The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.

The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.

[email protected]

The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.

The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.

[email protected]

The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.

The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.

[email protected]

ABSTRACT

Cryotherapy is the use of the anti-inflammatory and analgesic properties of ice to facilitate healing. Cryotherapy mediates these salutatory effects by reducing blood flow to the site of injury, down-regulating the production of inflammatory and pain-inducing prostaglandins, and diminishing the conductive ability of nerve endings. It is commonly used postoperatively in orthopedics to decrease analgesic requirements and blood loss as well as to increase range of motion, despite limited literature on its ability to produce such therapeutic effects in clinical practice. This article examines the available literature and the scientific evidence for the use and efficacy of cryotherapy in post-surgical orthopedic patients. It also reviews the potential pitfalls associated with improper use. Overall, this review seeks to provide insight into when, or whether, cryotherapy is appropriate for orthopedic patients during surgical recovery.

Continue to: Cold therapy has been a mainstay of medical treatment...

Cold therapy has been a mainstay of medical treatment since the days of Hippocrates. Initially used by ancient Egyptians to mitigate inflammation and by Hippocrates himself to treat hemorrhage, the therapeutic applications of ice evolved throughout history to become part of the treatment algorithm for a variety of health conditions.¹ Ice made an ideal numbing agent for limb amputations and an anesthetic for certain cancers, but truly became ubiquitous when the first cold pack meant for medicinal use was patented in the early 1970s.^1,2 Despite their armamentarium of advanced treatment modalities, physicians in the modern era continue to prescribe cryotherapy for their patients, particularly in the field of orthopedics. Most athletes know the “RICE” (Rest, Ice, Compression, Elevation) protocol and utilize it to minimize inflammation associated with soft tissue injuries.

Inflammation is a physiologic response to noxious stimuli. Cell damage results in the production of inflammatory mediators including prostaglandins, which play a crucial role in the vasodilation and pain associated with inflammation. Vasodilation and increased blood flow manifest as swelling, which can cause pain by putting pressure on nerve endings. The inflammatory prostaglandin E₂ (PGE₂) causes local increases in temperature and mediates pain.^3,4 The application of cold therapy attenuates inflammatory microvascular and hemodynamic changes, reducing some of the deleterious effects of inflammation and minimizing pain. Animal models demonstrate that cryotherapy restores functional capillary density, reverses tumor necrosis factor-α (TNF-α)-induced microvasculature damage, and reduces the production of thrombogenic thromboxanes in injured soft tissue.⁵ Additionally, cold therapy after knee arthroscopy is associated with lower concentrations of PGE₂ in the knee.³ Local cooling acts at the cellular level to decrease edema, reduce pain, and slow blood flow to the affected area, with the overall effect of alleviating inflammation.^4,5

Cryotherapy is standard practice in postoperative orthopedic care, but there is limited literature demonstrating its efficacy in this setting. In addition, the advent of more advanced wearable cooling systems necessitates a thorough comparison of the various cryotherapy mechanisms both from healthcare and economic perspectives. The goal of this article is to examine the benefits of cryotherapy in the postoperative management of orthopedic surgical interventions and to review the effectiveness of differing types of cryotherapy. A secondary goal of this article is to review the literature on the adverse effects of cryotherapy in order to increase physician awareness of this issue and highlight the importance of patient education when utilizing cryotherapy postoperatively.

BENEFITS OF CRYOTHERAPY

Three standard types of cryotherapy are prescribed as postoperative therapy in orthopedics: compressive cryotherapy, continuous flow cryotherapy, and the application of ice. All aim to decrease the amount of inflammation of the surgical site, reduce patient pain, and aid in the recovery process. The application of ice or other cooling pack devices without compression is the most commonly used method, likely because it is the most economical and user-friendly cryotherapy option. Compressive cryotherapy is the application of ice or an ice pack secured to the site with a bandage or other device in a manner that also applies pressure to the site of injury. Finally, continuous flow cryotherapy systems are typically connected to a refrigeration control unit and apply compressive cooling through the uninterrupted flow of cold water or gas through a wrap around the injured site. Examples include the Game Ready^® (CoolSystems, Inc.), Cryo/Cuff^® IC Cooler (DJO Global), and Hilotherm Homecare (Hilotherm GmbH) systems, which are marketed as an improvement over traditional forms of cold therapy, as they are capable of cooling for hours at a time, allow for nighttime use, and provide the operator with temperature control.^6-8

Postoperative cryotherapy is prescribed for a wide variety of orthopedic procedures, including anterior cruciate ligament (ACL) reconstruction surgery, rotator cuff surgery, and total knee arthroplasty (TKA). Current literature includes many studies monitoring postoperative outcomes in patients using cryotherapy as part of their treatment regimen, with the primary endpoints being visual analog scale (VAS) scores, analgesic consumption, and range of motion (ROM).^9-16 As demonstrated by in Table 1, these studies do not provide conclusive evidence that cryotherapy significantly alters postoperative outcomes, despite its ubiquitous use by the orthopedics community. In fact, the literature reflects a seeming lack of consensus regarding the effect of cryotherapy on analgesic requirements, pain, and joint mobility following procedures. Interestingly, of the studies represented in Table 1, only half analyzed all 3 postoperative measures (analgesic consumption, pain, and ROM). Furthermore, solely Morsi¹³ concluded that cryotherapy resulted in significant improvements in all 3 outcome measures in a trial involving only 30 patients. Kullenberg and colleagues¹² performed the largest study, but still included only 86 patients. In addition, all the studies focused on 1 joint or procedure. Thus, despite evidence that cryotherapy reduces inflammation at a molecular level, current literature does not unequivocally support the common belief that cryotherapy benefits patients in practice. More robust studies that include an analysis of analgesic consumption, VAS scores, and ROM (at minimum) and compare the relative efficacy of cryotherapy across joint types and procedures are necessary to determine whether postoperative cryotherapy in orthopedics is appropriate.

Table 1. Results from Studies that Compared Cryotherapy to Standard Care Within the First 2 Weeks Following Surgery

Continue to: ADVANCED CRYOTHERAPY DEVICES...

ADVANCED CRYOTHERAPY DEVICES

Several recent studies explored the relative postoperative benefits of advanced cryotherapeutics in lieu of the traditional ice pack.^6,7,17-21 As reflected in Table 2, these studies, much like the literature comparing cryotherapy to the control, do not reveal significant benefits of continuous flow cryotherapy after surgery. In fact, the only outcome measure that was found to differ significantly in more than 1 study was ROM. Though the makers of advanced cryotherapy systems market them as a vast improvement over traditional forms of cold therapy, there is insufficient evidence to support such claims. Even the most robust study that included 280 patients failed to show significant differences in the analgesic use and ROM after surgery.²⁰ Of note, all but 1 study compared traditional and advanced cryotherapy following procedures on the knee. Additional research exploring outcomes after surgery on other joints is necessary before any conclusions can be made regarding postoperative benefits or risks within orthopedics more generally.

RISKS AND ADVERSE EFFECTS OF CRYOTHERAPY

A rigorous analysis of the benefits of cryotherapy ought to incorporate other factors in addition to improvements in analgesic consumption, VAS score, and ROM. These include the financial and time investment involved in the use of continuous flow cryotherapy, which the majority of studies do not consider. Though many authors acknowledge that continuous flow cryotherapy is expensive, to our knowledge, none have yet performed a formal economic analysis of the cost of advanced cryotherapy to the patient as well as to the healthcare system at large.^{6,7,13,18,22-24} Dickinson and colleagues²⁴ calculated the total cost of cryotherapy and rehabilitation following rotator cuff repair, but addressed only the up-front cost of the cold therapy system. For context, Table 3 summarizes the retail cost of the most popular cryotherapy devices on the market. Based on this information alone, it seems reasonable to conclude that these systems are associated with significantly more cost than traditional forms of cold therapy, and therefore would be an undesirable option for patients or hospital systems. Nevertheless, cost considerations are more nuanced than a simple comparison of price, necessitating more advanced economic analyses. Substantial savings may be on the table if future studies are able to prove postoperative cryotherapy shortens hospital stays, reduces medication costs, and results in fewer physical therapy sessions. Moreover, if all this is true, patients may experience quicker recovery and have overall greater post-procedure satisfaction.

Table 3. Cost of Most Popular Cryotherapy Units

Patient education required for optimal use of advanced cold therapy is another aspect of cryotherapy that is poorly represented in the literature. As Dickinson and colleagues²⁴ point out, because it eliminates some dependency on the patient to remember to ice appropriately, continuous flow cryotherapy may have a positive impact on compliance and therefore yield improved outcomes.²⁴ Hospital staff may be required to spend additional time with patients. However, this is necessary to ensure proper understanding on how to operate the system and avoid adverse outcomes. Patients may also find the large coolers inconvenient and may therefore be reluctant to use them, finding traditional ice more manageable. Future studies should consider gathering data on patient education, compliance, and overall reception/satisfaction to complete a more holistic investigation of the role of postoperative cryotherapy in orthopedics.

Cryotherapy is not without adverse outcomes, which have been documented primarily in the form of case study reports. Relevant case studies cited adverse outcomes including frostbite/skin loss, compartment syndrome, and perniosis as potential dangers of postoperative cryotherapy in orthopedics (Table 4).^25-30 As an example, a patient recovering from patellar-tendon repair experienced bilateral frostbite and skin loss following 2 weeks of uninterrupted use of cryotherapy without any barrier between his skin and the system.²⁹ A similar case study described 2 female patients, one recovering from a TKA and the other from a tibial revision of arthroplasty, who used cryotherapy systems without cessation and experienced frostbite and skin necrosis over the entirety of their knees.²⁶ A third case study exploring 4 incidents of patellar frostbite and necrosis following knee arthroscopies proposed that poor patient understanding of proper cryotherapy use as well as poor recognition of the signs of frostbite contributed to these adverse outcomes. Furthermore, the cryotherapy brace used by all 4 patients included a feature designed to counteract patellar inflammation that also may have increased the likelihood of frostbite in this area due to poor tissue insulation. The authors noted that following the incidents, the makers of the brace removed patellar coverage to prevent future occurrences.³⁰

Abbreviations: ACL, anterior cruciate ligament; TKA, total knee arthroplasty.

Frostbite linked to cryotherapy has also occurred following orthopedic procedures outside the knee. Brown and Hahn²⁵ described 2 young females who developed skin necrosis following podiatric surgeries and constant cold therapy for roughly a week. Notably, 1 patient had cold sensitivity, which likely put her at an increased baseline risk of experiencing frostbite while using cryotherapy. Tissue necrosis is not the only danger of cold therapy discussed in this study. Surprisingly, 1 patient also developed compartment syndrome.²⁵ Khajavi and colleagues²⁷ also documented postoperative compartment syndrome in a patient following an arthroscopic osteochondral autograft transfer, which they attributed to reperfusion injury in the wake of first-degree frostbite. Hospital personnel also instructed this patient to use his cryotherapy system without interruption at the coldest temperature tolerable, contrary to manufacturer’s instructions.²⁷

Continue to: King and colleagues...

King and colleagues²⁸ described 2 cases of patients complaining of nodules, papules, and plaques soon after ACL reconstruction and the initiation of cryotherapy. A histological examination of their skin lesions demonstrated the presence of a perivascular and periadnexal superficial and deep lymphocytic infiltrate associated with perniosis. Dermatologists associated the perniosis with the cryotherapy cuff adhesive mechanisms, as their locations matched those of the lesions and symptoms subsided after cessation of cuff usage.²⁸

Cases of adverse effects with perioperative cryotherapy have also occurred at our own institution. The authors obtained informed written consent from the patients to print and publish their images. In 2 separate incidents, patients overdid icing and experienced rather extreme side effects including burns and blisters (Figures 1 and 2). In light of these adverse events, the physicians have questioned whether RICE ought to be part of their standard perioperative recommendations. These physicians are not alone in their uncertainty. Interestingly, even Mirkin,³¹ who coined the RICE mnemonic, now believes that consistent icing post-injury actually inhibits the body’s natural inflammatory healing response, delaying rather than speeding recovery, and suggests that icing ought to be used for pain control only.

DISCUSSION

Though there is ample literature supporting the common belief that cryotherapy minimizes inflammation at the cellular level, whether or not it results in meaningful improvements in post-surgical orthopedic outcomes remains unclear. Table 1 reflects a dearth of evidence to support the widespread current practice of cold therapy following orthopedic procedures, but few studies could demonstrate a significant difference in the analgesic use, VAS score, or ROM between cryotherapy and control groups. It is worth noting that these studies used different cryotherapy systems. Though in theory the continuous flow cryotherapy systems are similarly designed, there are potential differences among them that have not been controlled for in this analysis. All studies had <90 participants and focused on a single joint or procedure, making it difficult to draw large scale conclusions about the utility of cold therapy in the postoperative orthopedic population at large. Furthermore, researchers measured endpoints at a range of time intervals that were inconsistent across studies. In some cases, the significance of the impact of cryotherapy on recovery within a single study differed based on the time point at which researchers measured outcomes.^12-14 This raises the question as to whether cryotherapy has no benefits, or whether they are simply time-dependent. Future studies should seek to ascertain whether there is a postoperative time window in which cryotherapy could potentially expedite the recovery process.

Similarly, Table 2 shows a lack of consensus regarding the effect of advanced cryotherapy when compared to traditional ice application on pain, analgesic use, and joint mobility after surgery. However, all but 1 of these studies focused on knee procedures. Therefore, our findings may not be applicable to orthopedic surgeries on other joints. Nevertheless, the use of advanced cryotherapy in postoperative orthopedic care may wane if researchers continue to show that it is no more beneficial than its far less expensive counterpart of ice and an ace bandage.

The case studies discussed in this review serve as cautionary tales of the dangers of cryotherapy when used improperly. Though frostbite and subsequent tissue necrosis seem most common, physicians should be made aware that compartment syndrome and perniosis are also possible consequences. Orthopedic patients perhaps have an increased risk of developing these side effects due to the nature of their injuries and the large cutaneous surface area to which cryotherapy is applied. These outcomes could seemingly be avoided with improved educational initiatives targeted at both healthcare personnel and patients. Orthopedic surgeons might consider adding a short, instructive video focusing on proper usage as well as signs of adverse events to their discharge protocol to limit occurrences of these pitfalls associated with cryotherapy.

CONCLUSION

There is inadequate literature to support the of use postoperative cryotherapy of any kind in the field of orthopedics at this time. More robust, standardized studies, and a formidable economic analysis of advanced cold therapy systems are necessary before physicians prescribing cryotherapy can be confident that they are augmenting patient recovery. Nevertheless, as new developments in medicinal cryotherapy occur, it may be possible for the orthopedic community to wield its salutatory effects to limit complications and improve post-surgical outcomes.

ABSTRACT

Cryotherapy is the use of the anti-inflammatory and analgesic properties of ice to facilitate healing. Cryotherapy mediates these salutatory effects by reducing blood flow to the site of injury, down-regulating the production of inflammatory and pain-inducing prostaglandins, and diminishing the conductive ability of nerve endings. It is commonly used postoperatively in orthopedics to decrease analgesic requirements and blood loss as well as to increase range of motion, despite limited literature on its ability to produce such therapeutic effects in clinical practice. This article examines the available literature and the scientific evidence for the use and efficacy of cryotherapy in post-surgical orthopedic patients. It also reviews the potential pitfalls associated with improper use. Overall, this review seeks to provide insight into when, or whether, cryotherapy is appropriate for orthopedic patients during surgical recovery.

Continue to: Cold therapy has been a mainstay of medical treatment...

Cold therapy has been a mainstay of medical treatment since the days of Hippocrates. Initially used by ancient Egyptians to mitigate inflammation and by Hippocrates himself to treat hemorrhage, the therapeutic applications of ice evolved throughout history to become part of the treatment algorithm for a variety of health conditions.¹ Ice made an ideal numbing agent for limb amputations and an anesthetic for certain cancers, but truly became ubiquitous when the first cold pack meant for medicinal use was patented in the early 1970s.^1,2 Despite their armamentarium of advanced treatment modalities, physicians in the modern era continue to prescribe cryotherapy for their patients, particularly in the field of orthopedics. Most athletes know the “RICE” (Rest, Ice, Compression, Elevation) protocol and utilize it to minimize inflammation associated with soft tissue injuries.

Inflammation is a physiologic response to noxious stimuli. Cell damage results in the production of inflammatory mediators including prostaglandins, which play a crucial role in the vasodilation and pain associated with inflammation. Vasodilation and increased blood flow manifest as swelling, which can cause pain by putting pressure on nerve endings. The inflammatory prostaglandin E₂ (PGE₂) causes local increases in temperature and mediates pain.^3,4 The application of cold therapy attenuates inflammatory microvascular and hemodynamic changes, reducing some of the deleterious effects of inflammation and minimizing pain. Animal models demonstrate that cryotherapy restores functional capillary density, reverses tumor necrosis factor-α (TNF-α)-induced microvasculature damage, and reduces the production of thrombogenic thromboxanes in injured soft tissue.⁵ Additionally, cold therapy after knee arthroscopy is associated with lower concentrations of PGE₂ in the knee.³ Local cooling acts at the cellular level to decrease edema, reduce pain, and slow blood flow to the affected area, with the overall effect of alleviating inflammation.^4,5

Cryotherapy is standard practice in postoperative orthopedic care, but there is limited literature demonstrating its efficacy in this setting. In addition, the advent of more advanced wearable cooling systems necessitates a thorough comparison of the various cryotherapy mechanisms both from healthcare and economic perspectives. The goal of this article is to examine the benefits of cryotherapy in the postoperative management of orthopedic surgical interventions and to review the effectiveness of differing types of cryotherapy. A secondary goal of this article is to review the literature on the adverse effects of cryotherapy in order to increase physician awareness of this issue and highlight the importance of patient education when utilizing cryotherapy postoperatively.

BENEFITS OF CRYOTHERAPY

Three standard types of cryotherapy are prescribed as postoperative therapy in orthopedics: compressive cryotherapy, continuous flow cryotherapy, and the application of ice. All aim to decrease the amount of inflammation of the surgical site, reduce patient pain, and aid in the recovery process. The application of ice or other cooling pack devices without compression is the most commonly used method, likely because it is the most economical and user-friendly cryotherapy option. Compressive cryotherapy is the application of ice or an ice pack secured to the site with a bandage or other device in a manner that also applies pressure to the site of injury. Finally, continuous flow cryotherapy systems are typically connected to a refrigeration control unit and apply compressive cooling through the uninterrupted flow of cold water or gas through a wrap around the injured site. Examples include the Game Ready^® (CoolSystems, Inc.), Cryo/Cuff^® IC Cooler (DJO Global), and Hilotherm Homecare (Hilotherm GmbH) systems, which are marketed as an improvement over traditional forms of cold therapy, as they are capable of cooling for hours at a time, allow for nighttime use, and provide the operator with temperature control.^6-8

Postoperative cryotherapy is prescribed for a wide variety of orthopedic procedures, including anterior cruciate ligament (ACL) reconstruction surgery, rotator cuff surgery, and total knee arthroplasty (TKA). Current literature includes many studies monitoring postoperative outcomes in patients using cryotherapy as part of their treatment regimen, with the primary endpoints being visual analog scale (VAS) scores, analgesic consumption, and range of motion (ROM).^9-16 As demonstrated by in Table 1, these studies do not provide conclusive evidence that cryotherapy significantly alters postoperative outcomes, despite its ubiquitous use by the orthopedics community. In fact, the literature reflects a seeming lack of consensus regarding the effect of cryotherapy on analgesic requirements, pain, and joint mobility following procedures. Interestingly, of the studies represented in Table 1, only half analyzed all 3 postoperative measures (analgesic consumption, pain, and ROM). Furthermore, solely Morsi¹³ concluded that cryotherapy resulted in significant improvements in all 3 outcome measures in a trial involving only 30 patients. Kullenberg and colleagues¹² performed the largest study, but still included only 86 patients. In addition, all the studies focused on 1 joint or procedure. Thus, despite evidence that cryotherapy reduces inflammation at a molecular level, current literature does not unequivocally support the common belief that cryotherapy benefits patients in practice. More robust studies that include an analysis of analgesic consumption, VAS scores, and ROM (at minimum) and compare the relative efficacy of cryotherapy across joint types and procedures are necessary to determine whether postoperative cryotherapy in orthopedics is appropriate.

Table 1. Results from Studies that Compared Cryotherapy to Standard Care Within the First 2 Weeks Following Surgery

Continue to: ADVANCED CRYOTHERAPY DEVICES...

ADVANCED CRYOTHERAPY DEVICES

Several recent studies explored the relative postoperative benefits of advanced cryotherapeutics in lieu of the traditional ice pack.^6,7,17-21 As reflected in Table 2, these studies, much like the literature comparing cryotherapy to the control, do not reveal significant benefits of continuous flow cryotherapy after surgery. In fact, the only outcome measure that was found to differ significantly in more than 1 study was ROM. Though the makers of advanced cryotherapy systems market them as a vast improvement over traditional forms of cold therapy, there is insufficient evidence to support such claims. Even the most robust study that included 280 patients failed to show significant differences in the analgesic use and ROM after surgery.²⁰ Of note, all but 1 study compared traditional and advanced cryotherapy following procedures on the knee. Additional research exploring outcomes after surgery on other joints is necessary before any conclusions can be made regarding postoperative benefits or risks within orthopedics more generally.

RISKS AND ADVERSE EFFECTS OF CRYOTHERAPY

A rigorous analysis of the benefits of cryotherapy ought to incorporate other factors in addition to improvements in analgesic consumption, VAS score, and ROM. These include the financial and time investment involved in the use of continuous flow cryotherapy, which the majority of studies do not consider. Though many authors acknowledge that continuous flow cryotherapy is expensive, to our knowledge, none have yet performed a formal economic analysis of the cost of advanced cryotherapy to the patient as well as to the healthcare system at large.^{6,7,13,18,22-24} Dickinson and colleagues²⁴ calculated the total cost of cryotherapy and rehabilitation following rotator cuff repair, but addressed only the up-front cost of the cold therapy system. For context, Table 3 summarizes the retail cost of the most popular cryotherapy devices on the market. Based on this information alone, it seems reasonable to conclude that these systems are associated with significantly more cost than traditional forms of cold therapy, and therefore would be an undesirable option for patients or hospital systems. Nevertheless, cost considerations are more nuanced than a simple comparison of price, necessitating more advanced economic analyses. Substantial savings may be on the table if future studies are able to prove postoperative cryotherapy shortens hospital stays, reduces medication costs, and results in fewer physical therapy sessions. Moreover, if all this is true, patients may experience quicker recovery and have overall greater post-procedure satisfaction.

Table 3. Cost of Most Popular Cryotherapy Units

Patient education required for optimal use of advanced cold therapy is another aspect of cryotherapy that is poorly represented in the literature. As Dickinson and colleagues²⁴ point out, because it eliminates some dependency on the patient to remember to ice appropriately, continuous flow cryotherapy may have a positive impact on compliance and therefore yield improved outcomes.²⁴ Hospital staff may be required to spend additional time with patients. However, this is necessary to ensure proper understanding on how to operate the system and avoid adverse outcomes. Patients may also find the large coolers inconvenient and may therefore be reluctant to use them, finding traditional ice more manageable. Future studies should consider gathering data on patient education, compliance, and overall reception/satisfaction to complete a more holistic investigation of the role of postoperative cryotherapy in orthopedics.

Cryotherapy is not without adverse outcomes, which have been documented primarily in the form of case study reports. Relevant case studies cited adverse outcomes including frostbite/skin loss, compartment syndrome, and perniosis as potential dangers of postoperative cryotherapy in orthopedics (Table 4).^25-30 As an example, a patient recovering from patellar-tendon repair experienced bilateral frostbite and skin loss following 2 weeks of uninterrupted use of cryotherapy without any barrier between his skin and the system.²⁹ A similar case study described 2 female patients, one recovering from a TKA and the other from a tibial revision of arthroplasty, who used cryotherapy systems without cessation and experienced frostbite and skin necrosis over the entirety of their knees.²⁶ A third case study exploring 4 incidents of patellar frostbite and necrosis following knee arthroscopies proposed that poor patient understanding of proper cryotherapy use as well as poor recognition of the signs of frostbite contributed to these adverse outcomes. Furthermore, the cryotherapy brace used by all 4 patients included a feature designed to counteract patellar inflammation that also may have increased the likelihood of frostbite in this area due to poor tissue insulation. The authors noted that following the incidents, the makers of the brace removed patellar coverage to prevent future occurrences.³⁰

Abbreviations: ACL, anterior cruciate ligament; TKA, total knee arthroplasty.

Frostbite linked to cryotherapy has also occurred following orthopedic procedures outside the knee. Brown and Hahn²⁵ described 2 young females who developed skin necrosis following podiatric surgeries and constant cold therapy for roughly a week. Notably, 1 patient had cold sensitivity, which likely put her at an increased baseline risk of experiencing frostbite while using cryotherapy. Tissue necrosis is not the only danger of cold therapy discussed in this study. Surprisingly, 1 patient also developed compartment syndrome.²⁵ Khajavi and colleagues²⁷ also documented postoperative compartment syndrome in a patient following an arthroscopic osteochondral autograft transfer, which they attributed to reperfusion injury in the wake of first-degree frostbite. Hospital personnel also instructed this patient to use his cryotherapy system without interruption at the coldest temperature tolerable, contrary to manufacturer’s instructions.²⁷

Continue to: King and colleagues...

King and colleagues²⁸ described 2 cases of patients complaining of nodules, papules, and plaques soon after ACL reconstruction and the initiation of cryotherapy. A histological examination of their skin lesions demonstrated the presence of a perivascular and periadnexal superficial and deep lymphocytic infiltrate associated with perniosis. Dermatologists associated the perniosis with the cryotherapy cuff adhesive mechanisms, as their locations matched those of the lesions and symptoms subsided after cessation of cuff usage.²⁸

Cases of adverse effects with perioperative cryotherapy have also occurred at our own institution. The authors obtained informed written consent from the patients to print and publish their images. In 2 separate incidents, patients overdid icing and experienced rather extreme side effects including burns and blisters (Figures 1 and 2). In light of these adverse events, the physicians have questioned whether RICE ought to be part of their standard perioperative recommendations. These physicians are not alone in their uncertainty. Interestingly, even Mirkin,³¹ who coined the RICE mnemonic, now believes that consistent icing post-injury actually inhibits the body’s natural inflammatory healing response, delaying rather than speeding recovery, and suggests that icing ought to be used for pain control only.

DISCUSSION

Though there is ample literature supporting the common belief that cryotherapy minimizes inflammation at the cellular level, whether or not it results in meaningful improvements in post-surgical orthopedic outcomes remains unclear. Table 1 reflects a dearth of evidence to support the widespread current practice of cold therapy following orthopedic procedures, but few studies could demonstrate a significant difference in the analgesic use, VAS score, or ROM between cryotherapy and control groups. It is worth noting that these studies used different cryotherapy systems. Though in theory the continuous flow cryotherapy systems are similarly designed, there are potential differences among them that have not been controlled for in this analysis. All studies had <90 participants and focused on a single joint or procedure, making it difficult to draw large scale conclusions about the utility of cold therapy in the postoperative orthopedic population at large. Furthermore, researchers measured endpoints at a range of time intervals that were inconsistent across studies. In some cases, the significance of the impact of cryotherapy on recovery within a single study differed based on the time point at which researchers measured outcomes.^12-14 This raises the question as to whether cryotherapy has no benefits, or whether they are simply time-dependent. Future studies should seek to ascertain whether there is a postoperative time window in which cryotherapy could potentially expedite the recovery process.

Similarly, Table 2 shows a lack of consensus regarding the effect of advanced cryotherapy when compared to traditional ice application on pain, analgesic use, and joint mobility after surgery. However, all but 1 of these studies focused on knee procedures. Therefore, our findings may not be applicable to orthopedic surgeries on other joints. Nevertheless, the use of advanced cryotherapy in postoperative orthopedic care may wane if researchers continue to show that it is no more beneficial than its far less expensive counterpart of ice and an ace bandage.

The case studies discussed in this review serve as cautionary tales of the dangers of cryotherapy when used improperly. Though frostbite and subsequent tissue necrosis seem most common, physicians should be made aware that compartment syndrome and perniosis are also possible consequences. Orthopedic patients perhaps have an increased risk of developing these side effects due to the nature of their injuries and the large cutaneous surface area to which cryotherapy is applied. These outcomes could seemingly be avoided with improved educational initiatives targeted at both healthcare personnel and patients. Orthopedic surgeons might consider adding a short, instructive video focusing on proper usage as well as signs of adverse events to their discharge protocol to limit occurrences of these pitfalls associated with cryotherapy.

CONCLUSION

There is inadequate literature to support the of use postoperative cryotherapy of any kind in the field of orthopedics at this time. More robust, standardized studies, and a formidable economic analysis of advanced cold therapy systems are necessary before physicians prescribing cryotherapy can be confident that they are augmenting patient recovery. Nevertheless, as new developments in medicinal cryotherapy occur, it may be possible for the orthopedic community to wield its salutatory effects to limit complications and improve post-surgical outcomes.

ABSTRACT

Cryotherapy is the use of the anti-inflammatory and analgesic properties of ice to facilitate healing. Cryotherapy mediates these salutatory effects by reducing blood flow to the site of injury, down-regulating the production of inflammatory and pain-inducing prostaglandins, and diminishing the conductive ability of nerve endings. It is commonly used postoperatively in orthopedics to decrease analgesic requirements and blood loss as well as to increase range of motion, despite limited literature on its ability to produce such therapeutic effects in clinical practice. This article examines the available literature and the scientific evidence for the use and efficacy of cryotherapy in post-surgical orthopedic patients. It also reviews the potential pitfalls associated with improper use. Overall, this review seeks to provide insight into when, or whether, cryotherapy is appropriate for orthopedic patients during surgical recovery.

Continue to: Cold therapy has been a mainstay of medical treatment...

Cold therapy has been a mainstay of medical treatment since the days of Hippocrates. Initially used by ancient Egyptians to mitigate inflammation and by Hippocrates himself to treat hemorrhage, the therapeutic applications of ice evolved throughout history to become part of the treatment algorithm for a variety of health conditions.¹ Ice made an ideal numbing agent for limb amputations and an anesthetic for certain cancers, but truly became ubiquitous when the first cold pack meant for medicinal use was patented in the early 1970s.^1,2 Despite their armamentarium of advanced treatment modalities, physicians in the modern era continue to prescribe cryotherapy for their patients, particularly in the field of orthopedics. Most athletes know the “RICE” (Rest, Ice, Compression, Elevation) protocol and utilize it to minimize inflammation associated with soft tissue injuries.

Inflammation is a physiologic response to noxious stimuli. Cell damage results in the production of inflammatory mediators including prostaglandins, which play a crucial role in the vasodilation and pain associated with inflammation. Vasodilation and increased blood flow manifest as swelling, which can cause pain by putting pressure on nerve endings. The inflammatory prostaglandin E₂ (PGE₂) causes local increases in temperature and mediates pain.^3,4 The application of cold therapy attenuates inflammatory microvascular and hemodynamic changes, reducing some of the deleterious effects of inflammation and minimizing pain. Animal models demonstrate that cryotherapy restores functional capillary density, reverses tumor necrosis factor-α (TNF-α)-induced microvasculature damage, and reduces the production of thrombogenic thromboxanes in injured soft tissue.⁵ Additionally, cold therapy after knee arthroscopy is associated with lower concentrations of PGE₂ in the knee.³ Local cooling acts at the cellular level to decrease edema, reduce pain, and slow blood flow to the affected area, with the overall effect of alleviating inflammation.^4,5

Cryotherapy is standard practice in postoperative orthopedic care, but there is limited literature demonstrating its efficacy in this setting. In addition, the advent of more advanced wearable cooling systems necessitates a thorough comparison of the various cryotherapy mechanisms both from healthcare and economic perspectives. The goal of this article is to examine the benefits of cryotherapy in the postoperative management of orthopedic surgical interventions and to review the effectiveness of differing types of cryotherapy. A secondary goal of this article is to review the literature on the adverse effects of cryotherapy in order to increase physician awareness of this issue and highlight the importance of patient education when utilizing cryotherapy postoperatively.

BENEFITS OF CRYOTHERAPY

Three standard types of cryotherapy are prescribed as postoperative therapy in orthopedics: compressive cryotherapy, continuous flow cryotherapy, and the application of ice. All aim to decrease the amount of inflammation of the surgical site, reduce patient pain, and aid in the recovery process. The application of ice or other cooling pack devices without compression is the most commonly used method, likely because it is the most economical and user-friendly cryotherapy option. Compressive cryotherapy is the application of ice or an ice pack secured to the site with a bandage or other device in a manner that also applies pressure to the site of injury. Finally, continuous flow cryotherapy systems are typically connected to a refrigeration control unit and apply compressive cooling through the uninterrupted flow of cold water or gas through a wrap around the injured site. Examples include the Game Ready^® (CoolSystems, Inc.), Cryo/Cuff^® IC Cooler (DJO Global), and Hilotherm Homecare (Hilotherm GmbH) systems, which are marketed as an improvement over traditional forms of cold therapy, as they are capable of cooling for hours at a time, allow for nighttime use, and provide the operator with temperature control.^6-8

Postoperative cryotherapy is prescribed for a wide variety of orthopedic procedures, including anterior cruciate ligament (ACL) reconstruction surgery, rotator cuff surgery, and total knee arthroplasty (TKA). Current literature includes many studies monitoring postoperative outcomes in patients using cryotherapy as part of their treatment regimen, with the primary endpoints being visual analog scale (VAS) scores, analgesic consumption, and range of motion (ROM).^9-16 As demonstrated by in Table 1, these studies do not provide conclusive evidence that cryotherapy significantly alters postoperative outcomes, despite its ubiquitous use by the orthopedics community. In fact, the literature reflects a seeming lack of consensus regarding the effect of cryotherapy on analgesic requirements, pain, and joint mobility following procedures. Interestingly, of the studies represented in Table 1, only half analyzed all 3 postoperative measures (analgesic consumption, pain, and ROM). Furthermore, solely Morsi¹³ concluded that cryotherapy resulted in significant improvements in all 3 outcome measures in a trial involving only 30 patients. Kullenberg and colleagues¹² performed the largest study, but still included only 86 patients. In addition, all the studies focused on 1 joint or procedure. Thus, despite evidence that cryotherapy reduces inflammation at a molecular level, current literature does not unequivocally support the common belief that cryotherapy benefits patients in practice. More robust studies that include an analysis of analgesic consumption, VAS scores, and ROM (at minimum) and compare the relative efficacy of cryotherapy across joint types and procedures are necessary to determine whether postoperative cryotherapy in orthopedics is appropriate.

Table 1. Results from Studies that Compared Cryotherapy to Standard Care Within the First 2 Weeks Following Surgery

Continue to: ADVANCED CRYOTHERAPY DEVICES...

ADVANCED CRYOTHERAPY DEVICES

Several recent studies explored the relative postoperative benefits of advanced cryotherapeutics in lieu of the traditional ice pack.^6,7,17-21 As reflected in Table 2, these studies, much like the literature comparing cryotherapy to the control, do not reveal significant benefits of continuous flow cryotherapy after surgery. In fact, the only outcome measure that was found to differ significantly in more than 1 study was ROM. Though the makers of advanced cryotherapy systems market them as a vast improvement over traditional forms of cold therapy, there is insufficient evidence to support such claims. Even the most robust study that included 280 patients failed to show significant differences in the analgesic use and ROM after surgery.²⁰ Of note, all but 1 study compared traditional and advanced cryotherapy following procedures on the knee. Additional research exploring outcomes after surgery on other joints is necessary before any conclusions can be made regarding postoperative benefits or risks within orthopedics more generally.

RISKS AND ADVERSE EFFECTS OF CRYOTHERAPY

A rigorous analysis of the benefits of cryotherapy ought to incorporate other factors in addition to improvements in analgesic consumption, VAS score, and ROM. These include the financial and time investment involved in the use of continuous flow cryotherapy, which the majority of studies do not consider. Though many authors acknowledge that continuous flow cryotherapy is expensive, to our knowledge, none have yet performed a formal economic analysis of the cost of advanced cryotherapy to the patient as well as to the healthcare system at large.^{6,7,13,18,22-24} Dickinson and colleagues²⁴ calculated the total cost of cryotherapy and rehabilitation following rotator cuff repair, but addressed only the up-front cost of the cold therapy system. For context, Table 3 summarizes the retail cost of the most popular cryotherapy devices on the market. Based on this information alone, it seems reasonable to conclude that these systems are associated with significantly more cost than traditional forms of cold therapy, and therefore would be an undesirable option for patients or hospital systems. Nevertheless, cost considerations are more nuanced than a simple comparison of price, necessitating more advanced economic analyses. Substantial savings may be on the table if future studies are able to prove postoperative cryotherapy shortens hospital stays, reduces medication costs, and results in fewer physical therapy sessions. Moreover, if all this is true, patients may experience quicker recovery and have overall greater post-procedure satisfaction.

Table 3. Cost of Most Popular Cryotherapy Units

Patient education required for optimal use of advanced cold therapy is another aspect of cryotherapy that is poorly represented in the literature. As Dickinson and colleagues²⁴ point out, because it eliminates some dependency on the patient to remember to ice appropriately, continuous flow cryotherapy may have a positive impact on compliance and therefore yield improved outcomes.²⁴ Hospital staff may be required to spend additional time with patients. However, this is necessary to ensure proper understanding on how to operate the system and avoid adverse outcomes. Patients may also find the large coolers inconvenient and may therefore be reluctant to use them, finding traditional ice more manageable. Future studies should consider gathering data on patient education, compliance, and overall reception/satisfaction to complete a more holistic investigation of the role of postoperative cryotherapy in orthopedics.

Cryotherapy is not without adverse outcomes, which have been documented primarily in the form of case study reports. Relevant case studies cited adverse outcomes including frostbite/skin loss, compartment syndrome, and perniosis as potential dangers of postoperative cryotherapy in orthopedics (Table 4).^25-30 As an example, a patient recovering from patellar-tendon repair experienced bilateral frostbite and skin loss following 2 weeks of uninterrupted use of cryotherapy without any barrier between his skin and the system.²⁹ A similar case study described 2 female patients, one recovering from a TKA and the other from a tibial revision of arthroplasty, who used cryotherapy systems without cessation and experienced frostbite and skin necrosis over the entirety of their knees.²⁶ A third case study exploring 4 incidents of patellar frostbite and necrosis following knee arthroscopies proposed that poor patient understanding of proper cryotherapy use as well as poor recognition of the signs of frostbite contributed to these adverse outcomes. Furthermore, the cryotherapy brace used by all 4 patients included a feature designed to counteract patellar inflammation that also may have increased the likelihood of frostbite in this area due to poor tissue insulation. The authors noted that following the incidents, the makers of the brace removed patellar coverage to prevent future occurrences.³⁰

Abbreviations: ACL, anterior cruciate ligament; TKA, total knee arthroplasty.

Frostbite linked to cryotherapy has also occurred following orthopedic procedures outside the knee. Brown and Hahn²⁵ described 2 young females who developed skin necrosis following podiatric surgeries and constant cold therapy for roughly a week. Notably, 1 patient had cold sensitivity, which likely put her at an increased baseline risk of experiencing frostbite while using cryotherapy. Tissue necrosis is not the only danger of cold therapy discussed in this study. Surprisingly, 1 patient also developed compartment syndrome.²⁵ Khajavi and colleagues²⁷ also documented postoperative compartment syndrome in a patient following an arthroscopic osteochondral autograft transfer, which they attributed to reperfusion injury in the wake of first-degree frostbite. Hospital personnel also instructed this patient to use his cryotherapy system without interruption at the coldest temperature tolerable, contrary to manufacturer’s instructions.²⁷

Continue to: King and colleagues...

King and colleagues²⁸ described 2 cases of patients complaining of nodules, papules, and plaques soon after ACL reconstruction and the initiation of cryotherapy. A histological examination of their skin lesions demonstrated the presence of a perivascular and periadnexal superficial and deep lymphocytic infiltrate associated with perniosis. Dermatologists associated the perniosis with the cryotherapy cuff adhesive mechanisms, as their locations matched those of the lesions and symptoms subsided after cessation of cuff usage.²⁸

Cases of adverse effects with perioperative cryotherapy have also occurred at our own institution. The authors obtained informed written consent from the patients to print and publish their images. In 2 separate incidents, patients overdid icing and experienced rather extreme side effects including burns and blisters (Figures 1 and 2). In light of these adverse events, the physicians have questioned whether RICE ought to be part of their standard perioperative recommendations. These physicians are not alone in their uncertainty. Interestingly, even Mirkin,³¹ who coined the RICE mnemonic, now believes that consistent icing post-injury actually inhibits the body’s natural inflammatory healing response, delaying rather than speeding recovery, and suggests that icing ought to be used for pain control only.

DISCUSSION

Though there is ample literature supporting the common belief that cryotherapy minimizes inflammation at the cellular level, whether or not it results in meaningful improvements in post-surgical orthopedic outcomes remains unclear. Table 1 reflects a dearth of evidence to support the widespread current practice of cold therapy following orthopedic procedures, but few studies could demonstrate a significant difference in the analgesic use, VAS score, or ROM between cryotherapy and control groups. It is worth noting that these studies used different cryotherapy systems. Though in theory the continuous flow cryotherapy systems are similarly designed, there are potential differences among them that have not been controlled for in this analysis. All studies had <90 participants and focused on a single joint or procedure, making it difficult to draw large scale conclusions about the utility of cold therapy in the postoperative orthopedic population at large. Furthermore, researchers measured endpoints at a range of time intervals that were inconsistent across studies. In some cases, the significance of the impact of cryotherapy on recovery within a single study differed based on the time point at which researchers measured outcomes.^12-14 This raises the question as to whether cryotherapy has no benefits, or whether they are simply time-dependent. Future studies should seek to ascertain whether there is a postoperative time window in which cryotherapy could potentially expedite the recovery process.

Similarly, Table 2 shows a lack of consensus regarding the effect of advanced cryotherapy when compared to traditional ice application on pain, analgesic use, and joint mobility after surgery. However, all but 1 of these studies focused on knee procedures. Therefore, our findings may not be applicable to orthopedic surgeries on other joints. Nevertheless, the use of advanced cryotherapy in postoperative orthopedic care may wane if researchers continue to show that it is no more beneficial than its far less expensive counterpart of ice and an ace bandage.

The case studies discussed in this review serve as cautionary tales of the dangers of cryotherapy when used improperly. Though frostbite and subsequent tissue necrosis seem most common, physicians should be made aware that compartment syndrome and perniosis are also possible consequences. Orthopedic patients perhaps have an increased risk of developing these side effects due to the nature of their injuries and the large cutaneous surface area to which cryotherapy is applied. These outcomes could seemingly be avoided with improved educational initiatives targeted at both healthcare personnel and patients. Orthopedic surgeons might consider adding a short, instructive video focusing on proper usage as well as signs of adverse events to their discharge protocol to limit occurrences of these pitfalls associated with cryotherapy.

CONCLUSION

There is inadequate literature to support the of use postoperative cryotherapy of any kind in the field of orthopedics at this time. More robust, standardized studies, and a formidable economic analysis of advanced cold therapy systems are necessary before physicians prescribing cryotherapy can be confident that they are augmenting patient recovery. Nevertheless, as new developments in medicinal cryotherapy occur, it may be possible for the orthopedic community to wield its salutatory effects to limit complications and improve post-surgical outcomes.

The Food and Drug Administration has issued letters of warning to Chillin Mix Kratom and Mitra Distributing for making unproven medical claims about their kratom products – and therefore breaking federal law – according to a statement from FDA commissioner Scott Gottlieb, MD. These vendors both claimed that their kratom products could, among other things, “relieve” or “treat” opium/opioid withdrawal.

ThorPorre/commons.wikimedia.org

“To date, there have been no adequate and well-controlled studies involving the use of kratom as a treatment for opioid use withdrawal or other diseases in humans,” noted Dr. Gottlieb.

As Dr. Gottlieb pointed out in his statement, not only can fraudulent health claims pose direct health risks, they can also, in the case of kratom, deter or delay people who’re suffering from opioid use disorder from seeking FDA-approved treatments that have been demonstrated to be safe and effective.

[email protected]

The Food and Drug Administration has issued letters of warning to Chillin Mix Kratom and Mitra Distributing for making unproven medical claims about their kratom products – and therefore breaking federal law – according to a statement from FDA commissioner Scott Gottlieb, MD. These vendors both claimed that their kratom products could, among other things, “relieve” or “treat” opium/opioid withdrawal.

ThorPorre/commons.wikimedia.org

“To date, there have been no adequate and well-controlled studies involving the use of kratom as a treatment for opioid use withdrawal or other diseases in humans,” noted Dr. Gottlieb.

As Dr. Gottlieb pointed out in his statement, not only can fraudulent health claims pose direct health risks, they can also, in the case of kratom, deter or delay people who’re suffering from opioid use disorder from seeking FDA-approved treatments that have been demonstrated to be safe and effective.

[email protected]

The Food and Drug Administration has issued letters of warning to Chillin Mix Kratom and Mitra Distributing for making unproven medical claims about their kratom products – and therefore breaking federal law – according to a statement from FDA commissioner Scott Gottlieb, MD. These vendors both claimed that their kratom products could, among other things, “relieve” or “treat” opium/opioid withdrawal.

ThorPorre/commons.wikimedia.org

“To date, there have been no adequate and well-controlled studies involving the use of kratom as a treatment for opioid use withdrawal or other diseases in humans,” noted Dr. Gottlieb.

As Dr. Gottlieb pointed out in his statement, not only can fraudulent health claims pose direct health risks, they can also, in the case of kratom, deter or delay people who’re suffering from opioid use disorder from seeking FDA-approved treatments that have been demonstrated to be safe and effective.

[email protected]

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Concentrations of mutant huntingtin protein and neurofilament light proteins in cerebrospinal fluid and blood may be the first signs of progression in Huntington’s disease, according to a paper published online Sept. 12 in Science Translational Medicine.

designer491/Thinkstock

In a cohort of 40 Huntington’s mutation carriers with manifest disease, 20 carriers without clinical symptoms, and 20 healthy controls, researchers examined levels of mutant huntingtin (mHTT) and neurofilament light (NfL) protein in biofluids, in parallel with clinical evaluations and MRI imaging.

They found that concentrations of mHTT in the cerebrospinal fluid (CSF) and concentrations of NfL proteins in the CSF and plasma were significantly higher in participants with manifest Huntington’s disease (HD) than in those without manifest disease or in controls.

Researchers also saw that CSF concentrations of mHTT showed the earliest detectable change in progression of the disease, followed by plasma and CSF levels of NfL. After that came changes in caudate and global brain volume, motor score, word reading, and other clinical measures.

“These results suggest that as our understanding grows further, analysis of mHTT and NfL might be useful for developing HD therapeutics and for clinical management,” wrote Lauren M. Byrne of the Huntington’s Disease Centre at the University College London Institute of Neurology and her coauthors.

Plasma concentrations of NfL showed the strongest association with clinical severity, even after adjusting for the number of CAG (or cytosine, adenine, and guanine) repeats – a measure of disease severity – and age.

“Our previous work suggests that NfL is a dynamic marker of ongoing neuronal damage in HD that predicts subsequent progression,” the authors wrote. “This perhaps reflects that NfL, as a marker of axonal damage, has a more direct relationship with the development of clinical manifestations and brain atrophy.”

NfL concentrations in CSF more closely predicted brain volume than did plasma NfL or CSF concentrations of mHTT.

In participants who carried the Huntington’s mutation, CSF concentrations of mHTT and NfL were strongly correlated. Researchers also noted that mutation carriers had a significantly higher CSF-to-plasma ratio of NfL than did controls.

The study also showed that mHTT in the CSF and NfL in the cerebrospinal fluid and plasma, were very stable within individuals over 4-8 weeks.

“The very high intraclass correlation values of the three markers revealed them to be highly stable, suggesting that intraindividual variation in these analytes is likely to be a minimal source of noise in natural history and therapeutic studies,” the authors wrote.

This work was supported by the Medical Research Council U.K., the CHDI Foundation, the Wellcome Trust, the U.K. Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme, the U.K. Dementia Research Institute, F. Hoffmann-La Roche, the Horizon 2020 Framework Programme, and the Engineering and Physical Sciences Research Council. A number of authors disclosed consulting or serving on advisory boards for F. Hoffmann-La Roche and/or other companies. Three authors are full-time employees of F. Hoffmann-La Roche.

SOURCE: Byrne L et al. Sci Transl Med. 2018;10:eaat7108. doi: 10.1126/scitranslmed.aat7108.

Concentrations of mutant huntingtin protein and neurofilament light proteins in cerebrospinal fluid and blood may be the first signs of progression in Huntington’s disease, according to a paper published online Sept. 12 in Science Translational Medicine.

designer491/Thinkstock

In a cohort of 40 Huntington’s mutation carriers with manifest disease, 20 carriers without clinical symptoms, and 20 healthy controls, researchers examined levels of mutant huntingtin (mHTT) and neurofilament light (NfL) protein in biofluids, in parallel with clinical evaluations and MRI imaging.

They found that concentrations of mHTT in the cerebrospinal fluid (CSF) and concentrations of NfL proteins in the CSF and plasma were significantly higher in participants with manifest Huntington’s disease (HD) than in those without manifest disease or in controls.

Researchers also saw that CSF concentrations of mHTT showed the earliest detectable change in progression of the disease, followed by plasma and CSF levels of NfL. After that came changes in caudate and global brain volume, motor score, word reading, and other clinical measures.

“These results suggest that as our understanding grows further, analysis of mHTT and NfL might be useful for developing HD therapeutics and for clinical management,” wrote Lauren M. Byrne of the Huntington’s Disease Centre at the University College London Institute of Neurology and her coauthors.

Plasma concentrations of NfL showed the strongest association with clinical severity, even after adjusting for the number of CAG (or cytosine, adenine, and guanine) repeats – a measure of disease severity – and age.

“Our previous work suggests that NfL is a dynamic marker of ongoing neuronal damage in HD that predicts subsequent progression,” the authors wrote. “This perhaps reflects that NfL, as a marker of axonal damage, has a more direct relationship with the development of clinical manifestations and brain atrophy.”

NfL concentrations in CSF more closely predicted brain volume than did plasma NfL or CSF concentrations of mHTT.

In participants who carried the Huntington’s mutation, CSF concentrations of mHTT and NfL were strongly correlated. Researchers also noted that mutation carriers had a significantly higher CSF-to-plasma ratio of NfL than did controls.

The study also showed that mHTT in the CSF and NfL in the cerebrospinal fluid and plasma, were very stable within individuals over 4-8 weeks.

“The very high intraclass correlation values of the three markers revealed them to be highly stable, suggesting that intraindividual variation in these analytes is likely to be a minimal source of noise in natural history and therapeutic studies,” the authors wrote.

This work was supported by the Medical Research Council U.K., the CHDI Foundation, the Wellcome Trust, the U.K. Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme, the U.K. Dementia Research Institute, F. Hoffmann-La Roche, the Horizon 2020 Framework Programme, and the Engineering and Physical Sciences Research Council. A number of authors disclosed consulting or serving on advisory boards for F. Hoffmann-La Roche and/or other companies. Three authors are full-time employees of F. Hoffmann-La Roche.

SOURCE: Byrne L et al. Sci Transl Med. 2018;10:eaat7108. doi: 10.1126/scitranslmed.aat7108.

Concentrations of mutant huntingtin protein and neurofilament light proteins in cerebrospinal fluid and blood may be the first signs of progression in Huntington’s disease, according to a paper published online Sept. 12 in Science Translational Medicine.

designer491/Thinkstock

In a cohort of 40 Huntington’s mutation carriers with manifest disease, 20 carriers without clinical symptoms, and 20 healthy controls, researchers examined levels of mutant huntingtin (mHTT) and neurofilament light (NfL) protein in biofluids, in parallel with clinical evaluations and MRI imaging.

They found that concentrations of mHTT in the cerebrospinal fluid (CSF) and concentrations of NfL proteins in the CSF and plasma were significantly higher in participants with manifest Huntington’s disease (HD) than in those without manifest disease or in controls.

Researchers also saw that CSF concentrations of mHTT showed the earliest detectable change in progression of the disease, followed by plasma and CSF levels of NfL. After that came changes in caudate and global brain volume, motor score, word reading, and other clinical measures.

“These results suggest that as our understanding grows further, analysis of mHTT and NfL might be useful for developing HD therapeutics and for clinical management,” wrote Lauren M. Byrne of the Huntington’s Disease Centre at the University College London Institute of Neurology and her coauthors.

Plasma concentrations of NfL showed the strongest association with clinical severity, even after adjusting for the number of CAG (or cytosine, adenine, and guanine) repeats – a measure of disease severity – and age.

“Our previous work suggests that NfL is a dynamic marker of ongoing neuronal damage in HD that predicts subsequent progression,” the authors wrote. “This perhaps reflects that NfL, as a marker of axonal damage, has a more direct relationship with the development of clinical manifestations and brain atrophy.”

NfL concentrations in CSF more closely predicted brain volume than did plasma NfL or CSF concentrations of mHTT.

In participants who carried the Huntington’s mutation, CSF concentrations of mHTT and NfL were strongly correlated. Researchers also noted that mutation carriers had a significantly higher CSF-to-plasma ratio of NfL than did controls.

The study also showed that mHTT in the CSF and NfL in the cerebrospinal fluid and plasma, were very stable within individuals over 4-8 weeks.

“The very high intraclass correlation values of the three markers revealed them to be highly stable, suggesting that intraindividual variation in these analytes is likely to be a minimal source of noise in natural history and therapeutic studies,” the authors wrote.

This work was supported by the Medical Research Council U.K., the CHDI Foundation, the Wellcome Trust, the U.K. Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme, the U.K. Dementia Research Institute, F. Hoffmann-La Roche, the Horizon 2020 Framework Programme, and the Engineering and Physical Sciences Research Council. A number of authors disclosed consulting or serving on advisory boards for F. Hoffmann-La Roche and/or other companies. Three authors are full-time employees of F. Hoffmann-La Roche.

SOURCE: Byrne L et al. Sci Transl Med. 2018;10:eaat7108. doi: 10.1126/scitranslmed.aat7108.

A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.

Ryan McVay/Thinkstock

Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.

The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.

The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.

The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.

According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.

Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.

Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.

Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.

In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.

Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.

The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.

“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.

A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.

SOURCE: Pierot Laurent et al. J Neurointervent Surg. 2018 Aug 28. doi: 10.1136/neurintsurg-2018-014287.

*Updated Sept. 14, 2018.

A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.

Ryan McVay/Thinkstock

Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.

The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.

The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.

The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.

According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.

Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.

Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.

Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.

In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.

Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.

The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.

“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.

A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.

SOURCE: Pierot Laurent et al. J Neurointervent Surg. 2018 Aug 28. doi: 10.1136/neurintsurg-2018-014287.

*Updated Sept. 14, 2018.

A consensus working group from numerous international societies has published new guidelines for standards of practice in the treatment of acute ischemic stroke (AIS). The new guidelines differ somewhat from the Joint Commission guideline, released in 2015, primarily by raising the bar for the number of mechanical thrombectomy (MT) procedures that level 1 and level 2 stroke centers should perform annually in order to maintain a minimum safety threshold.

Ryan McVay/Thinkstock

Previous studies have shown lower mortality in high-volume centers, but setting minimum standards can be a challenge, especially in under-served countries and localities. The authors, led by first author Laurent Pierot, MD, PhD, of University Hospital Reims (France), acknowledge that newly established level 2 centers may struggle to meet the minimum requirement for MT procedures, but that this is acceptable as long as the volume is expected to meet the minimum within 12-24 months.

The guidelines were created by a working group of delegates from 13 international societies, including the American Society of Neuroradiology, European Stroke Organization, World Stroke Organization, and the Society of NeuroInterventional Surgery.

The publication in 2015 of studies showing the efficacy of MT in anterior circulation emergent large-vessel occlusion (ELVO) stroke patients reverberated through the stroke care community, but posed a challenge in delivering this therapy to populations in diverse localities that have no access to level 1 stroke centers.

The guidelines, published online in the Journal of NeuroInterventional Surgery, aim to ensure that facilities can handle not only the MT procedure, but also the medical management before, during, and after the procedure.

According to the new guidelines, level 2 centers should handle cases when a level 1 center cannot be reached within 2 hours. Level 2 centers should care for at least 100 AIS patients per year and should also have a relationship with a level 1 center to maintain staff training, teleconsultations, referrals, and other collaborations.

Previous studies have identified 35 or 36 MT procedures annually as a threshold to be considered “high volume,” a category that led to lower mortality. The new recommendations fall below that threshold because they are intended to apply broadly, to regions that may be under-served. In highly developed countries, stroke centers should follow regional or national guidelines that have higher limits.

Level 2 centers should perform at least 50 intracranial thrombectomy procedures for ELVO, and a total of 120 diagnostic or interventional neuroendovascular procedures per year. Individual interventionists should conduct at least 15 intracranial thrombectomy and 50 interventional neuroendovascular procedures per year.

Other recommendations cover additional details about personnel, as well as community and emergency medical services outreach.

In many ways, the recommendations are in line with the Joint Commission (TJC), according to David Tirschwell, MD, who is the medical director for the UW Medicine* Comprehensive Stroke Center at Harborview Medical Center, Seattle. He was not involved in the development of the new guidelines.

Dr. Tirschwell noted one key difference with respect to the number of MT procedures required to qualify. TJC offered no minimum annual procedures for Comprehensive Stroke Centers (equivalent to level 1), and only 15 for Thrombectomy Capable Stroke Centers (level 2), versus 50 in the new guidelines. The minimum procedure numbers are also higher for individual clinicians.

The guidelines also recommend that level 2 centers have at least three interventionalists on staff available at all times, while TJC does not address this element of staffing.

“The higher minimum number of procedures in the new international recommendations is a substantial difference and would make it harder for many hospitals to qualify, compared to the TJC requirements. As such, a lower number of hospitals may qualify, and such a barrier could prevent access to mechanical thrombectomy for many patients. On the other hand, the higher minimum number may ensure a higher quality of care, which can be seen as a strong positive feature,” Dr. Tirschwell said.

A spokesman for the Joint Commission and the American Heart Association indicated that they will review the new guidelines and consider whether to make changes to their 2015 guidelines.

SOURCE: Pierot Laurent et al. J Neurointervent Surg. 2018 Aug 28. doi: 10.1136/neurintsurg-2018-014287.

*Updated Sept. 14, 2018.

Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.

pixelheadphoto/ThinkStock

“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”

The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.

Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.

Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.

Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.

Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.

“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”

Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.

There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.

Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.

The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”

Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.

SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.

Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.

pixelheadphoto/ThinkStock

“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”

The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.

Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.

Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.

Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.

Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.

“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”

Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.

There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.

Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.

The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”

Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.

SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.

Women are at increased risk of developing depression during the perimenopausal transition, which can present with menopausal symptoms and affect women with no previous symptoms of depression, according to recent guidelines on perimenopausal depression copublished in the Journal of Women’s Health and Menopause.

pixelheadphoto/ThinkStock

“Epidemiologic findings, animal data, and clinical observations have shed some light into plausible mechanistic hypotheses on why some, but not all, women may be particularly sensitive to changes in the hormonal milieu experienced premenstrually, during the postpartum period or during the menopause transition,” Pauline M. Maki, PhD, past president of the North American Menopause Society (NAMS) and professor of psychiatry and psychology at the University of Illinois at Chicago, and her colleagues wrote. “The notion of a menopause-associated depression, however, has been the focus of clinical and scientific debate for years. The lack of consensus on this issue has also led to a lack of clarity in how to evaluate and treat depression in women during the menopausal transition and postmenopausal period.”

The guidelines were developed on behalf of the NAMS Board of Trustees and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Dr. Maki and her colleagues convened an 11-person expert panel on perimenopausal depression, which looked at the effects of factors such as epidemiology; clinical presentation; antidepressants; hormone therapy; and other therapies such as exercise, natural health products, and psychotherapy.

Most women who experience perimenopausal depression have previously undergone a major depressive episode (MDE), while major depressive disorder (MDD) onset at midlife is less common. However, even among women with no previous history of depression, the risk of perimenopausal depression – both depressive symptoms and MDE – is elevated for women at midlife. Studies suggest that 45%-68% of perimenopausal women have elevated depression symptoms.

Dr. Maki and her associates cited studies that showed women who underwent surgical menopause in the form of hysterectomy with and without oophorectomy and women with ovarian insufficiency also showed an elevated rate of depression.

Other risk factors for perimenopausal depression included sociodemographic (black race, financial difficulties) and psychosocial factors (adverse life events, low social support), anxiety, and menopausal symptoms such as interrupted sleep and vasomotor symptoms. Risk factors for MDD include use of antidepressants, premenstrual depressive symptoms, anxiety, menopausal sleep disturbance, sociodemographic factors such as high body mass index and black race, and psychosocial factors such as social isolation and upsetting life events.

Depressive symptoms in perimenopause present as classic depressive symptoms but may also be in combination with perimenopausal symptoms such as changes in weight, cognitive shifts, night sweats, hot flashes, and sexual and sleep disturbances. In addition, the stressors of life for women in midlife can further complicate depressive symptoms.

“Many women face a series of stressors including, but not exclusive to, caring for aging parents, death of parents, medical illness in self and family, adjusting to emotional and physical sequelae of surgical menopause and other health issues that are common to this stage of life, children leaving the home, and changes in marital status. With the onset of childbirth at an increasingly later age, women are often faced with the dual responsibility of raising young children amid caring for aging parents while navigating their careers and ensuing challenges,” Dr. Maki and her colleagues wrote. “These multiple demands are often faced without supports in place to identify or address the ensuing distress placed on a woman during this stage.”

Assessment and diagnosis should include factoring all these symptoms in and disentangling menopausal and psychiatric symptoms, evaluating women with past MDEs and MDD for a mood disorder, and use of differential diagnosis for psychiatric symptoms.

There is no menopause-specific mood disorder scale, Dr. Maki and her associates emphasized, but the Patient Health Questionnaire-9 can be used to categorize mood disorder diagnoses. There are “validated menopause symptom and health-related quality of life scales [that] include mood items” such as the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale.

Frontline treatment of MDE with traditional therapies such as antidepressants, cognitive behavioral therapy, and other psychotherapies is appropriate, while previous antidepressant trial and responses should be followed to find the best efficacy and tolerability for a women with a history of MDD. There is data on some SSRIs and serotonin norepinephrine reuptake inhibitors suggesting efficacy and tolerability at usual doses. Of note, Dr. Maki and her colleagues found estrogen therapy has some evidence for use as an antidepressant, but most studies on hormone therapy examined unopposed estrogen instead of estrogen plus progestogen, which has limited data.

The authors recommended exercise as a complement to psychotherapy and pharmacotherapies for perimenopausal women with depression, but said there is no available evidence to recommend “botanical or complementary/alternative approaches for treating depression related to the perimenopause.”

Several authors have reported honoraria, research support, consulting fees, and grants from numerous pharmaceutical companies, the National Pregnancy Registry for Atypical Antipsychotics; the Brain & Behavior Research Foundation; the Ontario Brain Institute; and the Ontario Ministry of Technology, Innovation, and Science. Six of the authors reported no relevant conflicts of interest.

SOURCE: Maki PM et al. J Womens Health. 2018 Sep 5. doi: 10.1089/jwh.2018.27099.mensocrec.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC

In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.

Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

[email protected]

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC

In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.

Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

[email protected]

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC

In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.

Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

[email protected]

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

The way we are paid as doctors is changing. In some cases, the delivery of orthopedic care could change from healthcare institutions’ most significant financial asset to one of their most detrimental liabilities. These changes provide a chance to improve both the quality and efficiency of the care we deliver, but we are unlikely to capitalize on this opportunity unless we understand this shifting paradigm. This change requires us to first appreciate the recent history of our reimbursement environment.

Traditionally, healthcare has been a relatively lucrative field, especially for those providing surgical care: doctors are paid “physician fees” by insurance companies (including Medicare), and institutions where procedures are performed are paid “facility fees.” Profits are measured as revenue (ie, reimbursement) minus costs of providing care, and while there has always been the potential to make more money by lowering costs, providers have historically had much more to gain by increasing their revenue. This fact has been exacerbated by the “fee-for-service” (FFS) payment model, which unintentionally encourages physicians to provide high volumes of care by “paying more for doing more.” For example, rather than being paid a fixed sum to care for a patient’s knee arthritis, each provider involved in the patient’s care is paid for each intervention. Clearly, this system encourages providers to maximize their interventions (ie, earning revenue) rather than search for ways to cut costs.

The Centers for Medicare and Medicaid Services (CMS) partially addressed this issue during the 1980s by introducing the Diagnosis Related Group (DRG).^1,2 Under this classification scheme, hospitals would be paid a pre-specified amount for a particular type of admission, often based on a specific procedure. For example, there is a DRG with a set payment for total knee arthroplasty (TKA).³ When reimbursement for the condition is set at a fixed amount, facilities are motivated to decrease their expenses since this is the only way to maximize the financial return for a given patient. This change, theoretically, encourages providers to cut their costs for providing a TKA as much as possible, potentially even to the point of sacrificing quality of care. As usual, when CMS makes a sweeping change, private insurers followed suit, and as a result, both government and corporate insurance is now structured around DRGs.

However, this was not a complete departure from FFS payment. We were still not paid to manage a patient’s knee arthritis as cheaply as possible; we were paid for each steroid injection, preoperative clinic visit, TKA (with numerous coding modifiers for complexity or comorbidities) as well as post-discharge admissions to skilled nursing and acute rehabilitation facilities. However, it was a start: for example, hospitals were no longer incentivized to keep TKA patients in house with a growing bill for each administered drug or therapy session. Yet, it is noteworthy that hospitals and physicians were still paid separately. This is important because doctors have historically made almost all treatment decisions and thereby determined the cost of care, yet hospitals have borne most of those costs, such as expensive implants or unplanned admissions, without a commensurate increase in reimbursement. As long as physicians are guaranteed their “fee,” they have little motivation to reduce those costs. Unsurprisingly, and as we well know, the advent of DRGs did not successfully curb our growing healthcare budget.

Recently, TKA and total hip arthroplasty reimbursement changed more dramatically. After experimenting with several pilots, CMS rolled out the Comprehensive Care for Joint Replacement (CJR) bundled payment program in 2015.^1,4 Participation in CJR is mandatory for most arthroplasty providers in approximately half of all “metropolitan” areas. In this scheme, hospital and physician pay is intertwined. Specifically, hospitals are held accountable for costs, so if the total Medicare bill for a patient’s TKA exceeds the “target price,” the hospital faces a penalty. Conversely, a charge below the target can earn a bonus payment.⁴ The hospital and surgeons must decide how they will share the bonus (or penalty), which creates an incentive to work together to lower costs.

Continue to: While bundled payments like CJR shift some...

While bundled payments like CJR shift some of the risk for high costs to the hospital and surgeon, a much more extreme example of this type of shift is capitation (ie, paying a healthcare institution a set amount per patient to care for whatever maladies arise). Insurers have experimented with various forms of capitation in the past, which led to the expansion of health management organizations (HMOs) during the 1990s. In theory, capitation should encourage providers to invest in disease prevention to minimize the need for costly interventions. However, more nefarious incentives developed, resulting in “cherry picking” healthy patients, which restricts access to care for sicker patients, and even withholds care from patients in need. The most infamous example was arguably “drive-through deliveries,” where newborns and their mothers were prematurely discharged following birth.⁵ As a result, the “HMO backlash” occurred, and capitation temporarily fell out of favor. The heart of the problem was a strong incentive to reduce the cost of care without a counterbalancing incentive to maintain quality. CJR and other modern programs attempt to avoid similar adverse incentives by requiring participants to meet certain quality criteria.⁶

Since the passage of the Affordable Care Act in 2010, capitation has reemerged under a new name: Accountable Care Organizations (ACOs). Numerous forms of ACO’s exist with differing payment schemes⁷, but the most comprehensive version, named Next Generation (Next Gen), allows providers to choose full capitation.⁸ While early ACOs focused on individual patients, Next Gen ACOs are also focused on “population health.” That is, they must demonstrate outcomes for individuals and the patient population as a whole, while simultaneously assuming all financial risk via capitation. Specifically, these ACO’s are paid an “all-inclusive population-based payment” for each patient based on how much that type of patient’s care is expected to cost for the year.⁹ The ACO then provides all necessary treatment and, if the ACO cannot provide a necessary intervention, it is responsible for funding that care at another institution. Appropriately, there has been an increased focus on quality to avoid unintentional incentives to withhold care. Specifically, CMS has introduced mandatory quality metrics in the domains of patient experience, care coordination, preventive care, and management of at-risk populations.¹⁰ At present, unfortunately, these metrics are not nearly comprehensive enough nor adequately validated to assess the quality of care,¹¹ especially for subspecialized fields like orthopedics where functional outcome scores are needed.

To date, very limited attention in the media or academic literature has been dedicated to subspecialty surgical care in the setting of ACOs even though implications for specialized surgeons could be immense. While ACOs bring numerous reporting requirements, the most essential first step for orthopedists in transition to this new reimbursement scheme will be a change in mindset. As explained above, orthopedics and other forms of specialized surgical care have traditionally been extremely profitable for healthcare institutions through relatively high revenue. However, within a capitated ACO all revenue has been paid upfront for each patient, and every orthopedic surgery performed represents a substantial cost to the institution rather than a large profit. For example, it has been reported that the average contribution margin earned by a hospital for an episode of care to provide a TKA (which includes postoperative care such as clinic visits, unplanned readmissions, and reoperations for complications) based on Medicare reimbursement is $11,726.¹² This figure consists of reimbursement (median, $24,149) less variable costs (median, $10,190). Additionally, the surgeon currently receives $1400 in physician fees.¹³ These earnings represent a significant financial benefit for both the facility and doctor in the current FFS environment. However, a capitated ACO caring for a TKA patient would already have received full payment for his care for the year. As a result, providing a TKA would not afford any further financial benefit and would, instead, mean a loss of $10,190 (the aforementioned variable cost for the episode of care) directly from the bottom line. The orthopedic department within that ACO, along with other departments, can be expected to share that loss. This implies that upon becoming an ACO, an institution’s orthopedics department will change from a major profit-center to a major cost-center.

Continue to: CMS must establish adequate quality assurance...

CMS must establish adequate quality assurance measures to ensure that ACOs do not withhold cost-effective care, like TKAs,^14,15 from their patients. Hopefully, for both professional and ethical reasons, providers will be active partners in this process. Groups like the International Consortium for Health Outcome Measurement, which has convened international expert panels to agree on comprehensive outcome sets for total joint arthroplasty and the management of low back pain, among other non-orthopedic conditions, may be useful examples in this process.^16-18

At the provider level, surgeons will be more likely to be salaried employees, contracting directly with the ACO rather than primarily working to earn physician fees from insurance providers. Surgeons will likely be judged (and rewarded financially) on their ability to direct nonoperative care, to find non-surgical solutions to problems that may currently be treated operatively, and to reduce costs for patients that require surgery. Additionally, with an increased focus on quality assurance, there will likely be more pressure from ACOs and CMS to demonstrate results of both operative and nonoperative care, likely in the forms of patient-reported metrics and objective measures of physical function. Surgeons will have a strong incentive to be leaders in the process of collecting such data.

It is also worth considering the position of orthopedic practices that are not part of an ACO. Some ACOs will not have the capacity to provide all (or possibly any) of the orthopedic care their patients require. When necessary, they will contract with outside orthopedic practices. Compared with CMS, ACOs are much smaller purchasers and can be expected to be more sensitive to price, likely negotiating intensely between local orthopedic providers. As a result, even orthopedists outside of ACOs may feel the cost pressure created by this new reimbursement model and may be driven to implement cost-reduction measures such as standardized implant choices and discharge pathways.

ACOs are in an active growth phase,^19,20 and recent updates to ACO policies make it clear that CMS intends for this trend to continue.⁸ Since ACOs are still a nascent reimbursement model, orthopedists will still do better financially, in almost all markets, by continuing to expend their energy and resources pursuing revenue, rather than cutting costs or demonstrating outcomes. However, as ACOs and population health gain traction, those orthopedists who recognize this shift and plan accordingly will have a definite strategic advantage, whether their practice is within an ACO, interacting with external ACOs, or both.

The way we are paid as doctors is changing. In some cases, the delivery of orthopedic care could change from healthcare institutions’ most significant financial asset to one of their most detrimental liabilities. These changes provide a chance to improve both the quality and efficiency of the care we deliver, but we are unlikely to capitalize on this opportunity unless we understand this shifting paradigm. This change requires us to first appreciate the recent history of our reimbursement environment.

Traditionally, healthcare has been a relatively lucrative field, especially for those providing surgical care: doctors are paid “physician fees” by insurance companies (including Medicare), and institutions where procedures are performed are paid “facility fees.” Profits are measured as revenue (ie, reimbursement) minus costs of providing care, and while there has always been the potential to make more money by lowering costs, providers have historically had much more to gain by increasing their revenue. This fact has been exacerbated by the “fee-for-service” (FFS) payment model, which unintentionally encourages physicians to provide high volumes of care by “paying more for doing more.” For example, rather than being paid a fixed sum to care for a patient’s knee arthritis, each provider involved in the patient’s care is paid for each intervention. Clearly, this system encourages providers to maximize their interventions (ie, earning revenue) rather than search for ways to cut costs.

The Centers for Medicare and Medicaid Services (CMS) partially addressed this issue during the 1980s by introducing the Diagnosis Related Group (DRG).^1,2 Under this classification scheme, hospitals would be paid a pre-specified amount for a particular type of admission, often based on a specific procedure. For example, there is a DRG with a set payment for total knee arthroplasty (TKA).³ When reimbursement for the condition is set at a fixed amount, facilities are motivated to decrease their expenses since this is the only way to maximize the financial return for a given patient. This change, theoretically, encourages providers to cut their costs for providing a TKA as much as possible, potentially even to the point of sacrificing quality of care. As usual, when CMS makes a sweeping change, private insurers followed suit, and as a result, both government and corporate insurance is now structured around DRGs.

However, this was not a complete departure from FFS payment. We were still not paid to manage a patient’s knee arthritis as cheaply as possible; we were paid for each steroid injection, preoperative clinic visit, TKA (with numerous coding modifiers for complexity or comorbidities) as well as post-discharge admissions to skilled nursing and acute rehabilitation facilities. However, it was a start: for example, hospitals were no longer incentivized to keep TKA patients in house with a growing bill for each administered drug or therapy session. Yet, it is noteworthy that hospitals and physicians were still paid separately. This is important because doctors have historically made almost all treatment decisions and thereby determined the cost of care, yet hospitals have borne most of those costs, such as expensive implants or unplanned admissions, without a commensurate increase in reimbursement. As long as physicians are guaranteed their “fee,” they have little motivation to reduce those costs. Unsurprisingly, and as we well know, the advent of DRGs did not successfully curb our growing healthcare budget.

Recently, TKA and total hip arthroplasty reimbursement changed more dramatically. After experimenting with several pilots, CMS rolled out the Comprehensive Care for Joint Replacement (CJR) bundled payment program in 2015.^1,4 Participation in CJR is mandatory for most arthroplasty providers in approximately half of all “metropolitan” areas. In this scheme, hospital and physician pay is intertwined. Specifically, hospitals are held accountable for costs, so if the total Medicare bill for a patient’s TKA exceeds the “target price,” the hospital faces a penalty. Conversely, a charge below the target can earn a bonus payment.⁴ The hospital and surgeons must decide how they will share the bonus (or penalty), which creates an incentive to work together to lower costs.

Continue to: While bundled payments like CJR shift some...

While bundled payments like CJR shift some of the risk for high costs to the hospital and surgeon, a much more extreme example of this type of shift is capitation (ie, paying a healthcare institution a set amount per patient to care for whatever maladies arise). Insurers have experimented with various forms of capitation in the past, which led to the expansion of health management organizations (HMOs) during the 1990s. In theory, capitation should encourage providers to invest in disease prevention to minimize the need for costly interventions. However, more nefarious incentives developed, resulting in “cherry picking” healthy patients, which restricts access to care for sicker patients, and even withholds care from patients in need. The most infamous example was arguably “drive-through deliveries,” where newborns and their mothers were prematurely discharged following birth.⁵ As a result, the “HMO backlash” occurred, and capitation temporarily fell out of favor. The heart of the problem was a strong incentive to reduce the cost of care without a counterbalancing incentive to maintain quality. CJR and other modern programs attempt to avoid similar adverse incentives by requiring participants to meet certain quality criteria.⁶

Since the passage of the Affordable Care Act in 2010, capitation has reemerged under a new name: Accountable Care Organizations (ACOs). Numerous forms of ACO’s exist with differing payment schemes⁷, but the most comprehensive version, named Next Generation (Next Gen), allows providers to choose full capitation.⁸ While early ACOs focused on individual patients, Next Gen ACOs are also focused on “population health.” That is, they must demonstrate outcomes for individuals and the patient population as a whole, while simultaneously assuming all financial risk via capitation. Specifically, these ACO’s are paid an “all-inclusive population-based payment” for each patient based on how much that type of patient’s care is expected to cost for the year.⁹ The ACO then provides all necessary treatment and, if the ACO cannot provide a necessary intervention, it is responsible for funding that care at another institution. Appropriately, there has been an increased focus on quality to avoid unintentional incentives to withhold care. Specifically, CMS has introduced mandatory quality metrics in the domains of patient experience, care coordination, preventive care, and management of at-risk populations.¹⁰ At present, unfortunately, these metrics are not nearly comprehensive enough nor adequately validated to assess the quality of care,¹¹ especially for subspecialized fields like orthopedics where functional outcome scores are needed.

To date, very limited attention in the media or academic literature has been dedicated to subspecialty surgical care in the setting of ACOs even though implications for specialized surgeons could be immense. While ACOs bring numerous reporting requirements, the most essential first step for orthopedists in transition to this new reimbursement scheme will be a change in mindset. As explained above, orthopedics and other forms of specialized surgical care have traditionally been extremely profitable for healthcare institutions through relatively high revenue. However, within a capitated ACO all revenue has been paid upfront for each patient, and every orthopedic surgery performed represents a substantial cost to the institution rather than a large profit. For example, it has been reported that the average contribution margin earned by a hospital for an episode of care to provide a TKA (which includes postoperative care such as clinic visits, unplanned readmissions, and reoperations for complications) based on Medicare reimbursement is $11,726.¹² This figure consists of reimbursement (median, $24,149) less variable costs (median, $10,190). Additionally, the surgeon currently receives $1400 in physician fees.¹³ These earnings represent a significant financial benefit for both the facility and doctor in the current FFS environment. However, a capitated ACO caring for a TKA patient would already have received full payment for his care for the year. As a result, providing a TKA would not afford any further financial benefit and would, instead, mean a loss of $10,190 (the aforementioned variable cost for the episode of care) directly from the bottom line. The orthopedic department within that ACO, along with other departments, can be expected to share that loss. This implies that upon becoming an ACO, an institution’s orthopedics department will change from a major profit-center to a major cost-center.

Continue to: CMS must establish adequate quality assurance...

CMS must establish adequate quality assurance measures to ensure that ACOs do not withhold cost-effective care, like TKAs,^14,15 from their patients. Hopefully, for both professional and ethical reasons, providers will be active partners in this process. Groups like the International Consortium for Health Outcome Measurement, which has convened international expert panels to agree on comprehensive outcome sets for total joint arthroplasty and the management of low back pain, among other non-orthopedic conditions, may be useful examples in this process.^16-18

At the provider level, surgeons will be more likely to be salaried employees, contracting directly with the ACO rather than primarily working to earn physician fees from insurance providers. Surgeons will likely be judged (and rewarded financially) on their ability to direct nonoperative care, to find non-surgical solutions to problems that may currently be treated operatively, and to reduce costs for patients that require surgery. Additionally, with an increased focus on quality assurance, there will likely be more pressure from ACOs and CMS to demonstrate results of both operative and nonoperative care, likely in the forms of patient-reported metrics and objective measures of physical function. Surgeons will have a strong incentive to be leaders in the process of collecting such data.

It is also worth considering the position of orthopedic practices that are not part of an ACO. Some ACOs will not have the capacity to provide all (or possibly any) of the orthopedic care their patients require. When necessary, they will contract with outside orthopedic practices. Compared with CMS, ACOs are much smaller purchasers and can be expected to be more sensitive to price, likely negotiating intensely between local orthopedic providers. As a result, even orthopedists outside of ACOs may feel the cost pressure created by this new reimbursement model and may be driven to implement cost-reduction measures such as standardized implant choices and discharge pathways.

ACOs are in an active growth phase,^19,20 and recent updates to ACO policies make it clear that CMS intends for this trend to continue.⁸ Since ACOs are still a nascent reimbursement model, orthopedists will still do better financially, in almost all markets, by continuing to expend their energy and resources pursuing revenue, rather than cutting costs or demonstrating outcomes. However, as ACOs and population health gain traction, those orthopedists who recognize this shift and plan accordingly will have a definite strategic advantage, whether their practice is within an ACO, interacting with external ACOs, or both.

The way we are paid as doctors is changing. In some cases, the delivery of orthopedic care could change from healthcare institutions’ most significant financial asset to one of their most detrimental liabilities. These changes provide a chance to improve both the quality and efficiency of the care we deliver, but we are unlikely to capitalize on this opportunity unless we understand this shifting paradigm. This change requires us to first appreciate the recent history of our reimbursement environment.

Traditionally, healthcare has been a relatively lucrative field, especially for those providing surgical care: doctors are paid “physician fees” by insurance companies (including Medicare), and institutions where procedures are performed are paid “facility fees.” Profits are measured as revenue (ie, reimbursement) minus costs of providing care, and while there has always been the potential to make more money by lowering costs, providers have historically had much more to gain by increasing their revenue. This fact has been exacerbated by the “fee-for-service” (FFS) payment model, which unintentionally encourages physicians to provide high volumes of care by “paying more for doing more.” For example, rather than being paid a fixed sum to care for a patient’s knee arthritis, each provider involved in the patient’s care is paid for each intervention. Clearly, this system encourages providers to maximize their interventions (ie, earning revenue) rather than search for ways to cut costs.

The Centers for Medicare and Medicaid Services (CMS) partially addressed this issue during the 1980s by introducing the Diagnosis Related Group (DRG).^1,2 Under this classification scheme, hospitals would be paid a pre-specified amount for a particular type of admission, often based on a specific procedure. For example, there is a DRG with a set payment for total knee arthroplasty (TKA).³ When reimbursement for the condition is set at a fixed amount, facilities are motivated to decrease their expenses since this is the only way to maximize the financial return for a given patient. This change, theoretically, encourages providers to cut their costs for providing a TKA as much as possible, potentially even to the point of sacrificing quality of care. As usual, when CMS makes a sweeping change, private insurers followed suit, and as a result, both government and corporate insurance is now structured around DRGs.

However, this was not a complete departure from FFS payment. We were still not paid to manage a patient’s knee arthritis as cheaply as possible; we were paid for each steroid injection, preoperative clinic visit, TKA (with numerous coding modifiers for complexity or comorbidities) as well as post-discharge admissions to skilled nursing and acute rehabilitation facilities. However, it was a start: for example, hospitals were no longer incentivized to keep TKA patients in house with a growing bill for each administered drug or therapy session. Yet, it is noteworthy that hospitals and physicians were still paid separately. This is important because doctors have historically made almost all treatment decisions and thereby determined the cost of care, yet hospitals have borne most of those costs, such as expensive implants or unplanned admissions, without a commensurate increase in reimbursement. As long as physicians are guaranteed their “fee,” they have little motivation to reduce those costs. Unsurprisingly, and as we well know, the advent of DRGs did not successfully curb our growing healthcare budget.

Recently, TKA and total hip arthroplasty reimbursement changed more dramatically. After experimenting with several pilots, CMS rolled out the Comprehensive Care for Joint Replacement (CJR) bundled payment program in 2015.^1,4 Participation in CJR is mandatory for most arthroplasty providers in approximately half of all “metropolitan” areas. In this scheme, hospital and physician pay is intertwined. Specifically, hospitals are held accountable for costs, so if the total Medicare bill for a patient’s TKA exceeds the “target price,” the hospital faces a penalty. Conversely, a charge below the target can earn a bonus payment.⁴ The hospital and surgeons must decide how they will share the bonus (or penalty), which creates an incentive to work together to lower costs.

Continue to: While bundled payments like CJR shift some...

While bundled payments like CJR shift some of the risk for high costs to the hospital and surgeon, a much more extreme example of this type of shift is capitation (ie, paying a healthcare institution a set amount per patient to care for whatever maladies arise). Insurers have experimented with various forms of capitation in the past, which led to the expansion of health management organizations (HMOs) during the 1990s. In theory, capitation should encourage providers to invest in disease prevention to minimize the need for costly interventions. However, more nefarious incentives developed, resulting in “cherry picking” healthy patients, which restricts access to care for sicker patients, and even withholds care from patients in need. The most infamous example was arguably “drive-through deliveries,” where newborns and their mothers were prematurely discharged following birth.⁵ As a result, the “HMO backlash” occurred, and capitation temporarily fell out of favor. The heart of the problem was a strong incentive to reduce the cost of care without a counterbalancing incentive to maintain quality. CJR and other modern programs attempt to avoid similar adverse incentives by requiring participants to meet certain quality criteria.⁶

Since the passage of the Affordable Care Act in 2010, capitation has reemerged under a new name: Accountable Care Organizations (ACOs). Numerous forms of ACO’s exist with differing payment schemes⁷, but the most comprehensive version, named Next Generation (Next Gen), allows providers to choose full capitation.⁸ While early ACOs focused on individual patients, Next Gen ACOs are also focused on “population health.” That is, they must demonstrate outcomes for individuals and the patient population as a whole, while simultaneously assuming all financial risk via capitation. Specifically, these ACO’s are paid an “all-inclusive population-based payment” for each patient based on how much that type of patient’s care is expected to cost for the year.⁹ The ACO then provides all necessary treatment and, if the ACO cannot provide a necessary intervention, it is responsible for funding that care at another institution. Appropriately, there has been an increased focus on quality to avoid unintentional incentives to withhold care. Specifically, CMS has introduced mandatory quality metrics in the domains of patient experience, care coordination, preventive care, and management of at-risk populations.¹⁰ At present, unfortunately, these metrics are not nearly comprehensive enough nor adequately validated to assess the quality of care,¹¹ especially for subspecialized fields like orthopedics where functional outcome scores are needed.

To date, very limited attention in the media or academic literature has been dedicated to subspecialty surgical care in the setting of ACOs even though implications for specialized surgeons could be immense. While ACOs bring numerous reporting requirements, the most essential first step for orthopedists in transition to this new reimbursement scheme will be a change in mindset. As explained above, orthopedics and other forms of specialized surgical care have traditionally been extremely profitable for healthcare institutions through relatively high revenue. However, within a capitated ACO all revenue has been paid upfront for each patient, and every orthopedic surgery performed represents a substantial cost to the institution rather than a large profit. For example, it has been reported that the average contribution margin earned by a hospital for an episode of care to provide a TKA (which includes postoperative care such as clinic visits, unplanned readmissions, and reoperations for complications) based on Medicare reimbursement is $11,726.¹² This figure consists of reimbursement (median, $24,149) less variable costs (median, $10,190). Additionally, the surgeon currently receives $1400 in physician fees.¹³ These earnings represent a significant financial benefit for both the facility and doctor in the current FFS environment. However, a capitated ACO caring for a TKA patient would already have received full payment for his care for the year. As a result, providing a TKA would not afford any further financial benefit and would, instead, mean a loss of $10,190 (the aforementioned variable cost for the episode of care) directly from the bottom line. The orthopedic department within that ACO, along with other departments, can be expected to share that loss. This implies that upon becoming an ACO, an institution’s orthopedics department will change from a major profit-center to a major cost-center.

Continue to: CMS must establish adequate quality assurance...

CMS must establish adequate quality assurance measures to ensure that ACOs do not withhold cost-effective care, like TKAs,^14,15 from their patients. Hopefully, for both professional and ethical reasons, providers will be active partners in this process. Groups like the International Consortium for Health Outcome Measurement, which has convened international expert panels to agree on comprehensive outcome sets for total joint arthroplasty and the management of low back pain, among other non-orthopedic conditions, may be useful examples in this process.^16-18

At the provider level, surgeons will be more likely to be salaried employees, contracting directly with the ACO rather than primarily working to earn physician fees from insurance providers. Surgeons will likely be judged (and rewarded financially) on their ability to direct nonoperative care, to find non-surgical solutions to problems that may currently be treated operatively, and to reduce costs for patients that require surgery. Additionally, with an increased focus on quality assurance, there will likely be more pressure from ACOs and CMS to demonstrate results of both operative and nonoperative care, likely in the forms of patient-reported metrics and objective measures of physical function. Surgeons will have a strong incentive to be leaders in the process of collecting such data.

It is also worth considering the position of orthopedic practices that are not part of an ACO. Some ACOs will not have the capacity to provide all (or possibly any) of the orthopedic care their patients require. When necessary, they will contract with outside orthopedic practices. Compared with CMS, ACOs are much smaller purchasers and can be expected to be more sensitive to price, likely negotiating intensely between local orthopedic providers. As a result, even orthopedists outside of ACOs may feel the cost pressure created by this new reimbursement model and may be driven to implement cost-reduction measures such as standardized implant choices and discharge pathways.

ACOs are in an active growth phase,^19,20 and recent updates to ACO policies make it clear that CMS intends for this trend to continue.⁸ Since ACOs are still a nascent reimbursement model, orthopedists will still do better financially, in almost all markets, by continuing to expend their energy and resources pursuing revenue, rather than cutting costs or demonstrating outcomes. However, as ACOs and population health gain traction, those orthopedists who recognize this shift and plan accordingly will have a definite strategic advantage, whether their practice is within an ACO, interacting with external ACOs, or both.

Active disease, failure of disease-modifying antirheumatic drug therapy, and an inability to taper glucocorticoid treatment are the main characteristics of difficult-to-treat RA, according to results of a survey of mostly European rheumatologists that also revealed a wide variation in views on the factors that contribute to the concept.

Ridofranz/Thinkstock

Some of the issues that survey respondents considered clinically relevant in difficult-to-treat RA are not covered by current EULAR management recommendations, Nadia M.T. Roodenrijs, of University Medical Center Utrecht, the Netherlands, and her colleagues noted in a study published online in Annals of the Rheumatic Diseases.

The investigators set out to determine what a range of rheumatologists from different countries considered to be the key characteristics of difficult-to-treat RA, which has an estimated prevalence of 5%-20%, depending on the criteria used. They also sought to identify the issues relating to work-up and management that were not covered by the current EULAR recommendations.

The online survey contained four multiple choice questions that asked about the necessity of incorporating disease activity level, fatigue, number of disease-modifying antirheumatic drugs (DMARDs) that failed, and the inability to taper glucocorticoids into the concept of difficult-to-treat RA. The survey also asked three open questions seeking additional clinically relevant views on difficult-to-treat RA.

A total of 410 respondents from 33 countries (96% European) completed the survey, which was sent to rheumatologists through the Emerging EULAR Network. Overall, half of the respondents selected “disease activity score assessing 28 joints using erythrocyte sedimentation rate [DAS28-ESR] greater than 3.2 or the presence of signs suggestive of active inflammatory disease activity with a DAS28-ESR of 3.2 or less” as characteristics of difficult-to-treat RA. About 42% of respondents included fatigue as a characteristic and 48% selected failure to two or more conventional DMARDs and two or more biological/targeted synthetic DMARDs. Furthermore, 89% of respondents identified the inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily to be a characteristic of difficult-to-treat RA.

Other clinically important issues identified by the respondents as currently missing from EULAR management recommendations included interfering comorbidities, especially cardiovascular disease, infection, and malignancy; extra-articular manifestations; and polypharmacy.

“The results of this survey underscore the difficulty in establishing an unambiguous concept of difficult-to-treat RA, which is seen as a heterogeneous condition not fully covered by EULAR recommendations,” the authors wrote.

The authors noted that their findings would help fuel discussion on the issues to include in the management recommendations for difficult-to-treat RA currently under consideration by a recently established EULAR task force.

The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.

SOURCE: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.

Active disease, failure of disease-modifying antirheumatic drug therapy, and an inability to taper glucocorticoid treatment are the main characteristics of difficult-to-treat RA, according to results of a survey of mostly European rheumatologists that also revealed a wide variation in views on the factors that contribute to the concept.

Ridofranz/Thinkstock

Some of the issues that survey respondents considered clinically relevant in difficult-to-treat RA are not covered by current EULAR management recommendations, Nadia M.T. Roodenrijs, of University Medical Center Utrecht, the Netherlands, and her colleagues noted in a study published online in Annals of the Rheumatic Diseases.

The investigators set out to determine what a range of rheumatologists from different countries considered to be the key characteristics of difficult-to-treat RA, which has an estimated prevalence of 5%-20%, depending on the criteria used. They also sought to identify the issues relating to work-up and management that were not covered by the current EULAR recommendations.

The online survey contained four multiple choice questions that asked about the necessity of incorporating disease activity level, fatigue, number of disease-modifying antirheumatic drugs (DMARDs) that failed, and the inability to taper glucocorticoids into the concept of difficult-to-treat RA. The survey also asked three open questions seeking additional clinically relevant views on difficult-to-treat RA.

A total of 410 respondents from 33 countries (96% European) completed the survey, which was sent to rheumatologists through the Emerging EULAR Network. Overall, half of the respondents selected “disease activity score assessing 28 joints using erythrocyte sedimentation rate [DAS28-ESR] greater than 3.2 or the presence of signs suggestive of active inflammatory disease activity with a DAS28-ESR of 3.2 or less” as characteristics of difficult-to-treat RA. About 42% of respondents included fatigue as a characteristic and 48% selected failure to two or more conventional DMARDs and two or more biological/targeted synthetic DMARDs. Furthermore, 89% of respondents identified the inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily to be a characteristic of difficult-to-treat RA.

Other clinically important issues identified by the respondents as currently missing from EULAR management recommendations included interfering comorbidities, especially cardiovascular disease, infection, and malignancy; extra-articular manifestations; and polypharmacy.

“The results of this survey underscore the difficulty in establishing an unambiguous concept of difficult-to-treat RA, which is seen as a heterogeneous condition not fully covered by EULAR recommendations,” the authors wrote.

The authors noted that their findings would help fuel discussion on the issues to include in the management recommendations for difficult-to-treat RA currently under consideration by a recently established EULAR task force.

The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.

SOURCE: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.

Active disease, failure of disease-modifying antirheumatic drug therapy, and an inability to taper glucocorticoid treatment are the main characteristics of difficult-to-treat RA, according to results of a survey of mostly European rheumatologists that also revealed a wide variation in views on the factors that contribute to the concept.

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Some of the issues that survey respondents considered clinically relevant in difficult-to-treat RA are not covered by current EULAR management recommendations, Nadia M.T. Roodenrijs, of University Medical Center Utrecht, the Netherlands, and her colleagues noted in a study published online in Annals of the Rheumatic Diseases.

The investigators set out to determine what a range of rheumatologists from different countries considered to be the key characteristics of difficult-to-treat RA, which has an estimated prevalence of 5%-20%, depending on the criteria used. They also sought to identify the issues relating to work-up and management that were not covered by the current EULAR recommendations.

The online survey contained four multiple choice questions that asked about the necessity of incorporating disease activity level, fatigue, number of disease-modifying antirheumatic drugs (DMARDs) that failed, and the inability to taper glucocorticoids into the concept of difficult-to-treat RA. The survey also asked three open questions seeking additional clinically relevant views on difficult-to-treat RA.

A total of 410 respondents from 33 countries (96% European) completed the survey, which was sent to rheumatologists through the Emerging EULAR Network. Overall, half of the respondents selected “disease activity score assessing 28 joints using erythrocyte sedimentation rate [DAS28-ESR] greater than 3.2 or the presence of signs suggestive of active inflammatory disease activity with a DAS28-ESR of 3.2 or less” as characteristics of difficult-to-treat RA. About 42% of respondents included fatigue as a characteristic and 48% selected failure to two or more conventional DMARDs and two or more biological/targeted synthetic DMARDs. Furthermore, 89% of respondents identified the inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily to be a characteristic of difficult-to-treat RA.

Other clinically important issues identified by the respondents as currently missing from EULAR management recommendations included interfering comorbidities, especially cardiovascular disease, infection, and malignancy; extra-articular manifestations; and polypharmacy.

“The results of this survey underscore the difficulty in establishing an unambiguous concept of difficult-to-treat RA, which is seen as a heterogeneous condition not fully covered by EULAR recommendations,” the authors wrote.

The authors noted that their findings would help fuel discussion on the issues to include in the management recommendations for difficult-to-treat RA currently under consideration by a recently established EULAR task force.

The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.

SOURCE: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.