Moving patients safely and efficiently through the admission process is always a priority for hospitalists. Is there a way to optimize and standardize the process?

“In hopes of improving admission efficiency, while simultaneously increasing quality of care, we decided to use Lean/Six Sigma methodology to streamline our admission process,” says Escher Howard-Williams, MD, lead author of an abstract called “Standardizing the Admission Process Using Lean/Six Sigma One Piece Flow.”¹

A basic tenet of the methodology is called “one piece flow” (OPF), the idea that standardized processes are more efficient and less prone to error when completed from start to finish without interruption. In the study, hospitalists committed to performing all patient admissions in OPF, focusing on one patient from initiation of chart review through exam, order entry and documentation, without interruption. Researchers then analyzed times, including time to call back to ED, time at initiation of chart review, time of evaluation of patient, time orders were placed, and time of sign-out note completed, before and after implementation of OPF. They found a substantial reduction in time of the admission process across all time points with OPF.

“When you are trying to improve quality of care in your institution, dissecting the overall work flow will allow you to discover areas that hinder the overall process,” Dr. Howard-Williams says. “Reframing your process to focus on providing excellent quality care will allow you to find workable solutions to improve the quality of care and efficiency in your practice. As part of this process, developing a team with an appropriate variety of members lays the foundation for success.”

Dr. Howard-Williams hopes that the study will inspire others to reflect on their own practices.

“If, during that reflection, they can identify areas that they would like to improve quality, we would encourage them to join us,” she says. “They will have the opportunity to build their personal work flow maps, find choke points and devise a plan for moving forward with new solutions.”
 

Reference

1. Howard-Williams E, Liles A, Stephens J, lanza-Kaduce K. Standardizing the admission process using Lean/Six Sigma One Piece Flow [abstract]. J Hosp Med. 2016;11(suppl 1). Available at: http://www.shmabstracts.com/abstract/standardizing-the-admission-process-using-lean-six-sigma-one-piece-flow/. Accessed March 7, 2017.

Moving patients safely and efficiently through the admission process is always a priority for hospitalists. Is there a way to optimize and standardize the process?

“In hopes of improving admission efficiency, while simultaneously increasing quality of care, we decided to use Lean/Six Sigma methodology to streamline our admission process,” says Escher Howard-Williams, MD, lead author of an abstract called “Standardizing the Admission Process Using Lean/Six Sigma One Piece Flow.”¹

A basic tenet of the methodology is called “one piece flow” (OPF), the idea that standardized processes are more efficient and less prone to error when completed from start to finish without interruption. In the study, hospitalists committed to performing all patient admissions in OPF, focusing on one patient from initiation of chart review through exam, order entry and documentation, without interruption. Researchers then analyzed times, including time to call back to ED, time at initiation of chart review, time of evaluation of patient, time orders were placed, and time of sign-out note completed, before and after implementation of OPF. They found a substantial reduction in time of the admission process across all time points with OPF.

“When you are trying to improve quality of care in your institution, dissecting the overall work flow will allow you to discover areas that hinder the overall process,” Dr. Howard-Williams says. “Reframing your process to focus on providing excellent quality care will allow you to find workable solutions to improve the quality of care and efficiency in your practice. As part of this process, developing a team with an appropriate variety of members lays the foundation for success.”

Dr. Howard-Williams hopes that the study will inspire others to reflect on their own practices.

“If, during that reflection, they can identify areas that they would like to improve quality, we would encourage them to join us,” she says. “They will have the opportunity to build their personal work flow maps, find choke points and devise a plan for moving forward with new solutions.”
 

Reference

1. Howard-Williams E, Liles A, Stephens J, lanza-Kaduce K. Standardizing the admission process using Lean/Six Sigma One Piece Flow [abstract]. J Hosp Med. 2016;11(suppl 1). Available at: http://www.shmabstracts.com/abstract/standardizing-the-admission-process-using-lean-six-sigma-one-piece-flow/. Accessed March 7, 2017.

Moving patients safely and efficiently through the admission process is always a priority for hospitalists. Is there a way to optimize and standardize the process?

“In hopes of improving admission efficiency, while simultaneously increasing quality of care, we decided to use Lean/Six Sigma methodology to streamline our admission process,” says Escher Howard-Williams, MD, lead author of an abstract called “Standardizing the Admission Process Using Lean/Six Sigma One Piece Flow.”¹

A basic tenet of the methodology is called “one piece flow” (OPF), the idea that standardized processes are more efficient and less prone to error when completed from start to finish without interruption. In the study, hospitalists committed to performing all patient admissions in OPF, focusing on one patient from initiation of chart review through exam, order entry and documentation, without interruption. Researchers then analyzed times, including time to call back to ED, time at initiation of chart review, time of evaluation of patient, time orders were placed, and time of sign-out note completed, before and after implementation of OPF. They found a substantial reduction in time of the admission process across all time points with OPF.

“When you are trying to improve quality of care in your institution, dissecting the overall work flow will allow you to discover areas that hinder the overall process,” Dr. Howard-Williams says. “Reframing your process to focus on providing excellent quality care will allow you to find workable solutions to improve the quality of care and efficiency in your practice. As part of this process, developing a team with an appropriate variety of members lays the foundation for success.”

Dr. Howard-Williams hopes that the study will inspire others to reflect on their own practices.

“If, during that reflection, they can identify areas that they would like to improve quality, we would encourage them to join us,” she says. “They will have the opportunity to build their personal work flow maps, find choke points and devise a plan for moving forward with new solutions.”
 

Reference

1. Howard-Williams E, Liles A, Stephens J, lanza-Kaduce K. Standardizing the admission process using Lean/Six Sigma One Piece Flow [abstract]. J Hosp Med. 2016;11(suppl 1). Available at: http://www.shmabstracts.com/abstract/standardizing-the-admission-process-using-lean-six-sigma-one-piece-flow/. Accessed March 7, 2017.

CLINICAL QUESTION: Can shock index (SI) in the ED predict the likelihood for hospital admission and inpatient mortality?

BACKGROUND: SI is defined as heart rate divided by systolic blood pressure. It is postulated to have an inverse relationship to cardiac output. SI has been studied as a prognostic metric of poor outcomes in patients with myocardial infarction, gastrointestinal hemorrhage, sepsis, and trauma. There are no large studies on SI in the general ED population.

This study identified potential thresholds for SI but did not validate them. Whether SI would be a useful tool for triage remains unanswered.

BOTTOM LINE: Initial SI greater than 1.2 at presentation to the ED was associated with increased likelihood of hospital admission and inpatient mortality.

CITATIONS: Balhara KS, Hsieh YH, Hamade B, et al. Clinical metrics in emergency medicine: the shock index and the probability of hospital admission and inpatient mortality. Emerg Med J. 2017 Feb;34(2):89-94.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: Can shock index (SI) in the ED predict the likelihood for hospital admission and inpatient mortality?

BACKGROUND: SI is defined as heart rate divided by systolic blood pressure. It is postulated to have an inverse relationship to cardiac output. SI has been studied as a prognostic metric of poor outcomes in patients with myocardial infarction, gastrointestinal hemorrhage, sepsis, and trauma. There are no large studies on SI in the general ED population.

This study identified potential thresholds for SI but did not validate them. Whether SI would be a useful tool for triage remains unanswered.

BOTTOM LINE: Initial SI greater than 1.2 at presentation to the ED was associated with increased likelihood of hospital admission and inpatient mortality.

CITATIONS: Balhara KS, Hsieh YH, Hamade B, et al. Clinical metrics in emergency medicine: the shock index and the probability of hospital admission and inpatient mortality. Emerg Med J. 2017 Feb;34(2):89-94.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: Can shock index (SI) in the ED predict the likelihood for hospital admission and inpatient mortality?

BACKGROUND: SI is defined as heart rate divided by systolic blood pressure. It is postulated to have an inverse relationship to cardiac output. SI has been studied as a prognostic metric of poor outcomes in patients with myocardial infarction, gastrointestinal hemorrhage, sepsis, and trauma. There are no large studies on SI in the general ED population.

This study identified potential thresholds for SI but did not validate them. Whether SI would be a useful tool for triage remains unanswered.

BOTTOM LINE: Initial SI greater than 1.2 at presentation to the ED was associated with increased likelihood of hospital admission and inpatient mortality.

CITATIONS: Balhara KS, Hsieh YH, Hamade B, et al. Clinical metrics in emergency medicine: the shock index and the probability of hospital admission and inpatient mortality. Emerg Med J. 2017 Feb;34(2):89-94.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

Throughout his marathon confirmation hearing, U.S. Supreme Court nominee Neil Gorsuch remained tight-lipped about how he might rule on major health care issues if confirmed to the country’s highest court, pledging to look at the facts of each case and rule according to the law.

The Senate Committee on the Judiciary wrapped up its nearly week-long questioning of Judge Gorsuch on March 23. Inquiries during the hearing ranged from Judge Gorsuch’s stance on abortion, to his support of religious freedom, to whether he would uphold President Trump’s controversial Executive Order on travel and immigration. Through it all, Judge Gorsuch, who presides over Denver’s 10th Circuit, kept his composure and refused to offer insight into which way he would lean when deciding such hot-button issues.

Wikimedia

agallegos@frontlinemedcom.com

On Twitter @legal_med

Throughout his marathon confirmation hearing, U.S. Supreme Court nominee Neil Gorsuch remained tight-lipped about how he might rule on major health care issues if confirmed to the country’s highest court, pledging to look at the facts of each case and rule according to the law.

The Senate Committee on the Judiciary wrapped up its nearly week-long questioning of Judge Gorsuch on March 23. Inquiries during the hearing ranged from Judge Gorsuch’s stance on abortion, to his support of religious freedom, to whether he would uphold President Trump’s controversial Executive Order on travel and immigration. Through it all, Judge Gorsuch, who presides over Denver’s 10th Circuit, kept his composure and refused to offer insight into which way he would lean when deciding such hot-button issues.

Wikimedia

agallegos@frontlinemedcom.com

On Twitter @legal_med

Throughout his marathon confirmation hearing, U.S. Supreme Court nominee Neil Gorsuch remained tight-lipped about how he might rule on major health care issues if confirmed to the country’s highest court, pledging to look at the facts of each case and rule according to the law.

The Senate Committee on the Judiciary wrapped up its nearly week-long questioning of Judge Gorsuch on March 23. Inquiries during the hearing ranged from Judge Gorsuch’s stance on abortion, to his support of religious freedom, to whether he would uphold President Trump’s controversial Executive Order on travel and immigration. Through it all, Judge Gorsuch, who presides over Denver’s 10th Circuit, kept his composure and refused to offer insight into which way he would lean when deciding such hot-button issues.

Wikimedia

agallegos@frontlinemedcom.com

On Twitter @legal_med

As a hospitalist, you typically have little, if any, contact with patients outside the hospital and, at most, you’ll only spend a couple of hours a year in front of any particular patient. The vast majority of the determinants of your patients’ health occur when you’re not there.

In a commentary in the New England Journal of Medicine entitled “Engineering Social Incentives for Health,” lead author David A. Asch, MD, MBA, addresses that issue.¹
 

“The motivation for the piece is that the people who are in a position to influence a patient’s health are their friends and family, and yet so much of how we have structured health care is between a clinician and a patient,” he says. “We often fail to engage the people in patients’ everyday lives, who can be quite willing partners in improving health care. There are all sorts of things they can do to help patients with hard-to-control diabetes or ... heart failure, or anything that might have put them in the hospital in the first place.”

The column describes a ladder of social engineering strategies, from very simple to complex. One example on the simple end might be to help a patient remember a daily medication by having him place the medication bottle where his partner can see him taking – or not taking – it. (The alternative is that medications are taken in a private place, such in the bathroom, where no one might be watching over the routine to keep the patient on track.)

Moving up the ladder, a hospitalist might help set up a network of other patients with heart failure, so that they can help each other in a kind of peer mentorship.

“These peer-to-peer connections might require Web-based platforms or social support groups, so that kind of activity is a lot more complicated, but the general theme is: Can hospitalists think about ways to constructively engage the social networks that already surround patients, so they don’t need to invoke the health system to do it?”

It’s long been known that people with more social support do better: People who are married do better; people who have more friends do better. “Up until now, it’s just been an observation,” Dr. Asch says. “I think we’re at a point where we could begin to prescribe social support in the way we might prescribe a diuretic. I’d like to try it out at least. I think that’s the call to action.”

Reference

1. Asch D, Rosin R. Engineering social incentives for health. NEJM. 2016;375:2511-2513.

As a hospitalist, you typically have little, if any, contact with patients outside the hospital and, at most, you’ll only spend a couple of hours a year in front of any particular patient. The vast majority of the determinants of your patients’ health occur when you’re not there.

In a commentary in the New England Journal of Medicine entitled “Engineering Social Incentives for Health,” lead author David A. Asch, MD, MBA, addresses that issue.¹
 

“The motivation for the piece is that the people who are in a position to influence a patient’s health are their friends and family, and yet so much of how we have structured health care is between a clinician and a patient,” he says. “We often fail to engage the people in patients’ everyday lives, who can be quite willing partners in improving health care. There are all sorts of things they can do to help patients with hard-to-control diabetes or ... heart failure, or anything that might have put them in the hospital in the first place.”

The column describes a ladder of social engineering strategies, from very simple to complex. One example on the simple end might be to help a patient remember a daily medication by having him place the medication bottle where his partner can see him taking – or not taking – it. (The alternative is that medications are taken in a private place, such in the bathroom, where no one might be watching over the routine to keep the patient on track.)

Moving up the ladder, a hospitalist might help set up a network of other patients with heart failure, so that they can help each other in a kind of peer mentorship.

“These peer-to-peer connections might require Web-based platforms or social support groups, so that kind of activity is a lot more complicated, but the general theme is: Can hospitalists think about ways to constructively engage the social networks that already surround patients, so they don’t need to invoke the health system to do it?”

It’s long been known that people with more social support do better: People who are married do better; people who have more friends do better. “Up until now, it’s just been an observation,” Dr. Asch says. “I think we’re at a point where we could begin to prescribe social support in the way we might prescribe a diuretic. I’d like to try it out at least. I think that’s the call to action.”

Reference

1. Asch D, Rosin R. Engineering social incentives for health. NEJM. 2016;375:2511-2513.

As a hospitalist, you typically have little, if any, contact with patients outside the hospital and, at most, you’ll only spend a couple of hours a year in front of any particular patient. The vast majority of the determinants of your patients’ health occur when you’re not there.

In a commentary in the New England Journal of Medicine entitled “Engineering Social Incentives for Health,” lead author David A. Asch, MD, MBA, addresses that issue.¹
 

“The motivation for the piece is that the people who are in a position to influence a patient’s health are their friends and family, and yet so much of how we have structured health care is between a clinician and a patient,” he says. “We often fail to engage the people in patients’ everyday lives, who can be quite willing partners in improving health care. There are all sorts of things they can do to help patients with hard-to-control diabetes or ... heart failure, or anything that might have put them in the hospital in the first place.”

The column describes a ladder of social engineering strategies, from very simple to complex. One example on the simple end might be to help a patient remember a daily medication by having him place the medication bottle where his partner can see him taking – or not taking – it. (The alternative is that medications are taken in a private place, such in the bathroom, where no one might be watching over the routine to keep the patient on track.)

Moving up the ladder, a hospitalist might help set up a network of other patients with heart failure, so that they can help each other in a kind of peer mentorship.

“These peer-to-peer connections might require Web-based platforms or social support groups, so that kind of activity is a lot more complicated, but the general theme is: Can hospitalists think about ways to constructively engage the social networks that already surround patients, so they don’t need to invoke the health system to do it?”

It’s long been known that people with more social support do better: People who are married do better; people who have more friends do better. “Up until now, it’s just been an observation,” Dr. Asch says. “I think we’re at a point where we could begin to prescribe social support in the way we might prescribe a diuretic. I’d like to try it out at least. I think that’s the call to action.”

Reference

1. Asch D, Rosin R. Engineering social incentives for health. NEJM. 2016;375:2511-2513.

Take-Home Points

• The location of a bicortical defect in proximity to a tibia plate does not appear to affect the torsional stiffness or torsional failure strength of the bone.

• External fixator pin placement should be based on considerations other than the potential for creating a distal stress riser after definitive fracture management.

A stress riser in cortical bone may be considered any abrupt change in the contour or consistency of the hollow structure, such as a surface defect, that not only weakens the bone but concentrates stresses at that transition point.¹ A cortical defect that is 20% of the bone diameter is associated with a 34% decrease in torsional strength, thus representing a “stress riser.”² High-energy and complex tibia fractures are often provisionally stabilized with external fixation that gives the soft tissues time to recover before definitive fracture fixation. Pin diameter for a medium-size tibia external fixator typically is 5.0 mm, resulting in a 10-mm defect in bicortical placement. Therefore, any tibia with a diameter of <50 mm is at risk for a stress riser fracture.

Although it had been established that sizable cortical defects can decrease the torsional strength of long bone,² the effect of a plate in close proximity to a defect secondary to an empty external-fixator pin site on torsional strength has not been determined. We conducted a study to evaluate this effect. The null hypothesis was there would be no difference in tibia torsional strength attributable to varying the proximity of a tibia midshaft plate to a 5.0-mm bicortical defect.

Methods

Forty fourth-generation, medium-size left composite tibias (Pacific Research Laboratories) were divided into 8 groups of 5 bones (Figure 1).

Torsion testing to failure was performed for all specimens in a manner similar to that described by Gardner and colleagues.³ Impression molds for the composite tibia constructed from polymethylmethacrylate encased the superior and distal ends, leaving 25.5 cm of exposed midshaft. This allowed the composites to be rigidly clamped into a materials testing system (858 Mini-Bionix; MTS) equipped with a 100.0-Nm torsional load cell (Figure 2).

Results

Graphical results for torsional stiffness are presented in Figure 3. R² for all stiffness calculations was >0.99.

Discussion

Many tibia fractures require provisional stabilization with an external fixator that spans the knee, because of the high-energy nature of the injury or other, higher-priority polytrauma concerns. When the patient or injury is suitable for definitive fixation, the external fixator typically is removed in favor of internal fixation with a plate and screws. Depending on the nature and location of the fracture and the subsequent plate, the empty cortical pin-site defects, often lying at varying distances from the distal end of the plate, can potentially serve as stress risers for fracture.⁴

Other studies have evaluated long-bone cortical defects biomechanically^1,2,4 and clinically,^5-7 and multiple studies have been conducted on the effects of plates on long-bone strength for fracture stabilization.^8-13 The present study evaluated the torsional strength of long bones in the presence of a bicortical defect and the proximity of the defect to a plate. There were no differences in stiffness or failure load between any of the groups of plated and unplated fourth-generation composite tibias tested to failure in torsion with varying distal bicortical defects. Hypothetically, one would expect the torsional stiffness of these specimens to increase with the mere addition of a metallic diaphyseal plate. However, this study demonstrated that the addition of a plate did not affect the torsional stiffness or strength of the tibias. Clinically, it is common practice to place external fixator pins as far as possible outside the planned incision site for definitive fracture fixation. Thus, we also hypothesized that the presence of a bicortical pin-site defect and its proximity to the plate would alter the torsional strength of the tibia specimens, and that the distal pin-site defect’s location farthest from the plate would exhibit greater strength, but this did not occur. Although other studies have shown that the presence of bicortical defects decreases the strength of long bones, we were unable to quantify this decrease because the 2 intact groups of composites, plated and unplated, survived failure testing.

This study had several limitations, first being the use of composite tibias as opposed to human cadaver bone. Although fourth-generation composite bone models have been validated as a suitable and accurate biomechanical substitute for cadaver specimens,¹⁴ anatomical variations in cadaver tibias may transfer forces differently through plates, screws, and distal pin sites. In order to test plated specimens against the unplated controls, we did not simulate a mid-shaft fracture in any of the tibias. The pin-site defects were intended to reflect the mechanical effects of bicortical defects immediately after pin removal and in the absence of any degree of bone healing. Finally, this study focused on pin-site defects that were distal to a midshaft plate and that may not represent the effects of bicortical pin-site defects proximal to the plate.

Given the results of this biomechanical study in composite tibias, varying the proximity of a bicortical defect to a plate does not affect the torsional stiffness or torsional failure strength of the bone. Placement of an intended bicortical defect should be based on considerations other than the potential for creating a distal stress riser after definitive fracture management.

Am J Orthop. 2017;46(2):E108-E111. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• The location of a bicortical defect in proximity to a tibia plate does not appear to affect the torsional stiffness or torsional failure strength of the bone.

• External fixator pin placement should be based on considerations other than the potential for creating a distal stress riser after definitive fracture management.

A stress riser in cortical bone may be considered any abrupt change in the contour or consistency of the hollow structure, such as a surface defect, that not only weakens the bone but concentrates stresses at that transition point.¹ A cortical defect that is 20% of the bone diameter is associated with a 34% decrease in torsional strength, thus representing a “stress riser.”² High-energy and complex tibia fractures are often provisionally stabilized with external fixation that gives the soft tissues time to recover before definitive fracture fixation. Pin diameter for a medium-size tibia external fixator typically is 5.0 mm, resulting in a 10-mm defect in bicortical placement. Therefore, any tibia with a diameter of <50 mm is at risk for a stress riser fracture.

Although it had been established that sizable cortical defects can decrease the torsional strength of long bone,² the effect of a plate in close proximity to a defect secondary to an empty external-fixator pin site on torsional strength has not been determined. We conducted a study to evaluate this effect. The null hypothesis was there would be no difference in tibia torsional strength attributable to varying the proximity of a tibia midshaft plate to a 5.0-mm bicortical defect.

Methods

Forty fourth-generation, medium-size left composite tibias (Pacific Research Laboratories) were divided into 8 groups of 5 bones (Figure 1).

Torsion testing to failure was performed for all specimens in a manner similar to that described by Gardner and colleagues.³ Impression molds for the composite tibia constructed from polymethylmethacrylate encased the superior and distal ends, leaving 25.5 cm of exposed midshaft. This allowed the composites to be rigidly clamped into a materials testing system (858 Mini-Bionix; MTS) equipped with a 100.0-Nm torsional load cell (Figure 2).

Results

Graphical results for torsional stiffness are presented in Figure 3. R² for all stiffness calculations was >0.99.

Discussion

Many tibia fractures require provisional stabilization with an external fixator that spans the knee, because of the high-energy nature of the injury or other, higher-priority polytrauma concerns. When the patient or injury is suitable for definitive fixation, the external fixator typically is removed in favor of internal fixation with a plate and screws. Depending on the nature and location of the fracture and the subsequent plate, the empty cortical pin-site defects, often lying at varying distances from the distal end of the plate, can potentially serve as stress risers for fracture.⁴

Other studies have evaluated long-bone cortical defects biomechanically^1,2,4 and clinically,^5-7 and multiple studies have been conducted on the effects of plates on long-bone strength for fracture stabilization.^8-13 The present study evaluated the torsional strength of long bones in the presence of a bicortical defect and the proximity of the defect to a plate. There were no differences in stiffness or failure load between any of the groups of plated and unplated fourth-generation composite tibias tested to failure in torsion with varying distal bicortical defects. Hypothetically, one would expect the torsional stiffness of these specimens to increase with the mere addition of a metallic diaphyseal plate. However, this study demonstrated that the addition of a plate did not affect the torsional stiffness or strength of the tibias. Clinically, it is common practice to place external fixator pins as far as possible outside the planned incision site for definitive fracture fixation. Thus, we also hypothesized that the presence of a bicortical pin-site defect and its proximity to the plate would alter the torsional strength of the tibia specimens, and that the distal pin-site defect’s location farthest from the plate would exhibit greater strength, but this did not occur. Although other studies have shown that the presence of bicortical defects decreases the strength of long bones, we were unable to quantify this decrease because the 2 intact groups of composites, plated and unplated, survived failure testing.

This study had several limitations, first being the use of composite tibias as opposed to human cadaver bone. Although fourth-generation composite bone models have been validated as a suitable and accurate biomechanical substitute for cadaver specimens,¹⁴ anatomical variations in cadaver tibias may transfer forces differently through plates, screws, and distal pin sites. In order to test plated specimens against the unplated controls, we did not simulate a mid-shaft fracture in any of the tibias. The pin-site defects were intended to reflect the mechanical effects of bicortical defects immediately after pin removal and in the absence of any degree of bone healing. Finally, this study focused on pin-site defects that were distal to a midshaft plate and that may not represent the effects of bicortical pin-site defects proximal to the plate.

Given the results of this biomechanical study in composite tibias, varying the proximity of a bicortical defect to a plate does not affect the torsional stiffness or torsional failure strength of the bone. Placement of an intended bicortical defect should be based on considerations other than the potential for creating a distal stress riser after definitive fracture management.

Am J Orthop. 2017;46(2):E108-E111. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• The location of a bicortical defect in proximity to a tibia plate does not appear to affect the torsional stiffness or torsional failure strength of the bone.

• External fixator pin placement should be based on considerations other than the potential for creating a distal stress riser after definitive fracture management.

A stress riser in cortical bone may be considered any abrupt change in the contour or consistency of the hollow structure, such as a surface defect, that not only weakens the bone but concentrates stresses at that transition point.¹ A cortical defect that is 20% of the bone diameter is associated with a 34% decrease in torsional strength, thus representing a “stress riser.”² High-energy and complex tibia fractures are often provisionally stabilized with external fixation that gives the soft tissues time to recover before definitive fracture fixation. Pin diameter for a medium-size tibia external fixator typically is 5.0 mm, resulting in a 10-mm defect in bicortical placement. Therefore, any tibia with a diameter of <50 mm is at risk for a stress riser fracture.

Although it had been established that sizable cortical defects can decrease the torsional strength of long bone,² the effect of a plate in close proximity to a defect secondary to an empty external-fixator pin site on torsional strength has not been determined. We conducted a study to evaluate this effect. The null hypothesis was there would be no difference in tibia torsional strength attributable to varying the proximity of a tibia midshaft plate to a 5.0-mm bicortical defect.

Methods

Forty fourth-generation, medium-size left composite tibias (Pacific Research Laboratories) were divided into 8 groups of 5 bones (Figure 1).

Torsion testing to failure was performed for all specimens in a manner similar to that described by Gardner and colleagues.³ Impression molds for the composite tibia constructed from polymethylmethacrylate encased the superior and distal ends, leaving 25.5 cm of exposed midshaft. This allowed the composites to be rigidly clamped into a materials testing system (858 Mini-Bionix; MTS) equipped with a 100.0-Nm torsional load cell (Figure 2).

Results

Graphical results for torsional stiffness are presented in Figure 3. R² for all stiffness calculations was >0.99.

Discussion

Many tibia fractures require provisional stabilization with an external fixator that spans the knee, because of the high-energy nature of the injury or other, higher-priority polytrauma concerns. When the patient or injury is suitable for definitive fixation, the external fixator typically is removed in favor of internal fixation with a plate and screws. Depending on the nature and location of the fracture and the subsequent plate, the empty cortical pin-site defects, often lying at varying distances from the distal end of the plate, can potentially serve as stress risers for fracture.⁴

Other studies have evaluated long-bone cortical defects biomechanically^1,2,4 and clinically,^5-7 and multiple studies have been conducted on the effects of plates on long-bone strength for fracture stabilization.^8-13 The present study evaluated the torsional strength of long bones in the presence of a bicortical defect and the proximity of the defect to a plate. There were no differences in stiffness or failure load between any of the groups of plated and unplated fourth-generation composite tibias tested to failure in torsion with varying distal bicortical defects. Hypothetically, one would expect the torsional stiffness of these specimens to increase with the mere addition of a metallic diaphyseal plate. However, this study demonstrated that the addition of a plate did not affect the torsional stiffness or strength of the tibias. Clinically, it is common practice to place external fixator pins as far as possible outside the planned incision site for definitive fracture fixation. Thus, we also hypothesized that the presence of a bicortical pin-site defect and its proximity to the plate would alter the torsional strength of the tibia specimens, and that the distal pin-site defect’s location farthest from the plate would exhibit greater strength, but this did not occur. Although other studies have shown that the presence of bicortical defects decreases the strength of long bones, we were unable to quantify this decrease because the 2 intact groups of composites, plated and unplated, survived failure testing.

This study had several limitations, first being the use of composite tibias as opposed to human cadaver bone. Although fourth-generation composite bone models have been validated as a suitable and accurate biomechanical substitute for cadaver specimens,¹⁴ anatomical variations in cadaver tibias may transfer forces differently through plates, screws, and distal pin sites. In order to test plated specimens against the unplated controls, we did not simulate a mid-shaft fracture in any of the tibias. The pin-site defects were intended to reflect the mechanical effects of bicortical defects immediately after pin removal and in the absence of any degree of bone healing. Finally, this study focused on pin-site defects that were distal to a midshaft plate and that may not represent the effects of bicortical pin-site defects proximal to the plate.

Given the results of this biomechanical study in composite tibias, varying the proximity of a bicortical defect to a plate does not affect the torsional stiffness or torsional failure strength of the bone. Placement of an intended bicortical defect should be based on considerations other than the potential for creating a distal stress riser after definitive fracture management.

Am J Orthop. 2017;46(2):E108-E111. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

The Onstep technique for inguinal hernia repair is associated with a lower incidence of postoperative pain during sexual activity than the Lichtenstein surgical technique, according to a paper published online in Surgery.

This study was a part of the Onli trial, the objective of which was to evaluate chronic pain and sexual dysfunction after inguinal hernia repair involving mesh fixation with sutures (Lichtenstein), compared with no mesh fixation (Onstep). The investigators reported the findings of a large study: 20.8% of inguinal repair patients experienced pain during sexual activity 1.4-1.7 years after their operation (Pain. 2006;122:258-63).

ChesiireCat/Thinkstock

The Onstep technique for inguinal hernia repair is associated with a lower incidence of postoperative pain during sexual activity than the Lichtenstein surgical technique, according to a paper published online in Surgery.

This study was a part of the Onli trial, the objective of which was to evaluate chronic pain and sexual dysfunction after inguinal hernia repair involving mesh fixation with sutures (Lichtenstein), compared with no mesh fixation (Onstep). The investigators reported the findings of a large study: 20.8% of inguinal repair patients experienced pain during sexual activity 1.4-1.7 years after their operation (Pain. 2006;122:258-63).

ChesiireCat/Thinkstock

The Onstep technique for inguinal hernia repair is associated with a lower incidence of postoperative pain during sexual activity than the Lichtenstein surgical technique, according to a paper published online in Surgery.

This study was a part of the Onli trial, the objective of which was to evaluate chronic pain and sexual dysfunction after inguinal hernia repair involving mesh fixation with sutures (Lichtenstein), compared with no mesh fixation (Onstep). The investigators reported the findings of a large study: 20.8% of inguinal repair patients experienced pain during sexual activity 1.4-1.7 years after their operation (Pain. 2006;122:258-63).

ChesiireCat/Thinkstock

ORLANDO – Early evidence suggests that OpenNotes is helping to engage patients and improve health outcomes while not creating undue burden for physicians.

A 2010 pilot project at Beth Israel Deaconess Medical Center in Boston, Geisinger Health System in Pennsylvania, and Harborview Medical Center in Seattle tested OpenNotes, a program that allows patients to see the entirety of a physician’s notes within their medical record and not just a summarized version.

Homer Chin, MD, of the department of medical informatics and outcomes research at Oregon Health & Science University, Portland, an associate with the OpenNotes Program, and physician champion for the Northwest OpenNotes Consortium, noted that a survey of the 105 primary care physicians participating in the pilot revealed they were apprehensive when they heard their visit notes would be completely available to patients.

Prior to the launch of the pilot, 24% of physicians expected significantly longer visits because of the availability of OpenNotes, 42% said they expected to spend more time addressing patient questions outside of visits, and 39% said they expected to spend more time writing/editing/dictating notes, Dr. Chin said at the annual meeting of the Healthcare Information and Management Systems Society.

Their concerns never quite materialized.

According to a survey of the participating physicians after the yearlong pilot, only 2% reported visits took significantly longer, 3% said they spent more time addressing patient questions outside of visits, and 11% said they spent more time writing/editing/dictating notes.

With regard to writing notes, “what we are finding is that most physicians are saying they are changing the way they write the note a little bit, but it is not taking more time,” Dr. Chin said. “They are just watching for certain terms and writing them in a different way, but it is not necessarily taking more time.”

More than 70% of patients who participated in the trial reported they are taking better care of themselves, more than 77% said they have a better understanding of their medical condition, more than 69% said they are better prepared for visits and more than 60% said they are more adherent to their prescription medication regimens.

Importantly, 85% said the availability of OpenNotes would affect their future choice of providers.

Dr. Chin also discussed the results of a survey of patients using OpenNotes in the Virginia Commonwealth University Health System in Richmond, noting that of roughly 420 respondents, 70% said their contact with their providers did not change, with nearly 20% saying they were contacting their provider less. Just over 40% said that reading their notes made them less worried about something health related, while a little more than 50% said there was no change. Nearly 85% said they thought seeing the notes helped them take better care of themselves. Nearly 90% of patients said that they understood some or all of their doctors’ notes.

Gregory Twachtman/Frontline Medical News

gtwachtman@frontlinemedcom.com

ORLANDO – Early evidence suggests that OpenNotes is helping to engage patients and improve health outcomes while not creating undue burden for physicians.

A 2010 pilot project at Beth Israel Deaconess Medical Center in Boston, Geisinger Health System in Pennsylvania, and Harborview Medical Center in Seattle tested OpenNotes, a program that allows patients to see the entirety of a physician’s notes within their medical record and not just a summarized version.

Homer Chin, MD, of the department of medical informatics and outcomes research at Oregon Health & Science University, Portland, an associate with the OpenNotes Program, and physician champion for the Northwest OpenNotes Consortium, noted that a survey of the 105 primary care physicians participating in the pilot revealed they were apprehensive when they heard their visit notes would be completely available to patients.

Prior to the launch of the pilot, 24% of physicians expected significantly longer visits because of the availability of OpenNotes, 42% said they expected to spend more time addressing patient questions outside of visits, and 39% said they expected to spend more time writing/editing/dictating notes, Dr. Chin said at the annual meeting of the Healthcare Information and Management Systems Society.

Their concerns never quite materialized.

According to a survey of the participating physicians after the yearlong pilot, only 2% reported visits took significantly longer, 3% said they spent more time addressing patient questions outside of visits, and 11% said they spent more time writing/editing/dictating notes.

With regard to writing notes, “what we are finding is that most physicians are saying they are changing the way they write the note a little bit, but it is not taking more time,” Dr. Chin said. “They are just watching for certain terms and writing them in a different way, but it is not necessarily taking more time.”

More than 70% of patients who participated in the trial reported they are taking better care of themselves, more than 77% said they have a better understanding of their medical condition, more than 69% said they are better prepared for visits and more than 60% said they are more adherent to their prescription medication regimens.

Importantly, 85% said the availability of OpenNotes would affect their future choice of providers.

Dr. Chin also discussed the results of a survey of patients using OpenNotes in the Virginia Commonwealth University Health System in Richmond, noting that of roughly 420 respondents, 70% said their contact with their providers did not change, with nearly 20% saying they were contacting their provider less. Just over 40% said that reading their notes made them less worried about something health related, while a little more than 50% said there was no change. Nearly 85% said they thought seeing the notes helped them take better care of themselves. Nearly 90% of patients said that they understood some or all of their doctors’ notes.

Gregory Twachtman/Frontline Medical News

gtwachtman@frontlinemedcom.com

ORLANDO – Early evidence suggests that OpenNotes is helping to engage patients and improve health outcomes while not creating undue burden for physicians.

A 2010 pilot project at Beth Israel Deaconess Medical Center in Boston, Geisinger Health System in Pennsylvania, and Harborview Medical Center in Seattle tested OpenNotes, a program that allows patients to see the entirety of a physician’s notes within their medical record and not just a summarized version.

Homer Chin, MD, of the department of medical informatics and outcomes research at Oregon Health & Science University, Portland, an associate with the OpenNotes Program, and physician champion for the Northwest OpenNotes Consortium, noted that a survey of the 105 primary care physicians participating in the pilot revealed they were apprehensive when they heard their visit notes would be completely available to patients.

Prior to the launch of the pilot, 24% of physicians expected significantly longer visits because of the availability of OpenNotes, 42% said they expected to spend more time addressing patient questions outside of visits, and 39% said they expected to spend more time writing/editing/dictating notes, Dr. Chin said at the annual meeting of the Healthcare Information and Management Systems Society.

Their concerns never quite materialized.

According to a survey of the participating physicians after the yearlong pilot, only 2% reported visits took significantly longer, 3% said they spent more time addressing patient questions outside of visits, and 11% said they spent more time writing/editing/dictating notes.

With regard to writing notes, “what we are finding is that most physicians are saying they are changing the way they write the note a little bit, but it is not taking more time,” Dr. Chin said. “They are just watching for certain terms and writing them in a different way, but it is not necessarily taking more time.”

More than 70% of patients who participated in the trial reported they are taking better care of themselves, more than 77% said they have a better understanding of their medical condition, more than 69% said they are better prepared for visits and more than 60% said they are more adherent to their prescription medication regimens.

Importantly, 85% said the availability of OpenNotes would affect their future choice of providers.

Dr. Chin also discussed the results of a survey of patients using OpenNotes in the Virginia Commonwealth University Health System in Richmond, noting that of roughly 420 respondents, 70% said their contact with their providers did not change, with nearly 20% saying they were contacting their provider less. Just over 40% said that reading their notes made them less worried about something health related, while a little more than 50% said there was no change. Nearly 85% said they thought seeing the notes helped them take better care of themselves. Nearly 90% of patients said that they understood some or all of their doctors’ notes.

Gregory Twachtman/Frontline Medical News

gtwachtman@frontlinemedcom.com

NATIONAL HARBOR, MD. – Patient-reported outcomes from a prospective cohort study of minimally invasive versus open surgery for women with endometrial cancer showed that the disability from open surgery persisted for longer than had previously been recognized. Further, for a subset of patients, impairment in sexual functioning was significant, and persistent, regardless of the type of surgery.

At 3 weeks after surgery, patients who had open surgery had greater pain as measured by the Brief Pain Inventory (minimally important difference greater than 1, P = .0004). By 3 months post surgery, responses on the Functional Assessment of Cancer Therapy–General were still significantly lower for the open-surgery group, compared with the minimally invasive group (P = .0011).

Although patients’ pain and overall state of health were better at 3 weeks post surgery, regardless of whether women had open, laparoscopic, or robotic surgery, the reduced overall quality of life experienced by patients who had open surgery persisted.

“What was a bit different from other studies … is that we found that this is maintained even at 3 months, and it was clinically and statistically different,” Sarah Ferguson, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology. “So that was really, I think, an interesting finding, that this doesn’t just impact the very short term. Three months is a fairly long time after a primary surgery, and [it’s] important for women to know this.”

Dr. Ferguson reported having no conflicts of interest.

koakes@frontlinemedcom.com
On Twitter @karioakes

NATIONAL HARBOR, MD. – Patient-reported outcomes from a prospective cohort study of minimally invasive versus open surgery for women with endometrial cancer showed that the disability from open surgery persisted for longer than had previously been recognized. Further, for a subset of patients, impairment in sexual functioning was significant, and persistent, regardless of the type of surgery.

At 3 weeks after surgery, patients who had open surgery had greater pain as measured by the Brief Pain Inventory (minimally important difference greater than 1, P = .0004). By 3 months post surgery, responses on the Functional Assessment of Cancer Therapy–General were still significantly lower for the open-surgery group, compared with the minimally invasive group (P = .0011).

Although patients’ pain and overall state of health were better at 3 weeks post surgery, regardless of whether women had open, laparoscopic, or robotic surgery, the reduced overall quality of life experienced by patients who had open surgery persisted.

“What was a bit different from other studies … is that we found that this is maintained even at 3 months, and it was clinically and statistically different,” Sarah Ferguson, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology. “So that was really, I think, an interesting finding, that this doesn’t just impact the very short term. Three months is a fairly long time after a primary surgery, and [it’s] important for women to know this.”

Dr. Ferguson reported having no conflicts of interest.

koakes@frontlinemedcom.com
On Twitter @karioakes

NATIONAL HARBOR, MD. – Patient-reported outcomes from a prospective cohort study of minimally invasive versus open surgery for women with endometrial cancer showed that the disability from open surgery persisted for longer than had previously been recognized. Further, for a subset of patients, impairment in sexual functioning was significant, and persistent, regardless of the type of surgery.

At 3 weeks after surgery, patients who had open surgery had greater pain as measured by the Brief Pain Inventory (minimally important difference greater than 1, P = .0004). By 3 months post surgery, responses on the Functional Assessment of Cancer Therapy–General were still significantly lower for the open-surgery group, compared with the minimally invasive group (P = .0011).

Although patients’ pain and overall state of health were better at 3 weeks post surgery, regardless of whether women had open, laparoscopic, or robotic surgery, the reduced overall quality of life experienced by patients who had open surgery persisted.

“What was a bit different from other studies … is that we found that this is maintained even at 3 months, and it was clinically and statistically different,” Sarah Ferguson, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology. “So that was really, I think, an interesting finding, that this doesn’t just impact the very short term. Three months is a fairly long time after a primary surgery, and [it’s] important for women to know this.”

Dr. Ferguson reported having no conflicts of interest.

koakes@frontlinemedcom.com
On Twitter @karioakes

The course of chronic psychiatric conditions, such as schizophrenia, differs from chronic medical conditions, such as diabetes. Some patients with chronic psychiatric conditions achieve remission and become symptom-free, while others continue to have lingering signs of disease for life.

Residual symptoms of schizophrenia are not fully defined in the literature, which poses a challenge because they are central in the overall treatment of schizophrenia spectrum disorders.¹ During this phase of schizophrenia, patients continue to have symptoms after psychosis has subsided. These patients might continue to have negative symptoms such as social and emotional withdrawal and low energy. Although frank psychotic behavior has disappeared, the patient might continue to hold strange beliefs. Pharmacotherapy is the primary treatment option for psychiatric conditions, but the psychosocial aspect may have greater importance when treating residual symptoms and patients with chronic psychiatric illness.²

A naturalistic study in Germany evaluated the occurrence and characteristics of residual symptoms in patients with schizophrenia.³ The authors used a Positive and Negative Syndrome Scale symptom severity score >1 for those purposes, which is possibly a stringent criterion to define residual symptoms. This multicenter study enrolled 399 individuals age 18 to 65 with a DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, delusional disorder, or schizoaffective disorder.³ Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms. Therefore, residual symptoms were highly prevalent in remitted patients. The most frequent residual symptoms were:

• blunted affect
• conceptual disorganization
• passive or apathetic social withdrawal
• emotional withdrawal
• lack of judgment and insight
• poor attention
• somatic concern
• difficulty with abstract thinking
• anxiety
• poor rapport.³

Of note, positive symptoms, such as delusions and hallucinatory behavior, were found in remitted patients at discharge (17% and 10%, respectively). The study concluded that the severity of residual symptoms was associated with relapse risk and had an overall negative impact on the outcome of patients with schizophrenia.³ The study noted that residual symptoms may be greater in number or volume than negative symptoms and questioned the origins of residual symptoms because most were present at baseline in more than two-third of patients.

Patients with residual symptoms of schizophrenia usually are older and therefore present specific management challenges for clinicians. Changes associated with aging, such as medical problems, cognitive deficits, and lack of social support, could create new care needs for this patient population. Although the biopsycho­social model used to treat chronic psychiatric conditions, especially schizophrenia, is preferred, older schizophrenia patients with residual symptoms often need more psychosocial interventions compared with young adults with schizophrenia.

Managing residual symptoms in schizophrenia

Few studies are devoted to pharmacological treatment of older adults with schizophrenia, likely because pharmacotherapy for older patients with schizophrenia can be challenging. Evidence-based treatment is based primarily on findings from younger patients who survived into later life. Clinicians often use the adage of geriatric psychiatry, “start low, go slow,” because older patients are susceptible to adverse effects associated with psychiatric medications, including cardiovascular, metabolic, anticholinergic, and extrapyramidal effects, orthostasis, sedation, falls, and neuroleptic malignant syndrome.

Older patients with schizophrenia are at an increased risk for extrapyramidal symptoms (EPS) and anticholinergic adverse effects, perhaps because of degeneration of dopaminergic and cholinergic neurons.⁴ Lowering the anticholinergic load by discontinuing or reducing the dosage of medications with anticholinergic properties, when possible, is a key principle when treating these patients. This tactic could help improve cognition and quality of life by decreasing the risk of other anticholinergic adverse effects, including delirium, constipation, urinary retention, and blurred vision.

Patients treated with typical antipsychotics are nearly twice as likely to develop tardive dyskinesia compared with those receiving atypical antipsychotics.⁵ Sedation, orthostatic hypotension, and anticholinergic effects can cause cognitive clouding, worsen cognitive impairment, and increase the risk of falls, especially in older patients.⁶ Clozapine and olanzapine have the strongest association with clinically significant weight gain and treatment-induced type 2 diabetes mellitus.⁷

The appropriate starting dosage of antipsychotics in older patients with schizophrenia is one-fourth of the starting adult dosage. Total daily maintenance dosages may be one-third to one-half of the adult dosage.⁶ Consensus guidelines for dosing atypical antipsychotics for older patients with schizophrenia are as shown in Table 1.⁸

Another point to consider when treating residual symptoms in patients with schizophrenia is to not discontinue antipsychotic medications. Relapse rates for these patients can occur up to 5 times higher than for those who continue treatment.¹⁰ A way to address this problem could be the use of depot antipsychotic medications, but there are no set recommendations for the use of long-acting injectable antipsychotics in older patients. These medications should be used with caution and at lowest effective dosages to offset potential adverse effects.

With the introduction of typical and atypical antipsychotics, the use of electroconvulsive therapy in older patients with schizophrenia has declined. In a 2009 meta-analysis of studies that included patients with refractory schizophrenia and repetitive transcranial magnetic stimulation (rTMS), results revealed a mixed effect size for controlled and uncontrolled studies. The authors stated the need for further controlled trials, assessing the efficacy of rTMS on negative and positive symptoms of schizophrenia.¹¹

Psychotherapy and psychosocial interventions

Patients with schizophrenia who have persistent psychotic symptoms while receiving adequate pharmacotherapy should be offered adjunctive cognitive, behaviorally oriented psychotherapy to reduce symptom severity. Cognitive-behavioral therapy (CBT) has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve patients’ mental state.¹² Amotivation and lack of insight can be particularly troublesome, which CBT can help address.¹² Psychoeducation can:

• empower patients to understand their illness
• help them cope with their disease
• be aware of symptom relapse
• seek help sooner rather than later.

Also, counseling and supportive therapy are recommended by the American Psychiatric Association guidelines. Providers should involve family and loved ones in this discussion, so that they can help collaborate with care and provide a supportive and non-judgmental environment.

Older patients with residual symptoms of schizophrenia are less likely to have completed their education, pursued a career, or developed long-lasting relationships. Family members who were their support system earlier in life, such as parents, often are unable to provide care for them by the time patients with schizophrenia become older. These patients also are less likely to get married or have children, meaning that they are more likely to live alone. The advent of the interdisciplinary team, integration of several therapeutic modalities, the provision of case managers, and assertive community treatment (ACT) teams has provided help with social support, relapses, and hospitalizations, for older patients with schizophrenia.¹³ Key elements of ACT include:

• a multidisciplinary team, including a medication prescriber
• a shared caseload among team members
• direct service provision by team members
• frequent patient contact
• low patient to staff ratios
• outreach to patients in the community.

Medical care

Patients with schizophrenia are at higher risk for several comorbid medical conditions, such as diabetes, coronary artery disease, and digestive and liver disorders, compared with individuals without schizophrenia. This risk is associated with numerous factors, including sedentary lifestyle, high rates of lifetime cigarette use (70% to 80% of schizophrenia outpatients age <67 smoke), poor self-management skills, frequent homelessness, and unhealthy diet.

Although substantial attention is devoted to the psychiatric and behavioral management of patients with schizophrenia, many barriers impede the detection and treatment of their medical conditions. Patients with schizophrenia could experience delays in diagnosing a medical disorder, leading to more acute comorbidities at the time of diagnosis and premature mortality. Studies have confirmed that cardiovascular diseases are the leading cause of premature death among psychiatric patients in the United States.¹⁴ Key risk factors include smoking, obesity, hypertension, dyslipidemia, diabetes, and lack of physical activity, all of which are more common among patients with schizophrenia compared with the general population.¹⁵ In addition, antipsychotics are associated with adverse metabolic effects.¹⁶

What are realistic treatment goals to manage residual symptoms in schizophrenia?

We believe that because remission in schizophrenia has been defined consensually, the bar for treatment expectations is set higher than it was 20 years ago. There can be patient-, family-, and system-related variables affecting the feasibility of treating residual symptoms. Providers who treat patients with schizophrenia should consider the following treatment goals:

• Prevent relapse and acute psychiatric hospitalization
• Use evidence-based strategies to minimize or monitor adverse effects
• Monitor compliance and consider use of depot antipsychotics combined with patients’ preference
• Facilitate ongoing safety assessment, including suicide risk
• Monitor negative and cognitive symptoms in addition to positive symptoms, using evidence-based management
• Encourage collaboration of care with family, caretakers, and other members of the treatment team
• Empower patients by providing psycho­education and social skills training and assisting in their vocational rehabilitation 
• Educate the patient and family about healthy lifestyle interventions and medical comorbidities common with schizophrenia
• Perform baseline screening and follow-up for early detection and treatment of medical comorbidities in patients with schizophrenia
• Improve functional status and quality of life.

In addition to meeting these treatment goals, a measurement-based method can be implemented to monitor improvement and status of the independent treatment domains. A collection of rating instruments can be found in Table 2.^17-30

Summing up

The clinical presentation of patients with residual symptoms of schizophrenia differs from that of other patients with schizophrenia. Our understanding of residual symptoms in schizophrenia has come a long way in the last decade; however, we are still far from pinning the complex nature of these symptoms, let alone their management. Given the risk of morbidity and disability, there clearly is a need for further investigation and investment of time and resources to support developing novel pharmacological treatment options to manage residual symptoms in patients with schizophrenia.

Because patients with residual symptoms of schizophrenia usually are older, psychiatrists should be responsible for implementing necessary screening assessments and should closely collaborate with primary care practitioners and other specialists, and when necessary, treat comorbid medical conditions. The importance of educating patients, their families, and the treatment team cannot be overlooked. Further, psychiatric treatment facilities should offer and promote healthy lifestyle interventions.

The course of chronic psychiatric conditions, such as schizophrenia, differs from chronic medical conditions, such as diabetes. Some patients with chronic psychiatric conditions achieve remission and become symptom-free, while others continue to have lingering signs of disease for life.

Residual symptoms of schizophrenia are not fully defined in the literature, which poses a challenge because they are central in the overall treatment of schizophrenia spectrum disorders.¹ During this phase of schizophrenia, patients continue to have symptoms after psychosis has subsided. These patients might continue to have negative symptoms such as social and emotional withdrawal and low energy. Although frank psychotic behavior has disappeared, the patient might continue to hold strange beliefs. Pharmacotherapy is the primary treatment option for psychiatric conditions, but the psychosocial aspect may have greater importance when treating residual symptoms and patients with chronic psychiatric illness.²

A naturalistic study in Germany evaluated the occurrence and characteristics of residual symptoms in patients with schizophrenia.³ The authors used a Positive and Negative Syndrome Scale symptom severity score >1 for those purposes, which is possibly a stringent criterion to define residual symptoms. This multicenter study enrolled 399 individuals age 18 to 65 with a DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, delusional disorder, or schizoaffective disorder.³ Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms. Therefore, residual symptoms were highly prevalent in remitted patients. The most frequent residual symptoms were:

• blunted affect
• conceptual disorganization
• passive or apathetic social withdrawal
• emotional withdrawal
• lack of judgment and insight
• poor attention
• somatic concern
• difficulty with abstract thinking
• anxiety
• poor rapport.³

Of note, positive symptoms, such as delusions and hallucinatory behavior, were found in remitted patients at discharge (17% and 10%, respectively). The study concluded that the severity of residual symptoms was associated with relapse risk and had an overall negative impact on the outcome of patients with schizophrenia.³ The study noted that residual symptoms may be greater in number or volume than negative symptoms and questioned the origins of residual symptoms because most were present at baseline in more than two-third of patients.

Patients with residual symptoms of schizophrenia usually are older and therefore present specific management challenges for clinicians. Changes associated with aging, such as medical problems, cognitive deficits, and lack of social support, could create new care needs for this patient population. Although the biopsycho­social model used to treat chronic psychiatric conditions, especially schizophrenia, is preferred, older schizophrenia patients with residual symptoms often need more psychosocial interventions compared with young adults with schizophrenia.

Managing residual symptoms in schizophrenia

Few studies are devoted to pharmacological treatment of older adults with schizophrenia, likely because pharmacotherapy for older patients with schizophrenia can be challenging. Evidence-based treatment is based primarily on findings from younger patients who survived into later life. Clinicians often use the adage of geriatric psychiatry, “start low, go slow,” because older patients are susceptible to adverse effects associated with psychiatric medications, including cardiovascular, metabolic, anticholinergic, and extrapyramidal effects, orthostasis, sedation, falls, and neuroleptic malignant syndrome.

Older patients with schizophrenia are at an increased risk for extrapyramidal symptoms (EPS) and anticholinergic adverse effects, perhaps because of degeneration of dopaminergic and cholinergic neurons.⁴ Lowering the anticholinergic load by discontinuing or reducing the dosage of medications with anticholinergic properties, when possible, is a key principle when treating these patients. This tactic could help improve cognition and quality of life by decreasing the risk of other anticholinergic adverse effects, including delirium, constipation, urinary retention, and blurred vision.

Patients treated with typical antipsychotics are nearly twice as likely to develop tardive dyskinesia compared with those receiving atypical antipsychotics.⁵ Sedation, orthostatic hypotension, and anticholinergic effects can cause cognitive clouding, worsen cognitive impairment, and increase the risk of falls, especially in older patients.⁶ Clozapine and olanzapine have the strongest association with clinically significant weight gain and treatment-induced type 2 diabetes mellitus.⁷

The appropriate starting dosage of antipsychotics in older patients with schizophrenia is one-fourth of the starting adult dosage. Total daily maintenance dosages may be one-third to one-half of the adult dosage.⁶ Consensus guidelines for dosing atypical antipsychotics for older patients with schizophrenia are as shown in Table 1.⁸

Another point to consider when treating residual symptoms in patients with schizophrenia is to not discontinue antipsychotic medications. Relapse rates for these patients can occur up to 5 times higher than for those who continue treatment.¹⁰ A way to address this problem could be the use of depot antipsychotic medications, but there are no set recommendations for the use of long-acting injectable antipsychotics in older patients. These medications should be used with caution and at lowest effective dosages to offset potential adverse effects.

With the introduction of typical and atypical antipsychotics, the use of electroconvulsive therapy in older patients with schizophrenia has declined. In a 2009 meta-analysis of studies that included patients with refractory schizophrenia and repetitive transcranial magnetic stimulation (rTMS), results revealed a mixed effect size for controlled and uncontrolled studies. The authors stated the need for further controlled trials, assessing the efficacy of rTMS on negative and positive symptoms of schizophrenia.¹¹

Psychotherapy and psychosocial interventions

Patients with schizophrenia who have persistent psychotic symptoms while receiving adequate pharmacotherapy should be offered adjunctive cognitive, behaviorally oriented psychotherapy to reduce symptom severity. Cognitive-behavioral therapy (CBT) has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve patients’ mental state.¹² Amotivation and lack of insight can be particularly troublesome, which CBT can help address.¹² Psychoeducation can:

• empower patients to understand their illness
• help them cope with their disease
• be aware of symptom relapse
• seek help sooner rather than later.

Also, counseling and supportive therapy are recommended by the American Psychiatric Association guidelines. Providers should involve family and loved ones in this discussion, so that they can help collaborate with care and provide a supportive and non-judgmental environment.

Older patients with residual symptoms of schizophrenia are less likely to have completed their education, pursued a career, or developed long-lasting relationships. Family members who were their support system earlier in life, such as parents, often are unable to provide care for them by the time patients with schizophrenia become older. These patients also are less likely to get married or have children, meaning that they are more likely to live alone. The advent of the interdisciplinary team, integration of several therapeutic modalities, the provision of case managers, and assertive community treatment (ACT) teams has provided help with social support, relapses, and hospitalizations, for older patients with schizophrenia.¹³ Key elements of ACT include:

• a multidisciplinary team, including a medication prescriber
• a shared caseload among team members
• direct service provision by team members
• frequent patient contact
• low patient to staff ratios
• outreach to patients in the community.

Medical care

Patients with schizophrenia are at higher risk for several comorbid medical conditions, such as diabetes, coronary artery disease, and digestive and liver disorders, compared with individuals without schizophrenia. This risk is associated with numerous factors, including sedentary lifestyle, high rates of lifetime cigarette use (70% to 80% of schizophrenia outpatients age <67 smoke), poor self-management skills, frequent homelessness, and unhealthy diet.

Although substantial attention is devoted to the psychiatric and behavioral management of patients with schizophrenia, many barriers impede the detection and treatment of their medical conditions. Patients with schizophrenia could experience delays in diagnosing a medical disorder, leading to more acute comorbidities at the time of diagnosis and premature mortality. Studies have confirmed that cardiovascular diseases are the leading cause of premature death among psychiatric patients in the United States.¹⁴ Key risk factors include smoking, obesity, hypertension, dyslipidemia, diabetes, and lack of physical activity, all of which are more common among patients with schizophrenia compared with the general population.¹⁵ In addition, antipsychotics are associated with adverse metabolic effects.¹⁶

What are realistic treatment goals to manage residual symptoms in schizophrenia?

We believe that because remission in schizophrenia has been defined consensually, the bar for treatment expectations is set higher than it was 20 years ago. There can be patient-, family-, and system-related variables affecting the feasibility of treating residual symptoms. Providers who treat patients with schizophrenia should consider the following treatment goals:

• Prevent relapse and acute psychiatric hospitalization
• Use evidence-based strategies to minimize or monitor adverse effects
• Monitor compliance and consider use of depot antipsychotics combined with patients’ preference
• Facilitate ongoing safety assessment, including suicide risk
• Monitor negative and cognitive symptoms in addition to positive symptoms, using evidence-based management
• Encourage collaboration of care with family, caretakers, and other members of the treatment team
• Empower patients by providing psycho­education and social skills training and assisting in their vocational rehabilitation 
• Educate the patient and family about healthy lifestyle interventions and medical comorbidities common with schizophrenia
• Perform baseline screening and follow-up for early detection and treatment of medical comorbidities in patients with schizophrenia
• Improve functional status and quality of life.

In addition to meeting these treatment goals, a measurement-based method can be implemented to monitor improvement and status of the independent treatment domains. A collection of rating instruments can be found in Table 2.^17-30

Summing up

The clinical presentation of patients with residual symptoms of schizophrenia differs from that of other patients with schizophrenia. Our understanding of residual symptoms in schizophrenia has come a long way in the last decade; however, we are still far from pinning the complex nature of these symptoms, let alone their management. Given the risk of morbidity and disability, there clearly is a need for further investigation and investment of time and resources to support developing novel pharmacological treatment options to manage residual symptoms in patients with schizophrenia.

Because patients with residual symptoms of schizophrenia usually are older, psychiatrists should be responsible for implementing necessary screening assessments and should closely collaborate with primary care practitioners and other specialists, and when necessary, treat comorbid medical conditions. The importance of educating patients, their families, and the treatment team cannot be overlooked. Further, psychiatric treatment facilities should offer and promote healthy lifestyle interventions.

The course of chronic psychiatric conditions, such as schizophrenia, differs from chronic medical conditions, such as diabetes. Some patients with chronic psychiatric conditions achieve remission and become symptom-free, while others continue to have lingering signs of disease for life.

Residual symptoms of schizophrenia are not fully defined in the literature, which poses a challenge because they are central in the overall treatment of schizophrenia spectrum disorders.¹ During this phase of schizophrenia, patients continue to have symptoms after psychosis has subsided. These patients might continue to have negative symptoms such as social and emotional withdrawal and low energy. Although frank psychotic behavior has disappeared, the patient might continue to hold strange beliefs. Pharmacotherapy is the primary treatment option for psychiatric conditions, but the psychosocial aspect may have greater importance when treating residual symptoms and patients with chronic psychiatric illness.²

A naturalistic study in Germany evaluated the occurrence and characteristics of residual symptoms in patients with schizophrenia.³ The authors used a Positive and Negative Syndrome Scale symptom severity score >1 for those purposes, which is possibly a stringent criterion to define residual symptoms. This multicenter study enrolled 399 individuals age 18 to 65 with a DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, delusional disorder, or schizoaffective disorder.³ Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms. Therefore, residual symptoms were highly prevalent in remitted patients. The most frequent residual symptoms were:

• blunted affect
• conceptual disorganization
• passive or apathetic social withdrawal
• emotional withdrawal
• lack of judgment and insight
• poor attention
• somatic concern
• difficulty with abstract thinking
• anxiety
• poor rapport.³

Of note, positive symptoms, such as delusions and hallucinatory behavior, were found in remitted patients at discharge (17% and 10%, respectively). The study concluded that the severity of residual symptoms was associated with relapse risk and had an overall negative impact on the outcome of patients with schizophrenia.³ The study noted that residual symptoms may be greater in number or volume than negative symptoms and questioned the origins of residual symptoms because most were present at baseline in more than two-third of patients.

Patients with residual symptoms of schizophrenia usually are older and therefore present specific management challenges for clinicians. Changes associated with aging, such as medical problems, cognitive deficits, and lack of social support, could create new care needs for this patient population. Although the biopsycho­social model used to treat chronic psychiatric conditions, especially schizophrenia, is preferred, older schizophrenia patients with residual symptoms often need more psychosocial interventions compared with young adults with schizophrenia.

Managing residual symptoms in schizophrenia

Few studies are devoted to pharmacological treatment of older adults with schizophrenia, likely because pharmacotherapy for older patients with schizophrenia can be challenging. Evidence-based treatment is based primarily on findings from younger patients who survived into later life. Clinicians often use the adage of geriatric psychiatry, “start low, go slow,” because older patients are susceptible to adverse effects associated with psychiatric medications, including cardiovascular, metabolic, anticholinergic, and extrapyramidal effects, orthostasis, sedation, falls, and neuroleptic malignant syndrome.

Older patients with schizophrenia are at an increased risk for extrapyramidal symptoms (EPS) and anticholinergic adverse effects, perhaps because of degeneration of dopaminergic and cholinergic neurons.⁴ Lowering the anticholinergic load by discontinuing or reducing the dosage of medications with anticholinergic properties, when possible, is a key principle when treating these patients. This tactic could help improve cognition and quality of life by decreasing the risk of other anticholinergic adverse effects, including delirium, constipation, urinary retention, and blurred vision.

Patients treated with typical antipsychotics are nearly twice as likely to develop tardive dyskinesia compared with those receiving atypical antipsychotics.⁵ Sedation, orthostatic hypotension, and anticholinergic effects can cause cognitive clouding, worsen cognitive impairment, and increase the risk of falls, especially in older patients.⁶ Clozapine and olanzapine have the strongest association with clinically significant weight gain and treatment-induced type 2 diabetes mellitus.⁷

The appropriate starting dosage of antipsychotics in older patients with schizophrenia is one-fourth of the starting adult dosage. Total daily maintenance dosages may be one-third to one-half of the adult dosage.⁶ Consensus guidelines for dosing atypical antipsychotics for older patients with schizophrenia are as shown in Table 1.⁸

Another point to consider when treating residual symptoms in patients with schizophrenia is to not discontinue antipsychotic medications. Relapse rates for these patients can occur up to 5 times higher than for those who continue treatment.¹⁰ A way to address this problem could be the use of depot antipsychotic medications, but there are no set recommendations for the use of long-acting injectable antipsychotics in older patients. These medications should be used with caution and at lowest effective dosages to offset potential adverse effects.

With the introduction of typical and atypical antipsychotics, the use of electroconvulsive therapy in older patients with schizophrenia has declined. In a 2009 meta-analysis of studies that included patients with refractory schizophrenia and repetitive transcranial magnetic stimulation (rTMS), results revealed a mixed effect size for controlled and uncontrolled studies. The authors stated the need for further controlled trials, assessing the efficacy of rTMS on negative and positive symptoms of schizophrenia.¹¹

Psychotherapy and psychosocial interventions

Patients with schizophrenia who have persistent psychotic symptoms while receiving adequate pharmacotherapy should be offered adjunctive cognitive, behaviorally oriented psychotherapy to reduce symptom severity. Cognitive-behavioral therapy (CBT) has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve patients’ mental state.¹² Amotivation and lack of insight can be particularly troublesome, which CBT can help address.¹² Psychoeducation can:

• empower patients to understand their illness
• help them cope with their disease
• be aware of symptom relapse
• seek help sooner rather than later.

Also, counseling and supportive therapy are recommended by the American Psychiatric Association guidelines. Providers should involve family and loved ones in this discussion, so that they can help collaborate with care and provide a supportive and non-judgmental environment.

Older patients with residual symptoms of schizophrenia are less likely to have completed their education, pursued a career, or developed long-lasting relationships. Family members who were their support system earlier in life, such as parents, often are unable to provide care for them by the time patients with schizophrenia become older. These patients also are less likely to get married or have children, meaning that they are more likely to live alone. The advent of the interdisciplinary team, integration of several therapeutic modalities, the provision of case managers, and assertive community treatment (ACT) teams has provided help with social support, relapses, and hospitalizations, for older patients with schizophrenia.¹³ Key elements of ACT include:

• a multidisciplinary team, including a medication prescriber
• a shared caseload among team members
• direct service provision by team members
• frequent patient contact
• low patient to staff ratios
• outreach to patients in the community.

Medical care

Patients with schizophrenia are at higher risk for several comorbid medical conditions, such as diabetes, coronary artery disease, and digestive and liver disorders, compared with individuals without schizophrenia. This risk is associated with numerous factors, including sedentary lifestyle, high rates of lifetime cigarette use (70% to 80% of schizophrenia outpatients age <67 smoke), poor self-management skills, frequent homelessness, and unhealthy diet.

Although substantial attention is devoted to the psychiatric and behavioral management of patients with schizophrenia, many barriers impede the detection and treatment of their medical conditions. Patients with schizophrenia could experience delays in diagnosing a medical disorder, leading to more acute comorbidities at the time of diagnosis and premature mortality. Studies have confirmed that cardiovascular diseases are the leading cause of premature death among psychiatric patients in the United States.¹⁴ Key risk factors include smoking, obesity, hypertension, dyslipidemia, diabetes, and lack of physical activity, all of which are more common among patients with schizophrenia compared with the general population.¹⁵ In addition, antipsychotics are associated with adverse metabolic effects.¹⁶

What are realistic treatment goals to manage residual symptoms in schizophrenia?

We believe that because remission in schizophrenia has been defined consensually, the bar for treatment expectations is set higher than it was 20 years ago. There can be patient-, family-, and system-related variables affecting the feasibility of treating residual symptoms. Providers who treat patients with schizophrenia should consider the following treatment goals:

• Prevent relapse and acute psychiatric hospitalization
• Use evidence-based strategies to minimize or monitor adverse effects
• Monitor compliance and consider use of depot antipsychotics combined with patients’ preference
• Facilitate ongoing safety assessment, including suicide risk
• Monitor negative and cognitive symptoms in addition to positive symptoms, using evidence-based management
• Encourage collaboration of care with family, caretakers, and other members of the treatment team
• Empower patients by providing psycho­education and social skills training and assisting in their vocational rehabilitation 
• Educate the patient and family about healthy lifestyle interventions and medical comorbidities common with schizophrenia
• Perform baseline screening and follow-up for early detection and treatment of medical comorbidities in patients with schizophrenia
• Improve functional status and quality of life.

In addition to meeting these treatment goals, a measurement-based method can be implemented to monitor improvement and status of the independent treatment domains. A collection of rating instruments can be found in Table 2.^17-30

Summing up

The clinical presentation of patients with residual symptoms of schizophrenia differs from that of other patients with schizophrenia. Our understanding of residual symptoms in schizophrenia has come a long way in the last decade; however, we are still far from pinning the complex nature of these symptoms, let alone their management. Given the risk of morbidity and disability, there clearly is a need for further investigation and investment of time and resources to support developing novel pharmacological treatment options to manage residual symptoms in patients with schizophrenia.

Because patients with residual symptoms of schizophrenia usually are older, psychiatrists should be responsible for implementing necessary screening assessments and should closely collaborate with primary care practitioners and other specialists, and when necessary, treat comorbid medical conditions. The importance of educating patients, their families, and the treatment team cannot be overlooked. Further, psychiatric treatment facilities should offer and promote healthy lifestyle interventions.

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”