Pregnant women are rarely included in clinical drug trials, creating a significant and potentially dangerous gap in knowledge. Now, a new draft guidance from the Food and Drug Administration broadens the discussion about these trials, suggesting issues to consider – including ethics and risks – when testing medications in pregnant women.

“The guidance opens the possibility of ethical conduct of trials in pregnant women but carefully lays out the caveats to be considered,” Christina Chambers, PhD, a perinatal epidemiologist at the University of California, San Diego, said in an interview. “With proper planning and thoughtful consultation with the relevant experts, this change in regulatory limitations will benefit pregnant women and their children.”

[polldaddy:9979976]

The draft guidance, released April 6 by the FDA, is “intended to advance scientific research in pregnant women, and discusses issues that should be considered within the framework of human subject protection regulations,” according to posting comments in the Federal Register.

The draft notes that in some cases, the lack of data about drugs may harm pregnant women and their fetuses by leading physicians to be fearful about prescribing medication. Conversely, physicians and pregnant women are often in the dark about the risks and benefits of medications that are prescribed and used, according to the draft.

In terms of research going forward, the guidance says “development of accessible treatment options for the pregnant population is a significant public health issue.”

• It is “ethically justifiable” to include pregnant women in clinical trials under specific circumstances. “Sponsors should consider meeting with the appropriate FDA review division early in the development phase to discuss when and how to include pregnant women in the drug development plan. These discussions should involve FDA experts in bioethics and maternal health.”
• “Pregnant women can be enrolled in clinical trials that involve greater than minimal risk to the fetuses if the trials offer the potential for direct clinical benefit to the enrolled pregnant women and/or their fetuses.”
• A new pregnancy during a randomized, blinded clinical trial should prompt unblinding “so that counseling may be offered based on whether the fetus has been exposed to the investigational drug, placebo, or control.”
• The pregnant woman may continue the trial if potential benefits outweigh the risks.
• In general, pregnant women should not be enrolled in phase 1 and phase 2 clinical trials. Instead, those trials should be completed first “in a nonpregnant population that include females of reproductive potential.”
• Several types of events may call for the cessation of a clinical trial that includes pregnant women, such as serious maternal or fetal adverse events.

The draft guidance should take note of the fact that birth defects often don’t appear for months or even longer, according to Gerald Briggs, BPharm, FCCP, clinical professor of pharmacy at the University of California, San Francisco. “Until first year of life or later, the babies need to be monitored,” he said in an interview.

Mr. Briggs, who led a 2015 report examining the role of pregnant women in phase 4 clinical drug trials, added that the document should take note of recommendations from clinical teratologists regarding the design of animal studies that should be performed prior to human trials (Am J Obstet Gynecol. 2015;213(6):810-5).

Comments on the draft guidance can be made at www.federalregister.gov and are due by June 8, 2018.

Dr. Chambers and Mr. Briggs reported no relevant disclosures.

Pregnant women are rarely included in clinical drug trials, creating a significant and potentially dangerous gap in knowledge. Now, a new draft guidance from the Food and Drug Administration broadens the discussion about these trials, suggesting issues to consider – including ethics and risks – when testing medications in pregnant women.

“The guidance opens the possibility of ethical conduct of trials in pregnant women but carefully lays out the caveats to be considered,” Christina Chambers, PhD, a perinatal epidemiologist at the University of California, San Diego, said in an interview. “With proper planning and thoughtful consultation with the relevant experts, this change in regulatory limitations will benefit pregnant women and their children.”

[polldaddy:9979976]

The draft guidance, released April 6 by the FDA, is “intended to advance scientific research in pregnant women, and discusses issues that should be considered within the framework of human subject protection regulations,” according to posting comments in the Federal Register.

The draft notes that in some cases, the lack of data about drugs may harm pregnant women and their fetuses by leading physicians to be fearful about prescribing medication. Conversely, physicians and pregnant women are often in the dark about the risks and benefits of medications that are prescribed and used, according to the draft.

In terms of research going forward, the guidance says “development of accessible treatment options for the pregnant population is a significant public health issue.”

• It is “ethically justifiable” to include pregnant women in clinical trials under specific circumstances. “Sponsors should consider meeting with the appropriate FDA review division early in the development phase to discuss when and how to include pregnant women in the drug development plan. These discussions should involve FDA experts in bioethics and maternal health.”
• “Pregnant women can be enrolled in clinical trials that involve greater than minimal risk to the fetuses if the trials offer the potential for direct clinical benefit to the enrolled pregnant women and/or their fetuses.”
• A new pregnancy during a randomized, blinded clinical trial should prompt unblinding “so that counseling may be offered based on whether the fetus has been exposed to the investigational drug, placebo, or control.”
• The pregnant woman may continue the trial if potential benefits outweigh the risks.
• In general, pregnant women should not be enrolled in phase 1 and phase 2 clinical trials. Instead, those trials should be completed first “in a nonpregnant population that include females of reproductive potential.”
• Several types of events may call for the cessation of a clinical trial that includes pregnant women, such as serious maternal or fetal adverse events.

The draft guidance should take note of the fact that birth defects often don’t appear for months or even longer, according to Gerald Briggs, BPharm, FCCP, clinical professor of pharmacy at the University of California, San Francisco. “Until first year of life or later, the babies need to be monitored,” he said in an interview.

Mr. Briggs, who led a 2015 report examining the role of pregnant women in phase 4 clinical drug trials, added that the document should take note of recommendations from clinical teratologists regarding the design of animal studies that should be performed prior to human trials (Am J Obstet Gynecol. 2015;213(6):810-5).

Comments on the draft guidance can be made at www.federalregister.gov and are due by June 8, 2018.

Dr. Chambers and Mr. Briggs reported no relevant disclosures.

Pregnant women are rarely included in clinical drug trials, creating a significant and potentially dangerous gap in knowledge. Now, a new draft guidance from the Food and Drug Administration broadens the discussion about these trials, suggesting issues to consider – including ethics and risks – when testing medications in pregnant women.

“The guidance opens the possibility of ethical conduct of trials in pregnant women but carefully lays out the caveats to be considered,” Christina Chambers, PhD, a perinatal epidemiologist at the University of California, San Diego, said in an interview. “With proper planning and thoughtful consultation with the relevant experts, this change in regulatory limitations will benefit pregnant women and their children.”

[polldaddy:9979976]

The draft guidance, released April 6 by the FDA, is “intended to advance scientific research in pregnant women, and discusses issues that should be considered within the framework of human subject protection regulations,” according to posting comments in the Federal Register.

The draft notes that in some cases, the lack of data about drugs may harm pregnant women and their fetuses by leading physicians to be fearful about prescribing medication. Conversely, physicians and pregnant women are often in the dark about the risks and benefits of medications that are prescribed and used, according to the draft.

In terms of research going forward, the guidance says “development of accessible treatment options for the pregnant population is a significant public health issue.”

• It is “ethically justifiable” to include pregnant women in clinical trials under specific circumstances. “Sponsors should consider meeting with the appropriate FDA review division early in the development phase to discuss when and how to include pregnant women in the drug development plan. These discussions should involve FDA experts in bioethics and maternal health.”
• “Pregnant women can be enrolled in clinical trials that involve greater than minimal risk to the fetuses if the trials offer the potential for direct clinical benefit to the enrolled pregnant women and/or their fetuses.”
• A new pregnancy during a randomized, blinded clinical trial should prompt unblinding “so that counseling may be offered based on whether the fetus has been exposed to the investigational drug, placebo, or control.”
• The pregnant woman may continue the trial if potential benefits outweigh the risks.
• In general, pregnant women should not be enrolled in phase 1 and phase 2 clinical trials. Instead, those trials should be completed first “in a nonpregnant population that include females of reproductive potential.”
• Several types of events may call for the cessation of a clinical trial that includes pregnant women, such as serious maternal or fetal adverse events.

The draft guidance should take note of the fact that birth defects often don’t appear for months or even longer, according to Gerald Briggs, BPharm, FCCP, clinical professor of pharmacy at the University of California, San Francisco. “Until first year of life or later, the babies need to be monitored,” he said in an interview.

Mr. Briggs, who led a 2015 report examining the role of pregnant women in phase 4 clinical drug trials, added that the document should take note of recommendations from clinical teratologists regarding the design of animal studies that should be performed prior to human trials (Am J Obstet Gynecol. 2015;213(6):810-5).

Comments on the draft guidance can be made at www.federalregister.gov and are due by June 8, 2018.

Dr. Chambers and Mr. Briggs reported no relevant disclosures.

From weekend warriors to pros, athletes are plagued by skin disorders. CMS finalizes measures to help combat the opioid crisis. Enrollment slides on health exchanges in 2018. And the sensitivity of vibration-based neuropathy detectors varies widely.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

From weekend warriors to pros, athletes are plagued by skin disorders. CMS finalizes measures to help combat the opioid crisis. Enrollment slides on health exchanges in 2018. And the sensitivity of vibration-based neuropathy detectors varies widely.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

From weekend warriors to pros, athletes are plagued by skin disorders. CMS finalizes measures to help combat the opioid crisis. Enrollment slides on health exchanges in 2018. And the sensitivity of vibration-based neuropathy detectors varies widely.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

According to the US Department of Veterans Affairs (VA) Pharmacy Benefits Management Service, about 80% of all outpatient prescriptions filled by the VA are sent to veterans by mail order, using the Centralized Mail Order Pharmacy (CMOP) network of highly automated pharmacies around the country.¹ During fiscal year (FY) 2016, the 7 VA CMOP facilities throughout the US processed 119.7 million outpatient prescriptions. Each day, these CMOPs process nearly 470,000 prescriptions, an evidence of the efficiency provided through this mail-order service.¹ The use of CMOP results in lower processing costs and increased convenience for veterans compared with filling prescriptions at pharmacies at individual VA facilities. Notably, VA CMOP has been rated “among the best” mail-order pharmacies in customer satisfaction according to the 2017 J.D. Power US Pharmacy Study.²

Background

Within the Fayetteville VA Medical Center (FVAMC) system in North Carolina, on-site patients receive a new prescription where an on-site pharmacy is available (at health care centers [HCC] and the medical center). For veterans seen at community-based outpatient clinics (CBOCs), emergent new prescriptions are filled through vouchers at contract community pharmacies, and nonemergent new prescriptions are filled by the CMOP (Figure 1). 

The appropriate use of the VA CMOP for refills is intended to allow on-site pharmacy staff to focus on providing customer service for veterans requesting medication counseling from a clinical pharmacist, as well as those with new, changing, or urgent prescription needs. Filling prescriptions through the CMOP also can help control the VA facility pharmacy budget.

Despite the established mail-order process, FVAMC staff noted a high volume of medication refill and partial-fill prescriptions being requested at the on-site pharmacy. When a veteran presented to a pharmacy requesting a medication refill, pharmacy staff members ordered a refill to be filled by the CMOP and provided a limited quantity, otherwise known as a partial fill, to serve as an emergency supply to supplement the veteran until the full quantity of the prescription arrived by mail. Partial fills also were completed for new prescriptions that veterans requested to pick up at the on-site pharmacy. For new 90-day supply prescriptions, pharmacy staff often filled a 30-day supply in addition to submitting the entire 90-day prescription through the CMOP, which led to an unnecessary increase in material expenditures and workload.Preliminary data noted the most frequently used partial-fill days’ supply to be 10 days. Due to the lack of partial-fill criteria, prescriptions of all classes, quantities, and days’ supplies were provided as partial fills. Prior to the implementation of this quality improvement (QI) project, there was no standard approach for how to handle these requests.

Partial fills do not provide copay reimbursement to the facility filling the prescription. In an effort to steward the funds provided to the FVAMC pharmacy department wisely, an evaluation was performed with reference to partial fills. During FY 2016, about $350,000 was spent on medications, materials, and workload associated with the partial filling of FVAMC prescriptions. With respect to unique individuals who were provided care over the course of FY 2015 and 2016, the number of unique patients served by local comparator hospitals increased by only 2%, while the number of unique patients served by FVAMC increased by 12%. This substantial growth in the number of veterans served places further emphasis on the necessity of stewarding the allotted pharmacy budget. Moreover, the excessive number of medication refill and partial-fill prescriptions filled at on-site VA pharmacies can contribute to increased wait times for veterans with urgent prescription needs.

In November 2016, FVAMC implemented an updated partial-fill guidance. Partial-fill process and refill education was provided for VA staff and veterans in an effort to allow all parties involved to use pharmacy services efficiently. This analysis reviewed the reduction in partial-fill expenditures with a secondary focus on workload expenditures following the execution of this education.

Methods

This project was deemed to be a QI project and did not require institutional review board approval. Implementation for this QI project began in November 2016. Baseline raw drug cost, number, and class of prescriptions partialed were retrospectively collected for a 90-day period prior to implementation using all available data. Postintervention data were collected for 90 days following the implementation phase to compare partial-fill expenditures and workload expenditures with baseline data.

Calculations

Materials included in the partial-fill expenditure calculation were prescription vials, prescription vial caps, and prescription labeling. Material cost per partial fill was determined by using the facility’s wholesaler acquisition unit costs to estimate a summed cost for an individual prescription vial and prescription vial cap. The estimated acquisition price of 7 prescription-labeling pages was used in the material calculation, as this was the average number of pages used when performing test partial fills.

The following equation was used to calculate total partial-fill expenditures for any specified time frame:

Total partial-fill expenditure = total raw drug cost + (material cost × number of partial fills)

In addition, the average personnel cost per partial-fill prescription was determined. Average workload expenditure per partial fill was calculated by filling a subset of 10 test prescriptions and multiplying the average time spent by an average of the general station (GS) rate for pharmacists and technicians. The average hourly rate of a GS-12 pharmacist was calculated based on an average of the 10 available pay grades within the GS-12 ranking. The average hourly rate of a GS-6 pharmacy technician was calculated based on an average of the 10 available pay grades within the GS-6 ranking.³ The average workload expenditures were calculated using the following equations:

Average pharmacist workload expenditure per partial fill = time (in hours) × average hourly rate.

Average technician workload expenditure per partial fill = time (in hours) × average hourly rate.

Partial-Fill Guidance

Updated partial-fill guidance was drafted designating acceptable prescriptions to be limited to those responsible for preventing hospitalization and treatment of acute illness. This guidance provided generalized examples of medication classes that could be acceptable for partial filling, though it was not intended to be an all-inclusive list. The guidance also noted examples of classes or groups that should not be partial filled for nonemergent reasons (vitamins, nonprescription items, antilipemics), as well as controlled substances. The refill-process education was reiterated throughout the entirety of the guidance. Specifically, if a pharmacy staff member was to perform a partial fill, a review explaining the appropriate refill process to the veteran also must be provided. If the medication was determined to be of emergent need and not yet transmitted for filling via the CMOP, the directive recommended to fill the entire quantity locally as a onetime fill.

If a onetime on-site fill was determined infeasible, partial-fill quantities were recommended to be limited to only a 7-day supply, and the full quantity filled through the CMOP. Anticipated mail wait time for CMOP prescription delivery was estimated to be less than 7 days based on experience, local pending queues, and guidance from the regional CMOP; however, time could vary among VA and CMOP facilities. Original prescriptions were to be filled for the entire quantity for the first fill at the on-site pharmacy if requested by the veteran. If the pharmacy had an insufficient quantity for an entire initial supply, it could then be partial filled for a 7-day supply and then filled through the CMOP.

The final portion of the partial-fill guidance pertained to the use of partial-fill justification codes. Prior to the execution of the partial-fill guidance, free text was entered into the comments field when processing a partial-fill prescription, as the prescription-processing system used requires a comment to proceed with the partial fill. The use of these codes served to streamline data collection in the postintervention phase and helped identify areas for further education following the close of this project.

Education

Education to the pharmacy staff was disseminated by various modalities, including in-person sessions and written and electronic correspondences. This written guidance was distributed to pharmacy staff by e-mail, the pharmacy newsletter (R_x-tra), signage posted throughout the outpatient pharmacies, and on the facility’s pharmacy Microsoft SharePoint (Redmond, WA) site. In-services provided during pharmacy staff meetings detailed information on the updated partial-fill guidance. A FVAMC Talent Management System (TMS) training module was developed and assigned to all pharmacy service staff to reiterate key points regarding this QI initiative (eAppendix).

Nonpharmacy staff were educated through staff and in-service meetings and e-mail correspondences. These in-services emphasized how nurses, medical support assistants, and health care providers (HCPs) could assist veterans by knowing the correct refill process, ensuring sufficient refills remained until the next appointment, and providing continual refill-process education.

Following implementation, all veterans receiving prescriptions through the on-site pharmacies in the FVAMC were provided a copy of the refill-process handout with each trip to the pharmacy. Nonpharmacy staff and HCPs also were provided this handout to distribute to patients. The intent of this handout was to clearly detail the various ways in which refills could be ordered and the time frame in which they should be ordered. The pharmacy became involved in new patient orientation classes for all veterans new to FVAMC. Digital signage and messaging was created and circulated throughout several of the FVAMC facilities.

Results

The results of calculations for material cost, personnel time spent, hourly employee rates, and average workload expenditure per partial fill are summarized in Table 1.

Following the implementation of partial-fill and refill-process education, there was a 54.3% decrease in the total number of partial fills from 5,596 in the 90 days prior to implementation, to 2,555 partials completed over the 90 days postimplementation. Regarding the primary objective, total partial-fill expenditures decreased from $52,015.44 to $44,063.01 (-15.3%). When dissecting the individual components of partial-fill expenditures, material expenditures decreased from $1,454.96 to $664.28 (-54.3%), and raw drug cost expenditures decreased from $50,596.48 to $43,398.73 (-14.3%). Workload expenditures also decreased from $27,140.60 to $12,391.75 (-54.3%).

Several points of descriptive information also were collected. The average days’ supply trended down from a mode of 10 days to 7 days. This reduction in days’ supply likely was seen because staff became more aware of the customary amount required to bridge the veteran until the CMOP supply arrived by mail. Postintervention data showed a 70% utilization of partial-fill reasoning codes. The reasons for partial filling of prescriptions are summarized in Table 2. 

Discussion

Following the implementation of the updated partial-fill guidance and provision of education to the FVAMC veterans and staff, a noteworthy cost savings was observed with respect to both material and workload expenditures. This large reduction in expenditure likely was not related to a reduction in the total prescription volume, as the number of total prescriptions filled by the CMOP and at FVAMC were similar in both the preliminary and postintervention periods. When the results of this 3-month QI project were extrapolated, the annual projected cost avoidance was $91,949.12.

Of note, there was no established process for adjudicating appeals to the partial-fill guidance. Any extenuating circumstances that fell outside the guidance were addressed by the outpatient pharmacy supervisor. There was no formal documentation for these disputed cases. Since there was no prespecified supervisory override code, the most appropriate partial-fill code was entered into the comments field for these scenarios. As such, there is no way to distinguish precisely how many of these partial fills were escalated to a supervisory level for a decision.

The positive fiscal impact noted from the implementation of this project should not be viewed as the only utility for such guidance. Though not directly measured within the confines of this project, a reduction in pharmacy staff time spent on partial-fill prescriptions will likely result in shorter pharmacy wait times, line lengths, and streamlining of pharmacy workflow. When the pharmacy staff is free to work on pressing issues rather than on continually educating veterans on the partial-fill or refill process, many will benefit. Veteran satisfaction was not directly measured during this project but could be an interesting topic to review as a future study.

Each VA facility is unique, with its own challenges for implementation of a project such as this. Nevertheless, the incorporation of a formal guidance and education process, perhaps adapted to the indi vidual facility’s needs may be considered for overall pharmacy operations QI.

Limitations

During the preliminary data collection period, FVAMC and its catchment area were impacted by a natural disaster, Hurricane Matthew. Based on a review of the text entered into the comments field for all partial fills, about 4% of the partial fills completed in the preliminary phase can be attributed to the hurricane. The effects of this hurricane may have potentially increased the number of partial fills completed in the preliminary phase compared with that in the postintervention phase, due to the number of veterans who were temporarily or permanently displaced from their homes. This increase in partial fills and associated expenses preintervention likely caused a slightly higher cost savings to be reflected in the postimplementation phase than what would have traditionally been observed without extenuating factors.

Several other limitations must be considered for this QI project. The implementation phase, during which all education and training was completed, was only 1 month. A longer implementation period and more opportunities to educate veterans and staff might have created a greater impact on the results. Additionally, because there were no data collected on New Patient Orientation attendance for this project, it is unclear exactly how many veterans received refill-process education through this outlet.

Though all staff members were trained on the appropriate process, it was discovered during interim analysis that several pharmacists were not following the partial-fill guidance, potentially negatively impacting the results. It is likely that staff would have benefited from continual reeducation of the process throughout the entirety of the project, as the restriction of partial filling was a novel concept to many. In addition to continual reeducation of current employees, any new hires would likely need this information as part of initial training.

Cost variance in the type of partial fills completed between the preliminary and postintervention phases also may have negatively impacted the results. The postintervention phase contained 2 high-cost classes of drugs (antivirals and immunoglobulins) that received multiple partial fills but were not partialed in the preliminary phase, which increased the raw drug cost in the postintervention phase.

Conclusion

The implementation of partial-fill and process education to FVAMC staff and veterans proved beneficial in reducing the expenditures and workload associated with partial-fill prescription processing. The continued use of the updated partial-fill guidance will provide a standardized approach for pharmacy staff when completing partial-fill prescriptions.

Facilities may consider annual reeducation on their guidance through a local TMS module, as well as occasional process reminders during staff meetings to improve staff adherence to the guidance. Moreover, the sustained incorporation of improved refill process education to new patients and with every prescription pickup could help guide the FVAMC veteran population to use pharmacy services more effectively. The adoption of such procedures may be useful for VA facilities’ health care system looking to maximize the use of funding provided for prescription services as well as improve veterans’ understanding of how to appropriately order prescription refills.

According to the US Department of Veterans Affairs (VA) Pharmacy Benefits Management Service, about 80% of all outpatient prescriptions filled by the VA are sent to veterans by mail order, using the Centralized Mail Order Pharmacy (CMOP) network of highly automated pharmacies around the country.¹ During fiscal year (FY) 2016, the 7 VA CMOP facilities throughout the US processed 119.7 million outpatient prescriptions. Each day, these CMOPs process nearly 470,000 prescriptions, an evidence of the efficiency provided through this mail-order service.¹ The use of CMOP results in lower processing costs and increased convenience for veterans compared with filling prescriptions at pharmacies at individual VA facilities. Notably, VA CMOP has been rated “among the best” mail-order pharmacies in customer satisfaction according to the 2017 J.D. Power US Pharmacy Study.²

Background

Within the Fayetteville VA Medical Center (FVAMC) system in North Carolina, on-site patients receive a new prescription where an on-site pharmacy is available (at health care centers [HCC] and the medical center). For veterans seen at community-based outpatient clinics (CBOCs), emergent new prescriptions are filled through vouchers at contract community pharmacies, and nonemergent new prescriptions are filled by the CMOP (Figure 1). 

The appropriate use of the VA CMOP for refills is intended to allow on-site pharmacy staff to focus on providing customer service for veterans requesting medication counseling from a clinical pharmacist, as well as those with new, changing, or urgent prescription needs. Filling prescriptions through the CMOP also can help control the VA facility pharmacy budget.

Despite the established mail-order process, FVAMC staff noted a high volume of medication refill and partial-fill prescriptions being requested at the on-site pharmacy. When a veteran presented to a pharmacy requesting a medication refill, pharmacy staff members ordered a refill to be filled by the CMOP and provided a limited quantity, otherwise known as a partial fill, to serve as an emergency supply to supplement the veteran until the full quantity of the prescription arrived by mail. Partial fills also were completed for new prescriptions that veterans requested to pick up at the on-site pharmacy. For new 90-day supply prescriptions, pharmacy staff often filled a 30-day supply in addition to submitting the entire 90-day prescription through the CMOP, which led to an unnecessary increase in material expenditures and workload.Preliminary data noted the most frequently used partial-fill days’ supply to be 10 days. Due to the lack of partial-fill criteria, prescriptions of all classes, quantities, and days’ supplies were provided as partial fills. Prior to the implementation of this quality improvement (QI) project, there was no standard approach for how to handle these requests.

Partial fills do not provide copay reimbursement to the facility filling the prescription. In an effort to steward the funds provided to the FVAMC pharmacy department wisely, an evaluation was performed with reference to partial fills. During FY 2016, about $350,000 was spent on medications, materials, and workload associated with the partial filling of FVAMC prescriptions. With respect to unique individuals who were provided care over the course of FY 2015 and 2016, the number of unique patients served by local comparator hospitals increased by only 2%, while the number of unique patients served by FVAMC increased by 12%. This substantial growth in the number of veterans served places further emphasis on the necessity of stewarding the allotted pharmacy budget. Moreover, the excessive number of medication refill and partial-fill prescriptions filled at on-site VA pharmacies can contribute to increased wait times for veterans with urgent prescription needs.

In November 2016, FVAMC implemented an updated partial-fill guidance. Partial-fill process and refill education was provided for VA staff and veterans in an effort to allow all parties involved to use pharmacy services efficiently. This analysis reviewed the reduction in partial-fill expenditures with a secondary focus on workload expenditures following the execution of this education.

Methods

This project was deemed to be a QI project and did not require institutional review board approval. Implementation for this QI project began in November 2016. Baseline raw drug cost, number, and class of prescriptions partialed were retrospectively collected for a 90-day period prior to implementation using all available data. Postintervention data were collected for 90 days following the implementation phase to compare partial-fill expenditures and workload expenditures with baseline data.

Calculations

Materials included in the partial-fill expenditure calculation were prescription vials, prescription vial caps, and prescription labeling. Material cost per partial fill was determined by using the facility’s wholesaler acquisition unit costs to estimate a summed cost for an individual prescription vial and prescription vial cap. The estimated acquisition price of 7 prescription-labeling pages was used in the material calculation, as this was the average number of pages used when performing test partial fills.

The following equation was used to calculate total partial-fill expenditures for any specified time frame:

Total partial-fill expenditure = total raw drug cost + (material cost × number of partial fills)

In addition, the average personnel cost per partial-fill prescription was determined. Average workload expenditure per partial fill was calculated by filling a subset of 10 test prescriptions and multiplying the average time spent by an average of the general station (GS) rate for pharmacists and technicians. The average hourly rate of a GS-12 pharmacist was calculated based on an average of the 10 available pay grades within the GS-12 ranking. The average hourly rate of a GS-6 pharmacy technician was calculated based on an average of the 10 available pay grades within the GS-6 ranking.³ The average workload expenditures were calculated using the following equations:

Average pharmacist workload expenditure per partial fill = time (in hours) × average hourly rate.

Average technician workload expenditure per partial fill = time (in hours) × average hourly rate.

Partial-Fill Guidance

Updated partial-fill guidance was drafted designating acceptable prescriptions to be limited to those responsible for preventing hospitalization and treatment of acute illness. This guidance provided generalized examples of medication classes that could be acceptable for partial filling, though it was not intended to be an all-inclusive list. The guidance also noted examples of classes or groups that should not be partial filled for nonemergent reasons (vitamins, nonprescription items, antilipemics), as well as controlled substances. The refill-process education was reiterated throughout the entirety of the guidance. Specifically, if a pharmacy staff member was to perform a partial fill, a review explaining the appropriate refill process to the veteran also must be provided. If the medication was determined to be of emergent need and not yet transmitted for filling via the CMOP, the directive recommended to fill the entire quantity locally as a onetime fill.

If a onetime on-site fill was determined infeasible, partial-fill quantities were recommended to be limited to only a 7-day supply, and the full quantity filled through the CMOP. Anticipated mail wait time for CMOP prescription delivery was estimated to be less than 7 days based on experience, local pending queues, and guidance from the regional CMOP; however, time could vary among VA and CMOP facilities. Original prescriptions were to be filled for the entire quantity for the first fill at the on-site pharmacy if requested by the veteran. If the pharmacy had an insufficient quantity for an entire initial supply, it could then be partial filled for a 7-day supply and then filled through the CMOP.

The final portion of the partial-fill guidance pertained to the use of partial-fill justification codes. Prior to the execution of the partial-fill guidance, free text was entered into the comments field when processing a partial-fill prescription, as the prescription-processing system used requires a comment to proceed with the partial fill. The use of these codes served to streamline data collection in the postintervention phase and helped identify areas for further education following the close of this project.

Education

Education to the pharmacy staff was disseminated by various modalities, including in-person sessions and written and electronic correspondences. This written guidance was distributed to pharmacy staff by e-mail, the pharmacy newsletter (R_x-tra), signage posted throughout the outpatient pharmacies, and on the facility’s pharmacy Microsoft SharePoint (Redmond, WA) site. In-services provided during pharmacy staff meetings detailed information on the updated partial-fill guidance. A FVAMC Talent Management System (TMS) training module was developed and assigned to all pharmacy service staff to reiterate key points regarding this QI initiative (eAppendix).

Nonpharmacy staff were educated through staff and in-service meetings and e-mail correspondences. These in-services emphasized how nurses, medical support assistants, and health care providers (HCPs) could assist veterans by knowing the correct refill process, ensuring sufficient refills remained until the next appointment, and providing continual refill-process education.

Following implementation, all veterans receiving prescriptions through the on-site pharmacies in the FVAMC were provided a copy of the refill-process handout with each trip to the pharmacy. Nonpharmacy staff and HCPs also were provided this handout to distribute to patients. The intent of this handout was to clearly detail the various ways in which refills could be ordered and the time frame in which they should be ordered. The pharmacy became involved in new patient orientation classes for all veterans new to FVAMC. Digital signage and messaging was created and circulated throughout several of the FVAMC facilities.

Results

The results of calculations for material cost, personnel time spent, hourly employee rates, and average workload expenditure per partial fill are summarized in Table 1.

Following the implementation of partial-fill and refill-process education, there was a 54.3% decrease in the total number of partial fills from 5,596 in the 90 days prior to implementation, to 2,555 partials completed over the 90 days postimplementation. Regarding the primary objective, total partial-fill expenditures decreased from $52,015.44 to $44,063.01 (-15.3%). When dissecting the individual components of partial-fill expenditures, material expenditures decreased from $1,454.96 to $664.28 (-54.3%), and raw drug cost expenditures decreased from $50,596.48 to $43,398.73 (-14.3%). Workload expenditures also decreased from $27,140.60 to $12,391.75 (-54.3%).

Several points of descriptive information also were collected. The average days’ supply trended down from a mode of 10 days to 7 days. This reduction in days’ supply likely was seen because staff became more aware of the customary amount required to bridge the veteran until the CMOP supply arrived by mail. Postintervention data showed a 70% utilization of partial-fill reasoning codes. The reasons for partial filling of prescriptions are summarized in Table 2. 

Discussion

Following the implementation of the updated partial-fill guidance and provision of education to the FVAMC veterans and staff, a noteworthy cost savings was observed with respect to both material and workload expenditures. This large reduction in expenditure likely was not related to a reduction in the total prescription volume, as the number of total prescriptions filled by the CMOP and at FVAMC were similar in both the preliminary and postintervention periods. When the results of this 3-month QI project were extrapolated, the annual projected cost avoidance was $91,949.12.

Of note, there was no established process for adjudicating appeals to the partial-fill guidance. Any extenuating circumstances that fell outside the guidance were addressed by the outpatient pharmacy supervisor. There was no formal documentation for these disputed cases. Since there was no prespecified supervisory override code, the most appropriate partial-fill code was entered into the comments field for these scenarios. As such, there is no way to distinguish precisely how many of these partial fills were escalated to a supervisory level for a decision.

The positive fiscal impact noted from the implementation of this project should not be viewed as the only utility for such guidance. Though not directly measured within the confines of this project, a reduction in pharmacy staff time spent on partial-fill prescriptions will likely result in shorter pharmacy wait times, line lengths, and streamlining of pharmacy workflow. When the pharmacy staff is free to work on pressing issues rather than on continually educating veterans on the partial-fill or refill process, many will benefit. Veteran satisfaction was not directly measured during this project but could be an interesting topic to review as a future study.

Each VA facility is unique, with its own challenges for implementation of a project such as this. Nevertheless, the incorporation of a formal guidance and education process, perhaps adapted to the indi vidual facility’s needs may be considered for overall pharmacy operations QI.

Limitations

During the preliminary data collection period, FVAMC and its catchment area were impacted by a natural disaster, Hurricane Matthew. Based on a review of the text entered into the comments field for all partial fills, about 4% of the partial fills completed in the preliminary phase can be attributed to the hurricane. The effects of this hurricane may have potentially increased the number of partial fills completed in the preliminary phase compared with that in the postintervention phase, due to the number of veterans who were temporarily or permanently displaced from their homes. This increase in partial fills and associated expenses preintervention likely caused a slightly higher cost savings to be reflected in the postimplementation phase than what would have traditionally been observed without extenuating factors.

Several other limitations must be considered for this QI project. The implementation phase, during which all education and training was completed, was only 1 month. A longer implementation period and more opportunities to educate veterans and staff might have created a greater impact on the results. Additionally, because there were no data collected on New Patient Orientation attendance for this project, it is unclear exactly how many veterans received refill-process education through this outlet.

Though all staff members were trained on the appropriate process, it was discovered during interim analysis that several pharmacists were not following the partial-fill guidance, potentially negatively impacting the results. It is likely that staff would have benefited from continual reeducation of the process throughout the entirety of the project, as the restriction of partial filling was a novel concept to many. In addition to continual reeducation of current employees, any new hires would likely need this information as part of initial training.

Cost variance in the type of partial fills completed between the preliminary and postintervention phases also may have negatively impacted the results. The postintervention phase contained 2 high-cost classes of drugs (antivirals and immunoglobulins) that received multiple partial fills but were not partialed in the preliminary phase, which increased the raw drug cost in the postintervention phase.

Conclusion

The implementation of partial-fill and process education to FVAMC staff and veterans proved beneficial in reducing the expenditures and workload associated with partial-fill prescription processing. The continued use of the updated partial-fill guidance will provide a standardized approach for pharmacy staff when completing partial-fill prescriptions.

Facilities may consider annual reeducation on their guidance through a local TMS module, as well as occasional process reminders during staff meetings to improve staff adherence to the guidance. Moreover, the sustained incorporation of improved refill process education to new patients and with every prescription pickup could help guide the FVAMC veteran population to use pharmacy services more effectively. The adoption of such procedures may be useful for VA facilities’ health care system looking to maximize the use of funding provided for prescription services as well as improve veterans’ understanding of how to appropriately order prescription refills.

According to the US Department of Veterans Affairs (VA) Pharmacy Benefits Management Service, about 80% of all outpatient prescriptions filled by the VA are sent to veterans by mail order, using the Centralized Mail Order Pharmacy (CMOP) network of highly automated pharmacies around the country.¹ During fiscal year (FY) 2016, the 7 VA CMOP facilities throughout the US processed 119.7 million outpatient prescriptions. Each day, these CMOPs process nearly 470,000 prescriptions, an evidence of the efficiency provided through this mail-order service.¹ The use of CMOP results in lower processing costs and increased convenience for veterans compared with filling prescriptions at pharmacies at individual VA facilities. Notably, VA CMOP has been rated “among the best” mail-order pharmacies in customer satisfaction according to the 2017 J.D. Power US Pharmacy Study.²

Background

Within the Fayetteville VA Medical Center (FVAMC) system in North Carolina, on-site patients receive a new prescription where an on-site pharmacy is available (at health care centers [HCC] and the medical center). For veterans seen at community-based outpatient clinics (CBOCs), emergent new prescriptions are filled through vouchers at contract community pharmacies, and nonemergent new prescriptions are filled by the CMOP (Figure 1). 

The appropriate use of the VA CMOP for refills is intended to allow on-site pharmacy staff to focus on providing customer service for veterans requesting medication counseling from a clinical pharmacist, as well as those with new, changing, or urgent prescription needs. Filling prescriptions through the CMOP also can help control the VA facility pharmacy budget.

Despite the established mail-order process, FVAMC staff noted a high volume of medication refill and partial-fill prescriptions being requested at the on-site pharmacy. When a veteran presented to a pharmacy requesting a medication refill, pharmacy staff members ordered a refill to be filled by the CMOP and provided a limited quantity, otherwise known as a partial fill, to serve as an emergency supply to supplement the veteran until the full quantity of the prescription arrived by mail. Partial fills also were completed for new prescriptions that veterans requested to pick up at the on-site pharmacy. For new 90-day supply prescriptions, pharmacy staff often filled a 30-day supply in addition to submitting the entire 90-day prescription through the CMOP, which led to an unnecessary increase in material expenditures and workload.Preliminary data noted the most frequently used partial-fill days’ supply to be 10 days. Due to the lack of partial-fill criteria, prescriptions of all classes, quantities, and days’ supplies were provided as partial fills. Prior to the implementation of this quality improvement (QI) project, there was no standard approach for how to handle these requests.

Partial fills do not provide copay reimbursement to the facility filling the prescription. In an effort to steward the funds provided to the FVAMC pharmacy department wisely, an evaluation was performed with reference to partial fills. During FY 2016, about $350,000 was spent on medications, materials, and workload associated with the partial filling of FVAMC prescriptions. With respect to unique individuals who were provided care over the course of FY 2015 and 2016, the number of unique patients served by local comparator hospitals increased by only 2%, while the number of unique patients served by FVAMC increased by 12%. This substantial growth in the number of veterans served places further emphasis on the necessity of stewarding the allotted pharmacy budget. Moreover, the excessive number of medication refill and partial-fill prescriptions filled at on-site VA pharmacies can contribute to increased wait times for veterans with urgent prescription needs.

In November 2016, FVAMC implemented an updated partial-fill guidance. Partial-fill process and refill education was provided for VA staff and veterans in an effort to allow all parties involved to use pharmacy services efficiently. This analysis reviewed the reduction in partial-fill expenditures with a secondary focus on workload expenditures following the execution of this education.

Methods

This project was deemed to be a QI project and did not require institutional review board approval. Implementation for this QI project began in November 2016. Baseline raw drug cost, number, and class of prescriptions partialed were retrospectively collected for a 90-day period prior to implementation using all available data. Postintervention data were collected for 90 days following the implementation phase to compare partial-fill expenditures and workload expenditures with baseline data.

Calculations

Materials included in the partial-fill expenditure calculation were prescription vials, prescription vial caps, and prescription labeling. Material cost per partial fill was determined by using the facility’s wholesaler acquisition unit costs to estimate a summed cost for an individual prescription vial and prescription vial cap. The estimated acquisition price of 7 prescription-labeling pages was used in the material calculation, as this was the average number of pages used when performing test partial fills.

The following equation was used to calculate total partial-fill expenditures for any specified time frame:

Total partial-fill expenditure = total raw drug cost + (material cost × number of partial fills)

In addition, the average personnel cost per partial-fill prescription was determined. Average workload expenditure per partial fill was calculated by filling a subset of 10 test prescriptions and multiplying the average time spent by an average of the general station (GS) rate for pharmacists and technicians. The average hourly rate of a GS-12 pharmacist was calculated based on an average of the 10 available pay grades within the GS-12 ranking. The average hourly rate of a GS-6 pharmacy technician was calculated based on an average of the 10 available pay grades within the GS-6 ranking.³ The average workload expenditures were calculated using the following equations:

Average pharmacist workload expenditure per partial fill = time (in hours) × average hourly rate.

Average technician workload expenditure per partial fill = time (in hours) × average hourly rate.

Partial-Fill Guidance

Updated partial-fill guidance was drafted designating acceptable prescriptions to be limited to those responsible for preventing hospitalization and treatment of acute illness. This guidance provided generalized examples of medication classes that could be acceptable for partial filling, though it was not intended to be an all-inclusive list. The guidance also noted examples of classes or groups that should not be partial filled for nonemergent reasons (vitamins, nonprescription items, antilipemics), as well as controlled substances. The refill-process education was reiterated throughout the entirety of the guidance. Specifically, if a pharmacy staff member was to perform a partial fill, a review explaining the appropriate refill process to the veteran also must be provided. If the medication was determined to be of emergent need and not yet transmitted for filling via the CMOP, the directive recommended to fill the entire quantity locally as a onetime fill.

If a onetime on-site fill was determined infeasible, partial-fill quantities were recommended to be limited to only a 7-day supply, and the full quantity filled through the CMOP. Anticipated mail wait time for CMOP prescription delivery was estimated to be less than 7 days based on experience, local pending queues, and guidance from the regional CMOP; however, time could vary among VA and CMOP facilities. Original prescriptions were to be filled for the entire quantity for the first fill at the on-site pharmacy if requested by the veteran. If the pharmacy had an insufficient quantity for an entire initial supply, it could then be partial filled for a 7-day supply and then filled through the CMOP.

The final portion of the partial-fill guidance pertained to the use of partial-fill justification codes. Prior to the execution of the partial-fill guidance, free text was entered into the comments field when processing a partial-fill prescription, as the prescription-processing system used requires a comment to proceed with the partial fill. The use of these codes served to streamline data collection in the postintervention phase and helped identify areas for further education following the close of this project.

Education

Education to the pharmacy staff was disseminated by various modalities, including in-person sessions and written and electronic correspondences. This written guidance was distributed to pharmacy staff by e-mail, the pharmacy newsletter (R_x-tra), signage posted throughout the outpatient pharmacies, and on the facility’s pharmacy Microsoft SharePoint (Redmond, WA) site. In-services provided during pharmacy staff meetings detailed information on the updated partial-fill guidance. A FVAMC Talent Management System (TMS) training module was developed and assigned to all pharmacy service staff to reiterate key points regarding this QI initiative (eAppendix).

Nonpharmacy staff were educated through staff and in-service meetings and e-mail correspondences. These in-services emphasized how nurses, medical support assistants, and health care providers (HCPs) could assist veterans by knowing the correct refill process, ensuring sufficient refills remained until the next appointment, and providing continual refill-process education.

Following implementation, all veterans receiving prescriptions through the on-site pharmacies in the FVAMC were provided a copy of the refill-process handout with each trip to the pharmacy. Nonpharmacy staff and HCPs also were provided this handout to distribute to patients. The intent of this handout was to clearly detail the various ways in which refills could be ordered and the time frame in which they should be ordered. The pharmacy became involved in new patient orientation classes for all veterans new to FVAMC. Digital signage and messaging was created and circulated throughout several of the FVAMC facilities.

Results

The results of calculations for material cost, personnel time spent, hourly employee rates, and average workload expenditure per partial fill are summarized in Table 1.

Following the implementation of partial-fill and refill-process education, there was a 54.3% decrease in the total number of partial fills from 5,596 in the 90 days prior to implementation, to 2,555 partials completed over the 90 days postimplementation. Regarding the primary objective, total partial-fill expenditures decreased from $52,015.44 to $44,063.01 (-15.3%). When dissecting the individual components of partial-fill expenditures, material expenditures decreased from $1,454.96 to $664.28 (-54.3%), and raw drug cost expenditures decreased from $50,596.48 to $43,398.73 (-14.3%). Workload expenditures also decreased from $27,140.60 to $12,391.75 (-54.3%).

Several points of descriptive information also were collected. The average days’ supply trended down from a mode of 10 days to 7 days. This reduction in days’ supply likely was seen because staff became more aware of the customary amount required to bridge the veteran until the CMOP supply arrived by mail. Postintervention data showed a 70% utilization of partial-fill reasoning codes. The reasons for partial filling of prescriptions are summarized in Table 2. 

Discussion

Following the implementation of the updated partial-fill guidance and provision of education to the FVAMC veterans and staff, a noteworthy cost savings was observed with respect to both material and workload expenditures. This large reduction in expenditure likely was not related to a reduction in the total prescription volume, as the number of total prescriptions filled by the CMOP and at FVAMC were similar in both the preliminary and postintervention periods. When the results of this 3-month QI project were extrapolated, the annual projected cost avoidance was $91,949.12.

Of note, there was no established process for adjudicating appeals to the partial-fill guidance. Any extenuating circumstances that fell outside the guidance were addressed by the outpatient pharmacy supervisor. There was no formal documentation for these disputed cases. Since there was no prespecified supervisory override code, the most appropriate partial-fill code was entered into the comments field for these scenarios. As such, there is no way to distinguish precisely how many of these partial fills were escalated to a supervisory level for a decision.

The positive fiscal impact noted from the implementation of this project should not be viewed as the only utility for such guidance. Though not directly measured within the confines of this project, a reduction in pharmacy staff time spent on partial-fill prescriptions will likely result in shorter pharmacy wait times, line lengths, and streamlining of pharmacy workflow. When the pharmacy staff is free to work on pressing issues rather than on continually educating veterans on the partial-fill or refill process, many will benefit. Veteran satisfaction was not directly measured during this project but could be an interesting topic to review as a future study.

Each VA facility is unique, with its own challenges for implementation of a project such as this. Nevertheless, the incorporation of a formal guidance and education process, perhaps adapted to the indi vidual facility’s needs may be considered for overall pharmacy operations QI.

Limitations

During the preliminary data collection period, FVAMC and its catchment area were impacted by a natural disaster, Hurricane Matthew. Based on a review of the text entered into the comments field for all partial fills, about 4% of the partial fills completed in the preliminary phase can be attributed to the hurricane. The effects of this hurricane may have potentially increased the number of partial fills completed in the preliminary phase compared with that in the postintervention phase, due to the number of veterans who were temporarily or permanently displaced from their homes. This increase in partial fills and associated expenses preintervention likely caused a slightly higher cost savings to be reflected in the postimplementation phase than what would have traditionally been observed without extenuating factors.

Several other limitations must be considered for this QI project. The implementation phase, during which all education and training was completed, was only 1 month. A longer implementation period and more opportunities to educate veterans and staff might have created a greater impact on the results. Additionally, because there were no data collected on New Patient Orientation attendance for this project, it is unclear exactly how many veterans received refill-process education through this outlet.

Though all staff members were trained on the appropriate process, it was discovered during interim analysis that several pharmacists were not following the partial-fill guidance, potentially negatively impacting the results. It is likely that staff would have benefited from continual reeducation of the process throughout the entirety of the project, as the restriction of partial filling was a novel concept to many. In addition to continual reeducation of current employees, any new hires would likely need this information as part of initial training.

Cost variance in the type of partial fills completed between the preliminary and postintervention phases also may have negatively impacted the results. The postintervention phase contained 2 high-cost classes of drugs (antivirals and immunoglobulins) that received multiple partial fills but were not partialed in the preliminary phase, which increased the raw drug cost in the postintervention phase.

Conclusion

The implementation of partial-fill and process education to FVAMC staff and veterans proved beneficial in reducing the expenditures and workload associated with partial-fill prescription processing. The continued use of the updated partial-fill guidance will provide a standardized approach for pharmacy staff when completing partial-fill prescriptions.

Facilities may consider annual reeducation on their guidance through a local TMS module, as well as occasional process reminders during staff meetings to improve staff adherence to the guidance. Moreover, the sustained incorporation of improved refill process education to new patients and with every prescription pickup could help guide the FVAMC veteran population to use pharmacy services more effectively. The adoption of such procedures may be useful for VA facilities’ health care system looking to maximize the use of funding provided for prescription services as well as improve veterans’ understanding of how to appropriately order prescription refills.

Exercise might help compensate for a high genetic risk of cardiovascular disease, according to the findings of a large prospective observational cohort study.

High-risk individuals in the top cardiorespiratory fitness tertile had a 49% lower risk of coronary heart disease (hazard ratio, 0.51; 95% confidence interval, 0.38-0.69) and a 60% lower risk of atrial fibrillation (HR, 0.40; 95% CI, 0.30-0.55) compared with those in the bottom fitness tertile, reported Emmi Tikkanen, PhD, of Stanford (Calif.) University, and her associates. The study was published in Circulation.

Little is known about whether exercise offsets genetic risk for cardiovascular disease. For the study, the researchers measured grip strength, cardiorespiratory fitness (based on net oxygen consumption while riding a stationary bicycle), cardiovascular events, and mortality among 482,702 participants in the UK Biobank longitudinal cohort study. More than half of individuals were women and none had baseline evidence of heart disease. The researchers stratified cases of coronary artery disease (CHD) and atrial fibrillation (AF) by whether individuals were at high, intermediate, or low genetic risk based on genome-wide association data.

Over a median follow-up period of 6.1 years (interquartile range, 5.4 to 6.8 years), there were nearly 21,000 cardiovascular events, including more than 8,000 cases of CHD and nearly 10,000 cases of AF. For all risk groups, increased grip strength and cardiorespiratory fitness were associated with a significantly lower risk of CHD and AF (P less than .001), even after adjustment for demographic factors, diabetes, smoking, systolic blood pressure, body mass index, and use of lipid-lowering medications.

The researchers did not look closely at types or durations of exercise. “Future studies evaluating the effects of strength versus aerobic training on subclinical or clinical cardiovascular outcomes could help to tailor exercise programs for individuals with elevated genetic risk for these diseases,” they wrote.

Funders included the National Institutes of Health, Knut and Alice Wallenberg Foundation, Finnish Cultural Foundation, Finnish Foundation for Cardiovascular Research, and Emil Aaltonen Foundation. Coauthor Erik Ingelsson, MD, disclosed advisory relationships with Precision Wellness and Olink Proteomics. The other authors reported having no conflicts of interest.

SOURCE: Tikkanen E et al. Circulation. 2018 Apr 9. doi: 10.1161/CIRCULATIONAHA.117.032432.

Exercise might help compensate for a high genetic risk of cardiovascular disease, according to the findings of a large prospective observational cohort study.

High-risk individuals in the top cardiorespiratory fitness tertile had a 49% lower risk of coronary heart disease (hazard ratio, 0.51; 95% confidence interval, 0.38-0.69) and a 60% lower risk of atrial fibrillation (HR, 0.40; 95% CI, 0.30-0.55) compared with those in the bottom fitness tertile, reported Emmi Tikkanen, PhD, of Stanford (Calif.) University, and her associates. The study was published in Circulation.

Little is known about whether exercise offsets genetic risk for cardiovascular disease. For the study, the researchers measured grip strength, cardiorespiratory fitness (based on net oxygen consumption while riding a stationary bicycle), cardiovascular events, and mortality among 482,702 participants in the UK Biobank longitudinal cohort study. More than half of individuals were women and none had baseline evidence of heart disease. The researchers stratified cases of coronary artery disease (CHD) and atrial fibrillation (AF) by whether individuals were at high, intermediate, or low genetic risk based on genome-wide association data.

Over a median follow-up period of 6.1 years (interquartile range, 5.4 to 6.8 years), there were nearly 21,000 cardiovascular events, including more than 8,000 cases of CHD and nearly 10,000 cases of AF. For all risk groups, increased grip strength and cardiorespiratory fitness were associated with a significantly lower risk of CHD and AF (P less than .001), even after adjustment for demographic factors, diabetes, smoking, systolic blood pressure, body mass index, and use of lipid-lowering medications.

The researchers did not look closely at types or durations of exercise. “Future studies evaluating the effects of strength versus aerobic training on subclinical or clinical cardiovascular outcomes could help to tailor exercise programs for individuals with elevated genetic risk for these diseases,” they wrote.

Funders included the National Institutes of Health, Knut and Alice Wallenberg Foundation, Finnish Cultural Foundation, Finnish Foundation for Cardiovascular Research, and Emil Aaltonen Foundation. Coauthor Erik Ingelsson, MD, disclosed advisory relationships with Precision Wellness and Olink Proteomics. The other authors reported having no conflicts of interest.

SOURCE: Tikkanen E et al. Circulation. 2018 Apr 9. doi: 10.1161/CIRCULATIONAHA.117.032432.

Exercise might help compensate for a high genetic risk of cardiovascular disease, according to the findings of a large prospective observational cohort study.

High-risk individuals in the top cardiorespiratory fitness tertile had a 49% lower risk of coronary heart disease (hazard ratio, 0.51; 95% confidence interval, 0.38-0.69) and a 60% lower risk of atrial fibrillation (HR, 0.40; 95% CI, 0.30-0.55) compared with those in the bottom fitness tertile, reported Emmi Tikkanen, PhD, of Stanford (Calif.) University, and her associates. The study was published in Circulation.

Little is known about whether exercise offsets genetic risk for cardiovascular disease. For the study, the researchers measured grip strength, cardiorespiratory fitness (based on net oxygen consumption while riding a stationary bicycle), cardiovascular events, and mortality among 482,702 participants in the UK Biobank longitudinal cohort study. More than half of individuals were women and none had baseline evidence of heart disease. The researchers stratified cases of coronary artery disease (CHD) and atrial fibrillation (AF) by whether individuals were at high, intermediate, or low genetic risk based on genome-wide association data.

Over a median follow-up period of 6.1 years (interquartile range, 5.4 to 6.8 years), there were nearly 21,000 cardiovascular events, including more than 8,000 cases of CHD and nearly 10,000 cases of AF. For all risk groups, increased grip strength and cardiorespiratory fitness were associated with a significantly lower risk of CHD and AF (P less than .001), even after adjustment for demographic factors, diabetes, smoking, systolic blood pressure, body mass index, and use of lipid-lowering medications.

The researchers did not look closely at types or durations of exercise. “Future studies evaluating the effects of strength versus aerobic training on subclinical or clinical cardiovascular outcomes could help to tailor exercise programs for individuals with elevated genetic risk for these diseases,” they wrote.

Funders included the National Institutes of Health, Knut and Alice Wallenberg Foundation, Finnish Cultural Foundation, Finnish Foundation for Cardiovascular Research, and Emil Aaltonen Foundation. Coauthor Erik Ingelsson, MD, disclosed advisory relationships with Precision Wellness and Olink Proteomics. The other authors reported having no conflicts of interest.

SOURCE: Tikkanen E et al. Circulation. 2018 Apr 9. doi: 10.1161/CIRCULATIONAHA.117.032432.

Cancer Research Center

Single-cell analysis has revealed key genetic events in a type of T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.

The team tracked the branching pattern of evolution in STIL-TAL1-positive T-ALL and identified mutations that may trigger development of the disease.

The researchers believe their findings could be used in minimal residual disease assessments as well as for the development of new targeted drugs.

Caroline Furness, MD, of Institute of Cancer Research in London, UK, and her colleagues described this research in Leukemia.

To determine the sequence of mutational events in STIL-TAL1-positive T-ALL, the researchers examined individual leukemia cells from 19 children and young adults with the disease, as well as 1 cell line with the STIL-TAL1 rearrangement (RPMI 8402).

The team found the STIL-TAL1 gene fusion and inactivation of the CDKN2A gene occurred very early in leukemia development.

The researchers said it was difficult to tell whether STIL-TAL1 fusion or CDKN2A loss are initiating events in this disease, and it isn’t clear which mutational event occurs first.

However, the team believes the STIL-TAL1 fusion is likely a founder or truncal event for this type of leukemia, so targeting the TAL1 regulatory complex could be an effective way to treat the disease.

The researchers also identified mutations in NOTCH1 and PTEN as secondary subclonal events.

Half of the samples examined had errors affecting PTEN, which suggests these events are key to maintaining leukemia growth and survival in STIL-TAL1-positive T-ALL, according to the researchers.

“We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development and which are important for driving its growth and spread,” Dr Furness said.

“Our study uncovered these crucial mutations in a type of leukemia that accounts for around a quarter of cases of T-cell leukemia in children and young adults. This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”

Cancer Research Center

Single-cell analysis has revealed key genetic events in a type of T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.

The team tracked the branching pattern of evolution in STIL-TAL1-positive T-ALL and identified mutations that may trigger development of the disease.

The researchers believe their findings could be used in minimal residual disease assessments as well as for the development of new targeted drugs.

Caroline Furness, MD, of Institute of Cancer Research in London, UK, and her colleagues described this research in Leukemia.

To determine the sequence of mutational events in STIL-TAL1-positive T-ALL, the researchers examined individual leukemia cells from 19 children and young adults with the disease, as well as 1 cell line with the STIL-TAL1 rearrangement (RPMI 8402).

The team found the STIL-TAL1 gene fusion and inactivation of the CDKN2A gene occurred very early in leukemia development.

The researchers said it was difficult to tell whether STIL-TAL1 fusion or CDKN2A loss are initiating events in this disease, and it isn’t clear which mutational event occurs first.

However, the team believes the STIL-TAL1 fusion is likely a founder or truncal event for this type of leukemia, so targeting the TAL1 regulatory complex could be an effective way to treat the disease.

The researchers also identified mutations in NOTCH1 and PTEN as secondary subclonal events.

Half of the samples examined had errors affecting PTEN, which suggests these events are key to maintaining leukemia growth and survival in STIL-TAL1-positive T-ALL, according to the researchers.

“We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development and which are important for driving its growth and spread,” Dr Furness said.

“Our study uncovered these crucial mutations in a type of leukemia that accounts for around a quarter of cases of T-cell leukemia in children and young adults. This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”

Cancer Research Center

Single-cell analysis has revealed key genetic events in a type of T-cell acute lymphoblastic leukemia (T-ALL), according to researchers.

The team tracked the branching pattern of evolution in STIL-TAL1-positive T-ALL and identified mutations that may trigger development of the disease.

The researchers believe their findings could be used in minimal residual disease assessments as well as for the development of new targeted drugs.

Caroline Furness, MD, of Institute of Cancer Research in London, UK, and her colleagues described this research in Leukemia.

To determine the sequence of mutational events in STIL-TAL1-positive T-ALL, the researchers examined individual leukemia cells from 19 children and young adults with the disease, as well as 1 cell line with the STIL-TAL1 rearrangement (RPMI 8402).

The team found the STIL-TAL1 gene fusion and inactivation of the CDKN2A gene occurred very early in leukemia development.

The researchers said it was difficult to tell whether STIL-TAL1 fusion or CDKN2A loss are initiating events in this disease, and it isn’t clear which mutational event occurs first.

However, the team believes the STIL-TAL1 fusion is likely a founder or truncal event for this type of leukemia, so targeting the TAL1 regulatory complex could be an effective way to treat the disease.

The researchers also identified mutations in NOTCH1 and PTEN as secondary subclonal events.

Half of the samples examined had errors affecting PTEN, which suggests these events are key to maintaining leukemia growth and survival in STIL-TAL1-positive T-ALL, according to the researchers.

“We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development and which are important for driving its growth and spread,” Dr Furness said.

“Our study uncovered these crucial mutations in a type of leukemia that accounts for around a quarter of cases of T-cell leukemia in children and young adults. This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”

Children born very preterm continue to display language difficulties compared with term controls at 13 years of age, with no evidence of developmental “catch up.”

Given the functional implications associated with language deficits, early language-based interventions should be considered for children born VP, investigators wrote in Pediatrics.

“Difficulties in language functioning in this cohort of children born VP remained stable from 2 to 13 years of age. Although generalized language deficits were observed, the VP group had marked difficulties on expressive components of language,” wrote Thi-Nhu-Ngoc Nguyen, BSc, of Monash University, Melbourne, and her associates.

©michaeljung/Thinkstock

[email protected]

Children born very preterm continue to display language difficulties compared with term controls at 13 years of age, with no evidence of developmental “catch up.”

Given the functional implications associated with language deficits, early language-based interventions should be considered for children born VP, investigators wrote in Pediatrics.

“Difficulties in language functioning in this cohort of children born VP remained stable from 2 to 13 years of age. Although generalized language deficits were observed, the VP group had marked difficulties on expressive components of language,” wrote Thi-Nhu-Ngoc Nguyen, BSc, of Monash University, Melbourne, and her associates.

©michaeljung/Thinkstock

[email protected]

Children born very preterm continue to display language difficulties compared with term controls at 13 years of age, with no evidence of developmental “catch up.”

Given the functional implications associated with language deficits, early language-based interventions should be considered for children born VP, investigators wrote in Pediatrics.

“Difficulties in language functioning in this cohort of children born VP remained stable from 2 to 13 years of age. Although generalized language deficits were observed, the VP group had marked difficulties on expressive components of language,” wrote Thi-Nhu-Ngoc Nguyen, BSc, of Monash University, Melbourne, and her associates.

©michaeljung/Thinkstock

[email protected]

ANSWER

The radiograph demonstrates no acute injury to the wrist. There is, however, a subtle nondisplaced fracture of the distal fifth metacarpal joint. The patient was given a wrist splint for symptomatic relief, and orthopedic follow-up was coordinated.

ANSWER

The radiograph demonstrates no acute injury to the wrist. There is, however, a subtle nondisplaced fracture of the distal fifth metacarpal joint. The patient was given a wrist splint for symptomatic relief, and orthopedic follow-up was coordinated.

ANSWER

The radiograph demonstrates no acute injury to the wrist. There is, however, a subtle nondisplaced fracture of the distal fifth metacarpal joint. The patient was given a wrist splint for symptomatic relief, and orthopedic follow-up was coordinated.

Clinical question: Can we use readily available data to risk stratify patients who present to the emergency department in acute heart failure (AHF)?

Background: Although cardiac biomarkers such as troponin and B-natriuretic peptide have general prognostic value in patients with AHF presenting to the emergency department, these values do not reliably aid in determining patients’ risk for unfavorable outcomes at the time of clinical decision making. Currently available published scores for risk-stratifying patients with AHF in the ED have limited applicability.

Bottom line: The MEESSI-AHF risk score may be a helpful tool in identifying the risk of 30-day mortality in patients who present to the ED with AHF, but it is currently unclear if the score can be generalized to other populations.

Citation: Miro O et al. Predicting 30-day mortality for patients with acute heart failure in the emergency department: A cohort study. Ann Intern Med. 2017 Nov 21;167(10):698-705.

Dr. Maleque is assistant professor of medicine in the division of hospital medicine, Emory University, Atlanta.

Clinical question: Can we use readily available data to risk stratify patients who present to the emergency department in acute heart failure (AHF)?

Background: Although cardiac biomarkers such as troponin and B-natriuretic peptide have general prognostic value in patients with AHF presenting to the emergency department, these values do not reliably aid in determining patients’ risk for unfavorable outcomes at the time of clinical decision making. Currently available published scores for risk-stratifying patients with AHF in the ED have limited applicability.

Bottom line: The MEESSI-AHF risk score may be a helpful tool in identifying the risk of 30-day mortality in patients who present to the ED with AHF, but it is currently unclear if the score can be generalized to other populations.

Citation: Miro O et al. Predicting 30-day mortality for patients with acute heart failure in the emergency department: A cohort study. Ann Intern Med. 2017 Nov 21;167(10):698-705.

Dr. Maleque is assistant professor of medicine in the division of hospital medicine, Emory University, Atlanta.

Clinical question: Can we use readily available data to risk stratify patients who present to the emergency department in acute heart failure (AHF)?

Background: Although cardiac biomarkers such as troponin and B-natriuretic peptide have general prognostic value in patients with AHF presenting to the emergency department, these values do not reliably aid in determining patients’ risk for unfavorable outcomes at the time of clinical decision making. Currently available published scores for risk-stratifying patients with AHF in the ED have limited applicability.

Bottom line: The MEESSI-AHF risk score may be a helpful tool in identifying the risk of 30-day mortality in patients who present to the ED with AHF, but it is currently unclear if the score can be generalized to other populations.

Citation: Miro O et al. Predicting 30-day mortality for patients with acute heart failure in the emergency department: A cohort study. Ann Intern Med. 2017 Nov 21;167(10):698-705.

Dr. Maleque is assistant professor of medicine in the division of hospital medicine, Emory University, Atlanta.

ORLANDO – In a video interview, Nasim Afsar, MD, SFHM, details the career road that led her to the “tremendous honor” of becoming president of the Society of Hospital Medicine.

Having been on the board of directors for 6 years was a profound experience, according to Dr. Afsar, and now as president she looks to take what she has learned and focus on the future of the field.

When asked about her overall vision for the coming year for the Society, Dr. Afsar said that she is committed to “an unrelenting focus on delivering value to our patients, our institutions, and society, and the way we do that is through population health management.”

ORLANDO – In a video interview, Nasim Afsar, MD, SFHM, details the career road that led her to the “tremendous honor” of becoming president of the Society of Hospital Medicine.

Having been on the board of directors for 6 years was a profound experience, according to Dr. Afsar, and now as president she looks to take what she has learned and focus on the future of the field.

When asked about her overall vision for the coming year for the Society, Dr. Afsar said that she is committed to “an unrelenting focus on delivering value to our patients, our institutions, and society, and the way we do that is through population health management.”

ORLANDO – In a video interview, Nasim Afsar, MD, SFHM, details the career road that led her to the “tremendous honor” of becoming president of the Society of Hospital Medicine.

Having been on the board of directors for 6 years was a profound experience, according to Dr. Afsar, and now as president she looks to take what she has learned and focus on the future of the field.

When asked about her overall vision for the coming year for the Society, Dr. Afsar said that she is committed to “an unrelenting focus on delivering value to our patients, our institutions, and society, and the way we do that is through population health management.”