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Improving Care and Reducing Length of Stay in Patients Undergoing Total Knee Replacement
Many improvements in health care today involve care coordination across the entire health care system. Active management of an orthopedic surgery service from a system perspective allows for improvements that can favorably impact readmissions and length of stay (LOS) for patients.1 The following is an example of a systemwide process improvement in total knee replacement (TKR) surgery that dramatically decreased 30-day readmissions and shortened the LOS during a 12-month period.\
Background
The VA is the largest integrated health care system in the U.S. VA hospitals use the VA Surgical Quality Improvement Program (VASQIP) to monitor surgical services. Initially known as the National Surgery Quality Improvement Program (NSQIP), the program began in 1994 to help provide reliable, valid information on patient presurgical factors, processes of care during surgery, and 30-day morbidity and mortality rates in VA hospitals.2 Since its inception, NSQIP has spread to the private sector and is now widely used throughout the U.S.
Using on-site data acquisition by specially trained and dedicated registered nurses, information on each surgical case is input into a quality program. Quarterly reports are distributed to each hospital, and a comparison of mortality, LOS, 30-day readmissions to the hospital, and other data are analyzed and presented by quarter and rolling 12-month time frames. Use of VASQIP data allows improvement of the structures and processes of care throughout the VA, providing safer surgery for veterans.
At the Phoenix VA Health Care System (PVAHCS) in Arizona, the third quarter 2014 report showed the rolling 12-month average LOS for orthopedic TKR patients was 3.5 days and corresponding 30-day readmissions were 7.9%. Using a systems improvement approach, the authors set a goal of reducing these metrics by 10%.
The orthopedic service engaged members of the hospitalist, anesthesia, physical therapy (PT), nursing, social work, primary care, and pharmacy services, as well as hospital administration. Twelve months later, the LOS for TKR patients declined 20% to 2.8 days. Corresponding 30-day readmissions declined for the patients with knee replacement to 3.4%—a 57% reduction in 1 year. Mortality for these 177 cases was zero.
To accomplish these improvements, the authors divided the surgical procedure into preoperative, perioperative, and postoperative time frames and looked at process improvement during each of these periods. The following is a summary of the various processes that the authors feel contributed to the reduced LOS and 30-day readmission rate. Although some of these interventions were in place before the study period, all the processes were standardized for TKRs through surgeon consensus, and each of the surgeons adopted all the processes during the study period.
Preoperative Processes
In the VA primary care-based model orthopedic surgery is accessed through a consult process in the electronic health record. The orthopedic surgery service reviews each new consult and makes recommendations for optimization at the time the consult was received. This process was used to work closely with primary care providers to preoperatively prepare patients. The orthopedic surgery service advocates smoking cessation, substance abuse treatment, weight loss with an ideal body mass index of ≤ 35, and diabetes mellitus (DM) management with a ≤ 7 hemoglobin A1c value.3-7
This management did not result in fewer patients receiving TKR. In fact, the volume of TKR patients increased by 8% over the study period. Although part of this increase could have been due to increased scheduling efficiency, the orthopedic surgery service worked closely with primary care, nutrition, and medicine services to optimize these patients so they could be placed on the schedule for surgery.
Preoperative Education
Physical therapy and the orthopedic preprocedure clinic provided preoperative education to patients, covering preoperative chlorhexidine body washes, home safety, use of a walker, anticipated LOS, use of ambulatory sequential compressive devices, use of a knee cooling device, as well as PT protocols during hospitalization.8 This helped increase postoperative patient adherence and helped patients anticipate an appropriate LOS. Health care providers worked with patients to understand their home environment and plan for caregivers to assist them in the immediate postoperative period.
Intraoperative Processes
Reducing Blood Loss
The orthopedic surgery service reviewed literature related to the efficacy and safety of tranexamic acid. Based on the literature, the orthopedic surgery service arrived at a consensus agreement to implement a topical tranexamic acid dose of 3 g/100 cc saline for each TKR. Presentation of the pertinent literature to the pharmacy service allowed placement of this medication on the formulary for intraoperative use in the TKR cases.
Specific processes were implemented that involved the orthopedic service ordering tranexamic acid in advance for each patient, pharmacy mixing the solution and having it ready in a timely manner, and the operating room sending a messenger to the pharmacy to pick up a sterile container of the tranexamic acid/saline solution. Postoperative blood loss and transfusions decreased. Less anemia contributed to better performance and less fatigue in PT, which helped move patients down a pathway for quicker discharge.9,10
DVT Mechanical Prophylaxis
The orthopedic surgery service was concerned about adherence with stationary sequential compressive devices for mechanical thromboembolic prophylaxis. Patients had to remove them for PT, ambulation in the halls, and visiting the restroom, and then nurses had to replace them. A literature review examined a mobile compressive device that could be maintained during ambulation, and a demonstration for the orthopedic surgery service was arranged. The orthopedic service decided to change to the newer device, and the mobile compression device was presented to the PVAHCS Therapeutics Committee. Subsequently the new device was implemented after the appropriate in-service of the various clinic, PT, ward, surgery, preoperative, and postoperative personnel.11 The device was initiated in the holding area prior to surgery, continued throughout the hospitalization, and taken home by the patient for 2 weeks of use following surgery. Patients were instructed to return the device to clinic at their 2-week follow-up appointment.
Infection Control
A dilute betadine lavage was instituted for each surgical case, using the pulsatile lavage followed by a lactated Ringer solution rinse prior to TKR implantation. Additionally, the wound was lavaged prior to closure with this dilute betadine solution.12
Pain Control
Immediately before surgery, patients received oral morphine sulfate and celecoxib. A local 2% lidocaine with epinephrine injection was used at the surgical incision and joint after the skin prep and immediately prior to the skin incision. Patients received a mixture of ropivicaine .5%/20 mL, morphine sulfate 10 mg, and toradol 30 mg at the capsular region prior to implantation of the total knee prosthesis. At the end of the procedure, an additional 20 mL of 2% lidocaine was injected into the joint once the capsule was closed. This improved postoperative pain, decreased postoperative opioid dosing, and allowed for earlier ambulation with PT.13
PostOperative Processes
Deep Vein Thrombosis (DVT) Chemoprophylaxis
Once the chest physician guidelines-approved stand-alone mobile compressive devices was implemented, orthopedic surgery service revisited the chemoprophylaxis for routine low-risk patients. Use of subcutaneously daily injections of 2.5 mg fondiparinux was switched to 81 mg enteric-coated aspirin administered orally twice daily. The authors believe this further reduced the postoperative bleeding and transfusion risks. There was not an increase in DVT or pulmonary embolism complications.14,15
Physical Therapy
Partnering with PT, a 2-day LOS protocol was established. Patients were introduced to this protocol in a preoperative PT teaching class, and it was reinforced during the hospital stay. Patients who had earlier cases in the day were seen by PT the day of surgery when staffing and scheduling permitted. Early ambulation contributed significantly to earlier discharge for patients.16 Early ambulation also has been shown to decrease thromboembolic complications in orthopedic total joint patients.
Pain and Nausea Management
Parenteral narcotics were avoided, and oral narcotics were implemented with a graduated dosing based on a 10-point pain scale
Use of a postoperative cooling device that circulated cool water through a pad over the patient’s knee was instituted to assist with pain control. The patient received instruction on this device at the preoperative education sessions and was given the device to continue at home postdischarge.
Hospitalist Comanagement
Comanagement of orthopedic patients with hospitalists has become a standard practice nationally. The orthopedic surgery service works closely with the hospitalist team who see each total joint patient on postoperative admission to the ward. The orthopedic team handles all aspects of PT, wound management, pain control, and DVT prophylaxis. The hospitalist focuses on the remainder of comorbid conditions such as DM, chronic obstructive pulmonary disease, and underlying cardiac conditions.
The American Society of Anesthesiologists (ASA) average score was 2.8 for these procedures. Despite comprehensive preoperative screening, older patients with more comorbidities (higher ASA score) are more prone to emerging complications.17 Integration of the hospitalist team into the care of every orthopedic total joint patient facilitates prompt recognition and mitigation of these complications as they occur, directly reducing overall severity and LOS and allowing safe recovery from the surgical procedure.18,19
Conclusion
At the start of this system improvement, the previous 12-month data showed 164 knee replacements with a 4.9-day VA national LOS and 3.5- day PVAHCS LOS. At the end of the 12-month system improvement, the VA national LOS for TKR was 4.8 days, and at PVAHCS it was 2.8 days.
The 30-day readmission rate was 8.4% nationally and 7.9% at PVAHCS. After the system improvements, the national 30-day readmission rate was 7.1%, while the PVAHCS rate dropped to less than half the national rate: 3.4%.
It is important to note, that the improvements in the aforementioned multiple processes could not have been possible without a dedicated effort from the multiple stakeholders involved. Hospitalists, primary care, PT, pharmacy, operating room staff, anesthesia, preprocedure staff, floor nurses, the Commodities and Therapeutics Committee, and administration all partnered with the orthopedic surgery service to produce the improvements in LOS and corresponding reduction in 30-day readmissions.
These data suggest that there does not need to be an inherent tradeoff between LOS and 30-day readmissions. Rather, both measures can be managed independently to produce improvements across the service. A team approach to process improvement can allow for increased efficiency while providing safer care for patients.
1. Dundon JM, Bosco J, Slover J, Yu S, Sayeed Y, Iorio R. Improvement in total joint replacement quality metrics, year one versus year three of the bundled payments for care improvement initiative. J Bone Joint Surg Am. 2016;98(23):1949-1953.
2. Itani KM. Fifteen years of the National Surgical Quality Improvement Program in review. Am J Surg. 2009;198(suppl 5):S9-S18.
3. Tayton ER, Frampton C, Hooper GJ, Young SW. The impact of patient and surgical factors on the rate of infection after primary total knee arthroplasty: an analysis of 64,566 joints from the New Zealand Joint Registry. Bone Joint J. 2016;98-B(3):334-340.
4. Heller S, Rezapoor M, Parvizi J. Minimising the risk of infection: a peri-operative checklist. Bone Joint J. 2016;98-B(1)(suppl A):18-22.
5. Thornqvist C, Gislason GH, Køber L, Jensen PF, Torp-Pedersen C, Andersson C. Body mass index and risk of perioperative cardiovascular adverse events and mortality in 34,744 Danish patients undergoing hip or knee replacement. Acta Orthop. 2014;85(5):456-462.
6. Stryker LS, Abdel MP, Morrey ME, Morrow MM, Kor DJ, Morrey BF. Elevated postoperative blood glucose and preoperative hemoglobin A1C are associated with increased wound complications following total joint arthroplasty. J Bone Joint Surg Am. 2013;95(9):808-814.
7. Akhavan S, Nguyen LC, Chan V, Saleh J, Bozic KJ. Impact of smoking cessation counseling prior to total joint arthroplasty. Orthopedics. 2017;40(2):e323-e328.
8. Kim DH, Spencer M, Davidson SM, et al. Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery. J Bone Joint Surg Am. 2010;92(9):1820-1826.
9. Goyal N, Chen DB, Harris IA, Rowden NJ, Kirsh G, MacDessi SJ. Intravenous vs intra-articular tranexamic acid in total knee arthroplasty: a randomized, double-blind trial. J Arthroplasty. 2017;32(1):28-32.
10. Phan DL, Ani F, Schwarzkopf R. Cost analysis of tranexamic acid in anemic total joint arthroplasty patients. J Arthroplasty. 2016;31(3):579-582.
11. Colwell CW Jr, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535.
12. Chundamala J, Wright JG. The efficacy and risks of using povidone-iodine irrigation to prevent surgical site infection: an evidence-based review. Can J Surg. 2007;50(6):473-481.
13. Fang R, Liu Z, Alijiang A, et al. Efficacy of intra-articular local anesthetics in total knee arthroplasty. Orthopedics. 2015;38(7):e573-e581.
14. Odeh K, Doran J, Yu S, Bolz N, Bosco J, Iorio R. Risk-stratified venous thromboembolism prophylaxis after total joint arthroplasty: aspirin and sequential pneumatic compression devices vs aggressive chemoprophylaxis. J Arthroplasty. 2016;31(suppl 9):78-82.
15. Parvizi J, Huang R, Restrepo C, et al. Low-dose aspirin is effective chemoprophylaxis against clinically important venous thromboembolism following total joint arthroplasty: a preliminary analysis. J Bone Joint Surg Am. 2017;99(2):91-98.
16. Robertson NB, Warganich T, Ghazarossian J, Khatod M. Implementation of an accelerated rehabilitation protocol for total joint arthroplasty in the managed care setting: the experience of one institution. Adv Orthop Surg. 2015;(2015):387197.
17. Hooper GJ, Rothwell AG, Hooper NM, Frampton C. The relationship between the American Society of Anesthesiologists physical rating and outcome following total hip and knee arthroplasty: an analysis of the New Zealand Joint Registry. J Bone Joint Surg Am. 2012;94(12):1065-1070.
18. Parry MC, Smith AJ, Blom AW. Early death following primary total knee arthroplasty. J Bone Joint Surg Am. 2011;93(10):948-953.
19. Parvizi J, Mui A, Purtill JJ, Sharkey PF, Hozack WJ, Rothman RH. Total joint arthroplasty: when do fatal or near-fatal complications occur? J Bone Joint Surg Am. 2007;89(1):27-32.
Many improvements in health care today involve care coordination across the entire health care system. Active management of an orthopedic surgery service from a system perspective allows for improvements that can favorably impact readmissions and length of stay (LOS) for patients.1 The following is an example of a systemwide process improvement in total knee replacement (TKR) surgery that dramatically decreased 30-day readmissions and shortened the LOS during a 12-month period.\
Background
The VA is the largest integrated health care system in the U.S. VA hospitals use the VA Surgical Quality Improvement Program (VASQIP) to monitor surgical services. Initially known as the National Surgery Quality Improvement Program (NSQIP), the program began in 1994 to help provide reliable, valid information on patient presurgical factors, processes of care during surgery, and 30-day morbidity and mortality rates in VA hospitals.2 Since its inception, NSQIP has spread to the private sector and is now widely used throughout the U.S.
Using on-site data acquisition by specially trained and dedicated registered nurses, information on each surgical case is input into a quality program. Quarterly reports are distributed to each hospital, and a comparison of mortality, LOS, 30-day readmissions to the hospital, and other data are analyzed and presented by quarter and rolling 12-month time frames. Use of VASQIP data allows improvement of the structures and processes of care throughout the VA, providing safer surgery for veterans.
At the Phoenix VA Health Care System (PVAHCS) in Arizona, the third quarter 2014 report showed the rolling 12-month average LOS for orthopedic TKR patients was 3.5 days and corresponding 30-day readmissions were 7.9%. Using a systems improvement approach, the authors set a goal of reducing these metrics by 10%.
The orthopedic service engaged members of the hospitalist, anesthesia, physical therapy (PT), nursing, social work, primary care, and pharmacy services, as well as hospital administration. Twelve months later, the LOS for TKR patients declined 20% to 2.8 days. Corresponding 30-day readmissions declined for the patients with knee replacement to 3.4%—a 57% reduction in 1 year. Mortality for these 177 cases was zero.
To accomplish these improvements, the authors divided the surgical procedure into preoperative, perioperative, and postoperative time frames and looked at process improvement during each of these periods. The following is a summary of the various processes that the authors feel contributed to the reduced LOS and 30-day readmission rate. Although some of these interventions were in place before the study period, all the processes were standardized for TKRs through surgeon consensus, and each of the surgeons adopted all the processes during the study period.
Preoperative Processes
In the VA primary care-based model orthopedic surgery is accessed through a consult process in the electronic health record. The orthopedic surgery service reviews each new consult and makes recommendations for optimization at the time the consult was received. This process was used to work closely with primary care providers to preoperatively prepare patients. The orthopedic surgery service advocates smoking cessation, substance abuse treatment, weight loss with an ideal body mass index of ≤ 35, and diabetes mellitus (DM) management with a ≤ 7 hemoglobin A1c value.3-7
This management did not result in fewer patients receiving TKR. In fact, the volume of TKR patients increased by 8% over the study period. Although part of this increase could have been due to increased scheduling efficiency, the orthopedic surgery service worked closely with primary care, nutrition, and medicine services to optimize these patients so they could be placed on the schedule for surgery.
Preoperative Education
Physical therapy and the orthopedic preprocedure clinic provided preoperative education to patients, covering preoperative chlorhexidine body washes, home safety, use of a walker, anticipated LOS, use of ambulatory sequential compressive devices, use of a knee cooling device, as well as PT protocols during hospitalization.8 This helped increase postoperative patient adherence and helped patients anticipate an appropriate LOS. Health care providers worked with patients to understand their home environment and plan for caregivers to assist them in the immediate postoperative period.
Intraoperative Processes
Reducing Blood Loss
The orthopedic surgery service reviewed literature related to the efficacy and safety of tranexamic acid. Based on the literature, the orthopedic surgery service arrived at a consensus agreement to implement a topical tranexamic acid dose of 3 g/100 cc saline for each TKR. Presentation of the pertinent literature to the pharmacy service allowed placement of this medication on the formulary for intraoperative use in the TKR cases.
Specific processes were implemented that involved the orthopedic service ordering tranexamic acid in advance for each patient, pharmacy mixing the solution and having it ready in a timely manner, and the operating room sending a messenger to the pharmacy to pick up a sterile container of the tranexamic acid/saline solution. Postoperative blood loss and transfusions decreased. Less anemia contributed to better performance and less fatigue in PT, which helped move patients down a pathway for quicker discharge.9,10
DVT Mechanical Prophylaxis
The orthopedic surgery service was concerned about adherence with stationary sequential compressive devices for mechanical thromboembolic prophylaxis. Patients had to remove them for PT, ambulation in the halls, and visiting the restroom, and then nurses had to replace them. A literature review examined a mobile compressive device that could be maintained during ambulation, and a demonstration for the orthopedic surgery service was arranged. The orthopedic service decided to change to the newer device, and the mobile compression device was presented to the PVAHCS Therapeutics Committee. Subsequently the new device was implemented after the appropriate in-service of the various clinic, PT, ward, surgery, preoperative, and postoperative personnel.11 The device was initiated in the holding area prior to surgery, continued throughout the hospitalization, and taken home by the patient for 2 weeks of use following surgery. Patients were instructed to return the device to clinic at their 2-week follow-up appointment.
Infection Control
A dilute betadine lavage was instituted for each surgical case, using the pulsatile lavage followed by a lactated Ringer solution rinse prior to TKR implantation. Additionally, the wound was lavaged prior to closure with this dilute betadine solution.12
Pain Control
Immediately before surgery, patients received oral morphine sulfate and celecoxib. A local 2% lidocaine with epinephrine injection was used at the surgical incision and joint after the skin prep and immediately prior to the skin incision. Patients received a mixture of ropivicaine .5%/20 mL, morphine sulfate 10 mg, and toradol 30 mg at the capsular region prior to implantation of the total knee prosthesis. At the end of the procedure, an additional 20 mL of 2% lidocaine was injected into the joint once the capsule was closed. This improved postoperative pain, decreased postoperative opioid dosing, and allowed for earlier ambulation with PT.13
PostOperative Processes
Deep Vein Thrombosis (DVT) Chemoprophylaxis
Once the chest physician guidelines-approved stand-alone mobile compressive devices was implemented, orthopedic surgery service revisited the chemoprophylaxis for routine low-risk patients. Use of subcutaneously daily injections of 2.5 mg fondiparinux was switched to 81 mg enteric-coated aspirin administered orally twice daily. The authors believe this further reduced the postoperative bleeding and transfusion risks. There was not an increase in DVT or pulmonary embolism complications.14,15
Physical Therapy
Partnering with PT, a 2-day LOS protocol was established. Patients were introduced to this protocol in a preoperative PT teaching class, and it was reinforced during the hospital stay. Patients who had earlier cases in the day were seen by PT the day of surgery when staffing and scheduling permitted. Early ambulation contributed significantly to earlier discharge for patients.16 Early ambulation also has been shown to decrease thromboembolic complications in orthopedic total joint patients.
Pain and Nausea Management
Parenteral narcotics were avoided, and oral narcotics were implemented with a graduated dosing based on a 10-point pain scale
Use of a postoperative cooling device that circulated cool water through a pad over the patient’s knee was instituted to assist with pain control. The patient received instruction on this device at the preoperative education sessions and was given the device to continue at home postdischarge.
Hospitalist Comanagement
Comanagement of orthopedic patients with hospitalists has become a standard practice nationally. The orthopedic surgery service works closely with the hospitalist team who see each total joint patient on postoperative admission to the ward. The orthopedic team handles all aspects of PT, wound management, pain control, and DVT prophylaxis. The hospitalist focuses on the remainder of comorbid conditions such as DM, chronic obstructive pulmonary disease, and underlying cardiac conditions.
The American Society of Anesthesiologists (ASA) average score was 2.8 for these procedures. Despite comprehensive preoperative screening, older patients with more comorbidities (higher ASA score) are more prone to emerging complications.17 Integration of the hospitalist team into the care of every orthopedic total joint patient facilitates prompt recognition and mitigation of these complications as they occur, directly reducing overall severity and LOS and allowing safe recovery from the surgical procedure.18,19
Conclusion
At the start of this system improvement, the previous 12-month data showed 164 knee replacements with a 4.9-day VA national LOS and 3.5- day PVAHCS LOS. At the end of the 12-month system improvement, the VA national LOS for TKR was 4.8 days, and at PVAHCS it was 2.8 days.
The 30-day readmission rate was 8.4% nationally and 7.9% at PVAHCS. After the system improvements, the national 30-day readmission rate was 7.1%, while the PVAHCS rate dropped to less than half the national rate: 3.4%.
It is important to note, that the improvements in the aforementioned multiple processes could not have been possible without a dedicated effort from the multiple stakeholders involved. Hospitalists, primary care, PT, pharmacy, operating room staff, anesthesia, preprocedure staff, floor nurses, the Commodities and Therapeutics Committee, and administration all partnered with the orthopedic surgery service to produce the improvements in LOS and corresponding reduction in 30-day readmissions.
These data suggest that there does not need to be an inherent tradeoff between LOS and 30-day readmissions. Rather, both measures can be managed independently to produce improvements across the service. A team approach to process improvement can allow for increased efficiency while providing safer care for patients.
Many improvements in health care today involve care coordination across the entire health care system. Active management of an orthopedic surgery service from a system perspective allows for improvements that can favorably impact readmissions and length of stay (LOS) for patients.1 The following is an example of a systemwide process improvement in total knee replacement (TKR) surgery that dramatically decreased 30-day readmissions and shortened the LOS during a 12-month period.\
Background
The VA is the largest integrated health care system in the U.S. VA hospitals use the VA Surgical Quality Improvement Program (VASQIP) to monitor surgical services. Initially known as the National Surgery Quality Improvement Program (NSQIP), the program began in 1994 to help provide reliable, valid information on patient presurgical factors, processes of care during surgery, and 30-day morbidity and mortality rates in VA hospitals.2 Since its inception, NSQIP has spread to the private sector and is now widely used throughout the U.S.
Using on-site data acquisition by specially trained and dedicated registered nurses, information on each surgical case is input into a quality program. Quarterly reports are distributed to each hospital, and a comparison of mortality, LOS, 30-day readmissions to the hospital, and other data are analyzed and presented by quarter and rolling 12-month time frames. Use of VASQIP data allows improvement of the structures and processes of care throughout the VA, providing safer surgery for veterans.
At the Phoenix VA Health Care System (PVAHCS) in Arizona, the third quarter 2014 report showed the rolling 12-month average LOS for orthopedic TKR patients was 3.5 days and corresponding 30-day readmissions were 7.9%. Using a systems improvement approach, the authors set a goal of reducing these metrics by 10%.
The orthopedic service engaged members of the hospitalist, anesthesia, physical therapy (PT), nursing, social work, primary care, and pharmacy services, as well as hospital administration. Twelve months later, the LOS for TKR patients declined 20% to 2.8 days. Corresponding 30-day readmissions declined for the patients with knee replacement to 3.4%—a 57% reduction in 1 year. Mortality for these 177 cases was zero.
To accomplish these improvements, the authors divided the surgical procedure into preoperative, perioperative, and postoperative time frames and looked at process improvement during each of these periods. The following is a summary of the various processes that the authors feel contributed to the reduced LOS and 30-day readmission rate. Although some of these interventions were in place before the study period, all the processes were standardized for TKRs through surgeon consensus, and each of the surgeons adopted all the processes during the study period.
Preoperative Processes
In the VA primary care-based model orthopedic surgery is accessed through a consult process in the electronic health record. The orthopedic surgery service reviews each new consult and makes recommendations for optimization at the time the consult was received. This process was used to work closely with primary care providers to preoperatively prepare patients. The orthopedic surgery service advocates smoking cessation, substance abuse treatment, weight loss with an ideal body mass index of ≤ 35, and diabetes mellitus (DM) management with a ≤ 7 hemoglobin A1c value.3-7
This management did not result in fewer patients receiving TKR. In fact, the volume of TKR patients increased by 8% over the study period. Although part of this increase could have been due to increased scheduling efficiency, the orthopedic surgery service worked closely with primary care, nutrition, and medicine services to optimize these patients so they could be placed on the schedule for surgery.
Preoperative Education
Physical therapy and the orthopedic preprocedure clinic provided preoperative education to patients, covering preoperative chlorhexidine body washes, home safety, use of a walker, anticipated LOS, use of ambulatory sequential compressive devices, use of a knee cooling device, as well as PT protocols during hospitalization.8 This helped increase postoperative patient adherence and helped patients anticipate an appropriate LOS. Health care providers worked with patients to understand their home environment and plan for caregivers to assist them in the immediate postoperative period.
Intraoperative Processes
Reducing Blood Loss
The orthopedic surgery service reviewed literature related to the efficacy and safety of tranexamic acid. Based on the literature, the orthopedic surgery service arrived at a consensus agreement to implement a topical tranexamic acid dose of 3 g/100 cc saline for each TKR. Presentation of the pertinent literature to the pharmacy service allowed placement of this medication on the formulary for intraoperative use in the TKR cases.
Specific processes were implemented that involved the orthopedic service ordering tranexamic acid in advance for each patient, pharmacy mixing the solution and having it ready in a timely manner, and the operating room sending a messenger to the pharmacy to pick up a sterile container of the tranexamic acid/saline solution. Postoperative blood loss and transfusions decreased. Less anemia contributed to better performance and less fatigue in PT, which helped move patients down a pathway for quicker discharge.9,10
DVT Mechanical Prophylaxis
The orthopedic surgery service was concerned about adherence with stationary sequential compressive devices for mechanical thromboembolic prophylaxis. Patients had to remove them for PT, ambulation in the halls, and visiting the restroom, and then nurses had to replace them. A literature review examined a mobile compressive device that could be maintained during ambulation, and a demonstration for the orthopedic surgery service was arranged. The orthopedic service decided to change to the newer device, and the mobile compression device was presented to the PVAHCS Therapeutics Committee. Subsequently the new device was implemented after the appropriate in-service of the various clinic, PT, ward, surgery, preoperative, and postoperative personnel.11 The device was initiated in the holding area prior to surgery, continued throughout the hospitalization, and taken home by the patient for 2 weeks of use following surgery. Patients were instructed to return the device to clinic at their 2-week follow-up appointment.
Infection Control
A dilute betadine lavage was instituted for each surgical case, using the pulsatile lavage followed by a lactated Ringer solution rinse prior to TKR implantation. Additionally, the wound was lavaged prior to closure with this dilute betadine solution.12
Pain Control
Immediately before surgery, patients received oral morphine sulfate and celecoxib. A local 2% lidocaine with epinephrine injection was used at the surgical incision and joint after the skin prep and immediately prior to the skin incision. Patients received a mixture of ropivicaine .5%/20 mL, morphine sulfate 10 mg, and toradol 30 mg at the capsular region prior to implantation of the total knee prosthesis. At the end of the procedure, an additional 20 mL of 2% lidocaine was injected into the joint once the capsule was closed. This improved postoperative pain, decreased postoperative opioid dosing, and allowed for earlier ambulation with PT.13
PostOperative Processes
Deep Vein Thrombosis (DVT) Chemoprophylaxis
Once the chest physician guidelines-approved stand-alone mobile compressive devices was implemented, orthopedic surgery service revisited the chemoprophylaxis for routine low-risk patients. Use of subcutaneously daily injections of 2.5 mg fondiparinux was switched to 81 mg enteric-coated aspirin administered orally twice daily. The authors believe this further reduced the postoperative bleeding and transfusion risks. There was not an increase in DVT or pulmonary embolism complications.14,15
Physical Therapy
Partnering with PT, a 2-day LOS protocol was established. Patients were introduced to this protocol in a preoperative PT teaching class, and it was reinforced during the hospital stay. Patients who had earlier cases in the day were seen by PT the day of surgery when staffing and scheduling permitted. Early ambulation contributed significantly to earlier discharge for patients.16 Early ambulation also has been shown to decrease thromboembolic complications in orthopedic total joint patients.
Pain and Nausea Management
Parenteral narcotics were avoided, and oral narcotics were implemented with a graduated dosing based on a 10-point pain scale
Use of a postoperative cooling device that circulated cool water through a pad over the patient’s knee was instituted to assist with pain control. The patient received instruction on this device at the preoperative education sessions and was given the device to continue at home postdischarge.
Hospitalist Comanagement
Comanagement of orthopedic patients with hospitalists has become a standard practice nationally. The orthopedic surgery service works closely with the hospitalist team who see each total joint patient on postoperative admission to the ward. The orthopedic team handles all aspects of PT, wound management, pain control, and DVT prophylaxis. The hospitalist focuses on the remainder of comorbid conditions such as DM, chronic obstructive pulmonary disease, and underlying cardiac conditions.
The American Society of Anesthesiologists (ASA) average score was 2.8 for these procedures. Despite comprehensive preoperative screening, older patients with more comorbidities (higher ASA score) are more prone to emerging complications.17 Integration of the hospitalist team into the care of every orthopedic total joint patient facilitates prompt recognition and mitigation of these complications as they occur, directly reducing overall severity and LOS and allowing safe recovery from the surgical procedure.18,19
Conclusion
At the start of this system improvement, the previous 12-month data showed 164 knee replacements with a 4.9-day VA national LOS and 3.5- day PVAHCS LOS. At the end of the 12-month system improvement, the VA national LOS for TKR was 4.8 days, and at PVAHCS it was 2.8 days.
The 30-day readmission rate was 8.4% nationally and 7.9% at PVAHCS. After the system improvements, the national 30-day readmission rate was 7.1%, while the PVAHCS rate dropped to less than half the national rate: 3.4%.
It is important to note, that the improvements in the aforementioned multiple processes could not have been possible without a dedicated effort from the multiple stakeholders involved. Hospitalists, primary care, PT, pharmacy, operating room staff, anesthesia, preprocedure staff, floor nurses, the Commodities and Therapeutics Committee, and administration all partnered with the orthopedic surgery service to produce the improvements in LOS and corresponding reduction in 30-day readmissions.
These data suggest that there does not need to be an inherent tradeoff between LOS and 30-day readmissions. Rather, both measures can be managed independently to produce improvements across the service. A team approach to process improvement can allow for increased efficiency while providing safer care for patients.
1. Dundon JM, Bosco J, Slover J, Yu S, Sayeed Y, Iorio R. Improvement in total joint replacement quality metrics, year one versus year three of the bundled payments for care improvement initiative. J Bone Joint Surg Am. 2016;98(23):1949-1953.
2. Itani KM. Fifteen years of the National Surgical Quality Improvement Program in review. Am J Surg. 2009;198(suppl 5):S9-S18.
3. Tayton ER, Frampton C, Hooper GJ, Young SW. The impact of patient and surgical factors on the rate of infection after primary total knee arthroplasty: an analysis of 64,566 joints from the New Zealand Joint Registry. Bone Joint J. 2016;98-B(3):334-340.
4. Heller S, Rezapoor M, Parvizi J. Minimising the risk of infection: a peri-operative checklist. Bone Joint J. 2016;98-B(1)(suppl A):18-22.
5. Thornqvist C, Gislason GH, Køber L, Jensen PF, Torp-Pedersen C, Andersson C. Body mass index and risk of perioperative cardiovascular adverse events and mortality in 34,744 Danish patients undergoing hip or knee replacement. Acta Orthop. 2014;85(5):456-462.
6. Stryker LS, Abdel MP, Morrey ME, Morrow MM, Kor DJ, Morrey BF. Elevated postoperative blood glucose and preoperative hemoglobin A1C are associated with increased wound complications following total joint arthroplasty. J Bone Joint Surg Am. 2013;95(9):808-814.
7. Akhavan S, Nguyen LC, Chan V, Saleh J, Bozic KJ. Impact of smoking cessation counseling prior to total joint arthroplasty. Orthopedics. 2017;40(2):e323-e328.
8. Kim DH, Spencer M, Davidson SM, et al. Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery. J Bone Joint Surg Am. 2010;92(9):1820-1826.
9. Goyal N, Chen DB, Harris IA, Rowden NJ, Kirsh G, MacDessi SJ. Intravenous vs intra-articular tranexamic acid in total knee arthroplasty: a randomized, double-blind trial. J Arthroplasty. 2017;32(1):28-32.
10. Phan DL, Ani F, Schwarzkopf R. Cost analysis of tranexamic acid in anemic total joint arthroplasty patients. J Arthroplasty. 2016;31(3):579-582.
11. Colwell CW Jr, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535.
12. Chundamala J, Wright JG. The efficacy and risks of using povidone-iodine irrigation to prevent surgical site infection: an evidence-based review. Can J Surg. 2007;50(6):473-481.
13. Fang R, Liu Z, Alijiang A, et al. Efficacy of intra-articular local anesthetics in total knee arthroplasty. Orthopedics. 2015;38(7):e573-e581.
14. Odeh K, Doran J, Yu S, Bolz N, Bosco J, Iorio R. Risk-stratified venous thromboembolism prophylaxis after total joint arthroplasty: aspirin and sequential pneumatic compression devices vs aggressive chemoprophylaxis. J Arthroplasty. 2016;31(suppl 9):78-82.
15. Parvizi J, Huang R, Restrepo C, et al. Low-dose aspirin is effective chemoprophylaxis against clinically important venous thromboembolism following total joint arthroplasty: a preliminary analysis. J Bone Joint Surg Am. 2017;99(2):91-98.
16. Robertson NB, Warganich T, Ghazarossian J, Khatod M. Implementation of an accelerated rehabilitation protocol for total joint arthroplasty in the managed care setting: the experience of one institution. Adv Orthop Surg. 2015;(2015):387197.
17. Hooper GJ, Rothwell AG, Hooper NM, Frampton C. The relationship between the American Society of Anesthesiologists physical rating and outcome following total hip and knee arthroplasty: an analysis of the New Zealand Joint Registry. J Bone Joint Surg Am. 2012;94(12):1065-1070.
18. Parry MC, Smith AJ, Blom AW. Early death following primary total knee arthroplasty. J Bone Joint Surg Am. 2011;93(10):948-953.
19. Parvizi J, Mui A, Purtill JJ, Sharkey PF, Hozack WJ, Rothman RH. Total joint arthroplasty: when do fatal or near-fatal complications occur? J Bone Joint Surg Am. 2007;89(1):27-32.
1. Dundon JM, Bosco J, Slover J, Yu S, Sayeed Y, Iorio R. Improvement in total joint replacement quality metrics, year one versus year three of the bundled payments for care improvement initiative. J Bone Joint Surg Am. 2016;98(23):1949-1953.
2. Itani KM. Fifteen years of the National Surgical Quality Improvement Program in review. Am J Surg. 2009;198(suppl 5):S9-S18.
3. Tayton ER, Frampton C, Hooper GJ, Young SW. The impact of patient and surgical factors on the rate of infection after primary total knee arthroplasty: an analysis of 64,566 joints from the New Zealand Joint Registry. Bone Joint J. 2016;98-B(3):334-340.
4. Heller S, Rezapoor M, Parvizi J. Minimising the risk of infection: a peri-operative checklist. Bone Joint J. 2016;98-B(1)(suppl A):18-22.
5. Thornqvist C, Gislason GH, Køber L, Jensen PF, Torp-Pedersen C, Andersson C. Body mass index and risk of perioperative cardiovascular adverse events and mortality in 34,744 Danish patients undergoing hip or knee replacement. Acta Orthop. 2014;85(5):456-462.
6. Stryker LS, Abdel MP, Morrey ME, Morrow MM, Kor DJ, Morrey BF. Elevated postoperative blood glucose and preoperative hemoglobin A1C are associated with increased wound complications following total joint arthroplasty. J Bone Joint Surg Am. 2013;95(9):808-814.
7. Akhavan S, Nguyen LC, Chan V, Saleh J, Bozic KJ. Impact of smoking cessation counseling prior to total joint arthroplasty. Orthopedics. 2017;40(2):e323-e328.
8. Kim DH, Spencer M, Davidson SM, et al. Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery. J Bone Joint Surg Am. 2010;92(9):1820-1826.
9. Goyal N, Chen DB, Harris IA, Rowden NJ, Kirsh G, MacDessi SJ. Intravenous vs intra-articular tranexamic acid in total knee arthroplasty: a randomized, double-blind trial. J Arthroplasty. 2017;32(1):28-32.
10. Phan DL, Ani F, Schwarzkopf R. Cost analysis of tranexamic acid in anemic total joint arthroplasty patients. J Arthroplasty. 2016;31(3):579-582.
11. Colwell CW Jr, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535.
12. Chundamala J, Wright JG. The efficacy and risks of using povidone-iodine irrigation to prevent surgical site infection: an evidence-based review. Can J Surg. 2007;50(6):473-481.
13. Fang R, Liu Z, Alijiang A, et al. Efficacy of intra-articular local anesthetics in total knee arthroplasty. Orthopedics. 2015;38(7):e573-e581.
14. Odeh K, Doran J, Yu S, Bolz N, Bosco J, Iorio R. Risk-stratified venous thromboembolism prophylaxis after total joint arthroplasty: aspirin and sequential pneumatic compression devices vs aggressive chemoprophylaxis. J Arthroplasty. 2016;31(suppl 9):78-82.
15. Parvizi J, Huang R, Restrepo C, et al. Low-dose aspirin is effective chemoprophylaxis against clinically important venous thromboembolism following total joint arthroplasty: a preliminary analysis. J Bone Joint Surg Am. 2017;99(2):91-98.
16. Robertson NB, Warganich T, Ghazarossian J, Khatod M. Implementation of an accelerated rehabilitation protocol for total joint arthroplasty in the managed care setting: the experience of one institution. Adv Orthop Surg. 2015;(2015):387197.
17. Hooper GJ, Rothwell AG, Hooper NM, Frampton C. The relationship between the American Society of Anesthesiologists physical rating and outcome following total hip and knee arthroplasty: an analysis of the New Zealand Joint Registry. J Bone Joint Surg Am. 2012;94(12):1065-1070.
18. Parry MC, Smith AJ, Blom AW. Early death following primary total knee arthroplasty. J Bone Joint Surg Am. 2011;93(10):948-953.
19. Parvizi J, Mui A, Purtill JJ, Sharkey PF, Hozack WJ, Rothman RH. Total joint arthroplasty: when do fatal or near-fatal complications occur? J Bone Joint Surg Am. 2007;89(1):27-32.
Insurance approvals are hard to get for new PCSK9 inhibitors
Insurance approval rates for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are strikingly low, according to a study published in Circulation.
Two approved PCSK9i drugs, alirocumab and evolocumab, were approved for coverage just 47% of the time. Because of their high price tag – about $14,000 per year – researchers had expected low rates of insurance coverage for the novel drugs, which encourage degradation of low-density lipoprotein cholesterol by blocking preserving LDL-C receptors in hepatocytes. However, they were surprised at the size of the problem.
“I think we knew that physicians were having challenges, but the number [of coverage approvals] was maybe lower than we expected,” Robert Yeh, MD, the study’s lead investigator, said in an interview. “Physicians and patients need to be aware that in perhaps the majority of cases, when they decide these drugs are going to be ones they want to prescribe, there may be a long procedure ahead of them, and they may ultimately not succeed in getting those medications.”
PCSK9 inhibitors are specifically approved for patients with familial hypercholesterolemia, or those with atherosclerotic cardiovascular disease who are unable to achieve satisfactory lipid levels through dietary measures and statin use.
Yet insurance coverage rates were low, even when patients met labeled indications. When the researchers examined the factors associated with insurance coverage, the most important factor was the type of insurance: Commercial third-party insurers approved the drugs about 24% of the time, while Medicare approved them nearly 61% of the time (P less than .01).
Older age, prescriptions by a cardiologist or other specialist, and a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) were also associated with higher rates of coverage by insurers (Circulation. 2017 Oct 30. doi: 10.1161/CIRCULATIONAHA.117.028430).
The researchers analyzed data from 9,357 patients with a prescription for a PCSK9 inhibitor. About 60% of the patients had a diagnosis of clinical ASCVD. In all, 4,397 patients (47%) had their prescriptions for PCSK9 inhibitor therapy covered, and 53% of coverage requests were rejected. Nearly 65% of patients who received approval went on to fill their prescription.
There was no association between LDL-C level and the likelihood of approval. In the 32 cases in which the LDL-C levels were 330 mg/dL or greater, 59% of patients were not approved for coverage.
Noncommercial payers were more likely to approve the medication (odds ratio, 12.32; 95% confidence interval, 7.09-21.39), as was Medicare (OR, 5.37; 95% CI, 4.23-6.80).
A recent cost-effectiveness analysis of evolocumab added to standard therapy showed that an annual cost of $9,669 would achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life year gained among patients with LDL levels 70 mg/dL or greater. (JAMA Cardiol. 2017;2[10]:1069-78). Evolocumab is currently listed at $14,523, putting it above that value.
“Now that clinical trial outcome data demonstrating reductions in major cardiovascular events and formal cost-effectiveness studies have identified value-based prices for these medications, it would be hoped that progress can be made such that a greater proportion of eligible patients can be treated,” Gregg C. Fonarow, MD, professor of cardiovascular medicine and science director at the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and the lead author of the cost-effectiveness study, said in an interview.
Both sets of findings cut to the heart of the debate over pricing of new medications. PCSK9 inhibitors have a clear benefit in lowering LDL and reducing risk of heart attack, but the drugs’ price tags may limit their availability.
“We need to not be afraid to discuss these issues in plain terms that are not emotional, so that we can get a better sense of what is the amount to spend on a therapy, even when it is effective but potentially pricey,” said Dr. Yeh, director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center, Boston. “This is a really important business, philosophical, medical, and ethical debate.”
The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
Insurance approval rates for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are strikingly low, according to a study published in Circulation.
Two approved PCSK9i drugs, alirocumab and evolocumab, were approved for coverage just 47% of the time. Because of their high price tag – about $14,000 per year – researchers had expected low rates of insurance coverage for the novel drugs, which encourage degradation of low-density lipoprotein cholesterol by blocking preserving LDL-C receptors in hepatocytes. However, they were surprised at the size of the problem.
“I think we knew that physicians were having challenges, but the number [of coverage approvals] was maybe lower than we expected,” Robert Yeh, MD, the study’s lead investigator, said in an interview. “Physicians and patients need to be aware that in perhaps the majority of cases, when they decide these drugs are going to be ones they want to prescribe, there may be a long procedure ahead of them, and they may ultimately not succeed in getting those medications.”
PCSK9 inhibitors are specifically approved for patients with familial hypercholesterolemia, or those with atherosclerotic cardiovascular disease who are unable to achieve satisfactory lipid levels through dietary measures and statin use.
Yet insurance coverage rates were low, even when patients met labeled indications. When the researchers examined the factors associated with insurance coverage, the most important factor was the type of insurance: Commercial third-party insurers approved the drugs about 24% of the time, while Medicare approved them nearly 61% of the time (P less than .01).
Older age, prescriptions by a cardiologist or other specialist, and a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) were also associated with higher rates of coverage by insurers (Circulation. 2017 Oct 30. doi: 10.1161/CIRCULATIONAHA.117.028430).
The researchers analyzed data from 9,357 patients with a prescription for a PCSK9 inhibitor. About 60% of the patients had a diagnosis of clinical ASCVD. In all, 4,397 patients (47%) had their prescriptions for PCSK9 inhibitor therapy covered, and 53% of coverage requests were rejected. Nearly 65% of patients who received approval went on to fill their prescription.
There was no association between LDL-C level and the likelihood of approval. In the 32 cases in which the LDL-C levels were 330 mg/dL or greater, 59% of patients were not approved for coverage.
Noncommercial payers were more likely to approve the medication (odds ratio, 12.32; 95% confidence interval, 7.09-21.39), as was Medicare (OR, 5.37; 95% CI, 4.23-6.80).
A recent cost-effectiveness analysis of evolocumab added to standard therapy showed that an annual cost of $9,669 would achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life year gained among patients with LDL levels 70 mg/dL or greater. (JAMA Cardiol. 2017;2[10]:1069-78). Evolocumab is currently listed at $14,523, putting it above that value.
“Now that clinical trial outcome data demonstrating reductions in major cardiovascular events and formal cost-effectiveness studies have identified value-based prices for these medications, it would be hoped that progress can be made such that a greater proportion of eligible patients can be treated,” Gregg C. Fonarow, MD, professor of cardiovascular medicine and science director at the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and the lead author of the cost-effectiveness study, said in an interview.
Both sets of findings cut to the heart of the debate over pricing of new medications. PCSK9 inhibitors have a clear benefit in lowering LDL and reducing risk of heart attack, but the drugs’ price tags may limit their availability.
“We need to not be afraid to discuss these issues in plain terms that are not emotional, so that we can get a better sense of what is the amount to spend on a therapy, even when it is effective but potentially pricey,” said Dr. Yeh, director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center, Boston. “This is a really important business, philosophical, medical, and ethical debate.”
The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
Insurance approval rates for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are strikingly low, according to a study published in Circulation.
Two approved PCSK9i drugs, alirocumab and evolocumab, were approved for coverage just 47% of the time. Because of their high price tag – about $14,000 per year – researchers had expected low rates of insurance coverage for the novel drugs, which encourage degradation of low-density lipoprotein cholesterol by blocking preserving LDL-C receptors in hepatocytes. However, they were surprised at the size of the problem.
“I think we knew that physicians were having challenges, but the number [of coverage approvals] was maybe lower than we expected,” Robert Yeh, MD, the study’s lead investigator, said in an interview. “Physicians and patients need to be aware that in perhaps the majority of cases, when they decide these drugs are going to be ones they want to prescribe, there may be a long procedure ahead of them, and they may ultimately not succeed in getting those medications.”
PCSK9 inhibitors are specifically approved for patients with familial hypercholesterolemia, or those with atherosclerotic cardiovascular disease who are unable to achieve satisfactory lipid levels through dietary measures and statin use.
Yet insurance coverage rates were low, even when patients met labeled indications. When the researchers examined the factors associated with insurance coverage, the most important factor was the type of insurance: Commercial third-party insurers approved the drugs about 24% of the time, while Medicare approved them nearly 61% of the time (P less than .01).
Older age, prescriptions by a cardiologist or other specialist, and a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) were also associated with higher rates of coverage by insurers (Circulation. 2017 Oct 30. doi: 10.1161/CIRCULATIONAHA.117.028430).
The researchers analyzed data from 9,357 patients with a prescription for a PCSK9 inhibitor. About 60% of the patients had a diagnosis of clinical ASCVD. In all, 4,397 patients (47%) had their prescriptions for PCSK9 inhibitor therapy covered, and 53% of coverage requests were rejected. Nearly 65% of patients who received approval went on to fill their prescription.
There was no association between LDL-C level and the likelihood of approval. In the 32 cases in which the LDL-C levels were 330 mg/dL or greater, 59% of patients were not approved for coverage.
Noncommercial payers were more likely to approve the medication (odds ratio, 12.32; 95% confidence interval, 7.09-21.39), as was Medicare (OR, 5.37; 95% CI, 4.23-6.80).
A recent cost-effectiveness analysis of evolocumab added to standard therapy showed that an annual cost of $9,669 would achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life year gained among patients with LDL levels 70 mg/dL or greater. (JAMA Cardiol. 2017;2[10]:1069-78). Evolocumab is currently listed at $14,523, putting it above that value.
“Now that clinical trial outcome data demonstrating reductions in major cardiovascular events and formal cost-effectiveness studies have identified value-based prices for these medications, it would be hoped that progress can be made such that a greater proportion of eligible patients can be treated,” Gregg C. Fonarow, MD, professor of cardiovascular medicine and science director at the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and the lead author of the cost-effectiveness study, said in an interview.
Both sets of findings cut to the heart of the debate over pricing of new medications. PCSK9 inhibitors have a clear benefit in lowering LDL and reducing risk of heart attack, but the drugs’ price tags may limit their availability.
“We need to not be afraid to discuss these issues in plain terms that are not emotional, so that we can get a better sense of what is the amount to spend on a therapy, even when it is effective but potentially pricey,” said Dr. Yeh, director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center, Boston. “This is a really important business, philosophical, medical, and ethical debate.”
The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
FROM CIRCULATION
Key clinical point:
Major finding: Just 47% of PCSK9 inhibitor prescriptions were approved by insurers.
Data source: Retrospective analysis of data from 9,357 patients who were prescribed a PCSK9 inhibitor.
Disclosures: The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
Protein may be therapeutic target for MM
Preclinical research suggests the protein BMI-1 may be a therapeutic target for multiple myeloma (MM).
Researchers found that BMI-1 inhibition, with a drug called PTC-209, induced apoptosis in MM cell lines and primary cells.
In addition, PTC-209’s anti-myeloma activity was enhanced by inhibitors targeting EZH2 and BET bromodomains.
The researchers reported these results in Oncotarget.
The team noted that previous studies have suggested epigenetic alterations are involved in the development of MM. They chose to focus the current study on BMI-1 because it’s part of a protein complex involved in epigenetic regulation and could therefore be a potential target for influencing MM development.
“We used the substance PTC-209, which we know inhibits BMI-1, and treated cultivated multiple myeloma cells,” said study author Mohammad Alzrigat, PhD, of Uppsala University in Uppsala, Sweden.
“We used both cell lines that are continuously kept as cultivated cells and cells that were purified from multiple myeloma patients, either newly diagnosed or at relapse. In all cases, we found that [PTC-209] decreased cell survival, which indicates that PTC-209 has an anti-myeloma effect.”
The researchers said PTC-209 demonstrated “potent anti-myeloma activity, reducing the viability of MM cell lines at concentrations ranging up to 1.6 μM over 48 hours of treatment.” INA-6 was the cell line that proved most responsive to PTC-209, and U266-1970 was the least responsive.
The team also found that a 10 μM concentration of PTC-209 reduced the viability of all primary MM cells. This anti-myeloma activity was independent of disease state (whether patients were newly diagnosed or had relapsed disease) and cytogenetic karyotype.
“Our study showed that PTC-209 most likely functions as an anti-myeloma agent by inhibiting the production of BMI-1,” said study author Helena Jernberg-Wiklund, PhD, also of Uppsala University.
“We also saw that when PTC-209 was combined with other substances that inhibit epigenetic alterations, the myeloma cells’ survival was reduced even further compared to when only PTC-209 was used.”
Specifically, the researchers observed synergistic and additive activity when PTC-209 was combined with the EZH2 inhibitor UNC1999 and the BET inhibitor JQ1.
“Our results have both increased our understanding of how epigenetic alterations affect cancer development and shown how inhibiting these mechanisms in combination could potentially be utilized for future treatment of multiple myeloma patients, especially at relapse,” Dr Jernberg-Wiklund said.
Preclinical research suggests the protein BMI-1 may be a therapeutic target for multiple myeloma (MM).
Researchers found that BMI-1 inhibition, with a drug called PTC-209, induced apoptosis in MM cell lines and primary cells.
In addition, PTC-209’s anti-myeloma activity was enhanced by inhibitors targeting EZH2 and BET bromodomains.
The researchers reported these results in Oncotarget.
The team noted that previous studies have suggested epigenetic alterations are involved in the development of MM. They chose to focus the current study on BMI-1 because it’s part of a protein complex involved in epigenetic regulation and could therefore be a potential target for influencing MM development.
“We used the substance PTC-209, which we know inhibits BMI-1, and treated cultivated multiple myeloma cells,” said study author Mohammad Alzrigat, PhD, of Uppsala University in Uppsala, Sweden.
“We used both cell lines that are continuously kept as cultivated cells and cells that were purified from multiple myeloma patients, either newly diagnosed or at relapse. In all cases, we found that [PTC-209] decreased cell survival, which indicates that PTC-209 has an anti-myeloma effect.”
The researchers said PTC-209 demonstrated “potent anti-myeloma activity, reducing the viability of MM cell lines at concentrations ranging up to 1.6 μM over 48 hours of treatment.” INA-6 was the cell line that proved most responsive to PTC-209, and U266-1970 was the least responsive.
The team also found that a 10 μM concentration of PTC-209 reduced the viability of all primary MM cells. This anti-myeloma activity was independent of disease state (whether patients were newly diagnosed or had relapsed disease) and cytogenetic karyotype.
“Our study showed that PTC-209 most likely functions as an anti-myeloma agent by inhibiting the production of BMI-1,” said study author Helena Jernberg-Wiklund, PhD, also of Uppsala University.
“We also saw that when PTC-209 was combined with other substances that inhibit epigenetic alterations, the myeloma cells’ survival was reduced even further compared to when only PTC-209 was used.”
Specifically, the researchers observed synergistic and additive activity when PTC-209 was combined with the EZH2 inhibitor UNC1999 and the BET inhibitor JQ1.
“Our results have both increased our understanding of how epigenetic alterations affect cancer development and shown how inhibiting these mechanisms in combination could potentially be utilized for future treatment of multiple myeloma patients, especially at relapse,” Dr Jernberg-Wiklund said.
Preclinical research suggests the protein BMI-1 may be a therapeutic target for multiple myeloma (MM).
Researchers found that BMI-1 inhibition, with a drug called PTC-209, induced apoptosis in MM cell lines and primary cells.
In addition, PTC-209’s anti-myeloma activity was enhanced by inhibitors targeting EZH2 and BET bromodomains.
The researchers reported these results in Oncotarget.
The team noted that previous studies have suggested epigenetic alterations are involved in the development of MM. They chose to focus the current study on BMI-1 because it’s part of a protein complex involved in epigenetic regulation and could therefore be a potential target for influencing MM development.
“We used the substance PTC-209, which we know inhibits BMI-1, and treated cultivated multiple myeloma cells,” said study author Mohammad Alzrigat, PhD, of Uppsala University in Uppsala, Sweden.
“We used both cell lines that are continuously kept as cultivated cells and cells that were purified from multiple myeloma patients, either newly diagnosed or at relapse. In all cases, we found that [PTC-209] decreased cell survival, which indicates that PTC-209 has an anti-myeloma effect.”
The researchers said PTC-209 demonstrated “potent anti-myeloma activity, reducing the viability of MM cell lines at concentrations ranging up to 1.6 μM over 48 hours of treatment.” INA-6 was the cell line that proved most responsive to PTC-209, and U266-1970 was the least responsive.
The team also found that a 10 μM concentration of PTC-209 reduced the viability of all primary MM cells. This anti-myeloma activity was independent of disease state (whether patients were newly diagnosed or had relapsed disease) and cytogenetic karyotype.
“Our study showed that PTC-209 most likely functions as an anti-myeloma agent by inhibiting the production of BMI-1,” said study author Helena Jernberg-Wiklund, PhD, also of Uppsala University.
“We also saw that when PTC-209 was combined with other substances that inhibit epigenetic alterations, the myeloma cells’ survival was reduced even further compared to when only PTC-209 was used.”
Specifically, the researchers observed synergistic and additive activity when PTC-209 was combined with the EZH2 inhibitor UNC1999 and the BET inhibitor JQ1.
“Our results have both increased our understanding of how epigenetic alterations affect cancer development and shown how inhibiting these mechanisms in combination could potentially be utilized for future treatment of multiple myeloma patients, especially at relapse,” Dr Jernberg-Wiklund said.
Update on Diabetes Medications
Location matters when it comes to thyroidectomy rates
Thyroidectomy rates differ widely across the United States, according to a cross-sectional analysis of Medicare beneficiaries, but researchers aren’t sure what’s driving the variation.
There was a 6.2-fold difference in thyroidectomy rates across U.S. hospital referral regions in 2014, ranging from 22 to 139 per 100,000 Medicare beneficiaries. The national average was 60 procedures per 100,000 Medicare beneficiaries, David O. Francis, MD, of the University of Wisconsin, Madison, and his coauthors, reported (JAMA Otolaryngol Head Neck Surg. 2017 Oct 12. doi: 10.1001/jamaoto.2017.1746).
The researchers conducted a cross-sectional analysis of 15,888 Medicare beneficiaries aged 65 years and older who underwent a thyroidectomy in 2014. Of the thyroidectomies performed, 7,056 were partial and 8,382 were total thyroidectomies. They compared the frequency of partial and total thyroidectomies to total prostatectomy rates (high variation) and hospitalizations for hip fractures (low variation).
The stark variation in thyroidectomy outpaced those in hip fracture hospitalization (2.2-fold variation) and radical prostatectomy (5.6-fold variation) across U.S. hospital referral regions.
Higher rates of thyroidectomy were seen in Southern, Central, and certain urban regions of the United States.
But the variation in rates did not correlate with health care availability, socioeconomic status, or the availability of surgeons. This suggests that variation is caused by something other than disease burden. The researchers speculated that the “variability in thyroid surgery rates in areas with similar access to surgical services largely relates to local beliefs and practice patterns.”
The researchers also noted that the findings, which are based on Medicare data, may not be generalizable to young patients who account for more than half of all thyroidectomies performed in the United States.
The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
Thyroidectomy rates differ widely across the United States, according to a cross-sectional analysis of Medicare beneficiaries, but researchers aren’t sure what’s driving the variation.
There was a 6.2-fold difference in thyroidectomy rates across U.S. hospital referral regions in 2014, ranging from 22 to 139 per 100,000 Medicare beneficiaries. The national average was 60 procedures per 100,000 Medicare beneficiaries, David O. Francis, MD, of the University of Wisconsin, Madison, and his coauthors, reported (JAMA Otolaryngol Head Neck Surg. 2017 Oct 12. doi: 10.1001/jamaoto.2017.1746).
The researchers conducted a cross-sectional analysis of 15,888 Medicare beneficiaries aged 65 years and older who underwent a thyroidectomy in 2014. Of the thyroidectomies performed, 7,056 were partial and 8,382 were total thyroidectomies. They compared the frequency of partial and total thyroidectomies to total prostatectomy rates (high variation) and hospitalizations for hip fractures (low variation).
The stark variation in thyroidectomy outpaced those in hip fracture hospitalization (2.2-fold variation) and radical prostatectomy (5.6-fold variation) across U.S. hospital referral regions.
Higher rates of thyroidectomy were seen in Southern, Central, and certain urban regions of the United States.
But the variation in rates did not correlate with health care availability, socioeconomic status, or the availability of surgeons. This suggests that variation is caused by something other than disease burden. The researchers speculated that the “variability in thyroid surgery rates in areas with similar access to surgical services largely relates to local beliefs and practice patterns.”
The researchers also noted that the findings, which are based on Medicare data, may not be generalizable to young patients who account for more than half of all thyroidectomies performed in the United States.
The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
Thyroidectomy rates differ widely across the United States, according to a cross-sectional analysis of Medicare beneficiaries, but researchers aren’t sure what’s driving the variation.
There was a 6.2-fold difference in thyroidectomy rates across U.S. hospital referral regions in 2014, ranging from 22 to 139 per 100,000 Medicare beneficiaries. The national average was 60 procedures per 100,000 Medicare beneficiaries, David O. Francis, MD, of the University of Wisconsin, Madison, and his coauthors, reported (JAMA Otolaryngol Head Neck Surg. 2017 Oct 12. doi: 10.1001/jamaoto.2017.1746).
The researchers conducted a cross-sectional analysis of 15,888 Medicare beneficiaries aged 65 years and older who underwent a thyroidectomy in 2014. Of the thyroidectomies performed, 7,056 were partial and 8,382 were total thyroidectomies. They compared the frequency of partial and total thyroidectomies to total prostatectomy rates (high variation) and hospitalizations for hip fractures (low variation).
The stark variation in thyroidectomy outpaced those in hip fracture hospitalization (2.2-fold variation) and radical prostatectomy (5.6-fold variation) across U.S. hospital referral regions.
Higher rates of thyroidectomy were seen in Southern, Central, and certain urban regions of the United States.
But the variation in rates did not correlate with health care availability, socioeconomic status, or the availability of surgeons. This suggests that variation is caused by something other than disease burden. The researchers speculated that the “variability in thyroid surgery rates in areas with similar access to surgical services largely relates to local beliefs and practice patterns.”
The researchers also noted that the findings, which are based on Medicare data, may not be generalizable to young patients who account for more than half of all thyroidectomies performed in the United States.
The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
FROM JAMA OTOLARYNGOLOGY–HEAD & NECK SURGERY
Key clinical point:
Major finding: Thyroidectomy rates vary 6.2-fold across U.S. hospital referral regions.
Data source: A cross-sectional analysis of Medicare data for 15,888 patients in 2014.
Disclosures: This study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
Better trials, more cooperation needed to improve continuous glucose monitoring devices
When continuous glucose monitoring (CGM) devices were first introduced, many thought they would revolutionize intensive insulin therapy for patients with diabetes. More than 15 years later, uptake is increasing but still remains low.
An expert working group convened by the doi: 10.2337/dci17-0043).
“The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes,” John R. Petrie, MD, of the University of Glasgow, Scotland, and members of the working group wrote in the joint scientific statement.
Barriers to the uptake of CGM devices include cost and “human factors” issues such as the need for more audible alarms and easier-to-read displays, according to the joint statement. A lack of standardization in displaying results and uncertainty over the best way to use CGM data are also obstacles to widespread adoption.
The working group called for a systematic premarketing and postapproval evaluation of CGM system performance, as well as greater investment in clinical trials, including head-to-head comparisons and large independent registry studies. Other recommendations include the need for standardization of glucose data reporting, improved consistency and accessibility of postmarketing safety reports, and increased communication and cooperation between the various stakeholder groups.
The most important recommendation from the working group is the call for stakeholders to cooperate and communicate regularly, said A. Jay Cohen, MD, medical director of the Endocrine Clinic in Memphis, Tenn.
“That’s going to drive the momentum of change that’s going to help patients, and it’s also going to drive innovation,” he said.
After reviewing the joint scientific statement, Dr. Cohen said he would strongly encourage collaboration between stakeholders in government, insurance, clinical practice, industry, and patients to advance the use of CGM systems.
“The CGM systems have been not evolutionary, but revolutionary, in improvement in care for persons with diabetes and their families,” Dr. Cohen said. “They are a game changer, and besides … this unequivocally saves employers and insurers money, so it’s very cost effective in a very intuitive way.”
The joint scientific statement is based on review of more than 50 data sources, including recent clinical trials, research abstracts, regulatory authority databases, manufacturing company documents, and the clinical experience of the committee members.
“The guidelines set forth by this scientific statement will greatly inform providers and further advance the standardization, accuracy, and safety of CGM systems,” William T. Cefalu, MD, chief scientific, medical, and mission officer of the ADA, said in a statement.
Most members of the working group have relationships with industry, but industry “is considered to have had no impact on the manuscript or its content by reviewers from the ADA and EASD.”
When continuous glucose monitoring (CGM) devices were first introduced, many thought they would revolutionize intensive insulin therapy for patients with diabetes. More than 15 years later, uptake is increasing but still remains low.
An expert working group convened by the doi: 10.2337/dci17-0043).
“The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes,” John R. Petrie, MD, of the University of Glasgow, Scotland, and members of the working group wrote in the joint scientific statement.
Barriers to the uptake of CGM devices include cost and “human factors” issues such as the need for more audible alarms and easier-to-read displays, according to the joint statement. A lack of standardization in displaying results and uncertainty over the best way to use CGM data are also obstacles to widespread adoption.
The working group called for a systematic premarketing and postapproval evaluation of CGM system performance, as well as greater investment in clinical trials, including head-to-head comparisons and large independent registry studies. Other recommendations include the need for standardization of glucose data reporting, improved consistency and accessibility of postmarketing safety reports, and increased communication and cooperation between the various stakeholder groups.
The most important recommendation from the working group is the call for stakeholders to cooperate and communicate regularly, said A. Jay Cohen, MD, medical director of the Endocrine Clinic in Memphis, Tenn.
“That’s going to drive the momentum of change that’s going to help patients, and it’s also going to drive innovation,” he said.
After reviewing the joint scientific statement, Dr. Cohen said he would strongly encourage collaboration between stakeholders in government, insurance, clinical practice, industry, and patients to advance the use of CGM systems.
“The CGM systems have been not evolutionary, but revolutionary, in improvement in care for persons with diabetes and their families,” Dr. Cohen said. “They are a game changer, and besides … this unequivocally saves employers and insurers money, so it’s very cost effective in a very intuitive way.”
The joint scientific statement is based on review of more than 50 data sources, including recent clinical trials, research abstracts, regulatory authority databases, manufacturing company documents, and the clinical experience of the committee members.
“The guidelines set forth by this scientific statement will greatly inform providers and further advance the standardization, accuracy, and safety of CGM systems,” William T. Cefalu, MD, chief scientific, medical, and mission officer of the ADA, said in a statement.
Most members of the working group have relationships with industry, but industry “is considered to have had no impact on the manuscript or its content by reviewers from the ADA and EASD.”
When continuous glucose monitoring (CGM) devices were first introduced, many thought they would revolutionize intensive insulin therapy for patients with diabetes. More than 15 years later, uptake is increasing but still remains low.
An expert working group convened by the doi: 10.2337/dci17-0043).
“The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes,” John R. Petrie, MD, of the University of Glasgow, Scotland, and members of the working group wrote in the joint scientific statement.
Barriers to the uptake of CGM devices include cost and “human factors” issues such as the need for more audible alarms and easier-to-read displays, according to the joint statement. A lack of standardization in displaying results and uncertainty over the best way to use CGM data are also obstacles to widespread adoption.
The working group called for a systematic premarketing and postapproval evaluation of CGM system performance, as well as greater investment in clinical trials, including head-to-head comparisons and large independent registry studies. Other recommendations include the need for standardization of glucose data reporting, improved consistency and accessibility of postmarketing safety reports, and increased communication and cooperation between the various stakeholder groups.
The most important recommendation from the working group is the call for stakeholders to cooperate and communicate regularly, said A. Jay Cohen, MD, medical director of the Endocrine Clinic in Memphis, Tenn.
“That’s going to drive the momentum of change that’s going to help patients, and it’s also going to drive innovation,” he said.
After reviewing the joint scientific statement, Dr. Cohen said he would strongly encourage collaboration between stakeholders in government, insurance, clinical practice, industry, and patients to advance the use of CGM systems.
“The CGM systems have been not evolutionary, but revolutionary, in improvement in care for persons with diabetes and their families,” Dr. Cohen said. “They are a game changer, and besides … this unequivocally saves employers and insurers money, so it’s very cost effective in a very intuitive way.”
The joint scientific statement is based on review of more than 50 data sources, including recent clinical trials, research abstracts, regulatory authority databases, manufacturing company documents, and the clinical experience of the committee members.
“The guidelines set forth by this scientific statement will greatly inform providers and further advance the standardization, accuracy, and safety of CGM systems,” William T. Cefalu, MD, chief scientific, medical, and mission officer of the ADA, said in a statement.
Most members of the working group have relationships with industry, but industry “is considered to have had no impact on the manuscript or its content by reviewers from the ADA and EASD.”
FROM DIABETES CARE
Generic, brand-name levothyroxine have similar cardiovascular outcomes
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
AT ATA 2017
Key clinical point:
Major finding: Patients taking brand-name versus generic levothyroxine had similar risks of hospitalization for atrial fibrillation (HR, 1.22; P = .19), myocardial infarction (0.86; P = .35), congestive heart failure (0.88; P = .41), and stroke (0.77; P = .05).
Data source: A retrospective cohort study of 87,902 propensity-matched hypothyroid patients starting generic or brand-name levothyroxine.
Disclosures: Dr. Smallridge reported that he had no relevant conflicts of interest.
Rethinking lithium: It keeps patients with unipolar depression out of the hospital
PARIS – What’s the most effective medication for preventing rehospitalization in patients previously admitted for severe unipolar depression?
The answer, based upon a study of all 123,712 patients hospitalized for severe unipolar depression in Finland during 1987-2012, might come as a surprise. The medication that most effectively kept patients from returning to the hospital wasn’t a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or an atypical antipsychotic. It was lithium, Markku Lahteenvuo, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Using comprehensive nationwide databases, he and his coinvestigators followed these 123,712 hospitalized patients for a mean of 7.9 years, during which 49,146 of them had a total of 153,784 rehospitalizations for mental disorders. The investigators analyzed what psychotropic drugs the patients were taking when rehospitalized, as well as the drugs they were taking when they were out of hospital. Individuals served as their own controls in order to eliminate selection bias.
In an analysis adjusted for time since diagnosis of unipolar depression, the temporal order of prescribed drugs, and other concomitant medications, the use of lithium was associated with a 53% reduction in the risk of readmission, compared with nonuse.
Patients using lithium as monotherapy for their depression were 69% less likely to be rehospitalized than if they were not, whereas patients on lithium with antidepressants had a more modest 50% reduction in rehospitalization risk, reported Dr. Lahteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland in Kuopio.
After lithium, clozapine was the drug associated with the next lowest risk of rehospitalization for a mental disorder. Patients on that drug were 35% less likely to be rehospitalized; however, clozapine wasn’t widely prescribed in patients with severe unipolar depression.
Antidepressants as a broad class were associated with a statistically significant 10% increase in risk of rehospitalization for a mental disorder. But within that category there were a couple of exceptions: Amitriptyline, which was widely prescribed, particularly in the early years of the study period, was associated with a 25% reduction in rehospitalization, compared with no use. And doxepin was associated with a 15% reduction.
Antipsychotics were associated with an overall 16% increased risk of rehospitalization, compared with no use. But there were some notable exceptions within this class of drugs. Both quetiapine and aripiprazole were associated with an 18% risk reduction.
The investigators also analyzed all-cause rehospitalizations, including acute myocardial infarction and all other somatic diseases, as well as mental disorders. During follow-up, 98,662 patients who had been hospitalized for severe unipolar depression had a collective total of 592,926 all-cause rehospitalizations.
Dr. Lahteenvuo said he had expected that lithium’s strong showing in preventing psychiatric rehospitalization might be offset by an increased risk of hospitalization for other conditions, because of the drug’s well-established association with thyroid, renal, and other toxicities. But that was not the case. Patients on lithium without antidepressants were 49% less likely to have an all-cause hospitalization than when they were not using the drug, and patients on lithium with antidepressants had a 42% reduction in risk.
”It seems that lithium also shielded the patients from going to the hospital for any somatic reason. So lithium seems to be safe and prevents various somatic hospitalizations as well. Whether that’s due to the drug’s enhancement of your ability to live your life, eat healthy, exercise, and give you energy to have good lifestyle habits, or it actually has an anti-inflammatory effect or other disease-modifying effect, we do not know,” Dr. Lahteenvuo said.
Lithium has traditionally been prescribed mainly as third-line therapy in treatment-refractory patients for severe unipolar depression. The Finnish data suggest it’s time to reconsider that strategy.
“We think lithium should be considered for a wider audience, keeping in mind of course that it can cause thyroid and kidney toxicity,” Dr. Lahteenvuo said.
Patients taking clozapine were 30% less likely to have an all-cause hospitalization than nonusers. Aripiprazole was associated with a 21% reduction in risk, quetiapine had a 12% risk reduction, amitriptyline had an 11% risk reduction, and doxepin had a 12% risk reduction.
In contrast, all-cause hospitalization was 12% more likely when patients were taking chronic benzodiazepines and 8% more likely while on hypnotics.
The full study results were published in the Lancet Psychiatry (2017 Jul;4[7]:547-53).
Dr. Lahteenvuo reported having no financial conflicts of interest related to the study, which was funded by the Finnish Ministry of Health.
PARIS – What’s the most effective medication for preventing rehospitalization in patients previously admitted for severe unipolar depression?
The answer, based upon a study of all 123,712 patients hospitalized for severe unipolar depression in Finland during 1987-2012, might come as a surprise. The medication that most effectively kept patients from returning to the hospital wasn’t a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or an atypical antipsychotic. It was lithium, Markku Lahteenvuo, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Using comprehensive nationwide databases, he and his coinvestigators followed these 123,712 hospitalized patients for a mean of 7.9 years, during which 49,146 of them had a total of 153,784 rehospitalizations for mental disorders. The investigators analyzed what psychotropic drugs the patients were taking when rehospitalized, as well as the drugs they were taking when they were out of hospital. Individuals served as their own controls in order to eliminate selection bias.
In an analysis adjusted for time since diagnosis of unipolar depression, the temporal order of prescribed drugs, and other concomitant medications, the use of lithium was associated with a 53% reduction in the risk of readmission, compared with nonuse.
Patients using lithium as monotherapy for their depression were 69% less likely to be rehospitalized than if they were not, whereas patients on lithium with antidepressants had a more modest 50% reduction in rehospitalization risk, reported Dr. Lahteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland in Kuopio.
After lithium, clozapine was the drug associated with the next lowest risk of rehospitalization for a mental disorder. Patients on that drug were 35% less likely to be rehospitalized; however, clozapine wasn’t widely prescribed in patients with severe unipolar depression.
Antidepressants as a broad class were associated with a statistically significant 10% increase in risk of rehospitalization for a mental disorder. But within that category there were a couple of exceptions: Amitriptyline, which was widely prescribed, particularly in the early years of the study period, was associated with a 25% reduction in rehospitalization, compared with no use. And doxepin was associated with a 15% reduction.
Antipsychotics were associated with an overall 16% increased risk of rehospitalization, compared with no use. But there were some notable exceptions within this class of drugs. Both quetiapine and aripiprazole were associated with an 18% risk reduction.
The investigators also analyzed all-cause rehospitalizations, including acute myocardial infarction and all other somatic diseases, as well as mental disorders. During follow-up, 98,662 patients who had been hospitalized for severe unipolar depression had a collective total of 592,926 all-cause rehospitalizations.
Dr. Lahteenvuo said he had expected that lithium’s strong showing in preventing psychiatric rehospitalization might be offset by an increased risk of hospitalization for other conditions, because of the drug’s well-established association with thyroid, renal, and other toxicities. But that was not the case. Patients on lithium without antidepressants were 49% less likely to have an all-cause hospitalization than when they were not using the drug, and patients on lithium with antidepressants had a 42% reduction in risk.
”It seems that lithium also shielded the patients from going to the hospital for any somatic reason. So lithium seems to be safe and prevents various somatic hospitalizations as well. Whether that’s due to the drug’s enhancement of your ability to live your life, eat healthy, exercise, and give you energy to have good lifestyle habits, or it actually has an anti-inflammatory effect or other disease-modifying effect, we do not know,” Dr. Lahteenvuo said.
Lithium has traditionally been prescribed mainly as third-line therapy in treatment-refractory patients for severe unipolar depression. The Finnish data suggest it’s time to reconsider that strategy.
“We think lithium should be considered for a wider audience, keeping in mind of course that it can cause thyroid and kidney toxicity,” Dr. Lahteenvuo said.
Patients taking clozapine were 30% less likely to have an all-cause hospitalization than nonusers. Aripiprazole was associated with a 21% reduction in risk, quetiapine had a 12% risk reduction, amitriptyline had an 11% risk reduction, and doxepin had a 12% risk reduction.
In contrast, all-cause hospitalization was 12% more likely when patients were taking chronic benzodiazepines and 8% more likely while on hypnotics.
The full study results were published in the Lancet Psychiatry (2017 Jul;4[7]:547-53).
Dr. Lahteenvuo reported having no financial conflicts of interest related to the study, which was funded by the Finnish Ministry of Health.
PARIS – What’s the most effective medication for preventing rehospitalization in patients previously admitted for severe unipolar depression?
The answer, based upon a study of all 123,712 patients hospitalized for severe unipolar depression in Finland during 1987-2012, might come as a surprise. The medication that most effectively kept patients from returning to the hospital wasn’t a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or an atypical antipsychotic. It was lithium, Markku Lahteenvuo, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Using comprehensive nationwide databases, he and his coinvestigators followed these 123,712 hospitalized patients for a mean of 7.9 years, during which 49,146 of them had a total of 153,784 rehospitalizations for mental disorders. The investigators analyzed what psychotropic drugs the patients were taking when rehospitalized, as well as the drugs they were taking when they were out of hospital. Individuals served as their own controls in order to eliminate selection bias.
In an analysis adjusted for time since diagnosis of unipolar depression, the temporal order of prescribed drugs, and other concomitant medications, the use of lithium was associated with a 53% reduction in the risk of readmission, compared with nonuse.
Patients using lithium as monotherapy for their depression were 69% less likely to be rehospitalized than if they were not, whereas patients on lithium with antidepressants had a more modest 50% reduction in rehospitalization risk, reported Dr. Lahteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland in Kuopio.
After lithium, clozapine was the drug associated with the next lowest risk of rehospitalization for a mental disorder. Patients on that drug were 35% less likely to be rehospitalized; however, clozapine wasn’t widely prescribed in patients with severe unipolar depression.
Antidepressants as a broad class were associated with a statistically significant 10% increase in risk of rehospitalization for a mental disorder. But within that category there were a couple of exceptions: Amitriptyline, which was widely prescribed, particularly in the early years of the study period, was associated with a 25% reduction in rehospitalization, compared with no use. And doxepin was associated with a 15% reduction.
Antipsychotics were associated with an overall 16% increased risk of rehospitalization, compared with no use. But there were some notable exceptions within this class of drugs. Both quetiapine and aripiprazole were associated with an 18% risk reduction.
The investigators also analyzed all-cause rehospitalizations, including acute myocardial infarction and all other somatic diseases, as well as mental disorders. During follow-up, 98,662 patients who had been hospitalized for severe unipolar depression had a collective total of 592,926 all-cause rehospitalizations.
Dr. Lahteenvuo said he had expected that lithium’s strong showing in preventing psychiatric rehospitalization might be offset by an increased risk of hospitalization for other conditions, because of the drug’s well-established association with thyroid, renal, and other toxicities. But that was not the case. Patients on lithium without antidepressants were 49% less likely to have an all-cause hospitalization than when they were not using the drug, and patients on lithium with antidepressants had a 42% reduction in risk.
”It seems that lithium also shielded the patients from going to the hospital for any somatic reason. So lithium seems to be safe and prevents various somatic hospitalizations as well. Whether that’s due to the drug’s enhancement of your ability to live your life, eat healthy, exercise, and give you energy to have good lifestyle habits, or it actually has an anti-inflammatory effect or other disease-modifying effect, we do not know,” Dr. Lahteenvuo said.
Lithium has traditionally been prescribed mainly as third-line therapy in treatment-refractory patients for severe unipolar depression. The Finnish data suggest it’s time to reconsider that strategy.
“We think lithium should be considered for a wider audience, keeping in mind of course that it can cause thyroid and kidney toxicity,” Dr. Lahteenvuo said.
Patients taking clozapine were 30% less likely to have an all-cause hospitalization than nonusers. Aripiprazole was associated with a 21% reduction in risk, quetiapine had a 12% risk reduction, amitriptyline had an 11% risk reduction, and doxepin had a 12% risk reduction.
In contrast, all-cause hospitalization was 12% more likely when patients were taking chronic benzodiazepines and 8% more likely while on hypnotics.
The full study results were published in the Lancet Psychiatry (2017 Jul;4[7]:547-53).
Dr. Lahteenvuo reported having no financial conflicts of interest related to the study, which was funded by the Finnish Ministry of Health.
AT THE ECNP CONGRESS
Key clinical point:
Major finding: Patients on lithium alone were 69% less likely to be rehospitalized for a mental disorder than nonusers.
Data source: This cohort study included all 123,712 Finnish patients who were hospitalized for severe unipolar depression during 1987-2012, along with rehospitalizations during a mean 7.9 years of follow-up.
Disclosures: The study was funded by the Finnish Ministry of Health. The presenter reported having no financial conflicts.
Early referral recommended for high-risk port-wine stain cases
In high-risk port-wine stain phenotypes – forehead, hemifacial, and median – early referral to a pediatric neurologist is the best way to enable early symptom recognition of Sturge-Weber syndrome (SWS), according to results of a literature review.
If imaging is desired, electroencephalography (EEG) is cheaper and more minimally invasive than MRI (Pediatr Dermatol. 2017 Oct 16. doi: 10.1111/pde.13304).
Of the 34 studies analyzed, none examined the correlation between early detection of presymptomatic SWS and earlier seizure detection. There were also no data to verify improved outcomes with early detection, Michaela Zallmann, MD, of the department of dermatology at Eastern Health, Monash University, Box Hill, Australia, and her coauthors reported. While this indicates a need for further studies, it also shows a need for improved education and clinical monitoring as standard practice.
Additionally, negative imaging results do not obviate the possibility of SWS diagnosis, the investigators reported. In the studies that recorded false negatives, MRI was negative in 3%-6% of infants who later became symptomatic. Of the seven infants with false-negative results, four were less than 6 months old when the initial imaging was conducted. The investigators noted that it is not known at what age a negative MRI can reliably exclude SWS.
When imaging was used for early detection, EEG was shown to be safer and less expensive than MRI, according to the review. Of children who were not anesthetized for MRI, 30%-50% showed considerable distress, while EEG was shown to be minimally invasive. Findings from a retrospective chart review show that 14 MRIs were performed to detect one asymptomatic case of SWS, costing $11,768. In comparison, EEG costs $87 for a routine outpatient study.
“Demonstrating brain involvement on MRI in infants with high-risk PWS may facilitate more stringent counseling and monitoring, but … a negative MRI does not obviate the need for neurologic counseling and monitoring,” the investigators wrote. “Allaying anxiety about diagnostic uncertainty is not achieved using a scan but through detailed education, appropriate clinical monitoring, and nuanced reassurance.”
The investigators did not report any financial disclosures.
In high-risk port-wine stain phenotypes – forehead, hemifacial, and median – early referral to a pediatric neurologist is the best way to enable early symptom recognition of Sturge-Weber syndrome (SWS), according to results of a literature review.
If imaging is desired, electroencephalography (EEG) is cheaper and more minimally invasive than MRI (Pediatr Dermatol. 2017 Oct 16. doi: 10.1111/pde.13304).
Of the 34 studies analyzed, none examined the correlation between early detection of presymptomatic SWS and earlier seizure detection. There were also no data to verify improved outcomes with early detection, Michaela Zallmann, MD, of the department of dermatology at Eastern Health, Monash University, Box Hill, Australia, and her coauthors reported. While this indicates a need for further studies, it also shows a need for improved education and clinical monitoring as standard practice.
Additionally, negative imaging results do not obviate the possibility of SWS diagnosis, the investigators reported. In the studies that recorded false negatives, MRI was negative in 3%-6% of infants who later became symptomatic. Of the seven infants with false-negative results, four were less than 6 months old when the initial imaging was conducted. The investigators noted that it is not known at what age a negative MRI can reliably exclude SWS.
When imaging was used for early detection, EEG was shown to be safer and less expensive than MRI, according to the review. Of children who were not anesthetized for MRI, 30%-50% showed considerable distress, while EEG was shown to be minimally invasive. Findings from a retrospective chart review show that 14 MRIs were performed to detect one asymptomatic case of SWS, costing $11,768. In comparison, EEG costs $87 for a routine outpatient study.
“Demonstrating brain involvement on MRI in infants with high-risk PWS may facilitate more stringent counseling and monitoring, but … a negative MRI does not obviate the need for neurologic counseling and monitoring,” the investigators wrote. “Allaying anxiety about diagnostic uncertainty is not achieved using a scan but through detailed education, appropriate clinical monitoring, and nuanced reassurance.”
The investigators did not report any financial disclosures.
In high-risk port-wine stain phenotypes – forehead, hemifacial, and median – early referral to a pediatric neurologist is the best way to enable early symptom recognition of Sturge-Weber syndrome (SWS), according to results of a literature review.
If imaging is desired, electroencephalography (EEG) is cheaper and more minimally invasive than MRI (Pediatr Dermatol. 2017 Oct 16. doi: 10.1111/pde.13304).
Of the 34 studies analyzed, none examined the correlation between early detection of presymptomatic SWS and earlier seizure detection. There were also no data to verify improved outcomes with early detection, Michaela Zallmann, MD, of the department of dermatology at Eastern Health, Monash University, Box Hill, Australia, and her coauthors reported. While this indicates a need for further studies, it also shows a need for improved education and clinical monitoring as standard practice.
Additionally, negative imaging results do not obviate the possibility of SWS diagnosis, the investigators reported. In the studies that recorded false negatives, MRI was negative in 3%-6% of infants who later became symptomatic. Of the seven infants with false-negative results, four were less than 6 months old when the initial imaging was conducted. The investigators noted that it is not known at what age a negative MRI can reliably exclude SWS.
When imaging was used for early detection, EEG was shown to be safer and less expensive than MRI, according to the review. Of children who were not anesthetized for MRI, 30%-50% showed considerable distress, while EEG was shown to be minimally invasive. Findings from a retrospective chart review show that 14 MRIs were performed to detect one asymptomatic case of SWS, costing $11,768. In comparison, EEG costs $87 for a routine outpatient study.
“Demonstrating brain involvement on MRI in infants with high-risk PWS may facilitate more stringent counseling and monitoring, but … a negative MRI does not obviate the need for neurologic counseling and monitoring,” the investigators wrote. “Allaying anxiety about diagnostic uncertainty is not achieved using a scan but through detailed education, appropriate clinical monitoring, and nuanced reassurance.”
The investigators did not report any financial disclosures.
Key clinical point:
Major finding: To identify one case of Sturge-Weber syndrome, MRI cost $11,768, compared with $87 for a routine outpatient EEG.
Data source: A literature review of 34 articles.
Disclosures: The investigators did not report any financial disclosures.
Lumateperone shows broad phase 3 potential for psychiatric disorders
PARIS – including Alzheimer’s disease, on the strength of strong performances in phase 2 studies, Cedric O’Gorman, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems, providing a unique mechanism of action well-suited for treatment of a range of neuropsychiatric disorders, observed Dr. O’Gorman, who was vice president of medical affairs at the drug’s developer, Intra-Cellular Therapies during the ECNP congress and is now senior vice president for clinical development and medical affairs at Axsome Therapeutics in New York.
At lower doses, lumateperone is a potent serotonin 5-HT2A receptor antagonist that shows promise as a treatment for primary insomnia as well as agitation and aggression in elderly patients with dementia. As the dose increases, lumateperone also serves as a mesolimbic and mesocortical dopamine receptor phosphoprotein modulator with dual properties, acting at the level of the dopamine D2 receptor both as a presynaptic partial agonist and a postsynaptic antagonist.
The drug also enhances NMDA- and AMPA-induced currents in medial prefrontal cortex pyramidal neurons via activation of the D1 receptor. These attributes provide antipsychotic and antidepressant efficacy.
Positron emission tomography studies in patients with schizophrenia have shown that lumateperone at 60 mg once daily effectively reduced psychosis symptoms at roughly 40% striatal D2 receptor occupancy, which is much lower than the occupancy level required by approved antipsychotic drugs. This attribute, coupled with the drug’s potent effects on serotonin 5-HT2A receptors, serotonin transporters, and D1 receptors, probably accounts for lumateperone’s antipsychotic efficacy and accompanying improved psychosocial function and minimal motor disturbances as demonstrated in the clinical trials, according to Dr. O’Gorman.
The two randomized, double-blind, multicenter, placebo-controlled phase 3 trials in schizophrenia totaled 1,146 patients. The trials included an arm in which patients were randomized to risperidone (Risperdal) at 4 mg/day. The lumateperone and risperidone groups showed similar improvement as measured by the Positive and Negative Syndrome Scale score.
However, lumateperone had a better safety profile, with significantly less weight gain than in the risperidone group. Moreover, lumateperone-treated patients didn’t experience the adverse changes in blood glucose, triglycerides, total cholesterol, and prolactin observed in the risperidone group.
The safety profile of lumateperone as documented in the various clinical trials to date is similar to placebo, Dr. O’Gorman reported.
PARIS – including Alzheimer’s disease, on the strength of strong performances in phase 2 studies, Cedric O’Gorman, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems, providing a unique mechanism of action well-suited for treatment of a range of neuropsychiatric disorders, observed Dr. O’Gorman, who was vice president of medical affairs at the drug’s developer, Intra-Cellular Therapies during the ECNP congress and is now senior vice president for clinical development and medical affairs at Axsome Therapeutics in New York.
At lower doses, lumateperone is a potent serotonin 5-HT2A receptor antagonist that shows promise as a treatment for primary insomnia as well as agitation and aggression in elderly patients with dementia. As the dose increases, lumateperone also serves as a mesolimbic and mesocortical dopamine receptor phosphoprotein modulator with dual properties, acting at the level of the dopamine D2 receptor both as a presynaptic partial agonist and a postsynaptic antagonist.
The drug also enhances NMDA- and AMPA-induced currents in medial prefrontal cortex pyramidal neurons via activation of the D1 receptor. These attributes provide antipsychotic and antidepressant efficacy.
Positron emission tomography studies in patients with schizophrenia have shown that lumateperone at 60 mg once daily effectively reduced psychosis symptoms at roughly 40% striatal D2 receptor occupancy, which is much lower than the occupancy level required by approved antipsychotic drugs. This attribute, coupled with the drug’s potent effects on serotonin 5-HT2A receptors, serotonin transporters, and D1 receptors, probably accounts for lumateperone’s antipsychotic efficacy and accompanying improved psychosocial function and minimal motor disturbances as demonstrated in the clinical trials, according to Dr. O’Gorman.
The two randomized, double-blind, multicenter, placebo-controlled phase 3 trials in schizophrenia totaled 1,146 patients. The trials included an arm in which patients were randomized to risperidone (Risperdal) at 4 mg/day. The lumateperone and risperidone groups showed similar improvement as measured by the Positive and Negative Syndrome Scale score.
However, lumateperone had a better safety profile, with significantly less weight gain than in the risperidone group. Moreover, lumateperone-treated patients didn’t experience the adverse changes in blood glucose, triglycerides, total cholesterol, and prolactin observed in the risperidone group.
The safety profile of lumateperone as documented in the various clinical trials to date is similar to placebo, Dr. O’Gorman reported.
PARIS – including Alzheimer’s disease, on the strength of strong performances in phase 2 studies, Cedric O’Gorman, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems, providing a unique mechanism of action well-suited for treatment of a range of neuropsychiatric disorders, observed Dr. O’Gorman, who was vice president of medical affairs at the drug’s developer, Intra-Cellular Therapies during the ECNP congress and is now senior vice president for clinical development and medical affairs at Axsome Therapeutics in New York.
At lower doses, lumateperone is a potent serotonin 5-HT2A receptor antagonist that shows promise as a treatment for primary insomnia as well as agitation and aggression in elderly patients with dementia. As the dose increases, lumateperone also serves as a mesolimbic and mesocortical dopamine receptor phosphoprotein modulator with dual properties, acting at the level of the dopamine D2 receptor both as a presynaptic partial agonist and a postsynaptic antagonist.
The drug also enhances NMDA- and AMPA-induced currents in medial prefrontal cortex pyramidal neurons via activation of the D1 receptor. These attributes provide antipsychotic and antidepressant efficacy.
Positron emission tomography studies in patients with schizophrenia have shown that lumateperone at 60 mg once daily effectively reduced psychosis symptoms at roughly 40% striatal D2 receptor occupancy, which is much lower than the occupancy level required by approved antipsychotic drugs. This attribute, coupled with the drug’s potent effects on serotonin 5-HT2A receptors, serotonin transporters, and D1 receptors, probably accounts for lumateperone’s antipsychotic efficacy and accompanying improved psychosocial function and minimal motor disturbances as demonstrated in the clinical trials, according to Dr. O’Gorman.
The two randomized, double-blind, multicenter, placebo-controlled phase 3 trials in schizophrenia totaled 1,146 patients. The trials included an arm in which patients were randomized to risperidone (Risperdal) at 4 mg/day. The lumateperone and risperidone groups showed similar improvement as measured by the Positive and Negative Syndrome Scale score.
However, lumateperone had a better safety profile, with significantly less weight gain than in the risperidone group. Moreover, lumateperone-treated patients didn’t experience the adverse changes in blood glucose, triglycerides, total cholesterol, and prolactin observed in the risperidone group.
The safety profile of lumateperone as documented in the various clinical trials to date is similar to placebo, Dr. O’Gorman reported.
EXPERT ANALYSIS FROM THE ECNP CONGRESS