Photo courtesy of ASH

SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.

Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.

Patients and treatment

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).

Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.

Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).

Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.

Efficacy

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).

Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.

Safety

BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:

• Nausea (46% and 38%)
• Peripheral sensory neuropathy (45% and 41%)
• Neutropenia (38% for both)
• Diarrhea (38% and 20%)
• Constipation (29% and 30%)
• Alopecia (26% and 25%)
• Pyrexia (26% and 19%)
• Vomiting (26% and 17%)
• Fatigue (24% and 20%)
• Anemia (21% and 16%).

This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.

Photo courtesy of ASH

SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.

Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.

Patients and treatment

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).

Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.

Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).

Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.

Efficacy

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).

Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.

Safety

BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:

• Nausea (46% and 38%)
• Peripheral sensory neuropathy (45% and 41%)
• Neutropenia (38% for both)
• Diarrhea (38% and 20%)
• Constipation (29% and 30%)
• Alopecia (26% and 25%)
• Pyrexia (26% and 19%)
• Vomiting (26% and 17%)
• Fatigue (24% and 20%)
• Anemia (21% and 16%).

This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.

Photo courtesy of ASH

SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.

Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.

Patients and treatment

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).

Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.

Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).

Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.

Efficacy

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).

Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.

Safety

BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:

• Nausea (46% and 38%)
• Peripheral sensory neuropathy (45% and 41%)
• Neutropenia (38% for both)
• Diarrhea (38% and 20%)
• Constipation (29% and 30%)
• Alopecia (26% and 25%)
• Pyrexia (26% and 19%)
• Vomiting (26% and 17%)
• Fatigue (24% and 20%)
• Anemia (21% and 16%).

This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

Health care is a constantly changing field, thanks to innovative research and technological advancements. And with optimal team practice and full practice authority, PAs and NPs are poised to drive further improvements to patient care. But while we all recognize the need to keep learning, some of the greatest lessons I’ve learned in my career have little to do with the “latest and greatest” tools—they are fundamentals of being a good person and effective health care provider. I would like to share some of them with you.

1 It’s OK to make a mistake, but be sure to own it and learn from it.

You can’t grow as a person or a provider if you can’t acknowledge failure and vow to improve. Don’t become complacent; a little bit of fear keeps us on our toes and hopefully out of trouble.

It always seems to be Friday at 4:45 pm when you receive that phone call from the pharmacist asking, “Did you really want to prescribe amoxicillin/clavulanate to Mrs. Jones? She’s allergic to penicillin.” You quickly check the EMR and don’t see that specific allergy listed. You choose an alternative medication and send the prescription back to the pharmacy.

But while many providers would stop there, assuming that they have solved the problem, I would advocate for calling the patient directly and addressing the issue head-on. The patient may be thinking, “What an idiot, she missed that in my chart.” Clearly, there was a breakdown in the process, but you are the one who is ultimately responsible.

A phone call to verify the allergy and the type of reaction is very valuable. It proves to the patient that you take patient care seriously and that you recognize that the system needs to be improved.

2 Find one thing in common with each patient, even if it is something small.

Maybe you grew up in the same town, or like the same sports team, or enjoy the same type of food. It isn’t difficult to find a commonality; a note in the patient’s chart ensures you’ll remember. That personal touch demonstrates that you care and increases the patient’s comfort with you.

This technique can make a huge difference with a “difficult” patient. One day, a new patient presented to my office for a change in bowel habits. He was clearly anxious and angry with his wife (who accompanied him) for “making me come here.”

Continue to: During the social history...

During the social history, I learned that he owned a trucking business. I asked what kind of trucks. He said, “Big ones!” I was more specific in my next attempt, asking, “Volvo, Peterbilt, International, or Kenworth?” He looked puzzled and said, “I see you know something about trucks.” I explained that my husband is a diesel mechanic and that we play “identify the truck” when travelling with our young sons. It turned out that my husband had worked on the patient’s truck the week before.

The dynamic of our encounter changed immediately, and we were able to schedule him for a much-needed colonoscopy. He was diagnosed with a large precancerous colon polyp, and I was relieved that our “connection” smoothed the way to getting him the care he needed.

3 Always remember that people are watching.

Nothing is truly private anymore. Social media can be a great forum for exchanging information and knowledge, but you could become the latest YouTube sensation (not necessarily in a positive way) at any time.

When a patient asks if he can record our visit to share with family, I wonder how many have done so without permission. The bottom line is that we, as health care professionals, have a high standard to live up to.

This was brought home to me in my work as a volunteer firefighter and EMT. One night I had barely finished loading a patient from a serious motor vehicle collision into a helicopter to be transferred to definitive care when my phone started buzzing. A photographer from the local newspaper—whom I didn’t even know was on scene—had snapped a picture of me in action and posted it to his online news site and social media accounts. Within 5 minutes, several coworkers had seen it and texted me. My surname across the bottom of my jacket provided a clear indication of where I was and what I was doing. I was absolutely shocked at how quickly news spread, and although nothing untoward or inappropriate was documented, it was unsettling to realize that I was “in the public eye” while I was focused on doing my job.

Continue to: That photo is now the screensaver...

That photo is now the screensaver on my computer. It’s a daily reminder that someone is always watching and I must conduct myself accordingly.

4 Don’t be afraid to speak up.

Don’t be a tattletale, but do stand up for what you know is right. When presented with a choice, always do the right thing, even if it is more difficult.

This is harder than it sounds; I know how tough it was for me to find my voice. But I did during the case of a middle-aged woman with a significant upper GI bleed. She had been in her normal state of health until she experienced a sudden onset of nausea and vomiting; her husband called EMS when she began vomiting large amounts of bright red blood. Her care plan involved multiple members of our GI service, as well as colleagues from an affiliated tertiary care hospital, and I spent hours coordinating care and obtaining the necessary consults. When the patient subsequently developed abdominal compartment syndrome and required bedside surgical intervention, the attending surgeon proceeded to dress me down in front of the entire ICU team, screaming, “Why isn’t Dr. So-and-so here caring for this patient? Why aren’t you doing anything to care for this woman?”

In the old days, I would have walked away without saying anything—that’s what was expected. But, my own hurt feelings aside, I couldn’t stop thinking, “What if he treats others like that? If I don’t speak up, I’m an accomplice to his bad behavior.” So I waited for his team to perform the urgent procedure and then politely asked if I could speak with him. I was shaking in my shoes when I began by asking if he had read my notes in the patient’s chart. He grudgingly said, “No.” I listed the physicians who had been consulted about this patient and documented the time the team had spent developing a safe treatment plan for her. I ended by saying that it was unfair and unprofessional for him to yell at me, particularly in front of our colleagues, and I asked how he would have felt if treated the same way. He apologized and agreed to approach me privately if he had concerns in future. I can honestly say that encounter changed our working relationship in a very positive manner. One of the most difficult experiences of my entire career helped me to grow as a professional.

Continue to: Each and every one of us is an educator...

5 Each and every one of us is an educator, even if we don’t consciously choose to be.

You can be an educator without being employed as a teacher. Educators go above and beyond to make sure that learning is student centered and that knowledge is received and understood. Every day, we educate patients, families, friends, neighbors, and other members of the health care team.

A few months ago, I began a new paramedic job at a different agency. During training, one of my coworkers made an offhand comment: “It’s your fault that I’m here.” At my puzzled expression, he continued, “You don’t remember, do you? When you did my last firefighter physical, we talked about the best way to get a full-time job as a firefighter. You recommended that I consider a job in EMS to gain additional experience and interface with the fire departments, so here I am and I love it.” At that point, I did recall our conversation—but what I had seen as simple small talk with a patient had really been an educational moment. I had a smile on my face the whole drive home as I thought about how my casual conversation had a positive effect on him and his career path.

PAs and NPs are educators even when they are not presenting in the classroom or serving as a clinical preceptor. It doesn’t matter if you are new to the profession or have been working for many years—you have valuable experience that can help someone else. Please remember that even small moments can make a large impact. Strive to be a good educator at all times.

Health care is a constantly changing field, thanks to innovative research and technological advancements. And with optimal team practice and full practice authority, PAs and NPs are poised to drive further improvements to patient care. But while we all recognize the need to keep learning, some of the greatest lessons I’ve learned in my career have little to do with the “latest and greatest” tools—they are fundamentals of being a good person and effective health care provider. I would like to share some of them with you.

1 It’s OK to make a mistake, but be sure to own it and learn from it.

You can’t grow as a person or a provider if you can’t acknowledge failure and vow to improve. Don’t become complacent; a little bit of fear keeps us on our toes and hopefully out of trouble.

It always seems to be Friday at 4:45 pm when you receive that phone call from the pharmacist asking, “Did you really want to prescribe amoxicillin/clavulanate to Mrs. Jones? She’s allergic to penicillin.” You quickly check the EMR and don’t see that specific allergy listed. You choose an alternative medication and send the prescription back to the pharmacy.

But while many providers would stop there, assuming that they have solved the problem, I would advocate for calling the patient directly and addressing the issue head-on. The patient may be thinking, “What an idiot, she missed that in my chart.” Clearly, there was a breakdown in the process, but you are the one who is ultimately responsible.

A phone call to verify the allergy and the type of reaction is very valuable. It proves to the patient that you take patient care seriously and that you recognize that the system needs to be improved.

2 Find one thing in common with each patient, even if it is something small.

Maybe you grew up in the same town, or like the same sports team, or enjoy the same type of food. It isn’t difficult to find a commonality; a note in the patient’s chart ensures you’ll remember. That personal touch demonstrates that you care and increases the patient’s comfort with you.

This technique can make a huge difference with a “difficult” patient. One day, a new patient presented to my office for a change in bowel habits. He was clearly anxious and angry with his wife (who accompanied him) for “making me come here.”

Continue to: During the social history...

During the social history, I learned that he owned a trucking business. I asked what kind of trucks. He said, “Big ones!” I was more specific in my next attempt, asking, “Volvo, Peterbilt, International, or Kenworth?” He looked puzzled and said, “I see you know something about trucks.” I explained that my husband is a diesel mechanic and that we play “identify the truck” when travelling with our young sons. It turned out that my husband had worked on the patient’s truck the week before.

The dynamic of our encounter changed immediately, and we were able to schedule him for a much-needed colonoscopy. He was diagnosed with a large precancerous colon polyp, and I was relieved that our “connection” smoothed the way to getting him the care he needed.

3 Always remember that people are watching.

Nothing is truly private anymore. Social media can be a great forum for exchanging information and knowledge, but you could become the latest YouTube sensation (not necessarily in a positive way) at any time.

When a patient asks if he can record our visit to share with family, I wonder how many have done so without permission. The bottom line is that we, as health care professionals, have a high standard to live up to.

This was brought home to me in my work as a volunteer firefighter and EMT. One night I had barely finished loading a patient from a serious motor vehicle collision into a helicopter to be transferred to definitive care when my phone started buzzing. A photographer from the local newspaper—whom I didn’t even know was on scene—had snapped a picture of me in action and posted it to his online news site and social media accounts. Within 5 minutes, several coworkers had seen it and texted me. My surname across the bottom of my jacket provided a clear indication of where I was and what I was doing. I was absolutely shocked at how quickly news spread, and although nothing untoward or inappropriate was documented, it was unsettling to realize that I was “in the public eye” while I was focused on doing my job.

Continue to: That photo is now the screensaver...

That photo is now the screensaver on my computer. It’s a daily reminder that someone is always watching and I must conduct myself accordingly.

4 Don’t be afraid to speak up.

Don’t be a tattletale, but do stand up for what you know is right. When presented with a choice, always do the right thing, even if it is more difficult.

This is harder than it sounds; I know how tough it was for me to find my voice. But I did during the case of a middle-aged woman with a significant upper GI bleed. She had been in her normal state of health until she experienced a sudden onset of nausea and vomiting; her husband called EMS when she began vomiting large amounts of bright red blood. Her care plan involved multiple members of our GI service, as well as colleagues from an affiliated tertiary care hospital, and I spent hours coordinating care and obtaining the necessary consults. When the patient subsequently developed abdominal compartment syndrome and required bedside surgical intervention, the attending surgeon proceeded to dress me down in front of the entire ICU team, screaming, “Why isn’t Dr. So-and-so here caring for this patient? Why aren’t you doing anything to care for this woman?”

In the old days, I would have walked away without saying anything—that’s what was expected. But, my own hurt feelings aside, I couldn’t stop thinking, “What if he treats others like that? If I don’t speak up, I’m an accomplice to his bad behavior.” So I waited for his team to perform the urgent procedure and then politely asked if I could speak with him. I was shaking in my shoes when I began by asking if he had read my notes in the patient’s chart. He grudgingly said, “No.” I listed the physicians who had been consulted about this patient and documented the time the team had spent developing a safe treatment plan for her. I ended by saying that it was unfair and unprofessional for him to yell at me, particularly in front of our colleagues, and I asked how he would have felt if treated the same way. He apologized and agreed to approach me privately if he had concerns in future. I can honestly say that encounter changed our working relationship in a very positive manner. One of the most difficult experiences of my entire career helped me to grow as a professional.

Continue to: Each and every one of us is an educator...

5 Each and every one of us is an educator, even if we don’t consciously choose to be.

You can be an educator without being employed as a teacher. Educators go above and beyond to make sure that learning is student centered and that knowledge is received and understood. Every day, we educate patients, families, friends, neighbors, and other members of the health care team.

A few months ago, I began a new paramedic job at a different agency. During training, one of my coworkers made an offhand comment: “It’s your fault that I’m here.” At my puzzled expression, he continued, “You don’t remember, do you? When you did my last firefighter physical, we talked about the best way to get a full-time job as a firefighter. You recommended that I consider a job in EMS to gain additional experience and interface with the fire departments, so here I am and I love it.” At that point, I did recall our conversation—but what I had seen as simple small talk with a patient had really been an educational moment. I had a smile on my face the whole drive home as I thought about how my casual conversation had a positive effect on him and his career path.

PAs and NPs are educators even when they are not presenting in the classroom or serving as a clinical preceptor. It doesn’t matter if you are new to the profession or have been working for many years—you have valuable experience that can help someone else. Please remember that even small moments can make a large impact. Strive to be a good educator at all times.

Health care is a constantly changing field, thanks to innovative research and technological advancements. And with optimal team practice and full practice authority, PAs and NPs are poised to drive further improvements to patient care. But while we all recognize the need to keep learning, some of the greatest lessons I’ve learned in my career have little to do with the “latest and greatest” tools—they are fundamentals of being a good person and effective health care provider. I would like to share some of them with you.

1 It’s OK to make a mistake, but be sure to own it and learn from it.

You can’t grow as a person or a provider if you can’t acknowledge failure and vow to improve. Don’t become complacent; a little bit of fear keeps us on our toes and hopefully out of trouble.

It always seems to be Friday at 4:45 pm when you receive that phone call from the pharmacist asking, “Did you really want to prescribe amoxicillin/clavulanate to Mrs. Jones? She’s allergic to penicillin.” You quickly check the EMR and don’t see that specific allergy listed. You choose an alternative medication and send the prescription back to the pharmacy.

But while many providers would stop there, assuming that they have solved the problem, I would advocate for calling the patient directly and addressing the issue head-on. The patient may be thinking, “What an idiot, she missed that in my chart.” Clearly, there was a breakdown in the process, but you are the one who is ultimately responsible.

A phone call to verify the allergy and the type of reaction is very valuable. It proves to the patient that you take patient care seriously and that you recognize that the system needs to be improved.

2 Find one thing in common with each patient, even if it is something small.

Maybe you grew up in the same town, or like the same sports team, or enjoy the same type of food. It isn’t difficult to find a commonality; a note in the patient’s chart ensures you’ll remember. That personal touch demonstrates that you care and increases the patient’s comfort with you.

This technique can make a huge difference with a “difficult” patient. One day, a new patient presented to my office for a change in bowel habits. He was clearly anxious and angry with his wife (who accompanied him) for “making me come here.”

Continue to: During the social history...

During the social history, I learned that he owned a trucking business. I asked what kind of trucks. He said, “Big ones!” I was more specific in my next attempt, asking, “Volvo, Peterbilt, International, or Kenworth?” He looked puzzled and said, “I see you know something about trucks.” I explained that my husband is a diesel mechanic and that we play “identify the truck” when travelling with our young sons. It turned out that my husband had worked on the patient’s truck the week before.

The dynamic of our encounter changed immediately, and we were able to schedule him for a much-needed colonoscopy. He was diagnosed with a large precancerous colon polyp, and I was relieved that our “connection” smoothed the way to getting him the care he needed.

3 Always remember that people are watching.

Nothing is truly private anymore. Social media can be a great forum for exchanging information and knowledge, but you could become the latest YouTube sensation (not necessarily in a positive way) at any time.

When a patient asks if he can record our visit to share with family, I wonder how many have done so without permission. The bottom line is that we, as health care professionals, have a high standard to live up to.

This was brought home to me in my work as a volunteer firefighter and EMT. One night I had barely finished loading a patient from a serious motor vehicle collision into a helicopter to be transferred to definitive care when my phone started buzzing. A photographer from the local newspaper—whom I didn’t even know was on scene—had snapped a picture of me in action and posted it to his online news site and social media accounts. Within 5 minutes, several coworkers had seen it and texted me. My surname across the bottom of my jacket provided a clear indication of where I was and what I was doing. I was absolutely shocked at how quickly news spread, and although nothing untoward or inappropriate was documented, it was unsettling to realize that I was “in the public eye” while I was focused on doing my job.

Continue to: That photo is now the screensaver...

That photo is now the screensaver on my computer. It’s a daily reminder that someone is always watching and I must conduct myself accordingly.

4 Don’t be afraid to speak up.

Don’t be a tattletale, but do stand up for what you know is right. When presented with a choice, always do the right thing, even if it is more difficult.

This is harder than it sounds; I know how tough it was for me to find my voice. But I did during the case of a middle-aged woman with a significant upper GI bleed. She had been in her normal state of health until she experienced a sudden onset of nausea and vomiting; her husband called EMS when she began vomiting large amounts of bright red blood. Her care plan involved multiple members of our GI service, as well as colleagues from an affiliated tertiary care hospital, and I spent hours coordinating care and obtaining the necessary consults. When the patient subsequently developed abdominal compartment syndrome and required bedside surgical intervention, the attending surgeon proceeded to dress me down in front of the entire ICU team, screaming, “Why isn’t Dr. So-and-so here caring for this patient? Why aren’t you doing anything to care for this woman?”

In the old days, I would have walked away without saying anything—that’s what was expected. But, my own hurt feelings aside, I couldn’t stop thinking, “What if he treats others like that? If I don’t speak up, I’m an accomplice to his bad behavior.” So I waited for his team to perform the urgent procedure and then politely asked if I could speak with him. I was shaking in my shoes when I began by asking if he had read my notes in the patient’s chart. He grudgingly said, “No.” I listed the physicians who had been consulted about this patient and documented the time the team had spent developing a safe treatment plan for her. I ended by saying that it was unfair and unprofessional for him to yell at me, particularly in front of our colleagues, and I asked how he would have felt if treated the same way. He apologized and agreed to approach me privately if he had concerns in future. I can honestly say that encounter changed our working relationship in a very positive manner. One of the most difficult experiences of my entire career helped me to grow as a professional.

Continue to: Each and every one of us is an educator...

5 Each and every one of us is an educator, even if we don’t consciously choose to be.

You can be an educator without being employed as a teacher. Educators go above and beyond to make sure that learning is student centered and that knowledge is received and understood. Every day, we educate patients, families, friends, neighbors, and other members of the health care team.

A few months ago, I began a new paramedic job at a different agency. During training, one of my coworkers made an offhand comment: “It’s your fault that I’m here.” At my puzzled expression, he continued, “You don’t remember, do you? When you did my last firefighter physical, we talked about the best way to get a full-time job as a firefighter. You recommended that I consider a job in EMS to gain additional experience and interface with the fire departments, so here I am and I love it.” At that point, I did recall our conversation—but what I had seen as simple small talk with a patient had really been an educational moment. I had a smile on my face the whole drive home as I thought about how my casual conversation had a positive effect on him and his career path.

PAs and NPs are educators even when they are not presenting in the classroom or serving as a clinical preceptor. It doesn’t matter if you are new to the profession or have been working for many years—you have valuable experience that can help someone else. Please remember that even small moments can make a large impact. Strive to be a good educator at all times.

A pictorial representation of carotid ultrasound coupled with a follow-up phone call from a nurse led to reduced cardiovascular disease risk at 1-year follow-up, according to a randomized, controlled study of northern Sweden residents at risk of cardiovascular disease.

pixologicstudio/Thinkstock.com

“Our study supports further attempts to solve the major problem of prevention failure because of low adherence, despite effective, cost-effective, and evidence-based medications and methods for a healthier lifestyle,” wrote lead author Ulf Näslund, of Umeå (Sweden) University, and his coauthors. The study was published online in the Lancet.

In this trial of 3,532 individuals who were aged 40-60 years with one or more conventional cardiovascular risk factors, the intervention group (1,749) received pictorial information of atherosclerosis as an add-on to normal care. Their primary care physician received the same information, and these participants also received a follow-up phone call from a nurse 2-4 weeks later. The other participants (1,783) received standard care but neither the presentation nor the phone call.

Both the Framingham risk score (FRS) and European Systematic Coronary Risk Evaluation (SCORE) were both used to assess outcomes; at 1-year follow-up, the intervention group had an FRS that decreased from baseline (–0.58; 95% confidence interval, –0.86 to –0.30), compared with an increase in the control group (0.35; 95% CI, 0.08-0.63). SCORE values increased twice as much in the control group (0.27; 95% CI, 0.23-0.30), compared with the intervention group (0.13; 95% CI, 0.09-0.18). The authors also observed no differential responses for education level, surmising that “this type of risk communication might contribute to reduction of the social gap in health.”

The authors shared their study’s limitations, including notable differences between dropouts and participants at 1-year follow-up with regard to metabolic risk factors and such fast-developing imaging technologies as CT and MRI out-dating ultrasound findings. They also acknowledged that more research needs to be undertaken to prove that these outcomes are genuine.

This study was funded by Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, and the Swedish Society of Medicine. No conflicts of interest were reported.

SOURCE: Näslund U et al. Lancet. 2018 Dec 3. doi: 10.1016/S0140-6736(18)32818-6.

A pictorial representation of carotid ultrasound coupled with a follow-up phone call from a nurse led to reduced cardiovascular disease risk at 1-year follow-up, according to a randomized, controlled study of northern Sweden residents at risk of cardiovascular disease.

pixologicstudio/Thinkstock.com

“Our study supports further attempts to solve the major problem of prevention failure because of low adherence, despite effective, cost-effective, and evidence-based medications and methods for a healthier lifestyle,” wrote lead author Ulf Näslund, of Umeå (Sweden) University, and his coauthors. The study was published online in the Lancet.

In this trial of 3,532 individuals who were aged 40-60 years with one or more conventional cardiovascular risk factors, the intervention group (1,749) received pictorial information of atherosclerosis as an add-on to normal care. Their primary care physician received the same information, and these participants also received a follow-up phone call from a nurse 2-4 weeks later. The other participants (1,783) received standard care but neither the presentation nor the phone call.

Both the Framingham risk score (FRS) and European Systematic Coronary Risk Evaluation (SCORE) were both used to assess outcomes; at 1-year follow-up, the intervention group had an FRS that decreased from baseline (–0.58; 95% confidence interval, –0.86 to –0.30), compared with an increase in the control group (0.35; 95% CI, 0.08-0.63). SCORE values increased twice as much in the control group (0.27; 95% CI, 0.23-0.30), compared with the intervention group (0.13; 95% CI, 0.09-0.18). The authors also observed no differential responses for education level, surmising that “this type of risk communication might contribute to reduction of the social gap in health.”

The authors shared their study’s limitations, including notable differences between dropouts and participants at 1-year follow-up with regard to metabolic risk factors and such fast-developing imaging technologies as CT and MRI out-dating ultrasound findings. They also acknowledged that more research needs to be undertaken to prove that these outcomes are genuine.

This study was funded by Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, and the Swedish Society of Medicine. No conflicts of interest were reported.

SOURCE: Näslund U et al. Lancet. 2018 Dec 3. doi: 10.1016/S0140-6736(18)32818-6.

A pictorial representation of carotid ultrasound coupled with a follow-up phone call from a nurse led to reduced cardiovascular disease risk at 1-year follow-up, according to a randomized, controlled study of northern Sweden residents at risk of cardiovascular disease.

pixologicstudio/Thinkstock.com

“Our study supports further attempts to solve the major problem of prevention failure because of low adherence, despite effective, cost-effective, and evidence-based medications and methods for a healthier lifestyle,” wrote lead author Ulf Näslund, of Umeå (Sweden) University, and his coauthors. The study was published online in the Lancet.

In this trial of 3,532 individuals who were aged 40-60 years with one or more conventional cardiovascular risk factors, the intervention group (1,749) received pictorial information of atherosclerosis as an add-on to normal care. Their primary care physician received the same information, and these participants also received a follow-up phone call from a nurse 2-4 weeks later. The other participants (1,783) received standard care but neither the presentation nor the phone call.

Both the Framingham risk score (FRS) and European Systematic Coronary Risk Evaluation (SCORE) were both used to assess outcomes; at 1-year follow-up, the intervention group had an FRS that decreased from baseline (–0.58; 95% confidence interval, –0.86 to –0.30), compared with an increase in the control group (0.35; 95% CI, 0.08-0.63). SCORE values increased twice as much in the control group (0.27; 95% CI, 0.23-0.30), compared with the intervention group (0.13; 95% CI, 0.09-0.18). The authors also observed no differential responses for education level, surmising that “this type of risk communication might contribute to reduction of the social gap in health.”

The authors shared their study’s limitations, including notable differences between dropouts and participants at 1-year follow-up with regard to metabolic risk factors and such fast-developing imaging technologies as CT and MRI out-dating ultrasound findings. They also acknowledged that more research needs to be undertaken to prove that these outcomes are genuine.

This study was funded by Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, and the Swedish Society of Medicine. No conflicts of interest were reported.

SOURCE: Näslund U et al. Lancet. 2018 Dec 3. doi: 10.1016/S0140-6736(18)32818-6.

NEW ORLEANS – The newer antiepileptic drugs (AEDs) and the established AEDs have similar tolerability, according to an analysis presented at the annual meeting of the American Epilepsy Society. Approximately one-third of patients with epilepsy discontinue their AEDs because of adverse drug reactions, according to the researchers. An increasing number of concomitant AEDs is associated with decreasing tolerability.

Previous research by Patrick Kwan, MBBChir, PhD, chair of neurology at the University of Melbourne and his colleagues indicated that the introduction of AEDs with new mechanisms of action in the past two decades has not changed seizure outcome overall in newly diagnosed epilepsy. Researchers had not studied the long-term tolerability of AEDs, however.

Dr. Kwan, Zhibin Chen, PhD, a biostatistician at the University of Melbourne, and their colleagues examined AED-induced adverse drug reactions over a 30-year period. They analyzed data for adults who were newly treated with AEDs at the epilepsy unit of the Western Infirmary in Glasgow during July 1, 1982–Oct. 31, 2012. All patients were followed prospectively until April 30, 2016, or death. The researchers systematically reviewed patient-reported adverse drug reactions and categorized them with the Medical Dictionary for Regulatory Activities. They defined adverse reactions that resulted in AED discontinuation as intolerable.

The investigators included 1,527 patients in their analysis. Approximately 56% of the sample was male, and the median age was 37 years. Participants tried a total of 2,766 AED regimens, including 2,028 (73%) as monotherapy and 738 (27%) as combination therapy. Among the monotherapies, 927 (46%) were established AEDs, and 1,101 (54%) were newer AEDs.

In all, 675 (44%) patients reported adverse drug reactions. These reports included 391 (26%) patients with nervous system disorders (e.g., tremor, sedation, and headaches), 272 (18%) with general disorders (e.g., fatigue, ataxia, and irritability), and 136 (9%) with psychiatric disorders (e.g., aggression, depression, and mood swings). A total of 498 (33%) patients had at least one intolerable adverse drug reaction.

The established and newer AEDs, when taken as monotherapy, had similar rates of intolerable adverse drug reactions (odds ratio, 1.09).The crude rate of intolerable adverse drug reactions appeared to increase for each additional AED regimen tried. Multivariable analysis indicated that women were more likely to report intolerable adverse drug reactions than men.

Compared with patients taking monotherapy, patients taking two AEDs had 1.67 times the risk of developing an intolerable adverse drug reaction, after data adjustments for number of previous AED regimens tried, previous intolerable adverse drug reaction, age, sex, pretreatment psychiatric comorbidity, and epilepsy type. The odds increased further in patients on three AEDs (OR, 2.38) and four AEDs (OR, 5.24). Patients who had intolerable adverse drug reactions to previous AED regimens had much greater odds of experiencing a further event (OR, 22.7).

After considering all the above factors, the researchers found that the odds of intolerable adverse drug reactions decreased for each additional AED regimen. When analyzing the 642 patients who took more than one AED regimen, they found that those who failed the first AED because of adverse drug reactions were more likely to develop intolerable adverse drug reactions to subsequent regimens (OR, 5.09). The odds of drug withdrawal because of adverse drug reaction increased 12-fold for each additional previous intolerable adverse drug reaction (OR, 13.3).

The investigators received no funding for this study.
 

This article was updated 12/4/18.

[email protected]

SOURCE: Alsfouk B et al. AES 2018, Abstract 2.275.

NEW ORLEANS – The newer antiepileptic drugs (AEDs) and the established AEDs have similar tolerability, according to an analysis presented at the annual meeting of the American Epilepsy Society. Approximately one-third of patients with epilepsy discontinue their AEDs because of adverse drug reactions, according to the researchers. An increasing number of concomitant AEDs is associated with decreasing tolerability.

Previous research by Patrick Kwan, MBBChir, PhD, chair of neurology at the University of Melbourne and his colleagues indicated that the introduction of AEDs with new mechanisms of action in the past two decades has not changed seizure outcome overall in newly diagnosed epilepsy. Researchers had not studied the long-term tolerability of AEDs, however.

Dr. Kwan, Zhibin Chen, PhD, a biostatistician at the University of Melbourne, and their colleagues examined AED-induced adverse drug reactions over a 30-year period. They analyzed data for adults who were newly treated with AEDs at the epilepsy unit of the Western Infirmary in Glasgow during July 1, 1982–Oct. 31, 2012. All patients were followed prospectively until April 30, 2016, or death. The researchers systematically reviewed patient-reported adverse drug reactions and categorized them with the Medical Dictionary for Regulatory Activities. They defined adverse reactions that resulted in AED discontinuation as intolerable.

The investigators included 1,527 patients in their analysis. Approximately 56% of the sample was male, and the median age was 37 years. Participants tried a total of 2,766 AED regimens, including 2,028 (73%) as monotherapy and 738 (27%) as combination therapy. Among the monotherapies, 927 (46%) were established AEDs, and 1,101 (54%) were newer AEDs.

In all, 675 (44%) patients reported adverse drug reactions. These reports included 391 (26%) patients with nervous system disorders (e.g., tremor, sedation, and headaches), 272 (18%) with general disorders (e.g., fatigue, ataxia, and irritability), and 136 (9%) with psychiatric disorders (e.g., aggression, depression, and mood swings). A total of 498 (33%) patients had at least one intolerable adverse drug reaction.

The established and newer AEDs, when taken as monotherapy, had similar rates of intolerable adverse drug reactions (odds ratio, 1.09).The crude rate of intolerable adverse drug reactions appeared to increase for each additional AED regimen tried. Multivariable analysis indicated that women were more likely to report intolerable adverse drug reactions than men.

Compared with patients taking monotherapy, patients taking two AEDs had 1.67 times the risk of developing an intolerable adverse drug reaction, after data adjustments for number of previous AED regimens tried, previous intolerable adverse drug reaction, age, sex, pretreatment psychiatric comorbidity, and epilepsy type. The odds increased further in patients on three AEDs (OR, 2.38) and four AEDs (OR, 5.24). Patients who had intolerable adverse drug reactions to previous AED regimens had much greater odds of experiencing a further event (OR, 22.7).

After considering all the above factors, the researchers found that the odds of intolerable adverse drug reactions decreased for each additional AED regimen. When analyzing the 642 patients who took more than one AED regimen, they found that those who failed the first AED because of adverse drug reactions were more likely to develop intolerable adverse drug reactions to subsequent regimens (OR, 5.09). The odds of drug withdrawal because of adverse drug reaction increased 12-fold for each additional previous intolerable adverse drug reaction (OR, 13.3).

The investigators received no funding for this study.
 

This article was updated 12/4/18.

[email protected]

SOURCE: Alsfouk B et al. AES 2018, Abstract 2.275.

NEW ORLEANS – The newer antiepileptic drugs (AEDs) and the established AEDs have similar tolerability, according to an analysis presented at the annual meeting of the American Epilepsy Society. Approximately one-third of patients with epilepsy discontinue their AEDs because of adverse drug reactions, according to the researchers. An increasing number of concomitant AEDs is associated with decreasing tolerability.

Previous research by Patrick Kwan, MBBChir, PhD, chair of neurology at the University of Melbourne and his colleagues indicated that the introduction of AEDs with new mechanisms of action in the past two decades has not changed seizure outcome overall in newly diagnosed epilepsy. Researchers had not studied the long-term tolerability of AEDs, however.

Dr. Kwan, Zhibin Chen, PhD, a biostatistician at the University of Melbourne, and their colleagues examined AED-induced adverse drug reactions over a 30-year period. They analyzed data for adults who were newly treated with AEDs at the epilepsy unit of the Western Infirmary in Glasgow during July 1, 1982–Oct. 31, 2012. All patients were followed prospectively until April 30, 2016, or death. The researchers systematically reviewed patient-reported adverse drug reactions and categorized them with the Medical Dictionary for Regulatory Activities. They defined adverse reactions that resulted in AED discontinuation as intolerable.

The investigators included 1,527 patients in their analysis. Approximately 56% of the sample was male, and the median age was 37 years. Participants tried a total of 2,766 AED regimens, including 2,028 (73%) as monotherapy and 738 (27%) as combination therapy. Among the monotherapies, 927 (46%) were established AEDs, and 1,101 (54%) were newer AEDs.

In all, 675 (44%) patients reported adverse drug reactions. These reports included 391 (26%) patients with nervous system disorders (e.g., tremor, sedation, and headaches), 272 (18%) with general disorders (e.g., fatigue, ataxia, and irritability), and 136 (9%) with psychiatric disorders (e.g., aggression, depression, and mood swings). A total of 498 (33%) patients had at least one intolerable adverse drug reaction.

The established and newer AEDs, when taken as monotherapy, had similar rates of intolerable adverse drug reactions (odds ratio, 1.09).The crude rate of intolerable adverse drug reactions appeared to increase for each additional AED regimen tried. Multivariable analysis indicated that women were more likely to report intolerable adverse drug reactions than men.

Compared with patients taking monotherapy, patients taking two AEDs had 1.67 times the risk of developing an intolerable adverse drug reaction, after data adjustments for number of previous AED regimens tried, previous intolerable adverse drug reaction, age, sex, pretreatment psychiatric comorbidity, and epilepsy type. The odds increased further in patients on three AEDs (OR, 2.38) and four AEDs (OR, 5.24). Patients who had intolerable adverse drug reactions to previous AED regimens had much greater odds of experiencing a further event (OR, 22.7).

After considering all the above factors, the researchers found that the odds of intolerable adverse drug reactions decreased for each additional AED regimen. When analyzing the 642 patients who took more than one AED regimen, they found that those who failed the first AED because of adverse drug reactions were more likely to develop intolerable adverse drug reactions to subsequent regimens (OR, 5.09). The odds of drug withdrawal because of adverse drug reaction increased 12-fold for each additional previous intolerable adverse drug reaction (OR, 13.3).

The investigators received no funding for this study.
 

This article was updated 12/4/18.

[email protected]

SOURCE: Alsfouk B et al. AES 2018, Abstract 2.275.

NEW ORLEANS – Women with epilepsy may have greater rates of infertility and impaired fecundity, compared with the general population, based on a retrospective study presented at the annual meeting of the American Epilepsy Society.

Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.

However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.

It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.

The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.

The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.

Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.

In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.

Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).

The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.

The investigation was funded by the Epilepsy Foundation and Lundbeck.

[email protected]

SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.

NEW ORLEANS – Women with epilepsy may have greater rates of infertility and impaired fecundity, compared with the general population, based on a retrospective study presented at the annual meeting of the American Epilepsy Society.

Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.

However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.

It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.

The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.

The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.

Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.

In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.

Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).

The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.

The investigation was funded by the Epilepsy Foundation and Lundbeck.

[email protected]

SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.

NEW ORLEANS – Women with epilepsy may have greater rates of infertility and impaired fecundity, compared with the general population, based on a retrospective study presented at the annual meeting of the American Epilepsy Society.

Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.

However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.

It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.

The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.

The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.

Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.

In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.

Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).

The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.

The investigation was funded by the Epilepsy Foundation and Lundbeck.

[email protected]

SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.

NEW ORLEANS – Among patients with psychogenic nonepileptic seizures, the risk of death is more than twice as great as among the general population, according to data presented at the annual meeting of the American Epilepsy Society. Patients with PNES have a mortality rate comparable to that of patients with drug-resistant epilepsy.

“This [finding] emphasizes the importance of correct diagnosis and identification of relevant pathologies in order to avoid preventable deaths in an important group of patients, where medical attention is often inappropriately directed to a dramatic but ultimately irrelevant clinical feature of the condition,” said Russell Nightscales, a first-year medical student at the University of Melbourne.*

Although PNES sometimes is mistaken for epilepsy and treated accordingly, it is a form of conversion disorder. The elevated risk of death among patients with epilepsy is understood, but few researchers have studied mortality in patients with PNES.

Mr. Nightscales and his colleagues conducted a retrospective cohort study of patients who had been admitted for a comprehensive epilepsy evaluation to one of two tertiary hospital video EEG monitoring (VEM) units in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. The investigators ascertained mortality and cause of death by linking patient data to the Australian National Death Index (NDI). When a coroner’s report was available, they refined the cause of death using information from the National Coronial Information System. Each patient’s diagnosis was based on the consensus opinion of experienced epileptologists at the Comprehensive Epilepsy Meeting following a review of the clinical history, VEM data, and investigations. The researchers compared mortality in patients with PNES, epilepsy, or both conditions. They extracted clinical data through medical record review. Finally, they determined lifetime history of psychiatric disorders through review of neuropsychiatric reports.

Of 3,152 patients who underwent VEM, the investigators included 2,076 patients in their analyses. Of this population, 631 patients had PNES, 1,339 had epilepsy, and 106 had both. The standardized mortality ratio (SMR) among patients with PNES was 2.6 times greater than among the general population. Patients with PNES between ages 30 and 39 had a ninefold higher risk of death, compared with the general population. The SMR of patients with epilepsy was 3.2. The investigators found no significant difference in the rate of mortality between any of the patient groups after excluding 17 patients with epilepsy and a known brain tumor at the time of VEM, who had a malignant neoplasm of the brain listed as their primary cause of death.

Death resulted from external causes in 20% of all deaths among patients with PNES and in 53% of deaths with a known cause among patients who died below the age of 50. Suicide accounted for 24% of deaths among patients with PNES in this age group. Neoplasia and cardiorespiratory causes were responsible for 51% of deaths with a known cause across all ages and 67% of those between ages 50 and 69. Among people with epilepsy, external causes accounted for 7% of all deaths. Neoplasia and cardiorespiratory causes were observed in 42% of people with epilepsy. Epilepsy was responsible for 28% of deaths with a known cause among patients with epilepsy

The research was funded by Australia’s National Health and Medical Research Council and the RMH Neuroscience Foundation.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 1.139.

*Correction 12/4/18: An earlier version of this article misstated the name of the presenter. Russell Nightscales presented this study.

NEW ORLEANS – Among patients with psychogenic nonepileptic seizures, the risk of death is more than twice as great as among the general population, according to data presented at the annual meeting of the American Epilepsy Society. Patients with PNES have a mortality rate comparable to that of patients with drug-resistant epilepsy.

“This [finding] emphasizes the importance of correct diagnosis and identification of relevant pathologies in order to avoid preventable deaths in an important group of patients, where medical attention is often inappropriately directed to a dramatic but ultimately irrelevant clinical feature of the condition,” said Russell Nightscales, a first-year medical student at the University of Melbourne.*

Although PNES sometimes is mistaken for epilepsy and treated accordingly, it is a form of conversion disorder. The elevated risk of death among patients with epilepsy is understood, but few researchers have studied mortality in patients with PNES.

Mr. Nightscales and his colleagues conducted a retrospective cohort study of patients who had been admitted for a comprehensive epilepsy evaluation to one of two tertiary hospital video EEG monitoring (VEM) units in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. The investigators ascertained mortality and cause of death by linking patient data to the Australian National Death Index (NDI). When a coroner’s report was available, they refined the cause of death using information from the National Coronial Information System. Each patient’s diagnosis was based on the consensus opinion of experienced epileptologists at the Comprehensive Epilepsy Meeting following a review of the clinical history, VEM data, and investigations. The researchers compared mortality in patients with PNES, epilepsy, or both conditions. They extracted clinical data through medical record review. Finally, they determined lifetime history of psychiatric disorders through review of neuropsychiatric reports.

Of 3,152 patients who underwent VEM, the investigators included 2,076 patients in their analyses. Of this population, 631 patients had PNES, 1,339 had epilepsy, and 106 had both. The standardized mortality ratio (SMR) among patients with PNES was 2.6 times greater than among the general population. Patients with PNES between ages 30 and 39 had a ninefold higher risk of death, compared with the general population. The SMR of patients with epilepsy was 3.2. The investigators found no significant difference in the rate of mortality between any of the patient groups after excluding 17 patients with epilepsy and a known brain tumor at the time of VEM, who had a malignant neoplasm of the brain listed as their primary cause of death.

Death resulted from external causes in 20% of all deaths among patients with PNES and in 53% of deaths with a known cause among patients who died below the age of 50. Suicide accounted for 24% of deaths among patients with PNES in this age group. Neoplasia and cardiorespiratory causes were responsible for 51% of deaths with a known cause across all ages and 67% of those between ages 50 and 69. Among people with epilepsy, external causes accounted for 7% of all deaths. Neoplasia and cardiorespiratory causes were observed in 42% of people with epilepsy. Epilepsy was responsible for 28% of deaths with a known cause among patients with epilepsy

The research was funded by Australia’s National Health and Medical Research Council and the RMH Neuroscience Foundation.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 1.139.

*Correction 12/4/18: An earlier version of this article misstated the name of the presenter. Russell Nightscales presented this study.

NEW ORLEANS – Among patients with psychogenic nonepileptic seizures, the risk of death is more than twice as great as among the general population, according to data presented at the annual meeting of the American Epilepsy Society. Patients with PNES have a mortality rate comparable to that of patients with drug-resistant epilepsy.

“This [finding] emphasizes the importance of correct diagnosis and identification of relevant pathologies in order to avoid preventable deaths in an important group of patients, where medical attention is often inappropriately directed to a dramatic but ultimately irrelevant clinical feature of the condition,” said Russell Nightscales, a first-year medical student at the University of Melbourne.*

Although PNES sometimes is mistaken for epilepsy and treated accordingly, it is a form of conversion disorder. The elevated risk of death among patients with epilepsy is understood, but few researchers have studied mortality in patients with PNES.

Mr. Nightscales and his colleagues conducted a retrospective cohort study of patients who had been admitted for a comprehensive epilepsy evaluation to one of two tertiary hospital video EEG monitoring (VEM) units in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. The investigators ascertained mortality and cause of death by linking patient data to the Australian National Death Index (NDI). When a coroner’s report was available, they refined the cause of death using information from the National Coronial Information System. Each patient’s diagnosis was based on the consensus opinion of experienced epileptologists at the Comprehensive Epilepsy Meeting following a review of the clinical history, VEM data, and investigations. The researchers compared mortality in patients with PNES, epilepsy, or both conditions. They extracted clinical data through medical record review. Finally, they determined lifetime history of psychiatric disorders through review of neuropsychiatric reports.

Of 3,152 patients who underwent VEM, the investigators included 2,076 patients in their analyses. Of this population, 631 patients had PNES, 1,339 had epilepsy, and 106 had both. The standardized mortality ratio (SMR) among patients with PNES was 2.6 times greater than among the general population. Patients with PNES between ages 30 and 39 had a ninefold higher risk of death, compared with the general population. The SMR of patients with epilepsy was 3.2. The investigators found no significant difference in the rate of mortality between any of the patient groups after excluding 17 patients with epilepsy and a known brain tumor at the time of VEM, who had a malignant neoplasm of the brain listed as their primary cause of death.

Death resulted from external causes in 20% of all deaths among patients with PNES and in 53% of deaths with a known cause among patients who died below the age of 50. Suicide accounted for 24% of deaths among patients with PNES in this age group. Neoplasia and cardiorespiratory causes were responsible for 51% of deaths with a known cause across all ages and 67% of those between ages 50 and 69. Among people with epilepsy, external causes accounted for 7% of all deaths. Neoplasia and cardiorespiratory causes were observed in 42% of people with epilepsy. Epilepsy was responsible for 28% of deaths with a known cause among patients with epilepsy

The research was funded by Australia’s National Health and Medical Research Council and the RMH Neuroscience Foundation.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 1.139.

*Correction 12/4/18: An earlier version of this article misstated the name of the presenter. Russell Nightscales presented this study.

NEW ORLEANS – A synthetic, transdermal, cannabidiol gel reduced the rate of seizures by half in a group of adults with treatment-resistant focal seizures who were participating in an open-label, long-term extension trial.

Michele G. Sullivan/MDedge News

A twice-daily, 390-mg dose of the gel, dubbed ZYN002 (Zynerba) for now, was consistently effective in the 24-month STAR 2 extension trial, John Messenheimer, MD, said at the annual meeting of the American Epilepsy Society.

ZYN002 provided continuing coverage for patients who had used the active compound in the randomized phase, and quickly reduced seizures in those who entered on placebo, said Dr. Messenheimer, a consultant neurologist from Moncure, N.C.

The synthetically produced cannabidiol (CBD) transdermal gel ZYN002 is formulated to be applied twice a day to the shoulder. In addition to incompletely controlled focal epilepsies, ZYN002 is also being investigated for fragile X syndrome, developmental and epileptic encephalopathies.

STAR 2 is the extension of STAR 1 (Synthetic Transdermal Cannabidiol for the Treatment of Epilepsy), a 12-week, phase 2a study of the gel. It randomized 181 patients to placebo or to 195 mg or 390 mg CBD gel twice daily.

Patients were a mean of about 40 years old. They had incompletely controlled focal epilepsies, experiencing about 10 seizures per month despite taking a median of three antiepileptic drugs (AEDs). The most commonly used AEDs were levetiracetam (45%), carbamazepine (41%), lamotrigine (33%), lacosamide (28%), and valproate (22%).

By the end of STAR 1, there was an median 18% reduction in seizures from baseline in the 195-mg group, and the 390-mg group experienced a 14% reduction. However, neither of these findings were statistically significant compared with placebo. Dr. Messenheimer said an unusually high 25% placebo response rate contributed to the nonsignificant findings.

Still, patients remained committed to the study, Dr. Messenheimer pointed out: 171 of the 174 STAR trial completers entered the STAR 2 extension. The entire cohort started on the 390-mg dose, and at month 5, they could titrate up to 585 mg or 780 mg daily, or reduce the does to 195 mg twice daily.

At the 18-month point, 76 patients remained in the study. Five discontinued because of an adverse event. Sixty stopped because the gel was ineffective, and the rest exited the study on the decision of an investigator. Dr. Messenheimer presented a responder analysis on 63 of the remaining subjects with full data, as well as an intent-to-treat analysis on the entire STAR 2 cohort.

Among the entire cohort, continued treatment appeared to confer increasing benefit, he said in an interview. By 3 months, the median seizure reduction rate was 25%; it increased to 40% by 6 months and 48% by 9 months. For the next 9 months, the seizure reduction rate stayed steady, hovering at around 55%.

“Among all the patients, we saw an increase in efficacy over 18 months. Half of the patients stayed on 390 mg, and of the half that titrated to higher doses. Most of these went up to 780 mg, but we really didn’t see that the higher doses conferred much benefit over the 390.”

The 63-patient cohort could be viewed as a responder-only analysis, Dr. Messenheimer said, since most of the dropouts occurred in the first few months of the study. Nevertheless, the response rates in the entire 171-person cohort were quite similar, with a 49% reduction by 3 months that increased to a median 55% reduction by 18 months.

The gel was generally well tolerated, although Dr. Messenheimer pointed out three serious adverse events that were probably drug related: two cases of anxiety and one case of increased seizures. Other events that occurred in significantly more of the CBD groups were headaches (12%), upper respiratory infection (11%), lacerations (9%), and fatigue (6%).

There were no liver enzyme abnormalities.

Zynerba sponsored the study; Dr. Messenheimer is a paid consultant for Zynerba.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 2.253

NEW ORLEANS – A synthetic, transdermal, cannabidiol gel reduced the rate of seizures by half in a group of adults with treatment-resistant focal seizures who were participating in an open-label, long-term extension trial.

Michele G. Sullivan/MDedge News

A twice-daily, 390-mg dose of the gel, dubbed ZYN002 (Zynerba) for now, was consistently effective in the 24-month STAR 2 extension trial, John Messenheimer, MD, said at the annual meeting of the American Epilepsy Society.

ZYN002 provided continuing coverage for patients who had used the active compound in the randomized phase, and quickly reduced seizures in those who entered on placebo, said Dr. Messenheimer, a consultant neurologist from Moncure, N.C.

The synthetically produced cannabidiol (CBD) transdermal gel ZYN002 is formulated to be applied twice a day to the shoulder. In addition to incompletely controlled focal epilepsies, ZYN002 is also being investigated for fragile X syndrome, developmental and epileptic encephalopathies.

STAR 2 is the extension of STAR 1 (Synthetic Transdermal Cannabidiol for the Treatment of Epilepsy), a 12-week, phase 2a study of the gel. It randomized 181 patients to placebo or to 195 mg or 390 mg CBD gel twice daily.

Patients were a mean of about 40 years old. They had incompletely controlled focal epilepsies, experiencing about 10 seizures per month despite taking a median of three antiepileptic drugs (AEDs). The most commonly used AEDs were levetiracetam (45%), carbamazepine (41%), lamotrigine (33%), lacosamide (28%), and valproate (22%).

By the end of STAR 1, there was an median 18% reduction in seizures from baseline in the 195-mg group, and the 390-mg group experienced a 14% reduction. However, neither of these findings were statistically significant compared with placebo. Dr. Messenheimer said an unusually high 25% placebo response rate contributed to the nonsignificant findings.

Still, patients remained committed to the study, Dr. Messenheimer pointed out: 171 of the 174 STAR trial completers entered the STAR 2 extension. The entire cohort started on the 390-mg dose, and at month 5, they could titrate up to 585 mg or 780 mg daily, or reduce the does to 195 mg twice daily.

At the 18-month point, 76 patients remained in the study. Five discontinued because of an adverse event. Sixty stopped because the gel was ineffective, and the rest exited the study on the decision of an investigator. Dr. Messenheimer presented a responder analysis on 63 of the remaining subjects with full data, as well as an intent-to-treat analysis on the entire STAR 2 cohort.

Among the entire cohort, continued treatment appeared to confer increasing benefit, he said in an interview. By 3 months, the median seizure reduction rate was 25%; it increased to 40% by 6 months and 48% by 9 months. For the next 9 months, the seizure reduction rate stayed steady, hovering at around 55%.

“Among all the patients, we saw an increase in efficacy over 18 months. Half of the patients stayed on 390 mg, and of the half that titrated to higher doses. Most of these went up to 780 mg, but we really didn’t see that the higher doses conferred much benefit over the 390.”

The 63-patient cohort could be viewed as a responder-only analysis, Dr. Messenheimer said, since most of the dropouts occurred in the first few months of the study. Nevertheless, the response rates in the entire 171-person cohort were quite similar, with a 49% reduction by 3 months that increased to a median 55% reduction by 18 months.

The gel was generally well tolerated, although Dr. Messenheimer pointed out three serious adverse events that were probably drug related: two cases of anxiety and one case of increased seizures. Other events that occurred in significantly more of the CBD groups were headaches (12%), upper respiratory infection (11%), lacerations (9%), and fatigue (6%).

There were no liver enzyme abnormalities.

Zynerba sponsored the study; Dr. Messenheimer is a paid consultant for Zynerba.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 2.253

NEW ORLEANS – A synthetic, transdermal, cannabidiol gel reduced the rate of seizures by half in a group of adults with treatment-resistant focal seizures who were participating in an open-label, long-term extension trial.

Michele G. Sullivan/MDedge News

A twice-daily, 390-mg dose of the gel, dubbed ZYN002 (Zynerba) for now, was consistently effective in the 24-month STAR 2 extension trial, John Messenheimer, MD, said at the annual meeting of the American Epilepsy Society.

ZYN002 provided continuing coverage for patients who had used the active compound in the randomized phase, and quickly reduced seizures in those who entered on placebo, said Dr. Messenheimer, a consultant neurologist from Moncure, N.C.

The synthetically produced cannabidiol (CBD) transdermal gel ZYN002 is formulated to be applied twice a day to the shoulder. In addition to incompletely controlled focal epilepsies, ZYN002 is also being investigated for fragile X syndrome, developmental and epileptic encephalopathies.

STAR 2 is the extension of STAR 1 (Synthetic Transdermal Cannabidiol for the Treatment of Epilepsy), a 12-week, phase 2a study of the gel. It randomized 181 patients to placebo or to 195 mg or 390 mg CBD gel twice daily.

Patients were a mean of about 40 years old. They had incompletely controlled focal epilepsies, experiencing about 10 seizures per month despite taking a median of three antiepileptic drugs (AEDs). The most commonly used AEDs were levetiracetam (45%), carbamazepine (41%), lamotrigine (33%), lacosamide (28%), and valproate (22%).

By the end of STAR 1, there was an median 18% reduction in seizures from baseline in the 195-mg group, and the 390-mg group experienced a 14% reduction. However, neither of these findings were statistically significant compared with placebo. Dr. Messenheimer said an unusually high 25% placebo response rate contributed to the nonsignificant findings.

Still, patients remained committed to the study, Dr. Messenheimer pointed out: 171 of the 174 STAR trial completers entered the STAR 2 extension. The entire cohort started on the 390-mg dose, and at month 5, they could titrate up to 585 mg or 780 mg daily, or reduce the does to 195 mg twice daily.

At the 18-month point, 76 patients remained in the study. Five discontinued because of an adverse event. Sixty stopped because the gel was ineffective, and the rest exited the study on the decision of an investigator. Dr. Messenheimer presented a responder analysis on 63 of the remaining subjects with full data, as well as an intent-to-treat analysis on the entire STAR 2 cohort.

Among the entire cohort, continued treatment appeared to confer increasing benefit, he said in an interview. By 3 months, the median seizure reduction rate was 25%; it increased to 40% by 6 months and 48% by 9 months. For the next 9 months, the seizure reduction rate stayed steady, hovering at around 55%.

“Among all the patients, we saw an increase in efficacy over 18 months. Half of the patients stayed on 390 mg, and of the half that titrated to higher doses. Most of these went up to 780 mg, but we really didn’t see that the higher doses conferred much benefit over the 390.”

The 63-patient cohort could be viewed as a responder-only analysis, Dr. Messenheimer said, since most of the dropouts occurred in the first few months of the study. Nevertheless, the response rates in the entire 171-person cohort were quite similar, with a 49% reduction by 3 months that increased to a median 55% reduction by 18 months.

The gel was generally well tolerated, although Dr. Messenheimer pointed out three serious adverse events that were probably drug related: two cases of anxiety and one case of increased seizures. Other events that occurred in significantly more of the CBD groups were headaches (12%), upper respiratory infection (11%), lacerations (9%), and fatigue (6%).

There were no liver enzyme abnormalities.

Zynerba sponsored the study; Dr. Messenheimer is a paid consultant for Zynerba.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 2.253

ABSTRACT

The use of knotless suture anchors has increased in popularity; however, there is a paucity of literature examining the difference in clinical outcomes with traditional knotted fixation. It was hypothesized that knotless fixation would provide superior clinical outcomes, improved return to play (RTP), and lower revision rates as compared with traditional knotted fixation in the repair of SLAP IIb tears. Seventy-four athletes who underwent arthroscopic SLAP IIb repair with traditional (n = 42) and knotless anchors (n = 32) by a single surgeon were evaluated after a minimum 2-year follow. Demographic and surgical data, RTP, Kerlan-Jobe Orthopaedic Clinic (KJOC) score, American Shoulder and Elbow Surgeons (ASES) score, stability, strength, and pain scores were compared. Knotless anchors had slightly higher RTP (93.5% vs 90.2%, P = .94) and RTP at the same level (58.1% vs 53.7% P = .81) compared with knotted fixation, but the difference did not reach statistical significance. Knotless anchors were less likely to require revision surgery than traditional anchors (9% vs 17%, P = .50), but the difference was not statistically significant. When comparing knotless and traditional knotted suture anchor repair of type llb SLAP tears, knotless fixation required less revision surgery and had higher RTP, ASES, and KJOC scores; however, statistical significance was not achieved in this relatively small cohort.

Continue to: Injury of the anterosuperior...

Injury of the anterosuperior labrum near the biceps origin was first described by Andrews and colleagues in 1985 in overhead athletes.¹ The term SLAP, or a tear in the superior labrum anterior to posterior, was coined a few years later by Snyder and colleagues.² They described an injury to the superior labrum beginning posteriorly and extending anteriorly, including the “anchor” of the biceps tendon to the labrum. Snyder further delineated SLAP lesions into 4 subtypes, the most common being type II, which he described as “degenerative fraying of the labrum with additional detachment of the superior labrum and biceps from the glenoid resulting in an unstable labral anchor.”^2,3 Type II tears are of particular importance as they are the most common SLAP lesions, with an incidence of 55%, and comprise nearly 75% of SLAP repairs performed.^2,4

Morgan and colleagues further delineated type II SLAP tears into IIa (anterior), IIb (posterior), and IIc (combined). Their group found that SLAP IIb tears were the most common type in overhead throwers, accounting for 47% of overhead athletes with type II tears.⁵ Further, type IIb tears can have a significant impact in throwers, in part due to greater shoulder instability as well as anterior pseudolaxity.⁵ SLAP injuries typically have been difficult to successfully treat nonoperatively in overhead athletes.⁶ A study by Edwards and colleagues⁶ examined 39 patients with all types of SLAP tears. Although, in their study, nonoperative management failed in 20 patients and they required surgery, 10 of the 15 overhead athletes in whom nonoperative treatment did not fail initially returned to sport at a level equal to or better than their pre-injury level, indicating that nonoperative treatment may play a role in some patients’ recovery.⁶

Surgical outcomes of SLAP IIb repairs have traditionally been less predictable than those of other shoulder injuries. Some believe that traditional knotted anchors may be partially to blame by abrading the rotator cuff, possibly leading to rotator cuff tears and pain. Further, knotted anchors are typically bulkier and require more experience with tying and tensioning and, therefore, may lead to less consistent results.⁷ The purpose of this study was to investigate if knotless anchors result in more favorable outcomes in repair of type IIb SLAP lesions when compared with traditional knotted anchors. It was hypothesized that knotless fixation will provide superior clinical outcomes, improved return to play (RTP), and lower revision rates as compared with traditional knotted fixation in the repair of SLAP IIb tears.

METHODS

PATIENT SELECTION

The authors retrospectively reviewed SLAP tears repaired by the senior author from June 2000 to September 2015. The inclusion criteria consisted of all athletes at any level who were diagnosed intraoperatively with a type IIb SLAP tear as defined by Morgan and colleagues⁵ with a minimum 2-year follow-up. The exclusion criteria were any patients with a previous shoulder surgery and the presence of any labral pathology aside from a SLAP IIb tear. Patients with rotator cuff or biceps pathologies were included. In all included patients, an initial course of preoperative physical therapy, including strengthening and stabilization of the scapulothoracic joint, had failed. Patient-directed surveys evaluated RTP, as well as the Kerlan-Jobe Orthopaedic Clinic (KJOC) score, American Shoulder and Elbow Surgeons (ASES) score, stability, range of motion (ROM), strength, and pain scores, as previously described.^8-10 Institutional Review Board and informed consent approval were acquired prior to initiation of the study.

PATIENT EVALUATION

An appropriate preoperative history was taken, and physical examinations were performed, including evaluation of the scapulothoracic joint, as well as tests to evaluate the presence of a SLAP tear, anterior instability, posterior instability, multi-directional instability, and rotator cuff tears, as previously described.¹¹ Patients with a history and physical examination concerning SLAP pathology underwent an magnetic resonance imaging (MRI) arthrogram, which was used in conjunction with intraoperative findings to diagnose type IIb SLAP tears.

Continue to: SURGICAL TECHNIQUE

All surgeries were performed arthroscopically with the patient in the lateral decubitus position. The SLAP lesions were subsequently repaired using a technique similar to that described by Burkhart and colleagues.¹² The traditional knotted fixation incorporated the use of 3.0 Bio-FASTak (Arthrex) with #2 FiberWire (Arthrex). Knotless anchor fixation was performed using 2.9 mm × 12.5 mm or 2.4 mm × 11.3 mm BioComposite PushLock (Arthrex) suture anchors, based on the size of the glenoid, with LabralTape or SutureTape (Arthrex). Patients who had surgery before January 1, 2013 underwent fixation with traditional knotted fixation; after that date, patients underwent fixation with knotless anchors.

POSTOPERATIVE REHABILITATION

Patients underwent a strict postoperative protocol in which they were kept in a sling with an abduction pillow for the first 6 weeks and performed pendulum exercises and passive motion only. A formal physical therapy regimen started at 4 weeks with passive ROM, passive posterior capsular and internal rotation stretching, scapulothoracic mobility, and biceps, rotator cuff, and capsular stabilizer strengthening. At 10 weeks, patients began biceps, rotator cuff, and scapular stabilizer resistance exercises, and at 16 weeks, throwing athletes began an interval throwing program. Patients were first eligible to return to sport without limitation at 9 months.

STATISTICAL ANALYSIS

Return to play, KJOC, ASES, stability, ROM, strength, and pain scores were analyzed and compared using Fisher exact test, the Kruskal-Wallis test, and the Wilcoxon rank sum test, where appropriate. The level of statistical significance was α = 0.05.

RESULTS

Of the 74 athletes who met inclusion criteria, 28 were female (37.8%) and 46 (62.2%) were male. The average follow-up was 6.5 years with a minimum of 2 years and a maximum of 12 years. Forty-two (56.8%) patients underwent traditional knotted suture anchor fixation and 32 (43.2%) underwent knotless anchor fixation. The average age was 30.1 +/– 13.6 years, with a range of 14 to 64 years. The majority of athletes were right hand dominant (79.9%). Fifty-three (72%) were overhead athletes and 29 (39%) were throwing athletes (Table 1). The average age in the knotted group was 33.3 years: 29 of 42 (69%) were overhead athletes and 20 (47.6%) were throwing athletes. In the knotless group, the average age was 25.8 years: 24 of 32 (75.0%) were overhead athletes and 9 (28.1%) were throwing athletes. Primary sports at the time of injury are listed in Table 2. The average number of anchors used was 3.1, with 17 patients (23.0%) requiring ≤2 anchors, 39 (52.7%) requiring 3 anchors, and 18 (24.3%) requiring ≥4 anchors for repair. The number of anchors used was determined intraoperatively by the surgeon on the basis of the size and extent of the tear. Of the entire group of 74 patients, 91.9% returned to sport, 56.8% returned to the same level, 35.1% returned at a lower capacity, and 8.1% were unable to return to sport. Knotless anchors had a slightly higher overall RTP compared with traditional anchors (93.5% vs 90.2%, P = .94), as well as a higher RTP at the same level (58.1% vs 53.7%, P = .81). These differences were, however, not statistically significant (Table 3).

Abbreviation: SLAP, superior labrum anterior to posterior.

Knotless anchors were less likely to require revision surgery than traditional anchors (9% vs 17%, P = .50), but this difference was not statistically significant (Table 3). In the knotted group, 5 patients had revision surgery for rotator cuff tears, and 2 patients had recurrent SLAP tears. In the knotless group, 2 patients had revision surgeries for a torn rotator cuff, and 1 patient had a snapping scapula. A power analysis found that it would take over 300 athletes in each group to detect a significant difference in the revision rate between knotless and traditional anchors.

Continue to: Although KJOC...

Although KJOC (66.1 vs 65.6 P = .61) and ASES (86.3 vs 85.3 P = .79) scores were also superior with knotless anchors, these differences in scores were not statistically significant (Table 3). Pain was the only variable that was linked to decreased RTP, as patients who rated higher on a pain scale of 0 to 10 were less likely to return to their sport (P < .0001). There was no correlation in outcome measures or RTP with gender, age, number of anchors, or sport type (P > .05). There was no statistically significant difference in RTP, KJOC, or ASES scores between non-overhead and overhead athletes (Table 4). Overall return to sport in throwers was 85.7% (24/28), while 39.3% (11/28) returned at the same level, 46.4% (13/28) at a lower level, and 14.3% (4/28) did not return to sport.

DISCUSSION

There was no significant difference between knotted and knotless fixation in clinical outcomes or return to sport in the repair of SLAP IIb tears; however, there was a trend toward knotless anchors requiring less revision surgery and having higher RTP, ASES, and KJOC scores than knotted fixation. Despite the inclusion of 74 patients, this study was significantly underpowered, as a power analysis calculated that over 300 athletes would be required in each group to detect a difference in the revision rate.

SLAP tears, traditionally treated with knotted suture anchors, have yielded varying results in the literature, with good to excellent results being reported in 65% to 94% of patients.^13-17 The success of SLAP repairs in athletes, especially overhead athletes, remains a difficult problem, as they are common injuries, and RTP is less predictable. Studies differ with regard to the percentage of overhead athletes who are able to return to their previous level of sport, with ranges being reported from 22% to 92%.^16,18,19 In a systematic review of 198 patients, Sayde and colleagues¹⁶ found that 63% of overhead athletes treated with anchor fixation, tacks, or staples were able to return to their previous level of play. Morgan and colleagues⁵ found a higher return to sport when compared with other studies, reporting that 83% of patients undergoing SLAP repairs using traditional suture anchors had excellent results, and 87% of the 53 overhead athletes had excellent results based on UCLA shoulder scores. Further, 37 of the 44 pitchers examined (84%) were able to return to their pre-injury levels.⁵ This is in contrast to Friel and colleagues²⁰ who found that in 48 patients with type II SLAP tears treated with traditional anchors, 23% reported excellent and 56% reported good results in regards to UCLA shoulder scores. Friel and colleagues also found that 62% of all athletes and 59% of overhead athletes were able to return to their previous levels of sport, which is similar to the current study.²⁰ The large discrepancy in RTP at the pre-injury level between this study and that of Morgan and colleagues⁵ may be due to the shorter minimum follow-up of 1 year as well as the inclusion of all subtypes of SLAP II tears in the latter. The current study had a minimum 2-year follow-up period, with an average of 6.5 years, and was limited to SLAP IIb tears. With a longer follow-up period, patient outcomes and RTP, particularly in overhead sports, may deteriorate; therefore, the current study likely shows a more complete and accurate result.

Knotless anchors were originally introduced as a less time consuming, lower profile, and simpler device to learn and use for arthroscopic procedures.²¹ Kocaoglu and colleagues²² found that in Bankart repairs, the mean time per anchor placement for knotted anchors was 380 seconds, whereas placement of knotless anchors took on average 225 seconds. A learning curve also exists for proper and efficient knot tying.⁷ There is also variation in knot tying between surgeons, as evidenced by a wide range in both load to failure and knot height.⁷ A study performed by Hanypsiak and colleagues⁷ found that the surgical knot was the weakest portion of the suture-anchor construct, as the knot’s load to failure was less than the pullout strength of the anchor.

There is also concern for the added height associated with traditional knotted fixation, which has been supported by case reports of knot-induced glenoid erosion after arthroscopic fixation of a SLAP tear.²³ Hanypsiak and colleagues⁷ also found that the average knot height occupied 50% to 95% of the space between the humeral head and the acromion when the shoulder is in a neutral position, indicating that the higher profile knotted anchors may contact the undersurface of the acromion, which could affect the labral repair as well as cause rotator cuff injury. Abrasion of the rotator cuff by a prominent knot may cause pain, tearing, and disability. A recent study by Park and colleagues²⁴ reported on 11 patients with knot-induced pain after type II SLAP repair. All complained of sharp pain, with 64% also complaining of clicking. Knot location did not seem to matter, as there was no difference in preoperative symptoms, with 5 of the 11 patients having knots on the glenoid side of the repair on repeat arthroscopy. Patients with knots on the labral side did, however, have humeral head cartilage damage. The knots appeared to be the cause of pain and clicking, as after arthroscopic knot removal, dramatic pain relief was seen, with Constant and UCLA scores significantly improving in all 11 patients. All patients also had positive preoperative compression-rotation testing, and at 6 weeks after surgical knot removal, all were negative.²⁴

Continue to: Further, as shown by Dines and colleagues...

Further, as shown by Dines and colleagues²⁵, knotless anchors may help to better restore the meniscoid anatomy of the superior labrum better than knotted suture anchors. With regards to fixation strength, Uggen and colleagues²⁶, using a cadaveric model, found no difference in initial fixation strength of knotless and traditional suture anchor repair of SLAP II tears, and both restored glenohumeral rotation without over-constraining the shoulder.

Despite the shorter operative time, lower profile, and more consistent tensioning with knotless anchors, the literature is limited with regard to evaluating patient outcomes. In a study by Yung and colleagues¹³ 14 of the 16 patients with type II SLAP tears were treated with knotless anchors, and the authors found that 31.3% of patients had an excellent UCLA score while 43.8% had a good score. This is similar to the outcomes illustrated in studies by both Friel and colleagues²⁰ and Sayde and colleagues.¹⁶ In a more recent study, Yang and colleagues²⁷ did find some benefit in regard to ROM with knotless fixation. Their study consisted of 21 patients who underwent surgery with traditional knotted anchor fixation and 20 who underwent knotless horizontal mattress fixation. They found an average UCLA score of 37.6 and ASES score of 91.5 in patients undergoing knotless fixation, and the knotless fixation group had 5% greater total ROM, 15.6% more internal rotation at abduction, and 11.4% more external rotation at the side as compared with patients undergoing the traditional knotted technique. When compared with the current study, this study also had a significantly shorter follow-up period of 3 years.²⁷ In a 2017 study, Bents and colleagues²⁸ compared 44 patients who underwent knotless and 119 who underwent knotted fixation of SLAP tears. They found no statistically significant difference between knotless and knotted fixation in the ASES score, Visual Analog Scale (VAS), ASES, or Veterans RAND 12-Item Health Survey (VR-12) at 1 year postoperatively. Their outcomes were similar to those of the current study, but as in other mentioned literature, the study by Bents and colleagues²⁸ included multiple surgeons with different postoperative protocols, was not limited to SLAP IIb tears, and also had a shorter follow-up of 1 year. Like Kocaoglu and colleagues²², Bents and colleagues did find knotless anchors to be more efficient, as operative time was reduced by 5.3 minutes per anchor. This likely would have a significant impact on surgical cost and surgeon productivity.²⁸

One limitation of the current study was that despite the inclusion of >70 patients, the study was still significantly underpowered. It was determined that >300 patients in each group would be required to detect a significant difference in the revision rate between the 2 anchor types. Also, due to the retrospective nature of this study, no preoperative scores were collected. The inclusion of objective clinical measurements and follow-up imaging evaluating the rotator cuff and other anatomy would also be of interest.

Although statistical significance was not achieved, there was a trend toward knotless fixation requiring less revision surgery and having higher RTP, ASES, and KJOC scores when compared with traditional knotted fixation at 6.5-year follow-up. Larger studies with longer follow-up periods are necessary to determine the effects of knotted and knotless anchors on rotator cuff tears, patient reported outcomes, and RTP. These complications have been shown in the literature, mostly in case reports, and typically develop over a longer period.²³ Despite this, other advantages of knotless fixation, such as its lower profile, the ability to better provide consistent tensioning, and decreased surgical time are important to consider.

ABSTRACT

The use of knotless suture anchors has increased in popularity; however, there is a paucity of literature examining the difference in clinical outcomes with traditional knotted fixation. It was hypothesized that knotless fixation would provide superior clinical outcomes, improved return to play (RTP), and lower revision rates as compared with traditional knotted fixation in the repair of SLAP IIb tears. Seventy-four athletes who underwent arthroscopic SLAP IIb repair with traditional (n = 42) and knotless anchors (n = 32) by a single surgeon were evaluated after a minimum 2-year follow. Demographic and surgical data, RTP, Kerlan-Jobe Orthopaedic Clinic (KJOC) score, American Shoulder and Elbow Surgeons (ASES) score, stability, strength, and pain scores were compared. Knotless anchors had slightly higher RTP (93.5% vs 90.2%, P = .94) and RTP at the same level (58.1% vs 53.7% P = .81) compared with knotted fixation, but the difference did not reach statistical significance. Knotless anchors were less likely to require revision surgery than traditional anchors (9% vs 17%, P = .50), but the difference was not statistically significant. When comparing knotless and traditional knotted suture anchor repair of type llb SLAP tears, knotless fixation required less revision surgery and had higher RTP, ASES, and KJOC scores; however, statistical significance was not achieved in this relatively small cohort.

Continue to: Injury of the anterosuperior...

Injury of the anterosuperior labrum near the biceps origin was first described by Andrews and colleagues in 1985 in overhead athletes.¹ The term SLAP, or a tear in the superior labrum anterior to posterior, was coined a few years later by Snyder and colleagues.² They described an injury to the superior labrum beginning posteriorly and extending anteriorly, including the “anchor” of the biceps tendon to the labrum. Snyder further delineated SLAP lesions into 4 subtypes, the most common being type II, which he described as “degenerative fraying of the labrum with additional detachment of the superior labrum and biceps from the glenoid resulting in an unstable labral anchor.”^2,3 Type II tears are of particular importance as they are the most common SLAP lesions, with an incidence of 55%, and comprise nearly 75% of SLAP repairs performed.^2,4

Morgan and colleagues further delineated type II SLAP tears into IIa (anterior), IIb (posterior), and IIc (combined). Their group found that SLAP IIb tears were the most common type in overhead throwers, accounting for 47% of overhead athletes with type II tears.⁵ Further, type IIb tears can have a significant impact in throwers, in part due to greater shoulder instability as well as anterior pseudolaxity.⁵ SLAP injuries typically have been difficult to successfully treat nonoperatively in overhead athletes.⁶ A study by Edwards and colleagues⁶ examined 39 patients with all types of SLAP tears. Although, in their study, nonoperative management failed in 20 patients and they required surgery, 10 of the 15 overhead athletes in whom nonoperative treatment did not fail initially returned to sport at a level equal to or better than their pre-injury level, indicating that nonoperative treatment may play a role in some patients’ recovery.⁶

Surgical outcomes of SLAP IIb repairs have traditionally been less predictable than those of other shoulder injuries. Some believe that traditional knotted anchors may be partially to blame by abrading the rotator cuff, possibly leading to rotator cuff tears and pain. Further, knotted anchors are typically bulkier and require more experience with tying and tensioning and, therefore, may lead to less consistent results.⁷ The purpose of this study was to investigate if knotless anchors result in more favorable outcomes in repair of type IIb SLAP lesions when compared with traditional knotted anchors. It was hypothesized that knotless fixation will provide superior clinical outcomes, improved return to play (RTP), and lower revision rates as compared with traditional knotted fixation in the repair of SLAP IIb tears.

METHODS

PATIENT SELECTION

The authors retrospectively reviewed SLAP tears repaired by the senior author from June 2000 to September 2015. The inclusion criteria consisted of all athletes at any level who were diagnosed intraoperatively with a type IIb SLAP tear as defined by Morgan and colleagues⁵ with a minimum 2-year follow-up. The exclusion criteria were any patients with a previous shoulder surgery and the presence of any labral pathology aside from a SLAP IIb tear. Patients with rotator cuff or biceps pathologies were included. In all included patients, an initial course of preoperative physical therapy, including strengthening and stabilization of the scapulothoracic joint, had failed. Patient-directed surveys evaluated RTP, as well as the Kerlan-Jobe Orthopaedic Clinic (KJOC) score, American Shoulder and Elbow Surgeons (ASES) score, stability, range of motion (ROM), strength, and pain scores, as previously described.^8-10 Institutional Review Board and informed consent approval were acquired prior to initiation of the study.

PATIENT EVALUATION

An appropriate preoperative history was taken, and physical examinations were performed, including evaluation of the scapulothoracic joint, as well as tests to evaluate the presence of a SLAP tear, anterior instability, posterior instability, multi-directional instability, and rotator cuff tears, as previously described.¹¹ Patients with a history and physical examination concerning SLAP pathology underwent an magnetic resonance imaging (MRI) arthrogram, which was used in conjunction with intraoperative findings to diagnose type IIb SLAP tears.

Continue to: SURGICAL TECHNIQUE

All surgeries were performed arthroscopically with the patient in the lateral decubitus position. The SLAP lesions were subsequently repaired using a technique similar to that described by Burkhart and colleagues.¹² The traditional knotted fixation incorporated the use of 3.0 Bio-FASTak (Arthrex) with #2 FiberWire (Arthrex). Knotless anchor fixation was performed using 2.9 mm × 12.5 mm or 2.4 mm × 11.3 mm BioComposite PushLock (Arthrex) suture anchors, based on the size of the glenoid, with LabralTape or SutureTape (Arthrex). Patients who had surgery before January 1, 2013 underwent fixation with traditional knotted fixation; after that date, patients underwent fixation with knotless anchors.

POSTOPERATIVE REHABILITATION

Patients underwent a strict postoperative protocol in which they were kept in a sling with an abduction pillow for the first 6 weeks and performed pendulum exercises and passive motion only. A formal physical therapy regimen started at 4 weeks with passive ROM, passive posterior capsular and internal rotation stretching, scapulothoracic mobility, and biceps, rotator cuff, and capsular stabilizer strengthening. At 10 weeks, patients began biceps, rotator cuff, and scapular stabilizer resistance exercises, and at 16 weeks, throwing athletes began an interval throwing program. Patients were first eligible to return to sport without limitation at 9 months.

STATISTICAL ANALYSIS

Return to play, KJOC, ASES, stability, ROM, strength, and pain scores were analyzed and compared using Fisher exact test, the Kruskal-Wallis test, and the Wilcoxon rank sum test, where appropriate. The level of statistical significance was α = 0.05.

RESULTS

Of the 74 athletes who met inclusion criteria, 28 were female (37.8%) and 46 (62.2%) were male. The average follow-up was 6.5 years with a minimum of 2 years and a maximum of 12 years. Forty-two (56.8%) patients underwent traditional knotted suture anchor fixation and 32 (43.2%) underwent knotless anchor fixation. The average age was 30.1 +/– 13.6 years, with a range of 14 to 64 years. The majority of athletes were right hand dominant (79.9%). Fifty-three (72%) were overhead athletes and 29 (39%) were throwing athletes (Table 1). The average age in the knotted group was 33.3 years: 29 of 42 (69%) were overhead athletes and 20 (47.6%) were throwing athletes. In the knotless group, the average age was 25.8 years: 24 of 32 (75.0%) were overhead athletes and 9 (28.1%) were throwing athletes. Primary sports at the time of injury are listed in Table 2. The average number of anchors used was 3.1, with 17 patients (23.0%) requiring ≤2 anchors, 39 (52.7%) requiring 3 anchors, and 18 (24.3%) requiring ≥4 anchors for repair. The number of anchors used was determined intraoperatively by the surgeon on the basis of the size and extent of the tear. Of the entire group of 74 patients, 91.9% returned to sport, 56.8% returned to the same level, 35.1% returned at a lower capacity, and 8.1% were unable to return to sport. Knotless anchors had a slightly higher overall RTP compared with traditional anchors (93.5% vs 90.2%, P = .94), as well as a higher RTP at the same level (58.1% vs 53.7%, P = .81). These differences were, however, not statistically significant (Table 3).

Abbreviation: SLAP, superior labrum anterior to posterior.

Knotless anchors were less likely to require revision surgery than traditional anchors (9% vs 17%, P = .50), but this difference was not statistically significant (Table 3). In the knotted group, 5 patients had revision surgery for rotator cuff tears, and 2 patients had recurrent SLAP tears. In the knotless group, 2 patients had revision surgeries for a torn rotator cuff, and 1 patient had a snapping scapula. A power analysis found that it would take over 300 athletes in each group to detect a significant difference in the revision rate between knotless and traditional anchors.

Continue to: Although KJOC...

Although KJOC (66.1 vs 65.6 P = .61) and ASES (86.3 vs 85.3 P = .79) scores were also superior with knotless anchors, these differences in scores were not statistically significant (Table 3). Pain was the only variable that was linked to decreased RTP, as patients who rated higher on a pain scale of 0 to 10 were less likely to return to their sport (P < .0001). There was no correlation in outcome measures or RTP with gender, age, number of anchors, or sport type (P > .05). There was no statistically significant difference in RTP, KJOC, or ASES scores between non-overhead and overhead athletes (Table 4). Overall return to sport in throwers was 85.7% (24/28), while 39.3% (11/28) returned at the same level, 46.4% (13/28) at a lower level, and 14.3% (4/28) did not return to sport.

DISCUSSION

There was no significant difference between knotted and knotless fixation in clinical outcomes or return to sport in the repair of SLAP IIb tears; however, there was a trend toward knotless anchors requiring less revision surgery and having higher RTP, ASES, and KJOC scores than knotted fixation. Despite the inclusion of 74 patients, this study was significantly underpowered, as a power analysis calculated that over 300 athletes would be required in each group to detect a difference in the revision rate.

SLAP tears, traditionally treated with knotted suture anchors, have yielded varying results in the literature, with good to excellent results being reported in 65% to 94% of patients.^13-17 The success of SLAP repairs in athletes, especially overhead athletes, remains a difficult problem, as they are common injuries, and RTP is less predictable. Studies differ with regard to the percentage of overhead athletes who are able to return to their previous level of sport, with ranges being reported from 22% to 92%.^16,18,19 In a systematic review of 198 patients, Sayde and colleagues¹⁶ found that 63% of overhead athletes treated with anchor fixation, tacks, or staples were able to return to their previous level of play. Morgan and colleagues⁵ found a higher return to sport when compared with other studies, reporting that 83% of patients undergoing SLAP repairs using traditional suture anchors had excellent results, and 87% of the 53 overhead athletes had excellent results based on UCLA shoulder scores. Further, 37 of the 44 pitchers examined (84%) were able to return to their pre-injury levels.⁵ This is in contrast to Friel and colleagues²⁰ who found that in 48 patients with type II SLAP tears treated with traditional anchors, 23% reported excellent and 56% reported good results in regards to UCLA shoulder scores. Friel and colleagues also found that 62% of all athletes and 59% of overhead athletes were able to return to their previous levels of sport, which is similar to the current study.²⁰ The large discrepancy in RTP at the pre-injury level between this study and that of Morgan and colleagues⁵ may be due to the shorter minimum follow-up of 1 year as well as the inclusion of all subtypes of SLAP II tears in the latter. The current study had a minimum 2-year follow-up period, with an average of 6.5 years, and was limited to SLAP IIb tears. With a longer follow-up period, patient outcomes and RTP, particularly in overhead sports, may deteriorate; therefore, the current study likely shows a more complete and accurate result.

Knotless anchors were originally introduced as a less time consuming, lower profile, and simpler device to learn and use for arthroscopic procedures.²¹ Kocaoglu and colleagues²² found that in Bankart repairs, the mean time per anchor placement for knotted anchors was 380 seconds, whereas placement of knotless anchors took on average 225 seconds. A learning curve also exists for proper and efficient knot tying.⁷ There is also variation in knot tying between surgeons, as evidenced by a wide range in both load to failure and knot height.⁷ A study performed by Hanypsiak and colleagues⁷ found that the surgical knot was the weakest portion of the suture-anchor construct, as the knot’s load to failure was less than the pullout strength of the anchor.

There is also concern for the added height associated with traditional knotted fixation, which has been supported by case reports of knot-induced glenoid erosion after arthroscopic fixation of a SLAP tear.²³ Hanypsiak and colleagues⁷ also found that the average knot height occupied 50% to 95% of the space between the humeral head and the acromion when the shoulder is in a neutral position, indicating that the higher profile knotted anchors may contact the undersurface of the acromion, which could affect the labral repair as well as cause rotator cuff injury. Abrasion of the rotator cuff by a prominent knot may cause pain, tearing, and disability. A recent study by Park and colleagues²⁴ reported on 11 patients with knot-induced pain after type II SLAP repair. All complained of sharp pain, with 64% also complaining of clicking. Knot location did not seem to matter, as there was no difference in preoperative symptoms, with 5 of the 11 patients having knots on the glenoid side of the repair on repeat arthroscopy. Patients with knots on the labral side did, however, have humeral head cartilage damage. The knots appeared to be the cause of pain and clicking, as after arthroscopic knot removal, dramatic pain relief was seen, with Constant and UCLA scores significantly improving in all 11 patients. All patients also had positive preoperative compression-rotation testing, and at 6 weeks after surgical knot removal, all were negative.²⁴

Continue to: Further, as shown by Dines and colleagues...

Further, as shown by Dines and colleagues²⁵, knotless anchors may help to better restore the meniscoid anatomy of the superior labrum better than knotted suture anchors. With regards to fixation strength, Uggen and colleagues²⁶, using a cadaveric model, found no difference in initial fixation strength of knotless and traditional suture anchor repair of SLAP II tears, and both restored glenohumeral rotation without over-constraining the shoulder.

Despite the shorter operative time, lower profile, and more consistent tensioning with knotless anchors, the literature is limited with regard to evaluating patient outcomes. In a study by Yung and colleagues¹³ 14 of the 16 patients with type II SLAP tears were treated with knotless anchors, and the authors found that 31.3% of patients had an excellent UCLA score while 43.8% had a good score. This is similar to the outcomes illustrated in studies by both Friel and colleagues²⁰ and Sayde and colleagues.¹⁶ In a more recent study, Yang and colleagues²⁷ did find some benefit in regard to ROM with knotless fixation. Their study consisted of 21 patients who underwent surgery with traditional knotted anchor fixation and 20 who underwent knotless horizontal mattress fixation. They found an average UCLA score of 37.6 and ASES score of 91.5 in patients undergoing knotless fixation, and the knotless fixation group had 5% greater total ROM, 15.6% more internal rotation at abduction, and 11.4% more external rotation at the side as compared with patients undergoing the traditional knotted technique. When compared with the current study, this study also had a significantly shorter follow-up period of 3 years.²⁷ In a 2017 study, Bents and colleagues²⁸ compared 44 patients who underwent knotless and 119 who underwent knotted fixation of SLAP tears. They found no statistically significant difference between knotless and knotted fixation in the ASES score, Visual Analog Scale (VAS), ASES, or Veterans RAND 12-Item Health Survey (VR-12) at 1 year postoperatively. Their outcomes were similar to those of the current study, but as in other mentioned literature, the study by Bents and colleagues²⁸ included multiple surgeons with different postoperative protocols, was not limited to SLAP IIb tears, and also had a shorter follow-up of 1 year. Like Kocaoglu and colleagues²², Bents and colleagues did find knotless anchors to be more efficient, as operative time was reduced by 5.3 minutes per anchor. This likely would have a significant impact on surgical cost and surgeon productivity.²⁸

One limitation of the current study was that despite the inclusion of >70 patients, the study was still significantly underpowered. It was determined that >300 patients in each group would be required to detect a significant difference in the revision rate between the 2 anchor types. Also, due to the retrospective nature of this study, no preoperative scores were collected. The inclusion of objective clinical measurements and follow-up imaging evaluating the rotator cuff and other anatomy would also be of interest.

Although statistical significance was not achieved, there was a trend toward knotless fixation requiring less revision surgery and having higher RTP, ASES, and KJOC scores when compared with traditional knotted fixation at 6.5-year follow-up. Larger studies with longer follow-up periods are necessary to determine the effects of knotted and knotless anchors on rotator cuff tears, patient reported outcomes, and RTP. These complications have been shown in the literature, mostly in case reports, and typically develop over a longer period.²³ Despite this, other advantages of knotless fixation, such as its lower profile, the ability to better provide consistent tensioning, and decreased surgical time are important to consider.

ABSTRACT

The use of knotless suture anchors has increased in popularity; however, there is a paucity of literature examining the difference in clinical outcomes with traditional knotted fixation. It was hypothesized that knotless fixation would provide superior clinical outcomes, improved return to play (RTP), and lower revision rates as compared with traditional knotted fixation in the repair of SLAP IIb tears. Seventy-four athletes who underwent arthroscopic SLAP IIb repair with traditional (n = 42) and knotless anchors (n = 32) by a single surgeon were evaluated after a minimum 2-year follow. Demographic and surgical data, RTP, Kerlan-Jobe Orthopaedic Clinic (KJOC) score, American Shoulder and Elbow Surgeons (ASES) score, stability, strength, and pain scores were compared. Knotless anchors had slightly higher RTP (93.5% vs 90.2%, P = .94) and RTP at the same level (58.1% vs 53.7% P = .81) compared with knotted fixation, but the difference did not reach statistical significance. Knotless anchors were less likely to require revision surgery than traditional anchors (9% vs 17%, P = .50), but the difference was not statistically significant. When comparing knotless and traditional knotted suture anchor repair of type llb SLAP tears, knotless fixation required less revision surgery and had higher RTP, ASES, and KJOC scores; however, statistical significance was not achieved in this relatively small cohort.

Continue to: Injury of the anterosuperior...

Injury of the anterosuperior labrum near the biceps origin was first described by Andrews and colleagues in 1985 in overhead athletes.¹ The term SLAP, or a tear in the superior labrum anterior to posterior, was coined a few years later by Snyder and colleagues.² They described an injury to the superior labrum beginning posteriorly and extending anteriorly, including the “anchor” of the biceps tendon to the labrum. Snyder further delineated SLAP lesions into 4 subtypes, the most common being type II, which he described as “degenerative fraying of the labrum with additional detachment of the superior labrum and biceps from the glenoid resulting in an unstable labral anchor.”^2,3 Type II tears are of particular importance as they are the most common SLAP lesions, with an incidence of 55%, and comprise nearly 75% of SLAP repairs performed.^2,4

Morgan and colleagues further delineated type II SLAP tears into IIa (anterior), IIb (posterior), and IIc (combined). Their group found that SLAP IIb tears were the most common type in overhead throwers, accounting for 47% of overhead athletes with type II tears.⁵ Further, type IIb tears can have a significant impact in throwers, in part due to greater shoulder instability as well as anterior pseudolaxity.⁵ SLAP injuries typically have been difficult to successfully treat nonoperatively in overhead athletes.⁶ A study by Edwards and colleagues⁶ examined 39 patients with all types of SLAP tears. Although, in their study, nonoperative management failed in 20 patients and they required surgery, 10 of the 15 overhead athletes in whom nonoperative treatment did not fail initially returned to sport at a level equal to or better than their pre-injury level, indicating that nonoperative treatment may play a role in some patients’ recovery.⁶

Surgical outcomes of SLAP IIb repairs have traditionally been less predictable than those of other shoulder injuries. Some believe that traditional knotted anchors may be partially to blame by abrading the rotator cuff, possibly leading to rotator cuff tears and pain. Further, knotted anchors are typically bulkier and require more experience with tying and tensioning and, therefore, may lead to less consistent results.⁷ The purpose of this study was to investigate if knotless anchors result in more favorable outcomes in repair of type IIb SLAP lesions when compared with traditional knotted anchors. It was hypothesized that knotless fixation will provide superior clinical outcomes, improved return to play (RTP), and lower revision rates as compared with traditional knotted fixation in the repair of SLAP IIb tears.

METHODS

PATIENT SELECTION

The authors retrospectively reviewed SLAP tears repaired by the senior author from June 2000 to September 2015. The inclusion criteria consisted of all athletes at any level who were diagnosed intraoperatively with a type IIb SLAP tear as defined by Morgan and colleagues⁵ with a minimum 2-year follow-up. The exclusion criteria were any patients with a previous shoulder surgery and the presence of any labral pathology aside from a SLAP IIb tear. Patients with rotator cuff or biceps pathologies were included. In all included patients, an initial course of preoperative physical therapy, including strengthening and stabilization of the scapulothoracic joint, had failed. Patient-directed surveys evaluated RTP, as well as the Kerlan-Jobe Orthopaedic Clinic (KJOC) score, American Shoulder and Elbow Surgeons (ASES) score, stability, range of motion (ROM), strength, and pain scores, as previously described.^8-10 Institutional Review Board and informed consent approval were acquired prior to initiation of the study.

PATIENT EVALUATION

An appropriate preoperative history was taken, and physical examinations were performed, including evaluation of the scapulothoracic joint, as well as tests to evaluate the presence of a SLAP tear, anterior instability, posterior instability, multi-directional instability, and rotator cuff tears, as previously described.¹¹ Patients with a history and physical examination concerning SLAP pathology underwent an magnetic resonance imaging (MRI) arthrogram, which was used in conjunction with intraoperative findings to diagnose type IIb SLAP tears.

Continue to: SURGICAL TECHNIQUE

All surgeries were performed arthroscopically with the patient in the lateral decubitus position. The SLAP lesions were subsequently repaired using a technique similar to that described by Burkhart and colleagues.¹² The traditional knotted fixation incorporated the use of 3.0 Bio-FASTak (Arthrex) with #2 FiberWire (Arthrex). Knotless anchor fixation was performed using 2.9 mm × 12.5 mm or 2.4 mm × 11.3 mm BioComposite PushLock (Arthrex) suture anchors, based on the size of the glenoid, with LabralTape or SutureTape (Arthrex). Patients who had surgery before January 1, 2013 underwent fixation with traditional knotted fixation; after that date, patients underwent fixation with knotless anchors.

POSTOPERATIVE REHABILITATION

Patients underwent a strict postoperative protocol in which they were kept in a sling with an abduction pillow for the first 6 weeks and performed pendulum exercises and passive motion only. A formal physical therapy regimen started at 4 weeks with passive ROM, passive posterior capsular and internal rotation stretching, scapulothoracic mobility, and biceps, rotator cuff, and capsular stabilizer strengthening. At 10 weeks, patients began biceps, rotator cuff, and scapular stabilizer resistance exercises, and at 16 weeks, throwing athletes began an interval throwing program. Patients were first eligible to return to sport without limitation at 9 months.

STATISTICAL ANALYSIS

Return to play, KJOC, ASES, stability, ROM, strength, and pain scores were analyzed and compared using Fisher exact test, the Kruskal-Wallis test, and the Wilcoxon rank sum test, where appropriate. The level of statistical significance was α = 0.05.

RESULTS

Of the 74 athletes who met inclusion criteria, 28 were female (37.8%) and 46 (62.2%) were male. The average follow-up was 6.5 years with a minimum of 2 years and a maximum of 12 years. Forty-two (56.8%) patients underwent traditional knotted suture anchor fixation and 32 (43.2%) underwent knotless anchor fixation. The average age was 30.1 +/– 13.6 years, with a range of 14 to 64 years. The majority of athletes were right hand dominant (79.9%). Fifty-three (72%) were overhead athletes and 29 (39%) were throwing athletes (Table 1). The average age in the knotted group was 33.3 years: 29 of 42 (69%) were overhead athletes and 20 (47.6%) were throwing athletes. In the knotless group, the average age was 25.8 years: 24 of 32 (75.0%) were overhead athletes and 9 (28.1%) were throwing athletes. Primary sports at the time of injury are listed in Table 2. The average number of anchors used was 3.1, with 17 patients (23.0%) requiring ≤2 anchors, 39 (52.7%) requiring 3 anchors, and 18 (24.3%) requiring ≥4 anchors for repair. The number of anchors used was determined intraoperatively by the surgeon on the basis of the size and extent of the tear. Of the entire group of 74 patients, 91.9% returned to sport, 56.8% returned to the same level, 35.1% returned at a lower capacity, and 8.1% were unable to return to sport. Knotless anchors had a slightly higher overall RTP compared with traditional anchors (93.5% vs 90.2%, P = .94), as well as a higher RTP at the same level (58.1% vs 53.7%, P = .81). These differences were, however, not statistically significant (Table 3).

Abbreviation: SLAP, superior labrum anterior to posterior.

Knotless anchors were less likely to require revision surgery than traditional anchors (9% vs 17%, P = .50), but this difference was not statistically significant (Table 3). In the knotted group, 5 patients had revision surgery for rotator cuff tears, and 2 patients had recurrent SLAP tears. In the knotless group, 2 patients had revision surgeries for a torn rotator cuff, and 1 patient had a snapping scapula. A power analysis found that it would take over 300 athletes in each group to detect a significant difference in the revision rate between knotless and traditional anchors.

Continue to: Although KJOC...

Although KJOC (66.1 vs 65.6 P = .61) and ASES (86.3 vs 85.3 P = .79) scores were also superior with knotless anchors, these differences in scores were not statistically significant (Table 3). Pain was the only variable that was linked to decreased RTP, as patients who rated higher on a pain scale of 0 to 10 were less likely to return to their sport (P < .0001). There was no correlation in outcome measures or RTP with gender, age, number of anchors, or sport type (P > .05). There was no statistically significant difference in RTP, KJOC, or ASES scores between non-overhead and overhead athletes (Table 4). Overall return to sport in throwers was 85.7% (24/28), while 39.3% (11/28) returned at the same level, 46.4% (13/28) at a lower level, and 14.3% (4/28) did not return to sport.

DISCUSSION

There was no significant difference between knotted and knotless fixation in clinical outcomes or return to sport in the repair of SLAP IIb tears; however, there was a trend toward knotless anchors requiring less revision surgery and having higher RTP, ASES, and KJOC scores than knotted fixation. Despite the inclusion of 74 patients, this study was significantly underpowered, as a power analysis calculated that over 300 athletes would be required in each group to detect a difference in the revision rate.

SLAP tears, traditionally treated with knotted suture anchors, have yielded varying results in the literature, with good to excellent results being reported in 65% to 94% of patients.^13-17 The success of SLAP repairs in athletes, especially overhead athletes, remains a difficult problem, as they are common injuries, and RTP is less predictable. Studies differ with regard to the percentage of overhead athletes who are able to return to their previous level of sport, with ranges being reported from 22% to 92%.^16,18,19 In a systematic review of 198 patients, Sayde and colleagues¹⁶ found that 63% of overhead athletes treated with anchor fixation, tacks, or staples were able to return to their previous level of play. Morgan and colleagues⁵ found a higher return to sport when compared with other studies, reporting that 83% of patients undergoing SLAP repairs using traditional suture anchors had excellent results, and 87% of the 53 overhead athletes had excellent results based on UCLA shoulder scores. Further, 37 of the 44 pitchers examined (84%) were able to return to their pre-injury levels.⁵ This is in contrast to Friel and colleagues²⁰ who found that in 48 patients with type II SLAP tears treated with traditional anchors, 23% reported excellent and 56% reported good results in regards to UCLA shoulder scores. Friel and colleagues also found that 62% of all athletes and 59% of overhead athletes were able to return to their previous levels of sport, which is similar to the current study.²⁰ The large discrepancy in RTP at the pre-injury level between this study and that of Morgan and colleagues⁵ may be due to the shorter minimum follow-up of 1 year as well as the inclusion of all subtypes of SLAP II tears in the latter. The current study had a minimum 2-year follow-up period, with an average of 6.5 years, and was limited to SLAP IIb tears. With a longer follow-up period, patient outcomes and RTP, particularly in overhead sports, may deteriorate; therefore, the current study likely shows a more complete and accurate result.

Knotless anchors were originally introduced as a less time consuming, lower profile, and simpler device to learn and use for arthroscopic procedures.²¹ Kocaoglu and colleagues²² found that in Bankart repairs, the mean time per anchor placement for knotted anchors was 380 seconds, whereas placement of knotless anchors took on average 225 seconds. A learning curve also exists for proper and efficient knot tying.⁷ There is also variation in knot tying between surgeons, as evidenced by a wide range in both load to failure and knot height.⁷ A study performed by Hanypsiak and colleagues⁷ found that the surgical knot was the weakest portion of the suture-anchor construct, as the knot’s load to failure was less than the pullout strength of the anchor.

There is also concern for the added height associated with traditional knotted fixation, which has been supported by case reports of knot-induced glenoid erosion after arthroscopic fixation of a SLAP tear.²³ Hanypsiak and colleagues⁷ also found that the average knot height occupied 50% to 95% of the space between the humeral head and the acromion when the shoulder is in a neutral position, indicating that the higher profile knotted anchors may contact the undersurface of the acromion, which could affect the labral repair as well as cause rotator cuff injury. Abrasion of the rotator cuff by a prominent knot may cause pain, tearing, and disability. A recent study by Park and colleagues²⁴ reported on 11 patients with knot-induced pain after type II SLAP repair. All complained of sharp pain, with 64% also complaining of clicking. Knot location did not seem to matter, as there was no difference in preoperative symptoms, with 5 of the 11 patients having knots on the glenoid side of the repair on repeat arthroscopy. Patients with knots on the labral side did, however, have humeral head cartilage damage. The knots appeared to be the cause of pain and clicking, as after arthroscopic knot removal, dramatic pain relief was seen, with Constant and UCLA scores significantly improving in all 11 patients. All patients also had positive preoperative compression-rotation testing, and at 6 weeks after surgical knot removal, all were negative.²⁴

Continue to: Further, as shown by Dines and colleagues...

Further, as shown by Dines and colleagues²⁵, knotless anchors may help to better restore the meniscoid anatomy of the superior labrum better than knotted suture anchors. With regards to fixation strength, Uggen and colleagues²⁶, using a cadaveric model, found no difference in initial fixation strength of knotless and traditional suture anchor repair of SLAP II tears, and both restored glenohumeral rotation without over-constraining the shoulder.

Despite the shorter operative time, lower profile, and more consistent tensioning with knotless anchors, the literature is limited with regard to evaluating patient outcomes. In a study by Yung and colleagues¹³ 14 of the 16 patients with type II SLAP tears were treated with knotless anchors, and the authors found that 31.3% of patients had an excellent UCLA score while 43.8% had a good score. This is similar to the outcomes illustrated in studies by both Friel and colleagues²⁰ and Sayde and colleagues.¹⁶ In a more recent study, Yang and colleagues²⁷ did find some benefit in regard to ROM with knotless fixation. Their study consisted of 21 patients who underwent surgery with traditional knotted anchor fixation and 20 who underwent knotless horizontal mattress fixation. They found an average UCLA score of 37.6 and ASES score of 91.5 in patients undergoing knotless fixation, and the knotless fixation group had 5% greater total ROM, 15.6% more internal rotation at abduction, and 11.4% more external rotation at the side as compared with patients undergoing the traditional knotted technique. When compared with the current study, this study also had a significantly shorter follow-up period of 3 years.²⁷ In a 2017 study, Bents and colleagues²⁸ compared 44 patients who underwent knotless and 119 who underwent knotted fixation of SLAP tears. They found no statistically significant difference between knotless and knotted fixation in the ASES score, Visual Analog Scale (VAS), ASES, or Veterans RAND 12-Item Health Survey (VR-12) at 1 year postoperatively. Their outcomes were similar to those of the current study, but as in other mentioned literature, the study by Bents and colleagues²⁸ included multiple surgeons with different postoperative protocols, was not limited to SLAP IIb tears, and also had a shorter follow-up of 1 year. Like Kocaoglu and colleagues²², Bents and colleagues did find knotless anchors to be more efficient, as operative time was reduced by 5.3 minutes per anchor. This likely would have a significant impact on surgical cost and surgeon productivity.²⁸

One limitation of the current study was that despite the inclusion of >70 patients, the study was still significantly underpowered. It was determined that >300 patients in each group would be required to detect a significant difference in the revision rate between the 2 anchor types. Also, due to the retrospective nature of this study, no preoperative scores were collected. The inclusion of objective clinical measurements and follow-up imaging evaluating the rotator cuff and other anatomy would also be of interest.

Although statistical significance was not achieved, there was a trend toward knotless fixation requiring less revision surgery and having higher RTP, ASES, and KJOC scores when compared with traditional knotted fixation at 6.5-year follow-up. Larger studies with longer follow-up periods are necessary to determine the effects of knotted and knotless anchors on rotator cuff tears, patient reported outcomes, and RTP. These complications have been shown in the literature, mostly in case reports, and typically develop over a longer period.²³ Despite this, other advantages of knotless fixation, such as its lower profile, the ability to better provide consistent tensioning, and decreased surgical time are important to consider.