ABSTRACT

The articular surface replacement (ASR) monoblock metal-on-metal acetabular component was recalled due to a higher than expected early failure rate. We evaluated the survivorship of the device and variables that may be predictive of failure at a minimum of 5-year follow-up. A single-center, single-surgeon retrospective review was conducted in patients who received the DePuy Synthes ASR™ XL Acetabular hip system from December 2005 to November 2009. Mean values and percentages were calculated and compared using the Fisher’s exact test, simple logistic regression, and Student’s t-test. The significance level was P ≤ .05. This study included 29 patients (24 males, 5 females) with 32 ASR™ XL acetabular hip systems. Mean age and body mass index (BMI) reached 55.2 years and 28.9 kg/m², respectively. Mean postoperative follow-up was 6.2 years. A total of 2 patients (6.9%) died of an unrelated cause and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom were available for follow-up. The 5-year revision rate was 34.4% (10 patients with 11 hip replacements). Mean time to revision was 3.1 years. Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with the increased rate for hip failure. Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months following the revision. This study demonstrates a high rate of failure of ASR acetabular components used in total hip arthroplasty at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is required.

Continue to: Metal-on-metal...

Metal-on-metal (MoM) articulations have been widely explored as an alternative to polyethylene bearings in total hip arthroplasty (THA), with proposed benefits including improved range of motion, lower dislocation rates, and enhanced durability.¹ Comprising cobalt and chromium, these MoM bearings gained widespread popularity in the United States, particularly in younger and more active patients looking for longer lasting devices.

The articular surface replacement (ASR) acetabular system (DePuy Synthes) was approved for sale by the US Food and Drug Administration in 2003 and implanted in an estimated 93,000 cases.² Since then, however, the early failure rate of the prosthesis has been well documented,^3-5 leading to a formal global product recall in August 2010. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was amongst the first to report a 6.4% rate of failure of the device at 3 years when inserted with a Corail stem.⁶ An acceptable upper rate of hip prosthesis failure is considered to reach 1% per year, with the majority of implants reporting well below this value. A 10.9% failure rate at 5 years was documented when the prosthesis was inserted for resurfacing. The National Joint Registry of England and Wales confirmed these findings and observed a 13% and 12% rate of failure at 5 years for the acetabular and resurfacing systems, respectively.² With the notable failure of the ASR system, this study reports our single-center 5-year survivorship experience and evaluates any variable that might be predictive of an early failure to aid in patient counseling.

METHODS

A single-center, single-surgeon, retrospective review of a consecutive series of patients was performed from December 2005 to November 2009. This study included all patients who underwent a primary THA with a DePuy Synthes ASR™ XL Acetabular hip system. No patients were excluded. Institutional Review Board approval was obtained. Patient demographics comprising of age, gender, and body mass index (BMI) were recorded. The primary endpoint of this study was 5-year survivorship rates. Secondary endpoints included duration to revision surgery, blood cobalt and chromium levels, time interval of blood ion tests, acetabulum size, acetabular component abduction angle, and duration to follow-up.

Candidates for the ASR™ XL Acetabular hip system included young patients and/or those considered to be physically active. In a select few, ASR devices were implanted upon patient request.

All patients underwent primary total hip replacement with a DePuy Synthes ASR™ XL uncemented acetabular component and an uncemented femoral stem (DePuy Synthes, Summit, or Tri-Lock) inserted via a standard posterior approach (Figure 1). Acetabulum sizes ranged from 52 mm to 68 mm in diameter.

All patients were followed-up yearly in the outpatient setting. Routine (yearly) metal-ion level sampling (whole blood) was started in 2010 for all patients. Laboratory tests were conducted at a single laboratory (Lab Corp.). Abduction cup inclination angles were measured by the providing surgeon using digital radiology software (GE Centricity systems).

The Student’s t-test was used to compare mean values (such as age, BMI, and metal ion levels) between the failure and no-failure groups. The 2-sided Fisher’s exact test analyzed differences in gender. Simple logistic regression analyzed variables associated with the failure group. Significance was P ≤ .05.

Continue to: Results...

RESULTS

A total of 29 patients (24 males, 5 females) with 32 ASR hip replacements were included in this study. Indications for surgery comprised osteoarthritis (28 hips, 87.5%) and avascular necrosis of the hip (4 hips, 12.5%). Mean age and BMI were 55.2 years and 28.9 kg/m², respectively. A total of 2 patients (6.9%) died of an unrelated cause (1 myocardial infarct, 1 suicide), and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom finished a 5-year minimum follow-up.

No implant failures were noted in the first year. The 5-year revision rate reached 34.4% (10 patients with 11 hip replacements). Mean time to revision for this subgroup was 3.1 years. Overall, an implant failure was observed in 37.5% of patients (11 patients with 12 hip replacements) at a mean postoperative follow-up of 6.2 years (Figure 2). Indications for implant revision were pain in 11 (92.7%) cases and infection in 1 (8.3%).

Of the 11 hips revised due to pain, 9 were performed by the original surgeon (8 were completed with primary acetabular components, 1 with a revision shell). Figure 3 shows a bilateral revision performed with primary acetabular components and retained DePuy Synthes Pinnacle femoral stems. In all these cases except 1, the ASR component was grossly loose. One case presented with pseudotumor and impingement between the femoral prosthetic neck and acetabular component after migration of a loose component. After revision, the patient returned with substantial anterior hip pain and heterotopic ossification, and failed conservative treatment, requiring another surgery with prosthesis retention, removal of heterotopic ossification, and iliopsoas lengthening. The surgery successfully relieved the symptoms. No other patients required additional surgery after their revision. In comparison to the original ASR component, the revision shell was 2 to 4 mm larger in diameter. No patient required component revision at a mean of 2.9 years after the revision surgery.

The patient with secondary revision developed a hematogenous streptococcal infection after a dental procedure performed without prophylactic antibiotics. The patient was initially lost to follow-up after the primary surgery and reported no antecedent pain prior to the revision. A substantial metal fluid collection was identified in the hip at the time of débridement and without component loosening. After débridement, the patient developed persistent metal stained wound drainage, necessitating ultimate successful treatment with a 2-stage exchange procedure.

Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with an increased rate for hip failure (Table). Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. The upper limits of blood cobalt and chromium levels reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months after the revision (Figure 4).

Table. Variables Not Associated with Early ASR Failure

Continue to: Discussion...

DISCUSSION

According to the Center for Disease Control and Prevention, 310,800 total hip replacements were performed among inpatients aged 45 years and older in the US in 2010.⁷ Specifically, in the 55- to 64-year-old age group, the number of procedures performed tripled from 2000 through 2010. As younger and more active patients opt for hip replacements, a growing need for prosthesis with enhanced durability is observed.

Despite the early proposed advantages of large head MoM bearings, our retrospective study of the DePuy Synthes ASR™ XL Acetabular hip system yielded 15.6% and 34.4% failure rates at 3 and 5 years, respectively. These higher-than-expected rates of failure are consistent with published data. The British Hip Society reported a 21% to 35% revision rate at 4 years and 49% at 6 years for the ASR XL prosthesis.⁸ In comparison, other MoM prosthesis, on average, report a 12% to 15% rate of failure at 5 years.

Considerable controversy surrounds the causes of adverse wear failure in MoM bearings.^9,10 The non-modular design of the ASR prostheses is frequently implicated as a cause of early failure. The lack of a central hole in the 1-piece component compromises the tactile feel of insertion, thereby reducing the surgeon’s ability to assess complete seating.¹¹ This condition may potentially increase the abduction angle at the time of insertion. Screw fixation of the non-modular device is not possible. The ASR XL device (148^° to 160^°) is less than a hemisphere (180^°) in size and hence features a diminished functional articular surface, further compromising implant fixation.¹¹ The functional articular surface is defined as the optimal surface area (10 mm) needed for a MoM implant.¹² Griffin and colleagues¹³ reported a 48 mm ASR XL component, when implanted at 45^° of abduction, to function similar to an implant at 59^° of abduction, leading to diminished lubrication, metallosis, and edge loading. The version of the acetabular component may similarly and adversely affect implant wear characteristics. Furthermore, the variable thickness of the implant, which is thicker at the dome and thinner at the rim, may further promote edge loading by shifting the center of rotation of the femoral head out from the center of the acetabular prosthesis.¹¹ Studies have also shown that increased wear of the MoM articulation is associated with an acetabular component inclination angle in excess of 55^°10,14 and a failure of fixation at time of implantation.¹⁵ This study, however, found no correlation between the abduction angle and risk of early implant failure for the ASR acetabular component. No correlation was also detected between the acetabulum size and revision surgery.

The AOANJRR reported loosening (44%), infection (20%), metal sensitivity (12%), fracture (9%), and dislocation of prosthesis (7%) as the indications for revision surgery for the ASR prosthesis.⁶ Furthermore, a single-center retrospective review of 70 consecutive MoM THAs with ultra-large diameter femoral head and monoblock acetabular components showed that 17.1% required revision within 3 years for loosening, pain, and squeaking.¹ Overall, 28.6% of patients reported implant dysfunction. In this study, we observed a similar rate of failure at 3 years (15.6%) for pain (11) and infection (1). The revision surgery successfully relieved all of these symptoms. One patient presented with heterotopic ossification and anterior hip pain after the original revision and required additional surgery with prosthesis retention. No patient in this series required repeat component revisions at a mean of 2.9 years after surgery. In all but 1 case, primary acetabular components were used in the revision, and in all cases except that with infection, the femoral component was retained. Replacement shells were 2 to 4 mm larger in diameter than the original ASR component.

Recently, concerns have arisen regarding the long-term effects of serum cobalt and chromium metal ions levels. Studies have shown increased serum metal ion levels,¹⁵ groin pain,¹⁶ pseudotumor formation,¹⁷ and metallosis¹⁸ after the implantation of MoM bearings. In a case study by Mao and colleagues,¹⁹ 1 patient reported headaches, anorexia, continuous metallic taste in her mouth, and weight loss. A cerebrospinal fluid analysis revealed cobalt and chromium levels at 9 and 13 nmol/L, respectively, indicating that these metal ions can cross the blood-brain barrier. Another patient reported painful muscle fatigue, night cramps, fainting spells, cognitive decline, and an inability to climb stairs. His serum cobalt level reached 258 nmol/L (reference range, 0-20 nmol/L), and chromium level totaled 88 nmol/L (reference range, 0-100 nmol/L). At 8-week follow-up after revision surgery, the symptoms of the patient had resolved, with serum cobalt levels dropping to 42 nmol/L.¹⁹ None of the patients in this study presented with any signs or symptoms of metal toxicity. The upper limits of blood cobalt and chromium levels in our study population reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. However, we noted a similar drop in post-revision blood cobalt (91% decrease) and chromium (78% decrease) levels.

In summary, our data showed a high revision rate of the DePuy Synthes ASR™ XL Acetabular hip system. Our findings are consistent with internationally published data. In the absence of reliable predictors of early failure, continued close clinical surveillance and laboratory monitoring of these patients are warranted.

CONCLUSION

This study demonstrates the high failure rate of the DePuy Synthes ASR™ XL Acetabular hip system used in THA at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is therefore required. Metal levels dropped quickly after revision, and the revision surgery can generally be performed with slightly larger primary components. Symptomatic patients with ASR hip replacements, regardless of blood metal-ion levels, were candidates for the revision surgery. Not all failed hips exhibited substantially elevated metal levels. Asymptomatic patients with high blood metal-ion levels should be closely followed-up and revision surgery should be strongly considered, consistent with recently published guidelines.²⁰

ABSTRACT

The articular surface replacement (ASR) monoblock metal-on-metal acetabular component was recalled due to a higher than expected early failure rate. We evaluated the survivorship of the device and variables that may be predictive of failure at a minimum of 5-year follow-up. A single-center, single-surgeon retrospective review was conducted in patients who received the DePuy Synthes ASR™ XL Acetabular hip system from December 2005 to November 2009. Mean values and percentages were calculated and compared using the Fisher’s exact test, simple logistic regression, and Student’s t-test. The significance level was P ≤ .05. This study included 29 patients (24 males, 5 females) with 32 ASR™ XL acetabular hip systems. Mean age and body mass index (BMI) reached 55.2 years and 28.9 kg/m², respectively. Mean postoperative follow-up was 6.2 years. A total of 2 patients (6.9%) died of an unrelated cause and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom were available for follow-up. The 5-year revision rate was 34.4% (10 patients with 11 hip replacements). Mean time to revision was 3.1 years. Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with the increased rate for hip failure. Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months following the revision. This study demonstrates a high rate of failure of ASR acetabular components used in total hip arthroplasty at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is required.

Continue to: Metal-on-metal...

Metal-on-metal (MoM) articulations have been widely explored as an alternative to polyethylene bearings in total hip arthroplasty (THA), with proposed benefits including improved range of motion, lower dislocation rates, and enhanced durability.¹ Comprising cobalt and chromium, these MoM bearings gained widespread popularity in the United States, particularly in younger and more active patients looking for longer lasting devices.

The articular surface replacement (ASR) acetabular system (DePuy Synthes) was approved for sale by the US Food and Drug Administration in 2003 and implanted in an estimated 93,000 cases.² Since then, however, the early failure rate of the prosthesis has been well documented,^3-5 leading to a formal global product recall in August 2010. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was amongst the first to report a 6.4% rate of failure of the device at 3 years when inserted with a Corail stem.⁶ An acceptable upper rate of hip prosthesis failure is considered to reach 1% per year, with the majority of implants reporting well below this value. A 10.9% failure rate at 5 years was documented when the prosthesis was inserted for resurfacing. The National Joint Registry of England and Wales confirmed these findings and observed a 13% and 12% rate of failure at 5 years for the acetabular and resurfacing systems, respectively.² With the notable failure of the ASR system, this study reports our single-center 5-year survivorship experience and evaluates any variable that might be predictive of an early failure to aid in patient counseling.

METHODS

A single-center, single-surgeon, retrospective review of a consecutive series of patients was performed from December 2005 to November 2009. This study included all patients who underwent a primary THA with a DePuy Synthes ASR™ XL Acetabular hip system. No patients were excluded. Institutional Review Board approval was obtained. Patient demographics comprising of age, gender, and body mass index (BMI) were recorded. The primary endpoint of this study was 5-year survivorship rates. Secondary endpoints included duration to revision surgery, blood cobalt and chromium levels, time interval of blood ion tests, acetabulum size, acetabular component abduction angle, and duration to follow-up.

Candidates for the ASR™ XL Acetabular hip system included young patients and/or those considered to be physically active. In a select few, ASR devices were implanted upon patient request.

All patients underwent primary total hip replacement with a DePuy Synthes ASR™ XL uncemented acetabular component and an uncemented femoral stem (DePuy Synthes, Summit, or Tri-Lock) inserted via a standard posterior approach (Figure 1). Acetabulum sizes ranged from 52 mm to 68 mm in diameter.

All patients were followed-up yearly in the outpatient setting. Routine (yearly) metal-ion level sampling (whole blood) was started in 2010 for all patients. Laboratory tests were conducted at a single laboratory (Lab Corp.). Abduction cup inclination angles were measured by the providing surgeon using digital radiology software (GE Centricity systems).

The Student’s t-test was used to compare mean values (such as age, BMI, and metal ion levels) between the failure and no-failure groups. The 2-sided Fisher’s exact test analyzed differences in gender. Simple logistic regression analyzed variables associated with the failure group. Significance was P ≤ .05.

Continue to: Results...

RESULTS

A total of 29 patients (24 males, 5 females) with 32 ASR hip replacements were included in this study. Indications for surgery comprised osteoarthritis (28 hips, 87.5%) and avascular necrosis of the hip (4 hips, 12.5%). Mean age and BMI were 55.2 years and 28.9 kg/m², respectively. A total of 2 patients (6.9%) died of an unrelated cause (1 myocardial infarct, 1 suicide), and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom finished a 5-year minimum follow-up.

No implant failures were noted in the first year. The 5-year revision rate reached 34.4% (10 patients with 11 hip replacements). Mean time to revision for this subgroup was 3.1 years. Overall, an implant failure was observed in 37.5% of patients (11 patients with 12 hip replacements) at a mean postoperative follow-up of 6.2 years (Figure 2). Indications for implant revision were pain in 11 (92.7%) cases and infection in 1 (8.3%).

Of the 11 hips revised due to pain, 9 were performed by the original surgeon (8 were completed with primary acetabular components, 1 with a revision shell). Figure 3 shows a bilateral revision performed with primary acetabular components and retained DePuy Synthes Pinnacle femoral stems. In all these cases except 1, the ASR component was grossly loose. One case presented with pseudotumor and impingement between the femoral prosthetic neck and acetabular component after migration of a loose component. After revision, the patient returned with substantial anterior hip pain and heterotopic ossification, and failed conservative treatment, requiring another surgery with prosthesis retention, removal of heterotopic ossification, and iliopsoas lengthening. The surgery successfully relieved the symptoms. No other patients required additional surgery after their revision. In comparison to the original ASR component, the revision shell was 2 to 4 mm larger in diameter. No patient required component revision at a mean of 2.9 years after the revision surgery.

The patient with secondary revision developed a hematogenous streptococcal infection after a dental procedure performed without prophylactic antibiotics. The patient was initially lost to follow-up after the primary surgery and reported no antecedent pain prior to the revision. A substantial metal fluid collection was identified in the hip at the time of débridement and without component loosening. After débridement, the patient developed persistent metal stained wound drainage, necessitating ultimate successful treatment with a 2-stage exchange procedure.

Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with an increased rate for hip failure (Table). Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. The upper limits of blood cobalt and chromium levels reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months after the revision (Figure 4).

Table. Variables Not Associated with Early ASR Failure

Continue to: Discussion...

DISCUSSION

According to the Center for Disease Control and Prevention, 310,800 total hip replacements were performed among inpatients aged 45 years and older in the US in 2010.⁷ Specifically, in the 55- to 64-year-old age group, the number of procedures performed tripled from 2000 through 2010. As younger and more active patients opt for hip replacements, a growing need for prosthesis with enhanced durability is observed.

Despite the early proposed advantages of large head MoM bearings, our retrospective study of the DePuy Synthes ASR™ XL Acetabular hip system yielded 15.6% and 34.4% failure rates at 3 and 5 years, respectively. These higher-than-expected rates of failure are consistent with published data. The British Hip Society reported a 21% to 35% revision rate at 4 years and 49% at 6 years for the ASR XL prosthesis.⁸ In comparison, other MoM prosthesis, on average, report a 12% to 15% rate of failure at 5 years.

Considerable controversy surrounds the causes of adverse wear failure in MoM bearings.^9,10 The non-modular design of the ASR prostheses is frequently implicated as a cause of early failure. The lack of a central hole in the 1-piece component compromises the tactile feel of insertion, thereby reducing the surgeon’s ability to assess complete seating.¹¹ This condition may potentially increase the abduction angle at the time of insertion. Screw fixation of the non-modular device is not possible. The ASR XL device (148^° to 160^°) is less than a hemisphere (180^°) in size and hence features a diminished functional articular surface, further compromising implant fixation.¹¹ The functional articular surface is defined as the optimal surface area (10 mm) needed for a MoM implant.¹² Griffin and colleagues¹³ reported a 48 mm ASR XL component, when implanted at 45^° of abduction, to function similar to an implant at 59^° of abduction, leading to diminished lubrication, metallosis, and edge loading. The version of the acetabular component may similarly and adversely affect implant wear characteristics. Furthermore, the variable thickness of the implant, which is thicker at the dome and thinner at the rim, may further promote edge loading by shifting the center of rotation of the femoral head out from the center of the acetabular prosthesis.¹¹ Studies have also shown that increased wear of the MoM articulation is associated with an acetabular component inclination angle in excess of 55^°10,14 and a failure of fixation at time of implantation.¹⁵ This study, however, found no correlation between the abduction angle and risk of early implant failure for the ASR acetabular component. No correlation was also detected between the acetabulum size and revision surgery.

The AOANJRR reported loosening (44%), infection (20%), metal sensitivity (12%), fracture (9%), and dislocation of prosthesis (7%) as the indications for revision surgery for the ASR prosthesis.⁶ Furthermore, a single-center retrospective review of 70 consecutive MoM THAs with ultra-large diameter femoral head and monoblock acetabular components showed that 17.1% required revision within 3 years for loosening, pain, and squeaking.¹ Overall, 28.6% of patients reported implant dysfunction. In this study, we observed a similar rate of failure at 3 years (15.6%) for pain (11) and infection (1). The revision surgery successfully relieved all of these symptoms. One patient presented with heterotopic ossification and anterior hip pain after the original revision and required additional surgery with prosthesis retention. No patient in this series required repeat component revisions at a mean of 2.9 years after surgery. In all but 1 case, primary acetabular components were used in the revision, and in all cases except that with infection, the femoral component was retained. Replacement shells were 2 to 4 mm larger in diameter than the original ASR component.

Recently, concerns have arisen regarding the long-term effects of serum cobalt and chromium metal ions levels. Studies have shown increased serum metal ion levels,¹⁵ groin pain,¹⁶ pseudotumor formation,¹⁷ and metallosis¹⁸ after the implantation of MoM bearings. In a case study by Mao and colleagues,¹⁹ 1 patient reported headaches, anorexia, continuous metallic taste in her mouth, and weight loss. A cerebrospinal fluid analysis revealed cobalt and chromium levels at 9 and 13 nmol/L, respectively, indicating that these metal ions can cross the blood-brain barrier. Another patient reported painful muscle fatigue, night cramps, fainting spells, cognitive decline, and an inability to climb stairs. His serum cobalt level reached 258 nmol/L (reference range, 0-20 nmol/L), and chromium level totaled 88 nmol/L (reference range, 0-100 nmol/L). At 8-week follow-up after revision surgery, the symptoms of the patient had resolved, with serum cobalt levels dropping to 42 nmol/L.¹⁹ None of the patients in this study presented with any signs or symptoms of metal toxicity. The upper limits of blood cobalt and chromium levels in our study population reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. However, we noted a similar drop in post-revision blood cobalt (91% decrease) and chromium (78% decrease) levels.

In summary, our data showed a high revision rate of the DePuy Synthes ASR™ XL Acetabular hip system. Our findings are consistent with internationally published data. In the absence of reliable predictors of early failure, continued close clinical surveillance and laboratory monitoring of these patients are warranted.

CONCLUSION

This study demonstrates the high failure rate of the DePuy Synthes ASR™ XL Acetabular hip system used in THA at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is therefore required. Metal levels dropped quickly after revision, and the revision surgery can generally be performed with slightly larger primary components. Symptomatic patients with ASR hip replacements, regardless of blood metal-ion levels, were candidates for the revision surgery. Not all failed hips exhibited substantially elevated metal levels. Asymptomatic patients with high blood metal-ion levels should be closely followed-up and revision surgery should be strongly considered, consistent with recently published guidelines.²⁰

ABSTRACT

The articular surface replacement (ASR) monoblock metal-on-metal acetabular component was recalled due to a higher than expected early failure rate. We evaluated the survivorship of the device and variables that may be predictive of failure at a minimum of 5-year follow-up. A single-center, single-surgeon retrospective review was conducted in patients who received the DePuy Synthes ASR™ XL Acetabular hip system from December 2005 to November 2009. Mean values and percentages were calculated and compared using the Fisher’s exact test, simple logistic regression, and Student’s t-test. The significance level was P ≤ .05. This study included 29 patients (24 males, 5 females) with 32 ASR™ XL acetabular hip systems. Mean age and body mass index (BMI) reached 55.2 years and 28.9 kg/m², respectively. Mean postoperative follow-up was 6.2 years. A total of 2 patients (6.9%) died of an unrelated cause and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom were available for follow-up. The 5-year revision rate was 34.4% (10 patients with 11 hip replacements). Mean time to revision was 3.1 years. Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with the increased rate for hip failure. Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months following the revision. This study demonstrates a high rate of failure of ASR acetabular components used in total hip arthroplasty at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is required.

Continue to: Metal-on-metal...

Metal-on-metal (MoM) articulations have been widely explored as an alternative to polyethylene bearings in total hip arthroplasty (THA), with proposed benefits including improved range of motion, lower dislocation rates, and enhanced durability.¹ Comprising cobalt and chromium, these MoM bearings gained widespread popularity in the United States, particularly in younger and more active patients looking for longer lasting devices.

The articular surface replacement (ASR) acetabular system (DePuy Synthes) was approved for sale by the US Food and Drug Administration in 2003 and implanted in an estimated 93,000 cases.² Since then, however, the early failure rate of the prosthesis has been well documented,^3-5 leading to a formal global product recall in August 2010. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was amongst the first to report a 6.4% rate of failure of the device at 3 years when inserted with a Corail stem.⁶ An acceptable upper rate of hip prosthesis failure is considered to reach 1% per year, with the majority of implants reporting well below this value. A 10.9% failure rate at 5 years was documented when the prosthesis was inserted for resurfacing. The National Joint Registry of England and Wales confirmed these findings and observed a 13% and 12% rate of failure at 5 years for the acetabular and resurfacing systems, respectively.² With the notable failure of the ASR system, this study reports our single-center 5-year survivorship experience and evaluates any variable that might be predictive of an early failure to aid in patient counseling.

METHODS

A single-center, single-surgeon, retrospective review of a consecutive series of patients was performed from December 2005 to November 2009. This study included all patients who underwent a primary THA with a DePuy Synthes ASR™ XL Acetabular hip system. No patients were excluded. Institutional Review Board approval was obtained. Patient demographics comprising of age, gender, and body mass index (BMI) were recorded. The primary endpoint of this study was 5-year survivorship rates. Secondary endpoints included duration to revision surgery, blood cobalt and chromium levels, time interval of blood ion tests, acetabulum size, acetabular component abduction angle, and duration to follow-up.

Candidates for the ASR™ XL Acetabular hip system included young patients and/or those considered to be physically active. In a select few, ASR devices were implanted upon patient request.

All patients underwent primary total hip replacement with a DePuy Synthes ASR™ XL uncemented acetabular component and an uncemented femoral stem (DePuy Synthes, Summit, or Tri-Lock) inserted via a standard posterior approach (Figure 1). Acetabulum sizes ranged from 52 mm to 68 mm in diameter.

All patients were followed-up yearly in the outpatient setting. Routine (yearly) metal-ion level sampling (whole blood) was started in 2010 for all patients. Laboratory tests were conducted at a single laboratory (Lab Corp.). Abduction cup inclination angles were measured by the providing surgeon using digital radiology software (GE Centricity systems).

The Student’s t-test was used to compare mean values (such as age, BMI, and metal ion levels) between the failure and no-failure groups. The 2-sided Fisher’s exact test analyzed differences in gender. Simple logistic regression analyzed variables associated with the failure group. Significance was P ≤ .05.

Continue to: Results...

RESULTS

A total of 29 patients (24 males, 5 females) with 32 ASR hip replacements were included in this study. Indications for surgery comprised osteoarthritis (28 hips, 87.5%) and avascular necrosis of the hip (4 hips, 12.5%). Mean age and BMI were 55.2 years and 28.9 kg/m², respectively. A total of 2 patients (6.9%) died of an unrelated cause (1 myocardial infarct, 1 suicide), and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom finished a 5-year minimum follow-up.

No implant failures were noted in the first year. The 5-year revision rate reached 34.4% (10 patients with 11 hip replacements). Mean time to revision for this subgroup was 3.1 years. Overall, an implant failure was observed in 37.5% of patients (11 patients with 12 hip replacements) at a mean postoperative follow-up of 6.2 years (Figure 2). Indications for implant revision were pain in 11 (92.7%) cases and infection in 1 (8.3%).

Of the 11 hips revised due to pain, 9 were performed by the original surgeon (8 were completed with primary acetabular components, 1 with a revision shell). Figure 3 shows a bilateral revision performed with primary acetabular components and retained DePuy Synthes Pinnacle femoral stems. In all these cases except 1, the ASR component was grossly loose. One case presented with pseudotumor and impingement between the femoral prosthetic neck and acetabular component after migration of a loose component. After revision, the patient returned with substantial anterior hip pain and heterotopic ossification, and failed conservative treatment, requiring another surgery with prosthesis retention, removal of heterotopic ossification, and iliopsoas lengthening. The surgery successfully relieved the symptoms. No other patients required additional surgery after their revision. In comparison to the original ASR component, the revision shell was 2 to 4 mm larger in diameter. No patient required component revision at a mean of 2.9 years after the revision surgery.

The patient with secondary revision developed a hematogenous streptococcal infection after a dental procedure performed without prophylactic antibiotics. The patient was initially lost to follow-up after the primary surgery and reported no antecedent pain prior to the revision. A substantial metal fluid collection was identified in the hip at the time of débridement and without component loosening. After débridement, the patient developed persistent metal stained wound drainage, necessitating ultimate successful treatment with a 2-stage exchange procedure.

Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with an increased rate for hip failure (Table). Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. The upper limits of blood cobalt and chromium levels reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months after the revision (Figure 4).

Table. Variables Not Associated with Early ASR Failure

Continue to: Discussion...

DISCUSSION

According to the Center for Disease Control and Prevention, 310,800 total hip replacements were performed among inpatients aged 45 years and older in the US in 2010.⁷ Specifically, in the 55- to 64-year-old age group, the number of procedures performed tripled from 2000 through 2010. As younger and more active patients opt for hip replacements, a growing need for prosthesis with enhanced durability is observed.

Despite the early proposed advantages of large head MoM bearings, our retrospective study of the DePuy Synthes ASR™ XL Acetabular hip system yielded 15.6% and 34.4% failure rates at 3 and 5 years, respectively. These higher-than-expected rates of failure are consistent with published data. The British Hip Society reported a 21% to 35% revision rate at 4 years and 49% at 6 years for the ASR XL prosthesis.⁸ In comparison, other MoM prosthesis, on average, report a 12% to 15% rate of failure at 5 years.

Considerable controversy surrounds the causes of adverse wear failure in MoM bearings.^9,10 The non-modular design of the ASR prostheses is frequently implicated as a cause of early failure. The lack of a central hole in the 1-piece component compromises the tactile feel of insertion, thereby reducing the surgeon’s ability to assess complete seating.¹¹ This condition may potentially increase the abduction angle at the time of insertion. Screw fixation of the non-modular device is not possible. The ASR XL device (148^° to 160^°) is less than a hemisphere (180^°) in size and hence features a diminished functional articular surface, further compromising implant fixation.¹¹ The functional articular surface is defined as the optimal surface area (10 mm) needed for a MoM implant.¹² Griffin and colleagues¹³ reported a 48 mm ASR XL component, when implanted at 45^° of abduction, to function similar to an implant at 59^° of abduction, leading to diminished lubrication, metallosis, and edge loading. The version of the acetabular component may similarly and adversely affect implant wear characteristics. Furthermore, the variable thickness of the implant, which is thicker at the dome and thinner at the rim, may further promote edge loading by shifting the center of rotation of the femoral head out from the center of the acetabular prosthesis.¹¹ Studies have also shown that increased wear of the MoM articulation is associated with an acetabular component inclination angle in excess of 55^°10,14 and a failure of fixation at time of implantation.¹⁵ This study, however, found no correlation between the abduction angle and risk of early implant failure for the ASR acetabular component. No correlation was also detected between the acetabulum size and revision surgery.

The AOANJRR reported loosening (44%), infection (20%), metal sensitivity (12%), fracture (9%), and dislocation of prosthesis (7%) as the indications for revision surgery for the ASR prosthesis.⁶ Furthermore, a single-center retrospective review of 70 consecutive MoM THAs with ultra-large diameter femoral head and monoblock acetabular components showed that 17.1% required revision within 3 years for loosening, pain, and squeaking.¹ Overall, 28.6% of patients reported implant dysfunction. In this study, we observed a similar rate of failure at 3 years (15.6%) for pain (11) and infection (1). The revision surgery successfully relieved all of these symptoms. One patient presented with heterotopic ossification and anterior hip pain after the original revision and required additional surgery with prosthesis retention. No patient in this series required repeat component revisions at a mean of 2.9 years after surgery. In all but 1 case, primary acetabular components were used in the revision, and in all cases except that with infection, the femoral component was retained. Replacement shells were 2 to 4 mm larger in diameter than the original ASR component.

Recently, concerns have arisen regarding the long-term effects of serum cobalt and chromium metal ions levels. Studies have shown increased serum metal ion levels,¹⁵ groin pain,¹⁶ pseudotumor formation,¹⁷ and metallosis¹⁸ after the implantation of MoM bearings. In a case study by Mao and colleagues,¹⁹ 1 patient reported headaches, anorexia, continuous metallic taste in her mouth, and weight loss. A cerebrospinal fluid analysis revealed cobalt and chromium levels at 9 and 13 nmol/L, respectively, indicating that these metal ions can cross the blood-brain barrier. Another patient reported painful muscle fatigue, night cramps, fainting spells, cognitive decline, and an inability to climb stairs. His serum cobalt level reached 258 nmol/L (reference range, 0-20 nmol/L), and chromium level totaled 88 nmol/L (reference range, 0-100 nmol/L). At 8-week follow-up after revision surgery, the symptoms of the patient had resolved, with serum cobalt levels dropping to 42 nmol/L.¹⁹ None of the patients in this study presented with any signs or symptoms of metal toxicity. The upper limits of blood cobalt and chromium levels in our study population reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. However, we noted a similar drop in post-revision blood cobalt (91% decrease) and chromium (78% decrease) levels.

In summary, our data showed a high revision rate of the DePuy Synthes ASR™ XL Acetabular hip system. Our findings are consistent with internationally published data. In the absence of reliable predictors of early failure, continued close clinical surveillance and laboratory monitoring of these patients are warranted.

CONCLUSION

This study demonstrates the high failure rate of the DePuy Synthes ASR™ XL Acetabular hip system used in THA at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is therefore required. Metal levels dropped quickly after revision, and the revision surgery can generally be performed with slightly larger primary components. Symptomatic patients with ASR hip replacements, regardless of blood metal-ion levels, were candidates for the revision surgery. Not all failed hips exhibited substantially elevated metal levels. Asymptomatic patients with high blood metal-ion levels should be closely followed-up and revision surgery should be strongly considered, consistent with recently published guidelines.²⁰

BARCELONA – The immune checkpoint inhibitor pembrolizumab (Keytruda) did not significantly improve overall survival of advanced/metastatic gastric or gastroesophageal junction cancer compared with paclitaxel, the results of the KEYNOTE-061 study show.

Among 395 patients with gastric or gastroesophageal junction (GEJ) cancer who had expression of the programmed death ligand 1 (PD-L1) on 1% or more of their tumor cells, lymphocytes, and macrophages, median overall survival (OS) for patients treated with pembrolizumab was 9.1 months, compared with 8.3 months. This translated into a hazard ratio (HR) for death in the pembrolizumab arm of 0.82, but with the 95% confidence interval crossing 1.00, and a P value (.04205) that did not meet the prespecified threshold for significance (P equal to or less than .0135).

Neil Osterweil/MDedge News

Neil Osterweil/MDedge News

SOURCE: Shitara K. et al. ESMO World Congress on Gastrointestinal Cancer 2018. Abstract LBA-005.

BARCELONA – The immune checkpoint inhibitor pembrolizumab (Keytruda) did not significantly improve overall survival of advanced/metastatic gastric or gastroesophageal junction cancer compared with paclitaxel, the results of the KEYNOTE-061 study show.

Among 395 patients with gastric or gastroesophageal junction (GEJ) cancer who had expression of the programmed death ligand 1 (PD-L1) on 1% or more of their tumor cells, lymphocytes, and macrophages, median overall survival (OS) for patients treated with pembrolizumab was 9.1 months, compared with 8.3 months. This translated into a hazard ratio (HR) for death in the pembrolizumab arm of 0.82, but with the 95% confidence interval crossing 1.00, and a P value (.04205) that did not meet the prespecified threshold for significance (P equal to or less than .0135).

Neil Osterweil/MDedge News

Neil Osterweil/MDedge News

SOURCE: Shitara K. et al. ESMO World Congress on Gastrointestinal Cancer 2018. Abstract LBA-005.

BARCELONA – The immune checkpoint inhibitor pembrolizumab (Keytruda) did not significantly improve overall survival of advanced/metastatic gastric or gastroesophageal junction cancer compared with paclitaxel, the results of the KEYNOTE-061 study show.

Among 395 patients with gastric or gastroesophageal junction (GEJ) cancer who had expression of the programmed death ligand 1 (PD-L1) on 1% or more of their tumor cells, lymphocytes, and macrophages, median overall survival (OS) for patients treated with pembrolizumab was 9.1 months, compared with 8.3 months. This translated into a hazard ratio (HR) for death in the pembrolizumab arm of 0.82, but with the 95% confidence interval crossing 1.00, and a P value (.04205) that did not meet the prespecified threshold for significance (P equal to or less than .0135).

Neil Osterweil/MDedge News

Neil Osterweil/MDedge News

SOURCE: Shitara K. et al. ESMO World Congress on Gastrointestinal Cancer 2018. Abstract LBA-005.

BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.

Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.

Neil Osterweil/MDedge News

SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.

BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.

Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.

Neil Osterweil/MDedge News

SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.

BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.

Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.

Neil Osterweil/MDedge News

SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.

MALMO, SWEDEN – The combination of serum procalcitonin and C-reactive protein levels upon admission to a pediatric ICU displayed high utility for early diagnosis of serious bacterial infection in critically ill children in a large prospective observational study presented at the annual meeting of the European Society for Paediatric Infectious Diseases.

This winning combination significantly outperformed neutrophil gelatinase-associated lipocalin, activated partial thromboplastin time, and resistin, both individually and in various combinations, for the vital task of making a rapid distinction between infectious and noninfectious causes of pediatric systemic inflammatory response syndrome, reported Enitan D. Carrol, MD, professor of pediatric infection at the University of Liverpool (England).

Bruce Jancin/MDedge News

“One of the clinical dilemmas we face in intensive care is being able to differentiate between infectious and noninfectious causes of systemic inflammatory response syndrome. This is important because we need to identify which children have life-threatening infections so that we can promptly initiate antimicrobial therapy,” she explained.

One in four deaths in pediatric ICUs are infection related, Dr. Carrol noted.

“There is an urgent need for infection markers which, firstly, change early in the course of bacterial infection, secondly, correlate with real-time clinical progression, and thirdly, have a rapid turn-around time to allow effective clinical decision making,” she observed.

The combination of procalcitonin and C-reactive protein (CRP) levels measured at admission fits the bill, Dr. Carrol continued. Of the five biomarkers evaluated in her study – all backed by some supporting evidence of efficacy in earlier studies – the top two individual performers in terms of negative predictive value (NPV) were a CRP less than 4.2 mg/dL with a negative NPV of 99%, and a procalcitonin less than 1.52 ng/mL with an NPV of 96%. The positive predictive value of each of the biomarkers was 37%. The sensitivity and specificity of procalcitonin for diagnosis of serious bacterial infection were 78% and 80%, respectively. For CRP, the figures were 93% and 76%.

The combination of procalcitonin and CRP outperformed a multitude of other two-, three-, and four-biomarker combinations tested, with an area under the curve of 93% for combined sensitivity and specificity.

The study included 657 children admitted to the pediatric ICU at Alder Hey Children’s Hospital in Liverpool with systemic inflammatory response syndrome. All had blood samples measured for the five biomarkers on days 1-7. Clinicians were blinded as to the biomarker results. Ninety-two (14%) patients were ultimately found to have a serious bacterial infection – essentially, bacterial meningitis or septic shock – and 565 (86%) had a nonbacterial etiology.

The 28-day mortality rate was 9% in the group with serious bacterial infection, significantly higher than the 2% rate in the group with other causes of their systemic inflammatory response syndrome.

Longitudinal trends in procalcitonin and CRP as evidenced in the study can be used in clinical decision making, according to Dr. Carrol. Mean values of procalcitonin plummeted by 80% from day 1 to day 5 in response to antimicrobial therapy in the group with serious bacterial infections. In contrast, CRP levels rose sharply from day 1 to a peak on day 2, then fell, although the 50% drop from day 2 to day 5 in response to antimicrobial therapy wasn’t as pronounced as the change in procalcitonin.

“There is an additive benefit for both biomarkers compared with CRP alone. The problem with CRP on admission, as I’ve demonstrated in this study, is it often hasn’t risen yet early after admission. So although it gave the best area under the curve of any of the biomarkers, I think that combined with procalcitonin you get a much better descriminator,” Dr. Carrol said.

The median duration of ICU stay in the patients with serious bacterial infection at admission was 5 days, compared with 3 days when the cause of systemic inflammatory response syndrome lay elsewhere. Their median duration of ventilation was significantly longer, too: 4 days versus 2 in children without a serious bacterial infection.

Stepwise logistic regression analysis pinpointed several clinical variables as being associated with prolonged ICU stay.

[email protected]

MALMO, SWEDEN – The combination of serum procalcitonin and C-reactive protein levels upon admission to a pediatric ICU displayed high utility for early diagnosis of serious bacterial infection in critically ill children in a large prospective observational study presented at the annual meeting of the European Society for Paediatric Infectious Diseases.

This winning combination significantly outperformed neutrophil gelatinase-associated lipocalin, activated partial thromboplastin time, and resistin, both individually and in various combinations, for the vital task of making a rapid distinction between infectious and noninfectious causes of pediatric systemic inflammatory response syndrome, reported Enitan D. Carrol, MD, professor of pediatric infection at the University of Liverpool (England).

Bruce Jancin/MDedge News

“One of the clinical dilemmas we face in intensive care is being able to differentiate between infectious and noninfectious causes of systemic inflammatory response syndrome. This is important because we need to identify which children have life-threatening infections so that we can promptly initiate antimicrobial therapy,” she explained.

One in four deaths in pediatric ICUs are infection related, Dr. Carrol noted.

“There is an urgent need for infection markers which, firstly, change early in the course of bacterial infection, secondly, correlate with real-time clinical progression, and thirdly, have a rapid turn-around time to allow effective clinical decision making,” she observed.

The combination of procalcitonin and C-reactive protein (CRP) levels measured at admission fits the bill, Dr. Carrol continued. Of the five biomarkers evaluated in her study – all backed by some supporting evidence of efficacy in earlier studies – the top two individual performers in terms of negative predictive value (NPV) were a CRP less than 4.2 mg/dL with a negative NPV of 99%, and a procalcitonin less than 1.52 ng/mL with an NPV of 96%. The positive predictive value of each of the biomarkers was 37%. The sensitivity and specificity of procalcitonin for diagnosis of serious bacterial infection were 78% and 80%, respectively. For CRP, the figures were 93% and 76%.

The combination of procalcitonin and CRP outperformed a multitude of other two-, three-, and four-biomarker combinations tested, with an area under the curve of 93% for combined sensitivity and specificity.

The study included 657 children admitted to the pediatric ICU at Alder Hey Children’s Hospital in Liverpool with systemic inflammatory response syndrome. All had blood samples measured for the five biomarkers on days 1-7. Clinicians were blinded as to the biomarker results. Ninety-two (14%) patients were ultimately found to have a serious bacterial infection – essentially, bacterial meningitis or septic shock – and 565 (86%) had a nonbacterial etiology.

The 28-day mortality rate was 9% in the group with serious bacterial infection, significantly higher than the 2% rate in the group with other causes of their systemic inflammatory response syndrome.

Longitudinal trends in procalcitonin and CRP as evidenced in the study can be used in clinical decision making, according to Dr. Carrol. Mean values of procalcitonin plummeted by 80% from day 1 to day 5 in response to antimicrobial therapy in the group with serious bacterial infections. In contrast, CRP levels rose sharply from day 1 to a peak on day 2, then fell, although the 50% drop from day 2 to day 5 in response to antimicrobial therapy wasn’t as pronounced as the change in procalcitonin.

“There is an additive benefit for both biomarkers compared with CRP alone. The problem with CRP on admission, as I’ve demonstrated in this study, is it often hasn’t risen yet early after admission. So although it gave the best area under the curve of any of the biomarkers, I think that combined with procalcitonin you get a much better descriminator,” Dr. Carrol said.

The median duration of ICU stay in the patients with serious bacterial infection at admission was 5 days, compared with 3 days when the cause of systemic inflammatory response syndrome lay elsewhere. Their median duration of ventilation was significantly longer, too: 4 days versus 2 in children without a serious bacterial infection.

Stepwise logistic regression analysis pinpointed several clinical variables as being associated with prolonged ICU stay.

[email protected]

MALMO, SWEDEN – The combination of serum procalcitonin and C-reactive protein levels upon admission to a pediatric ICU displayed high utility for early diagnosis of serious bacterial infection in critically ill children in a large prospective observational study presented at the annual meeting of the European Society for Paediatric Infectious Diseases.

This winning combination significantly outperformed neutrophil gelatinase-associated lipocalin, activated partial thromboplastin time, and resistin, both individually and in various combinations, for the vital task of making a rapid distinction between infectious and noninfectious causes of pediatric systemic inflammatory response syndrome, reported Enitan D. Carrol, MD, professor of pediatric infection at the University of Liverpool (England).

Bruce Jancin/MDedge News

“One of the clinical dilemmas we face in intensive care is being able to differentiate between infectious and noninfectious causes of systemic inflammatory response syndrome. This is important because we need to identify which children have life-threatening infections so that we can promptly initiate antimicrobial therapy,” she explained.

One in four deaths in pediatric ICUs are infection related, Dr. Carrol noted.

“There is an urgent need for infection markers which, firstly, change early in the course of bacterial infection, secondly, correlate with real-time clinical progression, and thirdly, have a rapid turn-around time to allow effective clinical decision making,” she observed.

The combination of procalcitonin and C-reactive protein (CRP) levels measured at admission fits the bill, Dr. Carrol continued. Of the five biomarkers evaluated in her study – all backed by some supporting evidence of efficacy in earlier studies – the top two individual performers in terms of negative predictive value (NPV) were a CRP less than 4.2 mg/dL with a negative NPV of 99%, and a procalcitonin less than 1.52 ng/mL with an NPV of 96%. The positive predictive value of each of the biomarkers was 37%. The sensitivity and specificity of procalcitonin for diagnosis of serious bacterial infection were 78% and 80%, respectively. For CRP, the figures were 93% and 76%.

The combination of procalcitonin and CRP outperformed a multitude of other two-, three-, and four-biomarker combinations tested, with an area under the curve of 93% for combined sensitivity and specificity.

The study included 657 children admitted to the pediatric ICU at Alder Hey Children’s Hospital in Liverpool with systemic inflammatory response syndrome. All had blood samples measured for the five biomarkers on days 1-7. Clinicians were blinded as to the biomarker results. Ninety-two (14%) patients were ultimately found to have a serious bacterial infection – essentially, bacterial meningitis or septic shock – and 565 (86%) had a nonbacterial etiology.

The 28-day mortality rate was 9% in the group with serious bacterial infection, significantly higher than the 2% rate in the group with other causes of their systemic inflammatory response syndrome.

Longitudinal trends in procalcitonin and CRP as evidenced in the study can be used in clinical decision making, according to Dr. Carrol. Mean values of procalcitonin plummeted by 80% from day 1 to day 5 in response to antimicrobial therapy in the group with serious bacterial infections. In contrast, CRP levels rose sharply from day 1 to a peak on day 2, then fell, although the 50% drop from day 2 to day 5 in response to antimicrobial therapy wasn’t as pronounced as the change in procalcitonin.

“There is an additive benefit for both biomarkers compared with CRP alone. The problem with CRP on admission, as I’ve demonstrated in this study, is it often hasn’t risen yet early after admission. So although it gave the best area under the curve of any of the biomarkers, I think that combined with procalcitonin you get a much better descriminator,” Dr. Carrol said.

The median duration of ICU stay in the patients with serious bacterial infection at admission was 5 days, compared with 3 days when the cause of systemic inflammatory response syndrome lay elsewhere. Their median duration of ventilation was significantly longer, too: 4 days versus 2 in children without a serious bacterial infection.

Stepwise logistic regression analysis pinpointed several clinical variables as being associated with prolonged ICU stay.

[email protected]

Behavioral parent management training (PMT), which teaches parents concrete skills to increase their attention to positive behavior and to plan for their response to undesired behavior, has abundant evidence for success for many challenging child behaviors. But sometimes parents have a hard time managing their own emotional responses in the often highly triggering situation of family conflict. Mindfulness has the potential to provide a complement to the PMT skills. Studies are beginning to explore these possibilities.

Case summary

Zoe is a bright 5-year-old who has been “strong willed” and shown intense emotional responses since early in life. The usual 2-year-old temper tantrums increased over time. She has outbursts of yelling, kicking, and hitting, especially with transitions. Her parents tried behavioral parent training, but found it frustrating. If Zoe has been yelling and hitting earlier in the day, her mother feels hurt and angry and can’t bring herself to pay warm attention when Zoe is doing better. When Zoe refuses to pick up her room, her father is flooded with thoughts about his own father hitting him for the slightest disrespect. He thinks that he is a bad, weak father, and sometimes “sees red” and ends up yelling at Zoe instead of putting into place a calm consequence.

kali9/Getty Images

Discussion

Mindfulness is defined by Jon Kabat-Zinn as “paying attention in a particular way – on purpose, in the present moment, and nonjudgmentally.” A central feature of mindfulness is strengthening the ability to focus our attention. We learn to pay attention to aspects of the present moment, be that breathing, the sensations in our body, or the experiences of our senses. Often the first skill in behavioral training methods is getting parents to pay attention to their children by participating in child-led play or spending attentive time with older children. This means attending to what the child is doing or talking about rather than jumping in and taking over with suggestions, instructions, or judgments. This meshes very well with this central aspect of mindfulness.

As we practice paying attention, we observe that the mind naturally jumps around from what we mean to be attending to, to a host of distractions, worries, plans, memories, thoughts, and emotions. Mindfulness encourages practitioners to notice these thoughts, to avoid criticizing or judging oneself for becoming involved with these, but instead gently lead the mind back to what you had intended to focus on. This observation of the mind’s activity gives the mindfulness practitioner a bit of space from the thought or emotion itself. We are encouraged to name the thought or emotional processes we notice: “I am worrying, I am planning, I am remembering.”

In the heat of a difficult moment with the child, parents often are flooded with intense emotions (such as anger, fear, anxiety, panic, despair) and thoughts (such as “If my child keeps acting this way he is going to go to jail when he grows up,” “I am a terrible parent,” “Why is my child doing this to me?” or “He is just like his father”). These emotions and thoughts can drive intense, impulsive responses from the parents. As they practice mindfulness, they can gain the ability to observe themselves having these thoughts; observe harsh judgments of themselves or their children or their partners; have some space from them; and realize they may change in a few minutes or realize they may be painful but don’t necessarily have to spur impulsive action. In that moment, parents can give themselves time and space to think through possible actions, and then choose one.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures. Email her at [email protected].

Resources

“Mindful Parenting” (New York: Norton & Co., 2015).

“Integrating mindfulness with parent training: Effects of the mindfulness-enhanced strengthening families program” (Dev Psychol. 2015;51[1]:26-35).

“Everyday blessings: The inner work of mindful parenting,” (New York: Hyperion, 1997).

Behavioral parent management training (PMT), which teaches parents concrete skills to increase their attention to positive behavior and to plan for their response to undesired behavior, has abundant evidence for success for many challenging child behaviors. But sometimes parents have a hard time managing their own emotional responses in the often highly triggering situation of family conflict. Mindfulness has the potential to provide a complement to the PMT skills. Studies are beginning to explore these possibilities.

Case summary

Zoe is a bright 5-year-old who has been “strong willed” and shown intense emotional responses since early in life. The usual 2-year-old temper tantrums increased over time. She has outbursts of yelling, kicking, and hitting, especially with transitions. Her parents tried behavioral parent training, but found it frustrating. If Zoe has been yelling and hitting earlier in the day, her mother feels hurt and angry and can’t bring herself to pay warm attention when Zoe is doing better. When Zoe refuses to pick up her room, her father is flooded with thoughts about his own father hitting him for the slightest disrespect. He thinks that he is a bad, weak father, and sometimes “sees red” and ends up yelling at Zoe instead of putting into place a calm consequence.

kali9/Getty Images

Discussion

Mindfulness is defined by Jon Kabat-Zinn as “paying attention in a particular way – on purpose, in the present moment, and nonjudgmentally.” A central feature of mindfulness is strengthening the ability to focus our attention. We learn to pay attention to aspects of the present moment, be that breathing, the sensations in our body, or the experiences of our senses. Often the first skill in behavioral training methods is getting parents to pay attention to their children by participating in child-led play or spending attentive time with older children. This means attending to what the child is doing or talking about rather than jumping in and taking over with suggestions, instructions, or judgments. This meshes very well with this central aspect of mindfulness.

As we practice paying attention, we observe that the mind naturally jumps around from what we mean to be attending to, to a host of distractions, worries, plans, memories, thoughts, and emotions. Mindfulness encourages practitioners to notice these thoughts, to avoid criticizing or judging oneself for becoming involved with these, but instead gently lead the mind back to what you had intended to focus on. This observation of the mind’s activity gives the mindfulness practitioner a bit of space from the thought or emotion itself. We are encouraged to name the thought or emotional processes we notice: “I am worrying, I am planning, I am remembering.”

In the heat of a difficult moment with the child, parents often are flooded with intense emotions (such as anger, fear, anxiety, panic, despair) and thoughts (such as “If my child keeps acting this way he is going to go to jail when he grows up,” “I am a terrible parent,” “Why is my child doing this to me?” or “He is just like his father”). These emotions and thoughts can drive intense, impulsive responses from the parents. As they practice mindfulness, they can gain the ability to observe themselves having these thoughts; observe harsh judgments of themselves or their children or their partners; have some space from them; and realize they may change in a few minutes or realize they may be painful but don’t necessarily have to spur impulsive action. In that moment, parents can give themselves time and space to think through possible actions, and then choose one.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures. Email her at [email protected].

Resources

“Mindful Parenting” (New York: Norton & Co., 2015).

“Integrating mindfulness with parent training: Effects of the mindfulness-enhanced strengthening families program” (Dev Psychol. 2015;51[1]:26-35).

“Everyday blessings: The inner work of mindful parenting,” (New York: Hyperion, 1997).

Behavioral parent management training (PMT), which teaches parents concrete skills to increase their attention to positive behavior and to plan for their response to undesired behavior, has abundant evidence for success for many challenging child behaviors. But sometimes parents have a hard time managing their own emotional responses in the often highly triggering situation of family conflict. Mindfulness has the potential to provide a complement to the PMT skills. Studies are beginning to explore these possibilities.

Case summary

Zoe is a bright 5-year-old who has been “strong willed” and shown intense emotional responses since early in life. The usual 2-year-old temper tantrums increased over time. She has outbursts of yelling, kicking, and hitting, especially with transitions. Her parents tried behavioral parent training, but found it frustrating. If Zoe has been yelling and hitting earlier in the day, her mother feels hurt and angry and can’t bring herself to pay warm attention when Zoe is doing better. When Zoe refuses to pick up her room, her father is flooded with thoughts about his own father hitting him for the slightest disrespect. He thinks that he is a bad, weak father, and sometimes “sees red” and ends up yelling at Zoe instead of putting into place a calm consequence.

kali9/Getty Images

Discussion

Mindfulness is defined by Jon Kabat-Zinn as “paying attention in a particular way – on purpose, in the present moment, and nonjudgmentally.” A central feature of mindfulness is strengthening the ability to focus our attention. We learn to pay attention to aspects of the present moment, be that breathing, the sensations in our body, or the experiences of our senses. Often the first skill in behavioral training methods is getting parents to pay attention to their children by participating in child-led play or spending attentive time with older children. This means attending to what the child is doing or talking about rather than jumping in and taking over with suggestions, instructions, or judgments. This meshes very well with this central aspect of mindfulness.

As we practice paying attention, we observe that the mind naturally jumps around from what we mean to be attending to, to a host of distractions, worries, plans, memories, thoughts, and emotions. Mindfulness encourages practitioners to notice these thoughts, to avoid criticizing or judging oneself for becoming involved with these, but instead gently lead the mind back to what you had intended to focus on. This observation of the mind’s activity gives the mindfulness practitioner a bit of space from the thought or emotion itself. We are encouraged to name the thought or emotional processes we notice: “I am worrying, I am planning, I am remembering.”

In the heat of a difficult moment with the child, parents often are flooded with intense emotions (such as anger, fear, anxiety, panic, despair) and thoughts (such as “If my child keeps acting this way he is going to go to jail when he grows up,” “I am a terrible parent,” “Why is my child doing this to me?” or “He is just like his father”). These emotions and thoughts can drive intense, impulsive responses from the parents. As they practice mindfulness, they can gain the ability to observe themselves having these thoughts; observe harsh judgments of themselves or their children or their partners; have some space from them; and realize they may change in a few minutes or realize they may be painful but don’t necessarily have to spur impulsive action. In that moment, parents can give themselves time and space to think through possible actions, and then choose one.

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures. Email her at [email protected].

Resources

“Mindful Parenting” (New York: Norton & Co., 2015).

“Integrating mindfulness with parent training: Effects of the mindfulness-enhanced strengthening families program” (Dev Psychol. 2015;51[1]:26-35).

“Everyday blessings: The inner work of mindful parenting,” (New York: Hyperion, 1997).

Streptococcal intertrigo is an inflammatory, superficial eruption of intertriginous skin caused by group A beta-hemolytic streptococci. Frequently misdiagnosed, streptococcal intertrigo more commonly affects infants and toddlers but is rarely reported, especially compared with other Streptococcus pyogenes infections, including impetigo, erysipelas, and cellulitis.¹

Intertrigo, meaning “between” (inter) and “to rub” (terere) in Latin, describes any skin disorder involving two opposing skin surfaces that touch or rub to cause friction.² The continuous chaffing, coupled with moisture trapped within the skin folds, leads to irritation and maceration, which provides an ideal environment for pathogens to thrive. Thus, frictional dermatitides that arise may become secondarily infected with one or more microorganisms, such as Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, and even organisms less commonly associated with cutaneous infection, such as Proteus mirabilis.³

Courtesy Dr. Lawrence F. Eichenfield

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the university. They had no conflicts of interest or disclosures to report.


References

1. Pediatr Dermatol. 2014 Mar-Apr;31(2):e71-2.

2. Clin Dermatol. 2011 Mar-Apr;29(2):173-9.

3. Pediatrics. 2003 Dec;112(6 pt 1):1427-9.

4. BMJ Case Rep. 2018 Mar 20. doi: 10.1136/bcr-2018-224179.

5. Pediatr Infect Dis J. 2012 Aug;31(8):872-3.

6. J Pediatr. 2015 May;166(5):1318.

7. J Pediatr. 2015 Sep;167(3):687-93.e1-2.

8. Pediatrics in Review. 1991;12(8):248-55.

9. J Pediatr. 2017 May;184:230-1.e1.

Streptococcal intertrigo is an inflammatory, superficial eruption of intertriginous skin caused by group A beta-hemolytic streptococci. Frequently misdiagnosed, streptococcal intertrigo more commonly affects infants and toddlers but is rarely reported, especially compared with other Streptococcus pyogenes infections, including impetigo, erysipelas, and cellulitis.¹

Intertrigo, meaning “between” (inter) and “to rub” (terere) in Latin, describes any skin disorder involving two opposing skin surfaces that touch or rub to cause friction.² The continuous chaffing, coupled with moisture trapped within the skin folds, leads to irritation and maceration, which provides an ideal environment for pathogens to thrive. Thus, frictional dermatitides that arise may become secondarily infected with one or more microorganisms, such as Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, and even organisms less commonly associated with cutaneous infection, such as Proteus mirabilis.³

Courtesy Dr. Lawrence F. Eichenfield

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the university. They had no conflicts of interest or disclosures to report.


References

1. Pediatr Dermatol. 2014 Mar-Apr;31(2):e71-2.

2. Clin Dermatol. 2011 Mar-Apr;29(2):173-9.

3. Pediatrics. 2003 Dec;112(6 pt 1):1427-9.

4. BMJ Case Rep. 2018 Mar 20. doi: 10.1136/bcr-2018-224179.

5. Pediatr Infect Dis J. 2012 Aug;31(8):872-3.

6. J Pediatr. 2015 May;166(5):1318.

7. J Pediatr. 2015 Sep;167(3):687-93.e1-2.

8. Pediatrics in Review. 1991;12(8):248-55.

9. J Pediatr. 2017 May;184:230-1.e1.

Streptococcal intertrigo is an inflammatory, superficial eruption of intertriginous skin caused by group A beta-hemolytic streptococci. Frequently misdiagnosed, streptococcal intertrigo more commonly affects infants and toddlers but is rarely reported, especially compared with other Streptococcus pyogenes infections, including impetigo, erysipelas, and cellulitis.¹

Intertrigo, meaning “between” (inter) and “to rub” (terere) in Latin, describes any skin disorder involving two opposing skin surfaces that touch or rub to cause friction.² The continuous chaffing, coupled with moisture trapped within the skin folds, leads to irritation and maceration, which provides an ideal environment for pathogens to thrive. Thus, frictional dermatitides that arise may become secondarily infected with one or more microorganisms, such as Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, and even organisms less commonly associated with cutaneous infection, such as Proteus mirabilis.³

Courtesy Dr. Lawrence F. Eichenfield

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the university. They had no conflicts of interest or disclosures to report.


References

1. Pediatr Dermatol. 2014 Mar-Apr;31(2):e71-2.

2. Clin Dermatol. 2011 Mar-Apr;29(2):173-9.

3. Pediatrics. 2003 Dec;112(6 pt 1):1427-9.

4. BMJ Case Rep. 2018 Mar 20. doi: 10.1136/bcr-2018-224179.

5. Pediatr Infect Dis J. 2012 Aug;31(8):872-3.

6. J Pediatr. 2015 May;166(5):1318.

7. J Pediatr. 2015 Sep;167(3):687-93.e1-2.

8. Pediatrics in Review. 1991;12(8):248-55.

9. J Pediatr. 2017 May;184:230-1.e1.

LIVERPOOL, ENGLAND – Serum levels of the cardiac biomarker troponin might prove useful for assessing the risk of death from cardiovascular causes in patients with inflammatory arthritis, according to study findings presented at the British Society for Rheumatology annual conference.

“In this analysis we have shown that baseline troponin levels predict cardiovascular death in inflammatory arthritis, and this association is independent of the traditional risk factors, inflammation, and disease characteristics at baseline,” said study author Sarah Skeoch, MBChB, who works at the Arthritis Research UK Centre for Epidemiology in the division of musculoskeletal and dermatological sciences at the University of Manchester (England).

Sara Freeman/MDedge News

The median follow up was 11.2 years, totaling 11,237 person-years, and during that time 158 deaths occurred, of which 27 were due to ischemic events. The median time from inclusion in NOAR to death was 7.4 years.

When levels of hs-TnI were separated into tertiles, a 12.5-fold increased risk was observed when comparing patients in the highest (more than 7.7 pg/mL) to lowest tertiles (less than 5.2 pg/mL).

“The magnitude of risk between the highest and the lowest tertile was much greater than observed in the general population,” Dr. Skeoch said, and although not directly comparable, she said the hazard ratios were 12.5 and 1.67, “which again suggests that troponin may be an effective tool or addition to the risk prediction models in inflammatory arthritis.”

Unlike some biomarkers, assays to assess troponin are already available in the clinic, Dr. Skeoch commented, “so if further work by us and other groups do suggest a role for troponin, this could be translated fairly rapidly into clinical practice.”

Further research needs to look at why troponin is raised and what is its relationship to other risk factors. “There is a strong association with traditional risk factors such as lipids, so it would stand to reason that managing those risk factors, as well as lifestyle factors, would have a positive impact,” Dr. Skeoch suggested.

The NOAR register is funded by Arthritis Research UK and the U.K. National Institute for Health Research. Dr. Skeoch and her coauthors had no relevant financial conflicts of interest.

SOURCE: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.

LIVERPOOL, ENGLAND – Serum levels of the cardiac biomarker troponin might prove useful for assessing the risk of death from cardiovascular causes in patients with inflammatory arthritis, according to study findings presented at the British Society for Rheumatology annual conference.

“In this analysis we have shown that baseline troponin levels predict cardiovascular death in inflammatory arthritis, and this association is independent of the traditional risk factors, inflammation, and disease characteristics at baseline,” said study author Sarah Skeoch, MBChB, who works at the Arthritis Research UK Centre for Epidemiology in the division of musculoskeletal and dermatological sciences at the University of Manchester (England).

Sara Freeman/MDedge News

The median follow up was 11.2 years, totaling 11,237 person-years, and during that time 158 deaths occurred, of which 27 were due to ischemic events. The median time from inclusion in NOAR to death was 7.4 years.

When levels of hs-TnI were separated into tertiles, a 12.5-fold increased risk was observed when comparing patients in the highest (more than 7.7 pg/mL) to lowest tertiles (less than 5.2 pg/mL).

“The magnitude of risk between the highest and the lowest tertile was much greater than observed in the general population,” Dr. Skeoch said, and although not directly comparable, she said the hazard ratios were 12.5 and 1.67, “which again suggests that troponin may be an effective tool or addition to the risk prediction models in inflammatory arthritis.”

Unlike some biomarkers, assays to assess troponin are already available in the clinic, Dr. Skeoch commented, “so if further work by us and other groups do suggest a role for troponin, this could be translated fairly rapidly into clinical practice.”

Further research needs to look at why troponin is raised and what is its relationship to other risk factors. “There is a strong association with traditional risk factors such as lipids, so it would stand to reason that managing those risk factors, as well as lifestyle factors, would have a positive impact,” Dr. Skeoch suggested.

The NOAR register is funded by Arthritis Research UK and the U.K. National Institute for Health Research. Dr. Skeoch and her coauthors had no relevant financial conflicts of interest.

SOURCE: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.

LIVERPOOL, ENGLAND – Serum levels of the cardiac biomarker troponin might prove useful for assessing the risk of death from cardiovascular causes in patients with inflammatory arthritis, according to study findings presented at the British Society for Rheumatology annual conference.

“In this analysis we have shown that baseline troponin levels predict cardiovascular death in inflammatory arthritis, and this association is independent of the traditional risk factors, inflammation, and disease characteristics at baseline,” said study author Sarah Skeoch, MBChB, who works at the Arthritis Research UK Centre for Epidemiology in the division of musculoskeletal and dermatological sciences at the University of Manchester (England).

Sara Freeman/MDedge News

The median follow up was 11.2 years, totaling 11,237 person-years, and during that time 158 deaths occurred, of which 27 were due to ischemic events. The median time from inclusion in NOAR to death was 7.4 years.

When levels of hs-TnI were separated into tertiles, a 12.5-fold increased risk was observed when comparing patients in the highest (more than 7.7 pg/mL) to lowest tertiles (less than 5.2 pg/mL).

“The magnitude of risk between the highest and the lowest tertile was much greater than observed in the general population,” Dr. Skeoch said, and although not directly comparable, she said the hazard ratios were 12.5 and 1.67, “which again suggests that troponin may be an effective tool or addition to the risk prediction models in inflammatory arthritis.”

Unlike some biomarkers, assays to assess troponin are already available in the clinic, Dr. Skeoch commented, “so if further work by us and other groups do suggest a role for troponin, this could be translated fairly rapidly into clinical practice.”

Further research needs to look at why troponin is raised and what is its relationship to other risk factors. “There is a strong association with traditional risk factors such as lipids, so it would stand to reason that managing those risk factors, as well as lifestyle factors, would have a positive impact,” Dr. Skeoch suggested.

The NOAR register is funded by Arthritis Research UK and the U.K. National Institute for Health Research. Dr. Skeoch and her coauthors had no relevant financial conflicts of interest.

SOURCE: Skeoch S et al. BSR 2018. Rheumatology. 2018;57[Suppl. 3]:key075.192.

Treatment with tralokinumab, a fully human monoclonal antibody that binds to and neutralizes interleukin-13 (IL-13), was associated with improvements in disease symptoms in patients with moderate to severe atopic dermatitis (AD), in a recent phase 2b study published in the Journal of Allergy and Clinical Immunology.

The randomized, double-blind, placebo-controlled, dose-ranging study assigned 204 patients to receive placebo or 45 mg, 150 mg, or 300 mg of tralokinumab administered subcutaneously every second week for 12 weeks. The groups had similar demographics and disease characteristics. The patients were aged 15-75 years and had Eczema Area and Severity Index (EASI) scores of 12 or more and an Investigator Global Assessment (IGA) score of 3 or higher. The coprimary endpoints were change in EASI from baseline to week 12 and the percentage of patients with either 0 (clear) or 1 (almost clear) on the IGA scale.

The higher dosages of tralokinumab showed the greatest adjusted mean differences in EASI scores: reductions of 4.36 for the 150-mg group (P = .03) and 4.94 for the 300-mg group (P = .01), compared with placebo. The changes in the 300-mg group were apparent as early as 4 weeks into treatment and were maintained beyond the 12-week mark. The greatest differences, compared with placebo, in IGA were seen in the 300-mg group as well.

Furthermore, patients who had high levels of biomarkers associated with IL-13 showed greater improvements than those seen in the intention-to-treat population at large. By week 12, patient-reported pruritus was also improved, and there were improvements in Dermatology Quality of Life Index (which did not persist past 12 weeks).

Most treatment-emergent adverse events were considered only mild or moderate, and the few more serious events were deemed unrelated to the study drug. The most common adverse events were upper respiratory infections and headaches.

“Participants entering the study had not achieved an adequate response to stable topical glucocorticoids during the 2-week run-in period and, therefore, represent a population with moderate to severe AD and major unmet treatment needs,” the investigators wrote. “The clinically meaningful benefits observed by combining tralokinumab treatment with topical glucocorticoids suggests that tralokinumab could demonstrate improvements in participants whose symptoms cannot be effectively controlled by topical glucocorticoids alone.”

The study was funded by MedImmune, a member of the AstraZeneca Group. Five authors were or are employees of the company; the three remaining authors had disclosures related to numerous pharmaceutical companies, including two with disclosures that included MedImmune.

[email protected]

SOURCE: Wollenberg A et al. J Allergy Clin Immunol. 2018 Jun 12. doi: 10.1016/j.jaci.2018.05.029.

Treatment with tralokinumab, a fully human monoclonal antibody that binds to and neutralizes interleukin-13 (IL-13), was associated with improvements in disease symptoms in patients with moderate to severe atopic dermatitis (AD), in a recent phase 2b study published in the Journal of Allergy and Clinical Immunology.

The randomized, double-blind, placebo-controlled, dose-ranging study assigned 204 patients to receive placebo or 45 mg, 150 mg, or 300 mg of tralokinumab administered subcutaneously every second week for 12 weeks. The groups had similar demographics and disease characteristics. The patients were aged 15-75 years and had Eczema Area and Severity Index (EASI) scores of 12 or more and an Investigator Global Assessment (IGA) score of 3 or higher. The coprimary endpoints were change in EASI from baseline to week 12 and the percentage of patients with either 0 (clear) or 1 (almost clear) on the IGA scale.

The higher dosages of tralokinumab showed the greatest adjusted mean differences in EASI scores: reductions of 4.36 for the 150-mg group (P = .03) and 4.94 for the 300-mg group (P = .01), compared with placebo. The changes in the 300-mg group were apparent as early as 4 weeks into treatment and were maintained beyond the 12-week mark. The greatest differences, compared with placebo, in IGA were seen in the 300-mg group as well.

Furthermore, patients who had high levels of biomarkers associated with IL-13 showed greater improvements than those seen in the intention-to-treat population at large. By week 12, patient-reported pruritus was also improved, and there were improvements in Dermatology Quality of Life Index (which did not persist past 12 weeks).

Most treatment-emergent adverse events were considered only mild or moderate, and the few more serious events were deemed unrelated to the study drug. The most common adverse events were upper respiratory infections and headaches.

“Participants entering the study had not achieved an adequate response to stable topical glucocorticoids during the 2-week run-in period and, therefore, represent a population with moderate to severe AD and major unmet treatment needs,” the investigators wrote. “The clinically meaningful benefits observed by combining tralokinumab treatment with topical glucocorticoids suggests that tralokinumab could demonstrate improvements in participants whose symptoms cannot be effectively controlled by topical glucocorticoids alone.”

The study was funded by MedImmune, a member of the AstraZeneca Group. Five authors were or are employees of the company; the three remaining authors had disclosures related to numerous pharmaceutical companies, including two with disclosures that included MedImmune.

[email protected]

SOURCE: Wollenberg A et al. J Allergy Clin Immunol. 2018 Jun 12. doi: 10.1016/j.jaci.2018.05.029.

Treatment with tralokinumab, a fully human monoclonal antibody that binds to and neutralizes interleukin-13 (IL-13), was associated with improvements in disease symptoms in patients with moderate to severe atopic dermatitis (AD), in a recent phase 2b study published in the Journal of Allergy and Clinical Immunology.

The randomized, double-blind, placebo-controlled, dose-ranging study assigned 204 patients to receive placebo or 45 mg, 150 mg, or 300 mg of tralokinumab administered subcutaneously every second week for 12 weeks. The groups had similar demographics and disease characteristics. The patients were aged 15-75 years and had Eczema Area and Severity Index (EASI) scores of 12 or more and an Investigator Global Assessment (IGA) score of 3 or higher. The coprimary endpoints were change in EASI from baseline to week 12 and the percentage of patients with either 0 (clear) or 1 (almost clear) on the IGA scale.

The higher dosages of tralokinumab showed the greatest adjusted mean differences in EASI scores: reductions of 4.36 for the 150-mg group (P = .03) and 4.94 for the 300-mg group (P = .01), compared with placebo. The changes in the 300-mg group were apparent as early as 4 weeks into treatment and were maintained beyond the 12-week mark. The greatest differences, compared with placebo, in IGA were seen in the 300-mg group as well.

Furthermore, patients who had high levels of biomarkers associated with IL-13 showed greater improvements than those seen in the intention-to-treat population at large. By week 12, patient-reported pruritus was also improved, and there were improvements in Dermatology Quality of Life Index (which did not persist past 12 weeks).

Most treatment-emergent adverse events were considered only mild or moderate, and the few more serious events were deemed unrelated to the study drug. The most common adverse events were upper respiratory infections and headaches.

“Participants entering the study had not achieved an adequate response to stable topical glucocorticoids during the 2-week run-in period and, therefore, represent a population with moderate to severe AD and major unmet treatment needs,” the investigators wrote. “The clinically meaningful benefits observed by combining tralokinumab treatment with topical glucocorticoids suggests that tralokinumab could demonstrate improvements in participants whose symptoms cannot be effectively controlled by topical glucocorticoids alone.”

The study was funded by MedImmune, a member of the AstraZeneca Group. Five authors were or are employees of the company; the three remaining authors had disclosures related to numerous pharmaceutical companies, including two with disclosures that included MedImmune.

[email protected]

SOURCE: Wollenberg A et al. J Allergy Clin Immunol. 2018 Jun 12. doi: 10.1016/j.jaci.2018.05.029.

Small employers will more easily be able to band together to buy health insurance under rules issued June 19 by the Trump administration, but the change could raise premiums for plans sold through the Affordable Care Act’s (ACA’s) online marketplaces, analysts say.

The move loosens restrictions on so-called association health plans, allowing more businesses, including sole proprietors, to join forces to buy health coverage in bulk for their workers.

By effectively shifting small-business coverage into the large-group market, it exempts such plans from ACA requirements for 10 “essential” health benefits, such as mental health care and prescription drug coverage, prompting warnings of “junk insurance” from consumer advocates.

Supporters say the new Labor Department rules, which the government estimated could create health plans covering as many as 11 million people, will lead to more affordable choices for some employers.

When it comes to health insurance, “the regulatory burden on small businesses should certainly not be more than that on large companies,” Labor Secretary Alexander Acosta told reporters June 19.

Existing rules limit association plans to groups of employers in the same industry in the same region.

The new regulations eliminate the geographical restriction for similar employers, allowing, for example, family-owned auto-repair shops in multiple states to offer one big health plan, said Christopher Condeluci, a health benefits lawyer and former Senate Finance Committee aide.

The rules, to be implemented in stages into next year, also allow companies in different industries in the same region to form a group to offer coverage – even if the only reason is to provide health insurance.

Like other coverage under the ACA, association insurance plans will still be required to cover preexisting illnesses.

Analysts warn that, because these changes will likely siphon away employers with relatively healthy consumers from ACA coverage into less-expensive trade-association plans, the result could be higher costs in the online marketplaces.

“If you have a group that is healthier than average, you might get a better rate from one of these plans, and your broker is going to come and say, ‘Hey, I can get you a better deal,’ ” said Dan Mendelson, president of Avalere Health, a consulting firm.

That would mean that, on balance, consumers insured through ACA small-group and individual plans could be older, sicker, and more expensive, adding to years of erosion of the ACA marketplaces engineered by Republicans hostile to the law.

Loosening rules for association plans would lead to 3.2 million people leaving the ACA plans by 2022 and raising premiums for those remaining in individual markets by 3.5%, Avalere calculated this year.

America’s Health Insurance Plans, the largest medical insurance trade group, issued a statement saying the regulation “may lead to higher premiums” in ACA insurance and “could result in fewer insured Americans.”

Unlike ACA plans, association coverage does not have to include benefits across the broad “essential” categories, including hospitalization and emergency care.

The National Association of Insurance Commissioners previously warned that such plans “threaten the stability of the small group market” and “provide inadequate benefits and insufficient protection to consumers.”

The American Academy of Actuaries has expressed similar concerns.

Business groups praised the change, proposed in draft form earlier this year.

“We’ve been advocating for association health plans for almost 20 years, and we’re pleased to see the department moving aggressively forward,” said David French, senior vice president of government relations for the National Retail Federation.

Association plans have been around for decades, although enrollment has been more limited since the ACA’s passage. While some of the plans have worked well for their members, others have a checkered history.

In April, for example, Massachusetts regulators settled with Kansas-based Unified Life Insurance Company, which agreed to pay $2.8 million to resolve allegations that it engaged in deceptive practices, such as claiming it covered services that it did not.

The coverage “was sold across state lines and was issued through a third-party association,” according to a release from the Massachusetts attorney general’s office.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Small employers will more easily be able to band together to buy health insurance under rules issued June 19 by the Trump administration, but the change could raise premiums for plans sold through the Affordable Care Act’s (ACA’s) online marketplaces, analysts say.

The move loosens restrictions on so-called association health plans, allowing more businesses, including sole proprietors, to join forces to buy health coverage in bulk for their workers.

By effectively shifting small-business coverage into the large-group market, it exempts such plans from ACA requirements for 10 “essential” health benefits, such as mental health care and prescription drug coverage, prompting warnings of “junk insurance” from consumer advocates.

Supporters say the new Labor Department rules, which the government estimated could create health plans covering as many as 11 million people, will lead to more affordable choices for some employers.

When it comes to health insurance, “the regulatory burden on small businesses should certainly not be more than that on large companies,” Labor Secretary Alexander Acosta told reporters June 19.

Existing rules limit association plans to groups of employers in the same industry in the same region.

The new regulations eliminate the geographical restriction for similar employers, allowing, for example, family-owned auto-repair shops in multiple states to offer one big health plan, said Christopher Condeluci, a health benefits lawyer and former Senate Finance Committee aide.

The rules, to be implemented in stages into next year, also allow companies in different industries in the same region to form a group to offer coverage – even if the only reason is to provide health insurance.

Like other coverage under the ACA, association insurance plans will still be required to cover preexisting illnesses.

Analysts warn that, because these changes will likely siphon away employers with relatively healthy consumers from ACA coverage into less-expensive trade-association plans, the result could be higher costs in the online marketplaces.

“If you have a group that is healthier than average, you might get a better rate from one of these plans, and your broker is going to come and say, ‘Hey, I can get you a better deal,’ ” said Dan Mendelson, president of Avalere Health, a consulting firm.

That would mean that, on balance, consumers insured through ACA small-group and individual plans could be older, sicker, and more expensive, adding to years of erosion of the ACA marketplaces engineered by Republicans hostile to the law.

Loosening rules for association plans would lead to 3.2 million people leaving the ACA plans by 2022 and raising premiums for those remaining in individual markets by 3.5%, Avalere calculated this year.

America’s Health Insurance Plans, the largest medical insurance trade group, issued a statement saying the regulation “may lead to higher premiums” in ACA insurance and “could result in fewer insured Americans.”

Unlike ACA plans, association coverage does not have to include benefits across the broad “essential” categories, including hospitalization and emergency care.

The National Association of Insurance Commissioners previously warned that such plans “threaten the stability of the small group market” and “provide inadequate benefits and insufficient protection to consumers.”

The American Academy of Actuaries has expressed similar concerns.

Business groups praised the change, proposed in draft form earlier this year.

“We’ve been advocating for association health plans for almost 20 years, and we’re pleased to see the department moving aggressively forward,” said David French, senior vice president of government relations for the National Retail Federation.

Association plans have been around for decades, although enrollment has been more limited since the ACA’s passage. While some of the plans have worked well for their members, others have a checkered history.

In April, for example, Massachusetts regulators settled with Kansas-based Unified Life Insurance Company, which agreed to pay $2.8 million to resolve allegations that it engaged in deceptive practices, such as claiming it covered services that it did not.

The coverage “was sold across state lines and was issued through a third-party association,” according to a release from the Massachusetts attorney general’s office.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Small employers will more easily be able to band together to buy health insurance under rules issued June 19 by the Trump administration, but the change could raise premiums for plans sold through the Affordable Care Act’s (ACA’s) online marketplaces, analysts say.

The move loosens restrictions on so-called association health plans, allowing more businesses, including sole proprietors, to join forces to buy health coverage in bulk for their workers.

By effectively shifting small-business coverage into the large-group market, it exempts such plans from ACA requirements for 10 “essential” health benefits, such as mental health care and prescription drug coverage, prompting warnings of “junk insurance” from consumer advocates.

Supporters say the new Labor Department rules, which the government estimated could create health plans covering as many as 11 million people, will lead to more affordable choices for some employers.

When it comes to health insurance, “the regulatory burden on small businesses should certainly not be more than that on large companies,” Labor Secretary Alexander Acosta told reporters June 19.

Existing rules limit association plans to groups of employers in the same industry in the same region.

The new regulations eliminate the geographical restriction for similar employers, allowing, for example, family-owned auto-repair shops in multiple states to offer one big health plan, said Christopher Condeluci, a health benefits lawyer and former Senate Finance Committee aide.

The rules, to be implemented in stages into next year, also allow companies in different industries in the same region to form a group to offer coverage – even if the only reason is to provide health insurance.

Like other coverage under the ACA, association insurance plans will still be required to cover preexisting illnesses.

Analysts warn that, because these changes will likely siphon away employers with relatively healthy consumers from ACA coverage into less-expensive trade-association plans, the result could be higher costs in the online marketplaces.

“If you have a group that is healthier than average, you might get a better rate from one of these plans, and your broker is going to come and say, ‘Hey, I can get you a better deal,’ ” said Dan Mendelson, president of Avalere Health, a consulting firm.

That would mean that, on balance, consumers insured through ACA small-group and individual plans could be older, sicker, and more expensive, adding to years of erosion of the ACA marketplaces engineered by Republicans hostile to the law.

Loosening rules for association plans would lead to 3.2 million people leaving the ACA plans by 2022 and raising premiums for those remaining in individual markets by 3.5%, Avalere calculated this year.

America’s Health Insurance Plans, the largest medical insurance trade group, issued a statement saying the regulation “may lead to higher premiums” in ACA insurance and “could result in fewer insured Americans.”

Unlike ACA plans, association coverage does not have to include benefits across the broad “essential” categories, including hospitalization and emergency care.

The National Association of Insurance Commissioners previously warned that such plans “threaten the stability of the small group market” and “provide inadequate benefits and insufficient protection to consumers.”

The American Academy of Actuaries has expressed similar concerns.

Business groups praised the change, proposed in draft form earlier this year.

“We’ve been advocating for association health plans for almost 20 years, and we’re pleased to see the department moving aggressively forward,” said David French, senior vice president of government relations for the National Retail Federation.

Association plans have been around for decades, although enrollment has been more limited since the ACA’s passage. While some of the plans have worked well for their members, others have a checkered history.

In April, for example, Massachusetts regulators settled with Kansas-based Unified Life Insurance Company, which agreed to pay $2.8 million to resolve allegations that it engaged in deceptive practices, such as claiming it covered services that it did not.

The coverage “was sold across state lines and was issued through a third-party association,” according to a release from the Massachusetts attorney general’s office.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Among the reasons health care providers give for adolescent human papillomavirus (HPV) vaccination, U.S. parents ranked cancer prevention as the best, according to an analysis of a national survey.

Preventing a common infection also ranked highly as a reason for giving the vaccine, as did appeals to the vaccine’s lasting benefits and safety, the analysis showed.

Choreograph/Thinkstock

SOURCE: Gilkey MB et al. Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):762-7.

Among the reasons health care providers give for adolescent human papillomavirus (HPV) vaccination, U.S. parents ranked cancer prevention as the best, according to an analysis of a national survey.

Preventing a common infection also ranked highly as a reason for giving the vaccine, as did appeals to the vaccine’s lasting benefits and safety, the analysis showed.

Choreograph/Thinkstock

SOURCE: Gilkey MB et al. Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):762-7.

Among the reasons health care providers give for adolescent human papillomavirus (HPV) vaccination, U.S. parents ranked cancer prevention as the best, according to an analysis of a national survey.

Preventing a common infection also ranked highly as a reason for giving the vaccine, as did appeals to the vaccine’s lasting benefits and safety, the analysis showed.

Choreograph/Thinkstock

SOURCE: Gilkey MB et al. Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):762-7.