in cohort 2 discontinued emicizumab due to injection site erythema of mild intensity during the phase 1 portion of the study. And one of the patients without inhibitors in cohort 3 did not continue on to the phase 2 portion of the study because prior treatment was sufficiently effective.

Safety

The safety analysis included all 18 patients, and all of these patients experienced AEs—a total of 150 events. The most common AEs were nasopharyngitis (n=8), contusion (n=7), and injection site reactions (n=7).

The AEs were largely of mild or moderate intensity. There were 4 severe AEs, but none of them were related to emicizumab.

There were 14 treatment-related AEs in 7 patients, but all were resolved. There were no thromboembolic AEs or clinically significant abnormalities of coagulation tests.

There were no neutralizing anti-drug antibodies. Three patients developed anti-drug antibodies after starting emicizumab, but this did not affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of the mAb.

Efficacy

In cohort 1, the median ABR was 32.5 at baseline, 4.4 at 12 weeks, and 1.4 at last follow-up (median of 32.6 months).

In cohort 2, the median ABR was 18.3 at baseline, 0.0 at 12 weeks, and 0.2 at last follow-up (median of 27.0 months).

In cohort 3, the median ABR was 15.2 at baseline, 0.0 at 12 weeks, and 0.0 at last follow-up (median of 21.4 months).

Eight patients did not experience any bleeds—1 inhibitor patient in cohort 1, 3 inhibitor patients in cohort 2, 2 inhibitor patients in cohort 3, and 2 non-inhibitor patients in cohort 3.

Breakthrough bleeds were successfully treated with standard episodic treatment, FVIII products, or bypassing agents.

Based on these results, Dr Nogami said emicizumab prophylaxis has the potential to change the treatment paradigm of hemophilia A, irrespective of inhibitor status.

*Hanabusa H et al, Updated results of an ongoing long-term phase 1/2 study of emicizumab (ACE910) in hemophilia A patients with or without inhibitors, WFH 2016 World Congress, July 2016.

Monoclonal antibodies

Photo by Linda Bartlett

ORLANDO—Emicizumab, a bispecific monoclonal antibody (mAb), could potentially change the treatment paradigm of hemophilia A, according to a speaker at the World Federation of Hemophilia 2016 World Congress.

Results of a phase 1/2 study suggest that emicizumab can be safe and effective as once-weekly prophylaxis in patients with severe hemophilia A, whether or not they have factor VIII (FVIII) inhibitors.

There were no severe adverse events (AEs) or thromboembolic events associated with the mAb.

None of the patients developed neutralizing anti-drug antibodies, and the annualized bleeding rate (ABR) was low, with 8 of the 18 patients studied having no bleeds.

Keiji Nogami, MD, PhD, of Nara Medical University in Kashihara, Japan, presented these results at the congress.* This research was sponsored by Chugai Pharmaceutical Co., Ltd., which is co-developing emicizumab with Genentech.

The phase 1 part of this study included both healthy subjects and hemophilia A patients. Results in the healthy subjects were published in Blood, and early results in the patients were published in NEJM.

Patients and treatment

The 18 patients in this study had severe hemophilia A, and 11 had FVIII inhibitors. They were 12 to 58 years of age at baseline, and all were Japanese.

The patients received once-weekly subcutaneous injections of emicizumab at one of the following dose levels: 0.3 mg/kg (cohort 1), 1 mg/kg (cohort 2), or 3 mg/kg (cohort 3).

There were 6 patients in each cohort. Cohorts 1 and 2 each had 4 patients with inhibitors, and there were 3 patients with inhibitors in cohort 3.

For the phase 2 extension portion of the study, dose-escalation was allowed in cohorts 1 and 2. A total of 4 patients had their doses increased because of suboptimal bleeding control—3 in cohort 1 and 1 in cohort 2.

The mean follow-up was 32.6 months in cohort 1, 27.0 months in cohort 2, and 21.4 months in cohort 3.

One of the patients with inhibitors in cohort 2 discontinued emicizumab due to injection site erythema of mild intensity during the phase 1 portion of the study. And one of the patients without inhibitors in cohort 3 did not continue on to the phase 2 portion of the study because prior treatment was sufficiently effective.

Safety

The safety analysis included all 18 patients, and all of these patients experienced AEs—a total of 150 events. The most common AEs were nasopharyngitis (n=8), contusion (n=7), and injection site reactions (n=7).

The AEs were largely of mild or moderate intensity. There were 4 severe AEs, but none of them were related to emicizumab.

There were 14 treatment-related AEs in 7 patients, but all were resolved. There were no thromboembolic AEs or clinically significant abnormalities of coagulation tests.

There were no neutralizing anti-drug antibodies. Three patients developed anti-drug antibodies after starting emicizumab, but this did not affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of the mAb.

Efficacy

In cohort 1, the median ABR was 32.5 at baseline, 4.4 at 12 weeks, and 1.4 at last follow-up (median of 32.6 months).

In cohort 2, the median ABR was 18.3 at baseline, 0.0 at 12 weeks, and 0.2 at last follow-up (median of 27.0 months).

In cohort 3, the median ABR was 15.2 at baseline, 0.0 at 12 weeks, and 0.0 at last follow-up (median of 21.4 months).

Eight patients did not experience any bleeds—1 inhibitor patient in cohort 1, 3 inhibitor patients in cohort 2, 2 inhibitor patients in cohort 3, and 2 non-inhibitor patients in cohort 3.

Breakthrough bleeds were successfully treated with standard episodic treatment, FVIII products, or bypassing agents.

Based on these results, Dr Nogami said emicizumab prophylaxis has the potential to change the treatment paradigm of hemophilia A, irrespective of inhibitor status.

*Hanabusa H et al, Updated results of an ongoing long-term phase 1/2 study of emicizumab (ACE910) in hemophilia A patients with or without inhibitors, WFH 2016 World Congress, July 2016.

Woman at work

ORLANDO—Even mild or moderate hemophilia B can have a negative impact on the education and careers of patients, according to the B-HERO-S study.

Ninety-four percent of the patients studied said their disease had a negative impact on their education, and 95% said hemophilia had a negative impact on their work.

More than half of patients who had stopped working said they stopped due to hemophilia-related financial issues and/or complications.

These findings were presented in a poster at the World Federation of Hemophilia 2016 World Congress.* The study was sponsored by Novo Nordisk.

The previous HERO study revealed career challenges for patients with hemophilia A or B, but it covered mostly males with moderate or severe disease.

The B-HERO-S study, on the other hand, included only patients with hemophilia B, some of whom were female and most of whom had moderate or mild disease. (This study also included caregivers of children with hemophilia, but data on those subjects will not be discussed here.)

In all, there were 299 patients, 86 of whom were women. The patients had a median age of 29 (range, 18-70). Twenty-five percent had mild hemophilia, 63% had moderate disease, and 11% had severe hemophilia.

Education

Most of the patients (71%) had at least some college education, and 17% had graduated from college.

A majority of patients (94%) said their disease had a negative impact on their education. Seventy-five percent of the patients, including those with mild or moderate disease, said hemophilia had a moderate or large impact on their education.

Patients reported difficulty concentrating at school due to bleeds or pain (69%), difficulty attending school or participating in activities due to mobility issues (44%), and hemophilia-related absences (32%).

Career

Most of the patients (81%) were working full- or part-time when surveyed. Fifty-eight percent had office-based jobs, and 39% had jobs involving manual labor. Only 10% of patients said their disease affected their career choice.

Of the 58 patients (19%) who were not working at the time of the study, 62% had never worked. Of those who worked previously, 59% said they stopped due to hemophilia-related financial issues, and 55% said they stopped due to the disease itself and/or its complications.

Nearly all patients (95%) said their disease had a negative impact on their work. Seventy percent said the impact was moderate, 20% said it was small, and 5% said it was large.

Having moderate disease, comorbidities, a higher education, and/or receiving routine infusions were all associated with a higher impact.

Thirty percent of patients said that treatment allowed them to work in most situations. This was more likely in patients with mild hemophilia (41%) and those treated on-demand (48%).

Twenty-seven percent of patients with moderate hemophilia and 28% with severe disease said they could work in most situations. Twenty-seven percent of patients receiving routine infusions said they were able to work in most situations.

“The B-HERO-S study brought to light many challenges faced by some patients with mild/moderate hemophilia B, including affected women and girls,” said Michelle Witkop, of Northern Regional Bleeding Disorder Center in Traverse City, Michigan.

“With hemophilia treatment centers (HTCs) and local hemophilia chapters focused on proactive education in people with severe hemophilia and their families, B-HERO-S data tells us we need to make sure that those with mild/moderate hemophilia B come to the HTC for routine visits so that we can proactively address issues that might come up in school, activities, and career choice.”

*Cutter S et al, Impact of mild to severe hemophilia on education and work by US adult men and women and caregivers of children with hemophilia B: the bridging hemophilia B experiences results and opportunities into solutions (B-HERO-S) study, WFH 2016 World Congress, July 2016.

Woman at work

ORLANDO—Even mild or moderate hemophilia B can have a negative impact on the education and careers of patients, according to the B-HERO-S study.

Ninety-four percent of the patients studied said their disease had a negative impact on their education, and 95% said hemophilia had a negative impact on their work.

More than half of patients who had stopped working said they stopped due to hemophilia-related financial issues and/or complications.

These findings were presented in a poster at the World Federation of Hemophilia 2016 World Congress.* The study was sponsored by Novo Nordisk.

The previous HERO study revealed career challenges for patients with hemophilia A or B, but it covered mostly males with moderate or severe disease.

The B-HERO-S study, on the other hand, included only patients with hemophilia B, some of whom were female and most of whom had moderate or mild disease. (This study also included caregivers of children with hemophilia, but data on those subjects will not be discussed here.)

In all, there were 299 patients, 86 of whom were women. The patients had a median age of 29 (range, 18-70). Twenty-five percent had mild hemophilia, 63% had moderate disease, and 11% had severe hemophilia.

Education

Most of the patients (71%) had at least some college education, and 17% had graduated from college.

A majority of patients (94%) said their disease had a negative impact on their education. Seventy-five percent of the patients, including those with mild or moderate disease, said hemophilia had a moderate or large impact on their education.

Patients reported difficulty concentrating at school due to bleeds or pain (69%), difficulty attending school or participating in activities due to mobility issues (44%), and hemophilia-related absences (32%).

Career

Most of the patients (81%) were working full- or part-time when surveyed. Fifty-eight percent had office-based jobs, and 39% had jobs involving manual labor. Only 10% of patients said their disease affected their career choice.

Of the 58 patients (19%) who were not working at the time of the study, 62% had never worked. Of those who worked previously, 59% said they stopped due to hemophilia-related financial issues, and 55% said they stopped due to the disease itself and/or its complications.

Nearly all patients (95%) said their disease had a negative impact on their work. Seventy percent said the impact was moderate, 20% said it was small, and 5% said it was large.

Having moderate disease, comorbidities, a higher education, and/or receiving routine infusions were all associated with a higher impact.

Thirty percent of patients said that treatment allowed them to work in most situations. This was more likely in patients with mild hemophilia (41%) and those treated on-demand (48%).

Twenty-seven percent of patients with moderate hemophilia and 28% with severe disease said they could work in most situations. Twenty-seven percent of patients receiving routine infusions said they were able to work in most situations.

“The B-HERO-S study brought to light many challenges faced by some patients with mild/moderate hemophilia B, including affected women and girls,” said Michelle Witkop, of Northern Regional Bleeding Disorder Center in Traverse City, Michigan.

“With hemophilia treatment centers (HTCs) and local hemophilia chapters focused on proactive education in people with severe hemophilia and their families, B-HERO-S data tells us we need to make sure that those with mild/moderate hemophilia B come to the HTC for routine visits so that we can proactively address issues that might come up in school, activities, and career choice.”

*Cutter S et al, Impact of mild to severe hemophilia on education and work by US adult men and women and caregivers of children with hemophilia B: the bridging hemophilia B experiences results and opportunities into solutions (B-HERO-S) study, WFH 2016 World Congress, July 2016.

Woman at work

ORLANDO—Even mild or moderate hemophilia B can have a negative impact on the education and careers of patients, according to the B-HERO-S study.

Ninety-four percent of the patients studied said their disease had a negative impact on their education, and 95% said hemophilia had a negative impact on their work.

More than half of patients who had stopped working said they stopped due to hemophilia-related financial issues and/or complications.

These findings were presented in a poster at the World Federation of Hemophilia 2016 World Congress.* The study was sponsored by Novo Nordisk.

The previous HERO study revealed career challenges for patients with hemophilia A or B, but it covered mostly males with moderate or severe disease.

The B-HERO-S study, on the other hand, included only patients with hemophilia B, some of whom were female and most of whom had moderate or mild disease. (This study also included caregivers of children with hemophilia, but data on those subjects will not be discussed here.)

In all, there were 299 patients, 86 of whom were women. The patients had a median age of 29 (range, 18-70). Twenty-five percent had mild hemophilia, 63% had moderate disease, and 11% had severe hemophilia.

Education

Most of the patients (71%) had at least some college education, and 17% had graduated from college.

A majority of patients (94%) said their disease had a negative impact on their education. Seventy-five percent of the patients, including those with mild or moderate disease, said hemophilia had a moderate or large impact on their education.

Patients reported difficulty concentrating at school due to bleeds or pain (69%), difficulty attending school or participating in activities due to mobility issues (44%), and hemophilia-related absences (32%).

Career

Most of the patients (81%) were working full- or part-time when surveyed. Fifty-eight percent had office-based jobs, and 39% had jobs involving manual labor. Only 10% of patients said their disease affected their career choice.

Of the 58 patients (19%) who were not working at the time of the study, 62% had never worked. Of those who worked previously, 59% said they stopped due to hemophilia-related financial issues, and 55% said they stopped due to the disease itself and/or its complications.

Nearly all patients (95%) said their disease had a negative impact on their work. Seventy percent said the impact was moderate, 20% said it was small, and 5% said it was large.

Having moderate disease, comorbidities, a higher education, and/or receiving routine infusions were all associated with a higher impact.

Thirty percent of patients said that treatment allowed them to work in most situations. This was more likely in patients with mild hemophilia (41%) and those treated on-demand (48%).

Twenty-seven percent of patients with moderate hemophilia and 28% with severe disease said they could work in most situations. Twenty-seven percent of patients receiving routine infusions said they were able to work in most situations.

“The B-HERO-S study brought to light many challenges faced by some patients with mild/moderate hemophilia B, including affected women and girls,” said Michelle Witkop, of Northern Regional Bleeding Disorder Center in Traverse City, Michigan.

“With hemophilia treatment centers (HTCs) and local hemophilia chapters focused on proactive education in people with severe hemophilia and their families, B-HERO-S data tells us we need to make sure that those with mild/moderate hemophilia B come to the HTC for routine visits so that we can proactively address issues that might come up in school, activities, and career choice.”

*Cutter S et al, Impact of mild to severe hemophilia on education and work by US adult men and women and caregivers of children with hemophilia B: the bridging hemophilia B experiences results and opportunities into solutions (B-HERO-S) study, WFH 2016 World Congress, July 2016.

Megakaryocytes

in the bone marrow

A low-intensity type of laser therapy could provide a non-invasive, drug-free treatment option for thrombocytopenia, according to research published in Science Translational Medicine.

Researchers found that low-level laser (LLL) therapy increased the generation of platelets from megakaryocytes in vitro and had the same effect in mouse models of thrombocytopenia.

The team also identified the probable mechanism underlying this effect.

“Our study reveals, for the first time, that low-level laser therapy enhances platelet production in animals with thrombocytopenia but not in normal controls,” said study author Mei X. Wu, PhD, of Massachusetts General Hospital in Boston.

“This result suggests that a safe, drug-free method that does not depend on donated blood products can be developed for treating or preventing thrombocytopenia.”

LLLs emit low-powered laser light that does not heat its target tissue. LLLs are known to protect the function of mitochondria, and several conditions associated with impaired platelet production are characterized by abnormalities in the mitochondria of cells that give rise to platelets.

Dr Wu and her colleagues conducted a number of experiments to investigate whether LLLs’ ability to protect mitochondrial function could mitigate several forms of thrombocytopenia.

The team found that LLL treatment of megakaryocytes increased their size, accelerated the formation of proplatelets, and doubled the production of platelets.

Infusion of LLL-treated megakaryocytes into mice led to greater platelet production than did infusion of megakaryocytes treated with normal light.

One of the keys to determining the number of platelets generated from megakaryocytes was mitochondrial production of the energy molecule ATP.

LLL treatment greatly increased mitochondrial generation in polyploid megakaryocytes, but the increase was only slight in less mature megakaryocytes with only 2 copies of each chromosome.

Whole-body LLL treatment of mice with radiation-induced thrombocytopenia spurred the rapid maturation of megakaryocytes and restored platelet levels in a light-dose-dependent fashion.

Platelets from LLL-treated mice had normal structure and function. LLL treatment of normal mice did not raise levels of either megakaryocytes or platelets.

LLL treatment also restored platelet levels in mice with the autoimmune form of thrombocytopenia or with thrombocytopenia caused by chemotherapy.

In cultured human megakaryocytes, LLL treatment at dosage levels similar to those used in mice increased ATP production and platelet generation.

Dr Wu noted that LLL’s lack of an effect in animals without thrombocytopenia indicates it would probably avoid the potential complications of current drug treatments for thrombocytopenia, which act by increasing the production of megakaryocytes from their progenitors in the bone marrow.

“Directly stimulating the differentiation of [megakaryocytes] the way all current drugs do risks clotting if platelet levels rise too high,” Dr Wu said. “LLL appears to enhance [megakaryocytes’] inherent ability to produce platelets most effectively in response to low platelet levels in the circulation, a response that stops when platelet levels are normalized.”

“The fact that treatment only has an effect in polyploid cells, which are very rare, implies that it would not increase production of mitochondria in cancer cells or other cells. In fact, while LLL has been employed in research and in clinical treatment for decades, this is the first study reporting that it can promote mitochondrial biogenesis.”

Dr Wu added that the current primary obstacle to testing LLL in humans is the lack of a device large enough to treat either the entire body or enough bones to stimulate sufficient platelet production by megakaryocytes within the bone marrow, something her team plans to address.

She also noted that, while LLL will probably be beneficial for treatment of many forms of acquired thrombocytopenia, it may not be effective when the condition is caused by inborn genetic defects.

Megakaryocytes

in the bone marrow

A low-intensity type of laser therapy could provide a non-invasive, drug-free treatment option for thrombocytopenia, according to research published in Science Translational Medicine.

Researchers found that low-level laser (LLL) therapy increased the generation of platelets from megakaryocytes in vitro and had the same effect in mouse models of thrombocytopenia.

The team also identified the probable mechanism underlying this effect.

“Our study reveals, for the first time, that low-level laser therapy enhances platelet production in animals with thrombocytopenia but not in normal controls,” said study author Mei X. Wu, PhD, of Massachusetts General Hospital in Boston.

“This result suggests that a safe, drug-free method that does not depend on donated blood products can be developed for treating or preventing thrombocytopenia.”

LLLs emit low-powered laser light that does not heat its target tissue. LLLs are known to protect the function of mitochondria, and several conditions associated with impaired platelet production are characterized by abnormalities in the mitochondria of cells that give rise to platelets.

Dr Wu and her colleagues conducted a number of experiments to investigate whether LLLs’ ability to protect mitochondrial function could mitigate several forms of thrombocytopenia.

The team found that LLL treatment of megakaryocytes increased their size, accelerated the formation of proplatelets, and doubled the production of platelets.

Infusion of LLL-treated megakaryocytes into mice led to greater platelet production than did infusion of megakaryocytes treated with normal light.

One of the keys to determining the number of platelets generated from megakaryocytes was mitochondrial production of the energy molecule ATP.

LLL treatment greatly increased mitochondrial generation in polyploid megakaryocytes, but the increase was only slight in less mature megakaryocytes with only 2 copies of each chromosome.

Whole-body LLL treatment of mice with radiation-induced thrombocytopenia spurred the rapid maturation of megakaryocytes and restored platelet levels in a light-dose-dependent fashion.

Platelets from LLL-treated mice had normal structure and function. LLL treatment of normal mice did not raise levels of either megakaryocytes or platelets.

LLL treatment also restored platelet levels in mice with the autoimmune form of thrombocytopenia or with thrombocytopenia caused by chemotherapy.

In cultured human megakaryocytes, LLL treatment at dosage levels similar to those used in mice increased ATP production and platelet generation.

Dr Wu noted that LLL’s lack of an effect in animals without thrombocytopenia indicates it would probably avoid the potential complications of current drug treatments for thrombocytopenia, which act by increasing the production of megakaryocytes from their progenitors in the bone marrow.

“Directly stimulating the differentiation of [megakaryocytes] the way all current drugs do risks clotting if platelet levels rise too high,” Dr Wu said. “LLL appears to enhance [megakaryocytes’] inherent ability to produce platelets most effectively in response to low platelet levels in the circulation, a response that stops when platelet levels are normalized.”

“The fact that treatment only has an effect in polyploid cells, which are very rare, implies that it would not increase production of mitochondria in cancer cells or other cells. In fact, while LLL has been employed in research and in clinical treatment for decades, this is the first study reporting that it can promote mitochondrial biogenesis.”

Dr Wu added that the current primary obstacle to testing LLL in humans is the lack of a device large enough to treat either the entire body or enough bones to stimulate sufficient platelet production by megakaryocytes within the bone marrow, something her team plans to address.

She also noted that, while LLL will probably be beneficial for treatment of many forms of acquired thrombocytopenia, it may not be effective when the condition is caused by inborn genetic defects.

Megakaryocytes

in the bone marrow

A low-intensity type of laser therapy could provide a non-invasive, drug-free treatment option for thrombocytopenia, according to research published in Science Translational Medicine.

Researchers found that low-level laser (LLL) therapy increased the generation of platelets from megakaryocytes in vitro and had the same effect in mouse models of thrombocytopenia.

The team also identified the probable mechanism underlying this effect.

“Our study reveals, for the first time, that low-level laser therapy enhances platelet production in animals with thrombocytopenia but not in normal controls,” said study author Mei X. Wu, PhD, of Massachusetts General Hospital in Boston.

“This result suggests that a safe, drug-free method that does not depend on donated blood products can be developed for treating or preventing thrombocytopenia.”

LLLs emit low-powered laser light that does not heat its target tissue. LLLs are known to protect the function of mitochondria, and several conditions associated with impaired platelet production are characterized by abnormalities in the mitochondria of cells that give rise to platelets.

Dr Wu and her colleagues conducted a number of experiments to investigate whether LLLs’ ability to protect mitochondrial function could mitigate several forms of thrombocytopenia.

The team found that LLL treatment of megakaryocytes increased their size, accelerated the formation of proplatelets, and doubled the production of platelets.

Infusion of LLL-treated megakaryocytes into mice led to greater platelet production than did infusion of megakaryocytes treated with normal light.

One of the keys to determining the number of platelets generated from megakaryocytes was mitochondrial production of the energy molecule ATP.

LLL treatment greatly increased mitochondrial generation in polyploid megakaryocytes, but the increase was only slight in less mature megakaryocytes with only 2 copies of each chromosome.

Whole-body LLL treatment of mice with radiation-induced thrombocytopenia spurred the rapid maturation of megakaryocytes and restored platelet levels in a light-dose-dependent fashion.

Platelets from LLL-treated mice had normal structure and function. LLL treatment of normal mice did not raise levels of either megakaryocytes or platelets.

LLL treatment also restored platelet levels in mice with the autoimmune form of thrombocytopenia or with thrombocytopenia caused by chemotherapy.

In cultured human megakaryocytes, LLL treatment at dosage levels similar to those used in mice increased ATP production and platelet generation.

Dr Wu noted that LLL’s lack of an effect in animals without thrombocytopenia indicates it would probably avoid the potential complications of current drug treatments for thrombocytopenia, which act by increasing the production of megakaryocytes from their progenitors in the bone marrow.

“Directly stimulating the differentiation of [megakaryocytes] the way all current drugs do risks clotting if platelet levels rise too high,” Dr Wu said. “LLL appears to enhance [megakaryocytes’] inherent ability to produce platelets most effectively in response to low platelet levels in the circulation, a response that stops when platelet levels are normalized.”

“The fact that treatment only has an effect in polyploid cells, which are very rare, implies that it would not increase production of mitochondria in cancer cells or other cells. In fact, while LLL has been employed in research and in clinical treatment for decades, this is the first study reporting that it can promote mitochondrial biogenesis.”

Dr Wu added that the current primary obstacle to testing LLL in humans is the lack of a device large enough to treat either the entire body or enough bones to stimulate sufficient platelet production by megakaryocytes within the bone marrow, something her team plans to address.

She also noted that, while LLL will probably be beneficial for treatment of many forms of acquired thrombocytopenia, it may not be effective when the condition is caused by inborn genetic defects.

Burkitt lymphoma

Image by Ed Uthman

Preclinical research suggests a novel class of compounds are effective against pediatric and adult cancers, including lymphoma.

The compounds are amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length.

The RCn compounds proved cytotoxic in a range of cancer cell lines, including the Burkitt lymphoma cell line Ramos.

The lead compound, RC16, exhibited antitumor effects in vivo and enhanced the in vitro activity of 3 other anticancer agents.

Timothy Cripe, MD, PhD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these results in Pharmaceutical Research.

The investigators first evaluated the RCn compounds for cytotoxicity and mechanism of cell death in several adult and pediatric cancer cell lines.

“We tested RCn’s tumor killing efficacy in cell lines of numerous cancers, including sarcomas, lymphoma, and neuroblastoma,” Dr Cripe said. “We observed anticancer activity of the RCn amines in all the cancer cell lines analyzed.”

The investigators also found that RC16 was 10 times more effective in harming tumor cells than normal cells, including keratinocytes, fibroblasts, and umbilical vein endothelial cells.

In addition, RC16 demonstrated “significant antitumor effects” in several mouse models of malignancy, both when given intravenously and orally.

Because of the amphiphilic molecular structure of RC16, it self-assembled into micelles in water. This chemical structure allowed complexation of the anticancer drugs doxorubicin, etoposide, and paclitaxel.

The micelles significantly improved the in vitro antitumor activity of these drugs by enhancing their solubility in water.

“The antitumor activity of lipophilic amines was interesting because of its action on the mitochondria and lysosomes of cells,” said study author Isabella Orienti, PhD, of the University of Bologna in Italy.

“Moreover, their amphiphilic character improves their bioavailability. We correctly hypothesized these amphiphilic amines would have high antitumor activity and high bioavailability.”

“We are in the process of determining our next steps with testing this new drug,” Dr Cripe added. “This is a promising new therapy for adult and pediatric cancers, and we look forward to further testing its merits.”

Burkitt lymphoma

Image by Ed Uthman

Preclinical research suggests a novel class of compounds are effective against pediatric and adult cancers, including lymphoma.

The compounds are amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length.

The RCn compounds proved cytotoxic in a range of cancer cell lines, including the Burkitt lymphoma cell line Ramos.

The lead compound, RC16, exhibited antitumor effects in vivo and enhanced the in vitro activity of 3 other anticancer agents.

Timothy Cripe, MD, PhD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these results in Pharmaceutical Research.

The investigators first evaluated the RCn compounds for cytotoxicity and mechanism of cell death in several adult and pediatric cancer cell lines.

“We tested RCn’s tumor killing efficacy in cell lines of numerous cancers, including sarcomas, lymphoma, and neuroblastoma,” Dr Cripe said. “We observed anticancer activity of the RCn amines in all the cancer cell lines analyzed.”

The investigators also found that RC16 was 10 times more effective in harming tumor cells than normal cells, including keratinocytes, fibroblasts, and umbilical vein endothelial cells.

In addition, RC16 demonstrated “significant antitumor effects” in several mouse models of malignancy, both when given intravenously and orally.

Because of the amphiphilic molecular structure of RC16, it self-assembled into micelles in water. This chemical structure allowed complexation of the anticancer drugs doxorubicin, etoposide, and paclitaxel.

The micelles significantly improved the in vitro antitumor activity of these drugs by enhancing their solubility in water.

“The antitumor activity of lipophilic amines was interesting because of its action on the mitochondria and lysosomes of cells,” said study author Isabella Orienti, PhD, of the University of Bologna in Italy.

“Moreover, their amphiphilic character improves their bioavailability. We correctly hypothesized these amphiphilic amines would have high antitumor activity and high bioavailability.”

“We are in the process of determining our next steps with testing this new drug,” Dr Cripe added. “This is a promising new therapy for adult and pediatric cancers, and we look forward to further testing its merits.”

Burkitt lymphoma

Image by Ed Uthman

Preclinical research suggests a novel class of compounds are effective against pediatric and adult cancers, including lymphoma.

The compounds are amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length.

The RCn compounds proved cytotoxic in a range of cancer cell lines, including the Burkitt lymphoma cell line Ramos.

The lead compound, RC16, exhibited antitumor effects in vivo and enhanced the in vitro activity of 3 other anticancer agents.

Timothy Cripe, MD, PhD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these results in Pharmaceutical Research.

The investigators first evaluated the RCn compounds for cytotoxicity and mechanism of cell death in several adult and pediatric cancer cell lines.

“We tested RCn’s tumor killing efficacy in cell lines of numerous cancers, including sarcomas, lymphoma, and neuroblastoma,” Dr Cripe said. “We observed anticancer activity of the RCn amines in all the cancer cell lines analyzed.”

The investigators also found that RC16 was 10 times more effective in harming tumor cells than normal cells, including keratinocytes, fibroblasts, and umbilical vein endothelial cells.

In addition, RC16 demonstrated “significant antitumor effects” in several mouse models of malignancy, both when given intravenously and orally.

Because of the amphiphilic molecular structure of RC16, it self-assembled into micelles in water. This chemical structure allowed complexation of the anticancer drugs doxorubicin, etoposide, and paclitaxel.

The micelles significantly improved the in vitro antitumor activity of these drugs by enhancing their solubility in water.

“The antitumor activity of lipophilic amines was interesting because of its action on the mitochondria and lysosomes of cells,” said study author Isabella Orienti, PhD, of the University of Bologna in Italy.

“Moreover, their amphiphilic character improves their bioavailability. We correctly hypothesized these amphiphilic amines would have high antitumor activity and high bioavailability.”

“We are in the process of determining our next steps with testing this new drug,” Dr Cripe added. “This is a promising new therapy for adult and pediatric cancers, and we look forward to further testing its merits.”

An 83-year-old woman who was admitted to an emergency department for unsteadiness and dizziness was eventually diagnosed with primary biliary cirrhosis (PBC), according to a case report by Patrice Baptiste, MBBS, and F. Akinshipo.

Although admitted for unsteadiness, the patient denied falling over, loss of consciousness, chest pain, palpitations, and shortness of breath. Background conditions included hypertension, hypercholesterolemia, atrial fibrillation, a transient ischemic attack, varicose veins, and tinnitus. There was nothing significant in family history, and the patient was an occasional drinker but had never smoked.

An additional review of symptoms before investigation began found coryzal symptoms, dysuria, urinary frequency, and pruritus. After an initial investigation, viral hepatitis was suspected, but additional investigations and a series of negative test results for viral hepatitis led to a diagnosis of PBC. The patient was prescribed ursodeoxycholic acid and discharged from the emergency department.

“There were little findings in this patient’s presentation to suggest PBC; the revelation of pruritus was the only clue before the investigations were conducted,” the investigators wrote. “It is well known that patients can present with nonspecific symptoms or no symptoms at all. Therefore, PBC is an important differential to consider in elderly patients, especially when we know a large proportion of over 65-year-olds are diagnosed with PBC.”

Find the full case report in European Geriatric Medicine (2016 Mar 31. doi: 10.1016/j.eurger.2016.03.002).

lfranki@frontlinemedcom.com

An 83-year-old woman who was admitted to an emergency department for unsteadiness and dizziness was eventually diagnosed with primary biliary cirrhosis (PBC), according to a case report by Patrice Baptiste, MBBS, and F. Akinshipo.

Although admitted for unsteadiness, the patient denied falling over, loss of consciousness, chest pain, palpitations, and shortness of breath. Background conditions included hypertension, hypercholesterolemia, atrial fibrillation, a transient ischemic attack, varicose veins, and tinnitus. There was nothing significant in family history, and the patient was an occasional drinker but had never smoked.

An additional review of symptoms before investigation began found coryzal symptoms, dysuria, urinary frequency, and pruritus. After an initial investigation, viral hepatitis was suspected, but additional investigations and a series of negative test results for viral hepatitis led to a diagnosis of PBC. The patient was prescribed ursodeoxycholic acid and discharged from the emergency department.

“There were little findings in this patient’s presentation to suggest PBC; the revelation of pruritus was the only clue before the investigations were conducted,” the investigators wrote. “It is well known that patients can present with nonspecific symptoms or no symptoms at all. Therefore, PBC is an important differential to consider in elderly patients, especially when we know a large proportion of over 65-year-olds are diagnosed with PBC.”

Find the full case report in European Geriatric Medicine (2016 Mar 31. doi: 10.1016/j.eurger.2016.03.002).

lfranki@frontlinemedcom.com

An 83-year-old woman who was admitted to an emergency department for unsteadiness and dizziness was eventually diagnosed with primary biliary cirrhosis (PBC), according to a case report by Patrice Baptiste, MBBS, and F. Akinshipo.

Although admitted for unsteadiness, the patient denied falling over, loss of consciousness, chest pain, palpitations, and shortness of breath. Background conditions included hypertension, hypercholesterolemia, atrial fibrillation, a transient ischemic attack, varicose veins, and tinnitus. There was nothing significant in family history, and the patient was an occasional drinker but had never smoked.

An additional review of symptoms before investigation began found coryzal symptoms, dysuria, urinary frequency, and pruritus. After an initial investigation, viral hepatitis was suspected, but additional investigations and a series of negative test results for viral hepatitis led to a diagnosis of PBC. The patient was prescribed ursodeoxycholic acid and discharged from the emergency department.

“There were little findings in this patient’s presentation to suggest PBC; the revelation of pruritus was the only clue before the investigations were conducted,” the investigators wrote. “It is well known that patients can present with nonspecific symptoms or no symptoms at all. Therefore, PBC is an important differential to consider in elderly patients, especially when we know a large proportion of over 65-year-olds are diagnosed with PBC.”

Find the full case report in European Geriatric Medicine (2016 Mar 31. doi: 10.1016/j.eurger.2016.03.002).

lfranki@frontlinemedcom.com

BERLIN—A common medication used for the symptomatic treatment of dystonia has been shown to target brain abnormalities in the cerebral cortex in patients with cervical dystonia, according to a study presented at the 20th International Congress of Parkinson’s Disease and Movement Disorders.

Roxana G. Burciu, PhD, a postdoctoral fellow, and a team of researchers at the University of Florida, Gainesville, aimed to assess with fMRI task-related brain activity in patients with cervical dystonia with and without a single-dose administration of trihexyphenidyl, an anticholinergic medication. For decades, anticholinergic medications have been commonly prescribed for patients with varying types of dystonia, but their mechanism of action has not been determined. Although it was previously thought that anticholinergic medications primarily affect the basal ganglia, the results of this study are evidence that they are effective in other areas of the brain, particularly in the cerebral cortex.

Sixteen patients with idiopathic cervical dystonia were compared using a 3-T MRI scanner with 16 age- and gender-matched healthy individuals. Patients with cervical dystonia were scanned twice, both off medication and on average two hours after a single dose of trihexyphenidyl. Control subjects did not receive the medication and were only scanned once. While off medication, the patients had reduced motor activity, compared with the healthy subjects. After administration of trihexyphenidyl, there was an increase in motor-related activity in the middle frontal gyrus and primary somatosensory cortex. The results suggest that somatosensory processing in cervical dystonia can be acutely changed through trihexyphenidyl administration.

Roxana G. Burciu, PhD

Hyder A. Jinnah, MD, PhD, Professor of Neurosurgery, Human Genetics, and Pediatrics at Emory University School of Medicine in Atlanta, said, “The study by Burciu and colleagues is the first attempt to determine what part of the brain is influenced by anticholinergic drugs in dystonia. Before treatment, the patients with cervical dystonia showed abnormal activity in multiple brain regions. After treatment, the abnormal brain activity was at least partly corrected in two regions. Both of these regions were in the cerebral cortex, not the basal ganglia. This study provides clues towards which regions of the brain might be abnormal, and how trihexyphenidyl might correct these abnormalities.”

Dr. Jinnah added, “Like any good study, the findings from this study lead to many more questions than answers. Do the brain abnormalities found reflect a cause for dystonia or a consequence of it? Does the result mean that these medications work in the cortex, not the basal ganglia, as previously believed? Why do patients with cervical dystonia have brain abnormalities that show up when they use their hands, which are not affected? Does the drug affect the brains of normal people who do not have dystonia in the same way? How can we exploit this new information to improve the value of anticholinergics for patients with dystonia?”

BERLIN—A common medication used for the symptomatic treatment of dystonia has been shown to target brain abnormalities in the cerebral cortex in patients with cervical dystonia, according to a study presented at the 20th International Congress of Parkinson’s Disease and Movement Disorders.

Roxana G. Burciu, PhD, a postdoctoral fellow, and a team of researchers at the University of Florida, Gainesville, aimed to assess with fMRI task-related brain activity in patients with cervical dystonia with and without a single-dose administration of trihexyphenidyl, an anticholinergic medication. For decades, anticholinergic medications have been commonly prescribed for patients with varying types of dystonia, but their mechanism of action has not been determined. Although it was previously thought that anticholinergic medications primarily affect the basal ganglia, the results of this study are evidence that they are effective in other areas of the brain, particularly in the cerebral cortex.

Sixteen patients with idiopathic cervical dystonia were compared using a 3-T MRI scanner with 16 age- and gender-matched healthy individuals. Patients with cervical dystonia were scanned twice, both off medication and on average two hours after a single dose of trihexyphenidyl. Control subjects did not receive the medication and were only scanned once. While off medication, the patients had reduced motor activity, compared with the healthy subjects. After administration of trihexyphenidyl, there was an increase in motor-related activity in the middle frontal gyrus and primary somatosensory cortex. The results suggest that somatosensory processing in cervical dystonia can be acutely changed through trihexyphenidyl administration.

Roxana G. Burciu, PhD

Hyder A. Jinnah, MD, PhD, Professor of Neurosurgery, Human Genetics, and Pediatrics at Emory University School of Medicine in Atlanta, said, “The study by Burciu and colleagues is the first attempt to determine what part of the brain is influenced by anticholinergic drugs in dystonia. Before treatment, the patients with cervical dystonia showed abnormal activity in multiple brain regions. After treatment, the abnormal brain activity was at least partly corrected in two regions. Both of these regions were in the cerebral cortex, not the basal ganglia. This study provides clues towards which regions of the brain might be abnormal, and how trihexyphenidyl might correct these abnormalities.”

Dr. Jinnah added, “Like any good study, the findings from this study lead to many more questions than answers. Do the brain abnormalities found reflect a cause for dystonia or a consequence of it? Does the result mean that these medications work in the cortex, not the basal ganglia, as previously believed? Why do patients with cervical dystonia have brain abnormalities that show up when they use their hands, which are not affected? Does the drug affect the brains of normal people who do not have dystonia in the same way? How can we exploit this new information to improve the value of anticholinergics for patients with dystonia?”

BERLIN—A common medication used for the symptomatic treatment of dystonia has been shown to target brain abnormalities in the cerebral cortex in patients with cervical dystonia, according to a study presented at the 20th International Congress of Parkinson’s Disease and Movement Disorders.

Roxana G. Burciu, PhD, a postdoctoral fellow, and a team of researchers at the University of Florida, Gainesville, aimed to assess with fMRI task-related brain activity in patients with cervical dystonia with and without a single-dose administration of trihexyphenidyl, an anticholinergic medication. For decades, anticholinergic medications have been commonly prescribed for patients with varying types of dystonia, but their mechanism of action has not been determined. Although it was previously thought that anticholinergic medications primarily affect the basal ganglia, the results of this study are evidence that they are effective in other areas of the brain, particularly in the cerebral cortex.

Sixteen patients with idiopathic cervical dystonia were compared using a 3-T MRI scanner with 16 age- and gender-matched healthy individuals. Patients with cervical dystonia were scanned twice, both off medication and on average two hours after a single dose of trihexyphenidyl. Control subjects did not receive the medication and were only scanned once. While off medication, the patients had reduced motor activity, compared with the healthy subjects. After administration of trihexyphenidyl, there was an increase in motor-related activity in the middle frontal gyrus and primary somatosensory cortex. The results suggest that somatosensory processing in cervical dystonia can be acutely changed through trihexyphenidyl administration.

Roxana G. Burciu, PhD

Hyder A. Jinnah, MD, PhD, Professor of Neurosurgery, Human Genetics, and Pediatrics at Emory University School of Medicine in Atlanta, said, “The study by Burciu and colleagues is the first attempt to determine what part of the brain is influenced by anticholinergic drugs in dystonia. Before treatment, the patients with cervical dystonia showed abnormal activity in multiple brain regions. After treatment, the abnormal brain activity was at least partly corrected in two regions. Both of these regions were in the cerebral cortex, not the basal ganglia. This study provides clues towards which regions of the brain might be abnormal, and how trihexyphenidyl might correct these abnormalities.”

Dr. Jinnah added, “Like any good study, the findings from this study lead to many more questions than answers. Do the brain abnormalities found reflect a cause for dystonia or a consequence of it? Does the result mean that these medications work in the cortex, not the basal ganglia, as previously believed? Why do patients with cervical dystonia have brain abnormalities that show up when they use their hands, which are not affected? Does the drug affect the brains of normal people who do not have dystonia in the same way? How can we exploit this new information to improve the value of anticholinergics for patients with dystonia?”

SAN DIEGO—Sustained 24-hour pain relief is common among migraineurs who achieve pain freedom two hours after treatment, according to research presented at the 58th Annual Scientific Meeting of the American Headache Society. Factors that may predict recurrent headache after two-hour pain freedom include high headache frequency, allodynia, depression, and medication overuse.

Patients with migraine report that rapid pain relief without recurrence is an important outcome. Sagar Munjal, MD, Senior Director at Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories in Princeton, New Jersey, and colleagues examined data from the American Migraine Prevalence and Prevention Study to identify predictors of two-hour pain freedom and 24-hour sustained response to treatment.

Sagar Munjal, MD

The researchers specifically analyzed responses to two questions from the 2006 survey. The first question was, “After taking your migraine medication, are you pain-free within two hours for most attacks?” The second question was, “Does one dose usually relieve your headache and keep it away for at least 24 hours?” Participants who reported two-hour pain freedom and responded “half the time or more” to the second question were considered to have adequate 24-hour sustained pain relief. Participants who reported two-hour pain freedom and responded “never,” “rarely,” or “less than half the time” to the second question were considered to have inadequate sustained relief.

Dr. Munjal and colleagues used separate binary logistic regression models to evaluate sociodemographics, lifestyle characteristics, headache features, and treatment patterns. They removed variables that were not associated with the outcome from the final model. The factors that remained in the final model were age, gender, marital status, smoking status, allodynia, monthly headache frequency, migraine symptom severity, depression, and medication overuse.

The investigators examined data for 8,333 migraineurs age 18 or older. Approximately 44% of participants reported two-hour pain freedom. Of this population, 82% were female, and the mean age was 47. Among participants with two-hour pain freedom, about 74% reported 24-hour sustained pain relief.

Average headache pain intensity was the main variable that predicted two-hour pain freedom. Allodynia, depression, preventive migraine medication, BMI, female sex, and marital status also predicted two-hour pain freedom. The results indicate the desirability of a fast-acting medication that patients can take early or before pain intensity becomes severe, said Dr. Munjal.

In descending order of significance, predictors of inadequate sustained response were allodynia (odds ratio [OR], 1.55), depression (OR, 1.48), medication overuse (OR, 1.29), and higher monthly headache frequency (OR, 1.06). Insurance status, BMI, number of alcoholic beverages consumed per week, and headache pain severity were removed from the model for nonsignificance.

“These results underscore that unmet need exists for acute migraine treatment in the United States, especially among people with certain sociodemographic and headache characteristics,” said Dr. Munjal. “These data also supplement recent findings that poor treatment optimization is associated with increased risk of chronic migraine onset among people with episodic migraine.”

—Erik Greb

SAN DIEGO—Sustained 24-hour pain relief is common among migraineurs who achieve pain freedom two hours after treatment, according to research presented at the 58th Annual Scientific Meeting of the American Headache Society. Factors that may predict recurrent headache after two-hour pain freedom include high headache frequency, allodynia, depression, and medication overuse.

Patients with migraine report that rapid pain relief without recurrence is an important outcome. Sagar Munjal, MD, Senior Director at Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories in Princeton, New Jersey, and colleagues examined data from the American Migraine Prevalence and Prevention Study to identify predictors of two-hour pain freedom and 24-hour sustained response to treatment.

Sagar Munjal, MD

The researchers specifically analyzed responses to two questions from the 2006 survey. The first question was, “After taking your migraine medication, are you pain-free within two hours for most attacks?” The second question was, “Does one dose usually relieve your headache and keep it away for at least 24 hours?” Participants who reported two-hour pain freedom and responded “half the time or more” to the second question were considered to have adequate 24-hour sustained pain relief. Participants who reported two-hour pain freedom and responded “never,” “rarely,” or “less than half the time” to the second question were considered to have inadequate sustained relief.

Dr. Munjal and colleagues used separate binary logistic regression models to evaluate sociodemographics, lifestyle characteristics, headache features, and treatment patterns. They removed variables that were not associated with the outcome from the final model. The factors that remained in the final model were age, gender, marital status, smoking status, allodynia, monthly headache frequency, migraine symptom severity, depression, and medication overuse.

The investigators examined data for 8,333 migraineurs age 18 or older. Approximately 44% of participants reported two-hour pain freedom. Of this population, 82% were female, and the mean age was 47. Among participants with two-hour pain freedom, about 74% reported 24-hour sustained pain relief.

Average headache pain intensity was the main variable that predicted two-hour pain freedom. Allodynia, depression, preventive migraine medication, BMI, female sex, and marital status also predicted two-hour pain freedom. The results indicate the desirability of a fast-acting medication that patients can take early or before pain intensity becomes severe, said Dr. Munjal.

In descending order of significance, predictors of inadequate sustained response were allodynia (odds ratio [OR], 1.55), depression (OR, 1.48), medication overuse (OR, 1.29), and higher monthly headache frequency (OR, 1.06). Insurance status, BMI, number of alcoholic beverages consumed per week, and headache pain severity were removed from the model for nonsignificance.

“These results underscore that unmet need exists for acute migraine treatment in the United States, especially among people with certain sociodemographic and headache characteristics,” said Dr. Munjal. “These data also supplement recent findings that poor treatment optimization is associated with increased risk of chronic migraine onset among people with episodic migraine.”

—Erik Greb

SAN DIEGO—Sustained 24-hour pain relief is common among migraineurs who achieve pain freedom two hours after treatment, according to research presented at the 58th Annual Scientific Meeting of the American Headache Society. Factors that may predict recurrent headache after two-hour pain freedom include high headache frequency, allodynia, depression, and medication overuse.

Patients with migraine report that rapid pain relief without recurrence is an important outcome. Sagar Munjal, MD, Senior Director at Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories in Princeton, New Jersey, and colleagues examined data from the American Migraine Prevalence and Prevention Study to identify predictors of two-hour pain freedom and 24-hour sustained response to treatment.

Sagar Munjal, MD

The researchers specifically analyzed responses to two questions from the 2006 survey. The first question was, “After taking your migraine medication, are you pain-free within two hours for most attacks?” The second question was, “Does one dose usually relieve your headache and keep it away for at least 24 hours?” Participants who reported two-hour pain freedom and responded “half the time or more” to the second question were considered to have adequate 24-hour sustained pain relief. Participants who reported two-hour pain freedom and responded “never,” “rarely,” or “less than half the time” to the second question were considered to have inadequate sustained relief.

Dr. Munjal and colleagues used separate binary logistic regression models to evaluate sociodemographics, lifestyle characteristics, headache features, and treatment patterns. They removed variables that were not associated with the outcome from the final model. The factors that remained in the final model were age, gender, marital status, smoking status, allodynia, monthly headache frequency, migraine symptom severity, depression, and medication overuse.

The investigators examined data for 8,333 migraineurs age 18 or older. Approximately 44% of participants reported two-hour pain freedom. Of this population, 82% were female, and the mean age was 47. Among participants with two-hour pain freedom, about 74% reported 24-hour sustained pain relief.

Average headache pain intensity was the main variable that predicted two-hour pain freedom. Allodynia, depression, preventive migraine medication, BMI, female sex, and marital status also predicted two-hour pain freedom. The results indicate the desirability of a fast-acting medication that patients can take early or before pain intensity becomes severe, said Dr. Munjal.

In descending order of significance, predictors of inadequate sustained response were allodynia (odds ratio [OR], 1.55), depression (OR, 1.48), medication overuse (OR, 1.29), and higher monthly headache frequency (OR, 1.06). Insurance status, BMI, number of alcoholic beverages consumed per week, and headache pain severity were removed from the model for nonsignificance.

“These results underscore that unmet need exists for acute migraine treatment in the United States, especially among people with certain sociodemographic and headache characteristics,” said Dr. Munjal. “These data also supplement recent findings that poor treatment optimization is associated with increased risk of chronic migraine onset among people with episodic migraine.”

—Erik Greb

Prolonged hospitalizations for complicated patients with severe infections who need long courses of intravenous antibiotics, are common in many institutions.

Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective way to administer intravenous (IV) antimicrobial therapy to patients with the potential to decrease hospital length of stay (LOS). OPAT programs train motivated patients in self-administration of IV medications at home, in a stable environment. Ideally, infectious disease (ID) consultation should be involved to determine appropriate candidates for OPAT as well as a suitable drug regimen and duration of therapy.

A potential barrier to successful utilization of OPAT programs is the need for stable housing at discharge for home infusion services.

Challenge facing homeless patients

There is very little published data regarding the use of OPAT at a medical respite facility for homeless patients. This may be due to perceived concerns of difficulty in administering OPAT to these disadvantaged patients for multiple reasons such as unstable or no housing, inability to stay engaged in medical care, and underlying mental illness and substance abuse problems. In particular, active substance abuse, specifically injection drug use (IDU), is a significant problem.

Traditionally, homeless patients requiring ongoing parenteral therapy have remained inpatient for the duration of their course, which can cause significant inpatient discharge delays and increased LOS. Recommending long-term parenteral therapy as an inpatient for all patients who are homeless or have a history of IDU can lead to prolonged hospitalizations, increased health care costs and contribute to conflicts between patients and staff.

Our study, recently published in the Journal of Hospital Medicine (J Hosp Med. 2016 Apr 27. doi: 10.1002/jhm.2597), aimed to evaluate our experience with administering OPAT to homeless patients at a medical respite facility and to determine if patients could complete a successful treatment course of antibiotics for a variety of illnesses.

We demonstrated that 87% of homeless patients were able to complete a defined course of antibiotic therapy, and 64% were successfully treated with OPAT at medical respite. To our knowledge this is the first study evaluating this specific population (including those with homelessness, mental illness, substance abuse) in which OPAT was received at medical respite.

Our rate of adverse events was 7%, similar to other OPAT studies in the published literature. Our total readmission rate of 30% was similar to what current literature suggests. Our data suggest that providing OPAT to homeless patients is feasible at a medical respite facility with care coordination between members of a multidisciplinary team, including nursing, home infusion pharmacist, and ID clinic.

Partnering with medical respite programs is important, as home infusion services are not available otherwise to homeless patients. The recommendation for ID consultation is beneficial to determine candidacy for OPAT, including close scrutiny of social behaviors in the OPAT patient selection process, and can assist with transitions in care from inpatient to outpatient setting.

Homeless IDU patients remain a challenging population to treat with long term IV antibiotics. However, in certain circumstances, IDU alone may not be a reason to fully exclude someone from OPAT candidacy. Careful review of substance abuse history and evaluation of psychosocial factors are needed. Furthermore, an evaluation of the patient’s willingness to comply with care agreements while inpatient and at medical respite, and ensuring appropriate resources for chemical dependency treatment are needed. Early consideration of oral antimicrobial options if the patient is readmitted for complications/non-adherence should be encouraged.

Medical respite programs

Treating homeless IDU patients with OPAT is possible under close supervision at medical respite. Our patients sign an agreement to refrain from using their IV access for drug use. Security seals are used on all connections and tubing to prevent tampering. The IV access sites are inspected daily, and ID providers are contacted to discuss any patients suspicious of tampering with their IV to determine plan of care – either readmission or transition to oral antibiotics.

Medical respite programs are gaining in popularity in the United States. Medical respite can help engage patients in follow-up care and provide linkage to housing, mental health, and chemical dependency services. Many programs support harm reduction IDU practices and offer referrals for substance abuse treatment programs, which are not typically offered during inpatient admission in most hospitals.

Medical respite may continue to be a site of OPAT expansion, as there is continued pressure to discharge nonacute patients from the hospital. Moving forward, it may be beneficial for hospitals, public health departments, and communities to support these programs, which can assist with close monitoring of homeless patients receiving OPAT.

There are ongoing challenges for housed IDU patients who require OPAT, as medical respite placement and home infusion are generally not options, and skilled nursing facility placement can be difficult. Careful review of substance abuse history; evaluation of psychosocial factors, such as housing status; mental health history; and outpatient support systems are needed.

Again, ID consultation is highly recommended to determine appropriate IV therapy, and if possible, early transition to oral antimicrobial therapy, as well as duration of treatment for specific illnesses on a case-by-case basis. Close follow-up is needed to ensure patient compliance with prescribed antimicrobial regimen, sometimes requiring weekly visits.

OPAT is effective for many patients, and it is optimal to utilize ID consultation to determine appropriate candidates – particularly among homeless and IDU patients. OPAT can be successful in a closely monitored medical respite setting for homeless patients with multiple comorbidities, with the help of a multidisciplinary team. Medical respite OPAT can decrease LOS in patients who would otherwise require long hospitalizations, resulting in overall cost savings.

Shireesha Dhanireddy, MD, is medical director of the infectious disease clinic at Harborview Medical Center, Seattle. Alison Beieler, PA-C, MPAS, runs the OPAT program in the infectious disease clinic at Harborview Medical Center.

Prolonged hospitalizations for complicated patients with severe infections who need long courses of intravenous antibiotics, are common in many institutions.

Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective way to administer intravenous (IV) antimicrobial therapy to patients with the potential to decrease hospital length of stay (LOS). OPAT programs train motivated patients in self-administration of IV medications at home, in a stable environment. Ideally, infectious disease (ID) consultation should be involved to determine appropriate candidates for OPAT as well as a suitable drug regimen and duration of therapy.

A potential barrier to successful utilization of OPAT programs is the need for stable housing at discharge for home infusion services.

Challenge facing homeless patients

There is very little published data regarding the use of OPAT at a medical respite facility for homeless patients. This may be due to perceived concerns of difficulty in administering OPAT to these disadvantaged patients for multiple reasons such as unstable or no housing, inability to stay engaged in medical care, and underlying mental illness and substance abuse problems. In particular, active substance abuse, specifically injection drug use (IDU), is a significant problem.

Traditionally, homeless patients requiring ongoing parenteral therapy have remained inpatient for the duration of their course, which can cause significant inpatient discharge delays and increased LOS. Recommending long-term parenteral therapy as an inpatient for all patients who are homeless or have a history of IDU can lead to prolonged hospitalizations, increased health care costs and contribute to conflicts between patients and staff.

Our study, recently published in the Journal of Hospital Medicine (J Hosp Med. 2016 Apr 27. doi: 10.1002/jhm.2597), aimed to evaluate our experience with administering OPAT to homeless patients at a medical respite facility and to determine if patients could complete a successful treatment course of antibiotics for a variety of illnesses.

We demonstrated that 87% of homeless patients were able to complete a defined course of antibiotic therapy, and 64% were successfully treated with OPAT at medical respite. To our knowledge this is the first study evaluating this specific population (including those with homelessness, mental illness, substance abuse) in which OPAT was received at medical respite.

Our rate of adverse events was 7%, similar to other OPAT studies in the published literature. Our total readmission rate of 30% was similar to what current literature suggests. Our data suggest that providing OPAT to homeless patients is feasible at a medical respite facility with care coordination between members of a multidisciplinary team, including nursing, home infusion pharmacist, and ID clinic.

Partnering with medical respite programs is important, as home infusion services are not available otherwise to homeless patients. The recommendation for ID consultation is beneficial to determine candidacy for OPAT, including close scrutiny of social behaviors in the OPAT patient selection process, and can assist with transitions in care from inpatient to outpatient setting.

Homeless IDU patients remain a challenging population to treat with long term IV antibiotics. However, in certain circumstances, IDU alone may not be a reason to fully exclude someone from OPAT candidacy. Careful review of substance abuse history and evaluation of psychosocial factors are needed. Furthermore, an evaluation of the patient’s willingness to comply with care agreements while inpatient and at medical respite, and ensuring appropriate resources for chemical dependency treatment are needed. Early consideration of oral antimicrobial options if the patient is readmitted for complications/non-adherence should be encouraged.

Medical respite programs

Treating homeless IDU patients with OPAT is possible under close supervision at medical respite. Our patients sign an agreement to refrain from using their IV access for drug use. Security seals are used on all connections and tubing to prevent tampering. The IV access sites are inspected daily, and ID providers are contacted to discuss any patients suspicious of tampering with their IV to determine plan of care – either readmission or transition to oral antibiotics.

Medical respite programs are gaining in popularity in the United States. Medical respite can help engage patients in follow-up care and provide linkage to housing, mental health, and chemical dependency services. Many programs support harm reduction IDU practices and offer referrals for substance abuse treatment programs, which are not typically offered during inpatient admission in most hospitals.

Medical respite may continue to be a site of OPAT expansion, as there is continued pressure to discharge nonacute patients from the hospital. Moving forward, it may be beneficial for hospitals, public health departments, and communities to support these programs, which can assist with close monitoring of homeless patients receiving OPAT.

There are ongoing challenges for housed IDU patients who require OPAT, as medical respite placement and home infusion are generally not options, and skilled nursing facility placement can be difficult. Careful review of substance abuse history; evaluation of psychosocial factors, such as housing status; mental health history; and outpatient support systems are needed.

Again, ID consultation is highly recommended to determine appropriate IV therapy, and if possible, early transition to oral antimicrobial therapy, as well as duration of treatment for specific illnesses on a case-by-case basis. Close follow-up is needed to ensure patient compliance with prescribed antimicrobial regimen, sometimes requiring weekly visits.

OPAT is effective for many patients, and it is optimal to utilize ID consultation to determine appropriate candidates – particularly among homeless and IDU patients. OPAT can be successful in a closely monitored medical respite setting for homeless patients with multiple comorbidities, with the help of a multidisciplinary team. Medical respite OPAT can decrease LOS in patients who would otherwise require long hospitalizations, resulting in overall cost savings.

Shireesha Dhanireddy, MD, is medical director of the infectious disease clinic at Harborview Medical Center, Seattle. Alison Beieler, PA-C, MPAS, runs the OPAT program in the infectious disease clinic at Harborview Medical Center.

Prolonged hospitalizations for complicated patients with severe infections who need long courses of intravenous antibiotics, are common in many institutions.

Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective way to administer intravenous (IV) antimicrobial therapy to patients with the potential to decrease hospital length of stay (LOS). OPAT programs train motivated patients in self-administration of IV medications at home, in a stable environment. Ideally, infectious disease (ID) consultation should be involved to determine appropriate candidates for OPAT as well as a suitable drug regimen and duration of therapy.

A potential barrier to successful utilization of OPAT programs is the need for stable housing at discharge for home infusion services.

Challenge facing homeless patients

There is very little published data regarding the use of OPAT at a medical respite facility for homeless patients. This may be due to perceived concerns of difficulty in administering OPAT to these disadvantaged patients for multiple reasons such as unstable or no housing, inability to stay engaged in medical care, and underlying mental illness and substance abuse problems. In particular, active substance abuse, specifically injection drug use (IDU), is a significant problem.

Traditionally, homeless patients requiring ongoing parenteral therapy have remained inpatient for the duration of their course, which can cause significant inpatient discharge delays and increased LOS. Recommending long-term parenteral therapy as an inpatient for all patients who are homeless or have a history of IDU can lead to prolonged hospitalizations, increased health care costs and contribute to conflicts between patients and staff.

Our study, recently published in the Journal of Hospital Medicine (J Hosp Med. 2016 Apr 27. doi: 10.1002/jhm.2597), aimed to evaluate our experience with administering OPAT to homeless patients at a medical respite facility and to determine if patients could complete a successful treatment course of antibiotics for a variety of illnesses.

We demonstrated that 87% of homeless patients were able to complete a defined course of antibiotic therapy, and 64% were successfully treated with OPAT at medical respite. To our knowledge this is the first study evaluating this specific population (including those with homelessness, mental illness, substance abuse) in which OPAT was received at medical respite.

Our rate of adverse events was 7%, similar to other OPAT studies in the published literature. Our total readmission rate of 30% was similar to what current literature suggests. Our data suggest that providing OPAT to homeless patients is feasible at a medical respite facility with care coordination between members of a multidisciplinary team, including nursing, home infusion pharmacist, and ID clinic.

Partnering with medical respite programs is important, as home infusion services are not available otherwise to homeless patients. The recommendation for ID consultation is beneficial to determine candidacy for OPAT, including close scrutiny of social behaviors in the OPAT patient selection process, and can assist with transitions in care from inpatient to outpatient setting.

Homeless IDU patients remain a challenging population to treat with long term IV antibiotics. However, in certain circumstances, IDU alone may not be a reason to fully exclude someone from OPAT candidacy. Careful review of substance abuse history and evaluation of psychosocial factors are needed. Furthermore, an evaluation of the patient’s willingness to comply with care agreements while inpatient and at medical respite, and ensuring appropriate resources for chemical dependency treatment are needed. Early consideration of oral antimicrobial options if the patient is readmitted for complications/non-adherence should be encouraged.

Medical respite programs

Treating homeless IDU patients with OPAT is possible under close supervision at medical respite. Our patients sign an agreement to refrain from using their IV access for drug use. Security seals are used on all connections and tubing to prevent tampering. The IV access sites are inspected daily, and ID providers are contacted to discuss any patients suspicious of tampering with their IV to determine plan of care – either readmission or transition to oral antibiotics.

Medical respite programs are gaining in popularity in the United States. Medical respite can help engage patients in follow-up care and provide linkage to housing, mental health, and chemical dependency services. Many programs support harm reduction IDU practices and offer referrals for substance abuse treatment programs, which are not typically offered during inpatient admission in most hospitals.

Medical respite may continue to be a site of OPAT expansion, as there is continued pressure to discharge nonacute patients from the hospital. Moving forward, it may be beneficial for hospitals, public health departments, and communities to support these programs, which can assist with close monitoring of homeless patients receiving OPAT.

There are ongoing challenges for housed IDU patients who require OPAT, as medical respite placement and home infusion are generally not options, and skilled nursing facility placement can be difficult. Careful review of substance abuse history; evaluation of psychosocial factors, such as housing status; mental health history; and outpatient support systems are needed.

Again, ID consultation is highly recommended to determine appropriate IV therapy, and if possible, early transition to oral antimicrobial therapy, as well as duration of treatment for specific illnesses on a case-by-case basis. Close follow-up is needed to ensure patient compliance with prescribed antimicrobial regimen, sometimes requiring weekly visits.

OPAT is effective for many patients, and it is optimal to utilize ID consultation to determine appropriate candidates – particularly among homeless and IDU patients. OPAT can be successful in a closely monitored medical respite setting for homeless patients with multiple comorbidities, with the help of a multidisciplinary team. Medical respite OPAT can decrease LOS in patients who would otherwise require long hospitalizations, resulting in overall cost savings.

Shireesha Dhanireddy, MD, is medical director of the infectious disease clinic at Harborview Medical Center, Seattle. Alison Beieler, PA-C, MPAS, runs the OPAT program in the infectious disease clinic at Harborview Medical Center.

Poor physical performance was linked with an increased risk of dementia in a study of individuals age 90 and older who were followed for an average of 2.6 years. After controlling for various factors, poor standing balance had the strongest association with dementia, followed by poor performance in a four-meter walk test and a handgrip test. The study findings were published online ahead of print July 5 in the Journal of the American Geriatrics Society.

“The oldest old, people aged 90 and older, represent the fastest-growing segment of society with the highest rates of dementia; however, many of the traditional risk factors of dementia lose or change their effect in this age group. Therefore, it is crucial that we identify age-specific risk and protective factors for late-age dementia,” said lead author Szofia S. Bullain, MD, an Assistant Professor of Neurology at the University of California, Irvine. “The fact that we were able to detect impairment in physical performance two to three years before the onset of dementia suggests that poor physical performance may be a risk factor for, or an early sign of, developing late-age dementia.”

Dr. Bullain and colleagues conducted a population-based, longitudinal study to examine the relationship between physical performance and dementia in individuals age 90 and older without dementia. They enrolled 176 men and 402 women without dementia from the 90+ Study. Among the total cohort of 578, the mean age was 93.3. At baseline, 54% of the participants were cognitively normal, and 46% had cognitive impairment, but no dementia.

Szofia S. Bullain, MD

Physical performance measures included a four-meter walk, five chair stands, handgrip, and standing balance. Measures were scored from zero (unable to perform) to four (best performance). The outcome was dementia, diagnosed according to DSM-IV criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders.

Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range, seven months to nine years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HR, 1.9 to 2.5), followed by four-meter walk (HR, 1.1 to 1.8) and handgrip (HR, 1.0 to 2.0). The association with five chair stands was not significant.

The researchers next plan to examine the underlying pathologic processes, which may provide clues to new preventive and treatment strategies for late-age dementia.

—Glenn S. Williams

Poor physical performance was linked with an increased risk of dementia in a study of individuals age 90 and older who were followed for an average of 2.6 years. After controlling for various factors, poor standing balance had the strongest association with dementia, followed by poor performance in a four-meter walk test and a handgrip test. The study findings were published online ahead of print July 5 in the Journal of the American Geriatrics Society.

“The oldest old, people aged 90 and older, represent the fastest-growing segment of society with the highest rates of dementia; however, many of the traditional risk factors of dementia lose or change their effect in this age group. Therefore, it is crucial that we identify age-specific risk and protective factors for late-age dementia,” said lead author Szofia S. Bullain, MD, an Assistant Professor of Neurology at the University of California, Irvine. “The fact that we were able to detect impairment in physical performance two to three years before the onset of dementia suggests that poor physical performance may be a risk factor for, or an early sign of, developing late-age dementia.”

Dr. Bullain and colleagues conducted a population-based, longitudinal study to examine the relationship between physical performance and dementia in individuals age 90 and older without dementia. They enrolled 176 men and 402 women without dementia from the 90+ Study. Among the total cohort of 578, the mean age was 93.3. At baseline, 54% of the participants were cognitively normal, and 46% had cognitive impairment, but no dementia.

Szofia S. Bullain, MD

Physical performance measures included a four-meter walk, five chair stands, handgrip, and standing balance. Measures were scored from zero (unable to perform) to four (best performance). The outcome was dementia, diagnosed according to DSM-IV criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders.

Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range, seven months to nine years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HR, 1.9 to 2.5), followed by four-meter walk (HR, 1.1 to 1.8) and handgrip (HR, 1.0 to 2.0). The association with five chair stands was not significant.

The researchers next plan to examine the underlying pathologic processes, which may provide clues to new preventive and treatment strategies for late-age dementia.

—Glenn S. Williams

Poor physical performance was linked with an increased risk of dementia in a study of individuals age 90 and older who were followed for an average of 2.6 years. After controlling for various factors, poor standing balance had the strongest association with dementia, followed by poor performance in a four-meter walk test and a handgrip test. The study findings were published online ahead of print July 5 in the Journal of the American Geriatrics Society.

“The oldest old, people aged 90 and older, represent the fastest-growing segment of society with the highest rates of dementia; however, many of the traditional risk factors of dementia lose or change their effect in this age group. Therefore, it is crucial that we identify age-specific risk and protective factors for late-age dementia,” said lead author Szofia S. Bullain, MD, an Assistant Professor of Neurology at the University of California, Irvine. “The fact that we were able to detect impairment in physical performance two to three years before the onset of dementia suggests that poor physical performance may be a risk factor for, or an early sign of, developing late-age dementia.”

Dr. Bullain and colleagues conducted a population-based, longitudinal study to examine the relationship between physical performance and dementia in individuals age 90 and older without dementia. They enrolled 176 men and 402 women without dementia from the 90+ Study. Among the total cohort of 578, the mean age was 93.3. At baseline, 54% of the participants were cognitively normal, and 46% had cognitive impairment, but no dementia.

Szofia S. Bullain, MD

Physical performance measures included a four-meter walk, five chair stands, handgrip, and standing balance. Measures were scored from zero (unable to perform) to four (best performance). The outcome was dementia, diagnosed according to DSM-IV criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders.

Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range, seven months to nine years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HR, 1.9 to 2.5), followed by four-meter walk (HR, 1.1 to 1.8) and handgrip (HR, 1.0 to 2.0). The association with five chair stands was not significant.

The researchers next plan to examine the underlying pathologic processes, which may provide clues to new preventive and treatment strategies for late-age dementia.

—Glenn S. Williams