Photo by Jen Smith

SAN DIEGO—The KIT D816V inhibitor avapritinib can improve symptoms of systemic mastocytosis (SM), according to researchers.

Patients treated with avapritinib in a phase 1 trial had an overall response rate (ORR) of 83%, a 41% mean reduction in mastocytosis symptoms from baseline, and a 58% mean reduction in the most bothersome symptom domain.

Most adverse events (AEs) in this trial were grade 1 or 2. However, 66% of patients did have grade 3 or higher treatment-related AEs that necessitated dose reductions.

Jason R. Gotlib, MD, of Stanford University School of Medicine in California, presented these results, from the EXPLORER trial (NCT02561988), at the 2018 ASH Annual Meeting (abstract 351).

Patients and treatment

The trial enrolled 67 patients—90% with advanced SM and 10% with indolent or smoldering SM. The patients’ median age was 62 (range, 34 to 83), and 49% were female.

Patients had received a median of 3 (range, 0 to 3) prior therapies. Sixty percent of patients had received any prior therapy, and 23% had received midostaurin. Thirty-three percent were on steroid therapy at baseline.

Eighty-four percent of patients had the KIT D816V mutation, and 1% had the KIT D816Y mutation. Forty-five percent of patients had mutations in SRSF2, ASXL1, and RUNX1.

In the dose-escalation portion of the trial, patients received avapritinib at 30 mg to 400 mg once daily in continuous 28-day cycles. In the expansion portion of the trial, patients received avapritinib at 200 mg or 300 mg once daily.

Response

There were 29 patients evaluable for response. The ORR was 83% (n=24). The rate of complete response (CR) was 10% (n=3), the rate of CR with partial hematologic recovery (CRh) was 14% (n=4), and the partial response rate was 48% (n=14).

Ten percent (n=3) of patients had clinical improvement, 17% (n=5) had stable disease, and none of the patients progressed.

Among the 10 patients treated at a dose of 200 mg or lower, the ORR was 90% (n=9). The CR rate was 30% (n=3), the rate of CRh was 20% (n=2), and the partial response rate was 30% (n=3). Ten percent (n=1) of patients each had clinical improvement or stable disease.

Dr. Gotlib noted that responses have been durable and deepened over time.

At a median follow-up of 14 months, the median duration of response had not been reached. The 12-month response rate is 76%.

The median time to initial response is 2 months, and the median time to CR/CRh is 9 months.

Safety

Seventy-eight percent of patients (52/67) were still on treatment at last follow-up. Four percent (4/67) discontinued treatment due to related AEs, and 66% (44/67) had grade 3 or higher AEs that prompted dose reductions.

AEs prompting discontinuation included refractory ascites, encephalopathy, and intracranial bleeding. AEs necessitating dose reductions were largely hematologic events.

The most common AEs were periorbital edema (67%), anemia (52%), fatigue (37%), nausea (36%), diarrhea (34%), peripheral edema (34%), thrombocytopenia (31%) vomiting (28%), cognitive effects (28%), and hair color changes (25%).

The most common grade 3/4 AEs were anemia (26%), thrombocytopenia (17%), and neutropenia (10%). There were no treatment-related deaths.

Symptoms

For symptom assessment, patients completed the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF), a patient-reported outcomes (PRO) tool that included eight symptoms:

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Spots
• Itching
• Flushing
• Fatigue.

Symptoms were scored on a scale of 1 to 10. Results were analyzed as a total symptom score (TSS) combining all eight items, as a gastrointestinal domain (combining nausea, vomiting, diarrhea, and abdominal pain), and as a skin domain (combining itching, flushing, and spots). Analyses were based on 7-day average scores.

Among the 32 evaluable patients, there was a 41% reduction in TSS from baseline (P=0.043). Among the 16 most symptomatic patients, there was a 46% reduction in TSS from baseline (P=0.038).

In all 32 evaluable patients, there was a 58% reduction from baseline in the score for most bothersome symptom domain (gastrointestinal or skin; P=0.0034). In the 16 most symptomatic patients, there was 63% reduction from baseline (P=0.0038).

“This is the first advanced SM-specific PRO to demonstrate significant improvements in total symptom score,” Dr. Gotlib said. “The clinical activity and initial PRO data do support further evaluation of avapritinib in both advanced and indolent disease.”

Dr. Gotlib noted that the PATHFINDER trial (NCT03580655), a study of avapritinib in advanced SM, is now enrolling. And the PIONEER trial (NCT03731260), a study of avapritinib in patients with indolent or smoldering SM, is scheduled to begin at the end of the year.

The EXPLORER trial was sponsored by Blueprint Medicines Corporation. Dr. Gotlib reported relationships with Blueprint Medicines, Celgene, Incyte, Novartis, Deciphera, Gilead, Promedior, and Kartos.

Photo by Jen Smith

SAN DIEGO—The KIT D816V inhibitor avapritinib can improve symptoms of systemic mastocytosis (SM), according to researchers.

Patients treated with avapritinib in a phase 1 trial had an overall response rate (ORR) of 83%, a 41% mean reduction in mastocytosis symptoms from baseline, and a 58% mean reduction in the most bothersome symptom domain.

Most adverse events (AEs) in this trial were grade 1 or 2. However, 66% of patients did have grade 3 or higher treatment-related AEs that necessitated dose reductions.

Jason R. Gotlib, MD, of Stanford University School of Medicine in California, presented these results, from the EXPLORER trial (NCT02561988), at the 2018 ASH Annual Meeting (abstract 351).

Patients and treatment

The trial enrolled 67 patients—90% with advanced SM and 10% with indolent or smoldering SM. The patients’ median age was 62 (range, 34 to 83), and 49% were female.

Patients had received a median of 3 (range, 0 to 3) prior therapies. Sixty percent of patients had received any prior therapy, and 23% had received midostaurin. Thirty-three percent were on steroid therapy at baseline.

Eighty-four percent of patients had the KIT D816V mutation, and 1% had the KIT D816Y mutation. Forty-five percent of patients had mutations in SRSF2, ASXL1, and RUNX1.

In the dose-escalation portion of the trial, patients received avapritinib at 30 mg to 400 mg once daily in continuous 28-day cycles. In the expansion portion of the trial, patients received avapritinib at 200 mg or 300 mg once daily.

Response

There were 29 patients evaluable for response. The ORR was 83% (n=24). The rate of complete response (CR) was 10% (n=3), the rate of CR with partial hematologic recovery (CRh) was 14% (n=4), and the partial response rate was 48% (n=14).

Ten percent (n=3) of patients had clinical improvement, 17% (n=5) had stable disease, and none of the patients progressed.

Among the 10 patients treated at a dose of 200 mg or lower, the ORR was 90% (n=9). The CR rate was 30% (n=3), the rate of CRh was 20% (n=2), and the partial response rate was 30% (n=3). Ten percent (n=1) of patients each had clinical improvement or stable disease.

Dr. Gotlib noted that responses have been durable and deepened over time.

At a median follow-up of 14 months, the median duration of response had not been reached. The 12-month response rate is 76%.

The median time to initial response is 2 months, and the median time to CR/CRh is 9 months.

Safety

Seventy-eight percent of patients (52/67) were still on treatment at last follow-up. Four percent (4/67) discontinued treatment due to related AEs, and 66% (44/67) had grade 3 or higher AEs that prompted dose reductions.

AEs prompting discontinuation included refractory ascites, encephalopathy, and intracranial bleeding. AEs necessitating dose reductions were largely hematologic events.

The most common AEs were periorbital edema (67%), anemia (52%), fatigue (37%), nausea (36%), diarrhea (34%), peripheral edema (34%), thrombocytopenia (31%) vomiting (28%), cognitive effects (28%), and hair color changes (25%).

The most common grade 3/4 AEs were anemia (26%), thrombocytopenia (17%), and neutropenia (10%). There were no treatment-related deaths.

Symptoms

For symptom assessment, patients completed the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF), a patient-reported outcomes (PRO) tool that included eight symptoms:

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Spots
• Itching
• Flushing
• Fatigue.

Symptoms were scored on a scale of 1 to 10. Results were analyzed as a total symptom score (TSS) combining all eight items, as a gastrointestinal domain (combining nausea, vomiting, diarrhea, and abdominal pain), and as a skin domain (combining itching, flushing, and spots). Analyses were based on 7-day average scores.

Among the 32 evaluable patients, there was a 41% reduction in TSS from baseline (P=0.043). Among the 16 most symptomatic patients, there was a 46% reduction in TSS from baseline (P=0.038).

In all 32 evaluable patients, there was a 58% reduction from baseline in the score for most bothersome symptom domain (gastrointestinal or skin; P=0.0034). In the 16 most symptomatic patients, there was 63% reduction from baseline (P=0.0038).

“This is the first advanced SM-specific PRO to demonstrate significant improvements in total symptom score,” Dr. Gotlib said. “The clinical activity and initial PRO data do support further evaluation of avapritinib in both advanced and indolent disease.”

Dr. Gotlib noted that the PATHFINDER trial (NCT03580655), a study of avapritinib in advanced SM, is now enrolling. And the PIONEER trial (NCT03731260), a study of avapritinib in patients with indolent or smoldering SM, is scheduled to begin at the end of the year.

The EXPLORER trial was sponsored by Blueprint Medicines Corporation. Dr. Gotlib reported relationships with Blueprint Medicines, Celgene, Incyte, Novartis, Deciphera, Gilead, Promedior, and Kartos.

Photo by Jen Smith

SAN DIEGO—The KIT D816V inhibitor avapritinib can improve symptoms of systemic mastocytosis (SM), according to researchers.

Patients treated with avapritinib in a phase 1 trial had an overall response rate (ORR) of 83%, a 41% mean reduction in mastocytosis symptoms from baseline, and a 58% mean reduction in the most bothersome symptom domain.

Most adverse events (AEs) in this trial were grade 1 or 2. However, 66% of patients did have grade 3 or higher treatment-related AEs that necessitated dose reductions.

Jason R. Gotlib, MD, of Stanford University School of Medicine in California, presented these results, from the EXPLORER trial (NCT02561988), at the 2018 ASH Annual Meeting (abstract 351).

Patients and treatment

The trial enrolled 67 patients—90% with advanced SM and 10% with indolent or smoldering SM. The patients’ median age was 62 (range, 34 to 83), and 49% were female.

Patients had received a median of 3 (range, 0 to 3) prior therapies. Sixty percent of patients had received any prior therapy, and 23% had received midostaurin. Thirty-three percent were on steroid therapy at baseline.

Eighty-four percent of patients had the KIT D816V mutation, and 1% had the KIT D816Y mutation. Forty-five percent of patients had mutations in SRSF2, ASXL1, and RUNX1.

In the dose-escalation portion of the trial, patients received avapritinib at 30 mg to 400 mg once daily in continuous 28-day cycles. In the expansion portion of the trial, patients received avapritinib at 200 mg or 300 mg once daily.

Response

There were 29 patients evaluable for response. The ORR was 83% (n=24). The rate of complete response (CR) was 10% (n=3), the rate of CR with partial hematologic recovery (CRh) was 14% (n=4), and the partial response rate was 48% (n=14).

Ten percent (n=3) of patients had clinical improvement, 17% (n=5) had stable disease, and none of the patients progressed.

Among the 10 patients treated at a dose of 200 mg or lower, the ORR was 90% (n=9). The CR rate was 30% (n=3), the rate of CRh was 20% (n=2), and the partial response rate was 30% (n=3). Ten percent (n=1) of patients each had clinical improvement or stable disease.

Dr. Gotlib noted that responses have been durable and deepened over time.

At a median follow-up of 14 months, the median duration of response had not been reached. The 12-month response rate is 76%.

The median time to initial response is 2 months, and the median time to CR/CRh is 9 months.

Safety

Seventy-eight percent of patients (52/67) were still on treatment at last follow-up. Four percent (4/67) discontinued treatment due to related AEs, and 66% (44/67) had grade 3 or higher AEs that prompted dose reductions.

AEs prompting discontinuation included refractory ascites, encephalopathy, and intracranial bleeding. AEs necessitating dose reductions were largely hematologic events.

The most common AEs were periorbital edema (67%), anemia (52%), fatigue (37%), nausea (36%), diarrhea (34%), peripheral edema (34%), thrombocytopenia (31%) vomiting (28%), cognitive effects (28%), and hair color changes (25%).

The most common grade 3/4 AEs were anemia (26%), thrombocytopenia (17%), and neutropenia (10%). There were no treatment-related deaths.

Symptoms

For symptom assessment, patients completed the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF), a patient-reported outcomes (PRO) tool that included eight symptoms:

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Spots
• Itching
• Flushing
• Fatigue.

Symptoms were scored on a scale of 1 to 10. Results were analyzed as a total symptom score (TSS) combining all eight items, as a gastrointestinal domain (combining nausea, vomiting, diarrhea, and abdominal pain), and as a skin domain (combining itching, flushing, and spots). Analyses were based on 7-day average scores.

Among the 32 evaluable patients, there was a 41% reduction in TSS from baseline (P=0.043). Among the 16 most symptomatic patients, there was a 46% reduction in TSS from baseline (P=0.038).

In all 32 evaluable patients, there was a 58% reduction from baseline in the score for most bothersome symptom domain (gastrointestinal or skin; P=0.0034). In the 16 most symptomatic patients, there was 63% reduction from baseline (P=0.0038).

“This is the first advanced SM-specific PRO to demonstrate significant improvements in total symptom score,” Dr. Gotlib said. “The clinical activity and initial PRO data do support further evaluation of avapritinib in both advanced and indolent disease.”

Dr. Gotlib noted that the PATHFINDER trial (NCT03580655), a study of avapritinib in advanced SM, is now enrolling. And the PIONEER trial (NCT03731260), a study of avapritinib in patients with indolent or smoldering SM, is scheduled to begin at the end of the year.

The EXPLORER trial was sponsored by Blueprint Medicines Corporation. Dr. Gotlib reported relationships with Blueprint Medicines, Celgene, Incyte, Novartis, Deciphera, Gilead, Promedior, and Kartos.

LOS ANGELES – As obese, nondiabetic individuals become more insulin resistant, a decrease in insulin clearance is the first change to occur, according to Sun H. Kim, MD.

“You will often hear about how insulin resistance enhances demand on beta cells to increase insulin secretion, which leads to hyperinsulinemia,” Dr. Kim said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “While well accepted, this model ignores the role of insulin clearance rate in maintaining hyperinsulinemia in insulin resistance states.”

In an effort to understand the physiologic adaptation to insulin resistance prior to the development of type 2 diabetes mellitus, Dr. Kim, an associate professor of endocrinology at Stanford (Calif) University, Stanford, and her colleagues enrolled 91 adults who had a body mass index of at least 30 kg/m². The study was published in the March 2018 issue of Diabetologia. Each subject underwent a 75-g oral glucose tolerance test as well as the insulin suppression test to measure insulin resistance and the graded glucose infusion test to determine each subject’s insulin secretion rate and insulin clearance rate. For the graded glucose infusion test, the researchers increased the glucose infusion rate every 40 minutes, from 1 mg/kg per minute up to 8 mg/kg per minute. Next, they divided the cohort of obese individuals into tertiles of insulin resistance as quantified by the steady-state plasma glucose (SSPG): less than 9.7 mmol/L (tertile 1), 9.7-12.7 mmol/L (tertile 2), and 12.8 mmol/L or greater (tertile 3).

The mean age of subjects was 54 years. The mean SSPG level was 7.2 mmol/L among subjects in tertile 1, 11.3 mmol/L among those in tertile 2, and 14.3 mmol/L among those in tertile 3. The remainder of the demographics was similar. “Most importantly, body mass index among tertiles was nearly identical,” Dr. Kim said. “The only biomarker that was different was ALT, which increased with increasing tertiles. The individuals who were more insulin resistant likely had more fatty liver. We didn’t do imaging in this particular study.”

When the researchers evaluated oral glucose tolerance test data, they observed that subjects who were most insulin resistant had slightly higher glucose levels, “which we often see,” she said. “The body does try to keep glucose in a narrow range. What was dramatic were the insulin levels. The most insulin-resistant subjects had insulin levels that were double those of the least insulin-resistant subjects in tertile 1 during the oral glucose tolerance test.”

During the intravenous glucose infusion test, glucose levels rose similarly in the three groups, but those in tertile 3 had slightly higher glucose levels (P = .04). The insulin secretion rate, meanwhile, was similar among subjects in tertiles 1 and 2 but was increased significantly among subjects in tertile 3 (P less than .001). In contrast, the researchers observed a stepwise decline in insulin clearance rate from tertiles 1 to 3. Thus the insulin clearance rate was significantly different between subjects in tertile 1 and tertile 2 (P = .04) as well as between subjects in tertile 2 and those in tertile 3 (P less than .001).

“We propose that insulin resistance leads to an increase in intrahepatic fat, which decreases the insulin clearance rate and helps maintain euglycemia,” Dr. Kim concluded. “In the most insulin-resistant tertile, a decrease in insulin clearance rate is not sufficient, and an increase in the insulin secretion rate is also required. If you look at the relationship between insulin resistance and insulin clearance rate, there is a negative correlation, so the more insulin resistant you are, the lower your insulin clearance rate. However, there are insulin-resistant individuals who perhaps have higher insulin clearance rates than we think they should have. Could those individuals be at the highest risk to develop diabetes? That’s the story to which I don’t yet have an ending.” She reported having no financial disclosures.

[email protected]

SOURCE: Jung SH et al. Diabetologia. 2018;61(3):681-7.

LOS ANGELES – As obese, nondiabetic individuals become more insulin resistant, a decrease in insulin clearance is the first change to occur, according to Sun H. Kim, MD.

“You will often hear about how insulin resistance enhances demand on beta cells to increase insulin secretion, which leads to hyperinsulinemia,” Dr. Kim said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “While well accepted, this model ignores the role of insulin clearance rate in maintaining hyperinsulinemia in insulin resistance states.”

In an effort to understand the physiologic adaptation to insulin resistance prior to the development of type 2 diabetes mellitus, Dr. Kim, an associate professor of endocrinology at Stanford (Calif) University, Stanford, and her colleagues enrolled 91 adults who had a body mass index of at least 30 kg/m². The study was published in the March 2018 issue of Diabetologia. Each subject underwent a 75-g oral glucose tolerance test as well as the insulin suppression test to measure insulin resistance and the graded glucose infusion test to determine each subject’s insulin secretion rate and insulin clearance rate. For the graded glucose infusion test, the researchers increased the glucose infusion rate every 40 minutes, from 1 mg/kg per minute up to 8 mg/kg per minute. Next, they divided the cohort of obese individuals into tertiles of insulin resistance as quantified by the steady-state plasma glucose (SSPG): less than 9.7 mmol/L (tertile 1), 9.7-12.7 mmol/L (tertile 2), and 12.8 mmol/L or greater (tertile 3).

The mean age of subjects was 54 years. The mean SSPG level was 7.2 mmol/L among subjects in tertile 1, 11.3 mmol/L among those in tertile 2, and 14.3 mmol/L among those in tertile 3. The remainder of the demographics was similar. “Most importantly, body mass index among tertiles was nearly identical,” Dr. Kim said. “The only biomarker that was different was ALT, which increased with increasing tertiles. The individuals who were more insulin resistant likely had more fatty liver. We didn’t do imaging in this particular study.”

When the researchers evaluated oral glucose tolerance test data, they observed that subjects who were most insulin resistant had slightly higher glucose levels, “which we often see,” she said. “The body does try to keep glucose in a narrow range. What was dramatic were the insulin levels. The most insulin-resistant subjects had insulin levels that were double those of the least insulin-resistant subjects in tertile 1 during the oral glucose tolerance test.”

During the intravenous glucose infusion test, glucose levels rose similarly in the three groups, but those in tertile 3 had slightly higher glucose levels (P = .04). The insulin secretion rate, meanwhile, was similar among subjects in tertiles 1 and 2 but was increased significantly among subjects in tertile 3 (P less than .001). In contrast, the researchers observed a stepwise decline in insulin clearance rate from tertiles 1 to 3. Thus the insulin clearance rate was significantly different between subjects in tertile 1 and tertile 2 (P = .04) as well as between subjects in tertile 2 and those in tertile 3 (P less than .001).

“We propose that insulin resistance leads to an increase in intrahepatic fat, which decreases the insulin clearance rate and helps maintain euglycemia,” Dr. Kim concluded. “In the most insulin-resistant tertile, a decrease in insulin clearance rate is not sufficient, and an increase in the insulin secretion rate is also required. If you look at the relationship between insulin resistance and insulin clearance rate, there is a negative correlation, so the more insulin resistant you are, the lower your insulin clearance rate. However, there are insulin-resistant individuals who perhaps have higher insulin clearance rates than we think they should have. Could those individuals be at the highest risk to develop diabetes? That’s the story to which I don’t yet have an ending.” She reported having no financial disclosures.

[email protected]

SOURCE: Jung SH et al. Diabetologia. 2018;61(3):681-7.

LOS ANGELES – As obese, nondiabetic individuals become more insulin resistant, a decrease in insulin clearance is the first change to occur, according to Sun H. Kim, MD.

“You will often hear about how insulin resistance enhances demand on beta cells to increase insulin secretion, which leads to hyperinsulinemia,” Dr. Kim said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “While well accepted, this model ignores the role of insulin clearance rate in maintaining hyperinsulinemia in insulin resistance states.”

In an effort to understand the physiologic adaptation to insulin resistance prior to the development of type 2 diabetes mellitus, Dr. Kim, an associate professor of endocrinology at Stanford (Calif) University, Stanford, and her colleagues enrolled 91 adults who had a body mass index of at least 30 kg/m². The study was published in the March 2018 issue of Diabetologia. Each subject underwent a 75-g oral glucose tolerance test as well as the insulin suppression test to measure insulin resistance and the graded glucose infusion test to determine each subject’s insulin secretion rate and insulin clearance rate. For the graded glucose infusion test, the researchers increased the glucose infusion rate every 40 minutes, from 1 mg/kg per minute up to 8 mg/kg per minute. Next, they divided the cohort of obese individuals into tertiles of insulin resistance as quantified by the steady-state plasma glucose (SSPG): less than 9.7 mmol/L (tertile 1), 9.7-12.7 mmol/L (tertile 2), and 12.8 mmol/L or greater (tertile 3).

The mean age of subjects was 54 years. The mean SSPG level was 7.2 mmol/L among subjects in tertile 1, 11.3 mmol/L among those in tertile 2, and 14.3 mmol/L among those in tertile 3. The remainder of the demographics was similar. “Most importantly, body mass index among tertiles was nearly identical,” Dr. Kim said. “The only biomarker that was different was ALT, which increased with increasing tertiles. The individuals who were more insulin resistant likely had more fatty liver. We didn’t do imaging in this particular study.”

When the researchers evaluated oral glucose tolerance test data, they observed that subjects who were most insulin resistant had slightly higher glucose levels, “which we often see,” she said. “The body does try to keep glucose in a narrow range. What was dramatic were the insulin levels. The most insulin-resistant subjects had insulin levels that were double those of the least insulin-resistant subjects in tertile 1 during the oral glucose tolerance test.”

During the intravenous glucose infusion test, glucose levels rose similarly in the three groups, but those in tertile 3 had slightly higher glucose levels (P = .04). The insulin secretion rate, meanwhile, was similar among subjects in tertiles 1 and 2 but was increased significantly among subjects in tertile 3 (P less than .001). In contrast, the researchers observed a stepwise decline in insulin clearance rate from tertiles 1 to 3. Thus the insulin clearance rate was significantly different between subjects in tertile 1 and tertile 2 (P = .04) as well as between subjects in tertile 2 and those in tertile 3 (P less than .001).

“We propose that insulin resistance leads to an increase in intrahepatic fat, which decreases the insulin clearance rate and helps maintain euglycemia,” Dr. Kim concluded. “In the most insulin-resistant tertile, a decrease in insulin clearance rate is not sufficient, and an increase in the insulin secretion rate is also required. If you look at the relationship between insulin resistance and insulin clearance rate, there is a negative correlation, so the more insulin resistant you are, the lower your insulin clearance rate. However, there are insulin-resistant individuals who perhaps have higher insulin clearance rates than we think they should have. Could those individuals be at the highest risk to develop diabetes? That’s the story to which I don’t yet have an ending.” She reported having no financial disclosures.

[email protected]

SOURCE: Jung SH et al. Diabetologia. 2018;61(3):681-7.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved to treat overactive bladder, is highly efficacious and well tolerated when used to alleviate hot flashes, according to results of a randomized, controlled trial of 150 women reported by lead author Roberto A. Leon-Ferre, MD.

The women, about two-thirds of whom were breast cancer survivors taking tamoxifen or aromatase inhibitors, were having at least 28 hot flashes weekly at baseline. Results of the trial showed that the 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups).

There also was a significant difference in quality of life in favor of the drug and, in the higher-dose group, significantly better scores for mood and life enjoyment. In a video interview, Dr. Leon-Ferre discussed how oxybutynin compares with other available treatment options, which women are good or poor candidates for this drug, and how the findings have influenced his own practice.

Dr. Leon-Ferre of the Mayo Clinic, Rochester, Minn., disclosed that he had no relevant conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved to treat overactive bladder, is highly efficacious and well tolerated when used to alleviate hot flashes, according to results of a randomized, controlled trial of 150 women reported by lead author Roberto A. Leon-Ferre, MD.

The women, about two-thirds of whom were breast cancer survivors taking tamoxifen or aromatase inhibitors, were having at least 28 hot flashes weekly at baseline. Results of the trial showed that the 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups).

There also was a significant difference in quality of life in favor of the drug and, in the higher-dose group, significantly better scores for mood and life enjoyment. In a video interview, Dr. Leon-Ferre discussed how oxybutynin compares with other available treatment options, which women are good or poor candidates for this drug, and how the findings have influenced his own practice.

Dr. Leon-Ferre of the Mayo Clinic, Rochester, Minn., disclosed that he had no relevant conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved to treat overactive bladder, is highly efficacious and well tolerated when used to alleviate hot flashes, according to results of a randomized, controlled trial of 150 women reported by lead author Roberto A. Leon-Ferre, MD.

The women, about two-thirds of whom were breast cancer survivors taking tamoxifen or aromatase inhibitors, were having at least 28 hot flashes weekly at baseline. Results of the trial showed that the 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups).

There also was a significant difference in quality of life in favor of the drug and, in the higher-dose group, significantly better scores for mood and life enjoyment. In a video interview, Dr. Leon-Ferre discussed how oxybutynin compares with other available treatment options, which women are good or poor candidates for this drug, and how the findings have influenced his own practice.

Dr. Leon-Ferre of the Mayo Clinic, Rochester, Minn., disclosed that he had no relevant conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

NEW YORK – The rates of carotid artery revascularization with either endarterectomy or stenting declined precipitously over a recent 15-year period, at least among Medicare fee-for-service beneficiaries, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

A reduction in carotid endarterectomies (CEA) largely accounted for the decline during 1999-2014 although there was a cumulative decline in all carotid revascularization procedures when rates of CEA and stenting were combined, according to Brajesh K. Lal, MD, professor of surgery, University of Maryland Medical System, Baltimore.

In 1999, when enthusiasm for CEA appears to have peaked, 81,306 patients received this procedure, but a steady decline was observed until 2014, when 36,325 patients were being treated annually in the Medicare database. When calculated as endarterectomies per 100,000 beneficiaries, the rate declined from 298 to 128 (57%; P less than .001) over this 15-year period.

The number of stenting procedures had not reached its peak in 1999, when 10,416 were performed. Rather, the number performed annually nearly doubled to, 22.865 by 2006. However, it then began to decline and reached 10,208 by 2014, which was slightly fewer than in 1999, according to Dr. Lal.

These trends have been observed even though outcomes are getting better, at least for CEA, according to Dr. Lal. From the same pool of data, there was a 31% (1.1% vs. 1.6%) reduction from 1999 to 2014 in mortality at 30 days following CEA. For a composite of ischemic stroke and all-cause mortality, the rate fell 29.5% (3.1% vs. 4.4%). Both reductions were called statistically significant by Dr. Lal.

The improvements in CEA outcomes were observed even though “the treated patients got sicker when looking at comorbidities and risk factors, particularly hypertension, renal insufficiency, and diabetes,” Dr. Lal said.

Outcomes also improved among patients undergoing carotid stenting in general, although the patterns were described as “more complex.” In general, there was steady improvement on outcomes during 1999-2006, but there was no further gain and some lost ground during 2006-2014. For example, ischemic stroke or death fell from 7.0% in 1999 to 4.8% in 2006, but it had climbed back to 7.0% by 2014 with no net change when the first and last year were compared.

However, with risk adjustment, there was a reduction in in-hospital mortality (1.13% vs. 2.78%) over the study period for patients undergoing carotid stenting, according to Dr. Lal, who said this reached statistical significance. Like the CEA group, there was more comorbidity among those treated with stenting at the end, relative to the early part of the study period.

In the stenting group, patients with symptomatic carotid disease rose from 14.4% in 1999 to 25.9% in 2014. This tracks with Medicare policy, which required patients after 2005 to have symptomatic disease for reimbursement, according to Dr. Lal. Prior to 2005, reimbursement was granted for patients participating in clinical trials only.

The rates of carotid revascularization are not evenly distributed geographically in the United States, according to the Medicare data. Endarterectomy in particular has been more common in the south and Midwest than on either coast. This was true in 1999 and remained so in 2014. The distribution was similar for stenting, although it was also relatively common in the southwest in the early part of the study period.

In the beginning of the study, the increased rate of stenting might have contributed to the decline in endarterectomy, but there are several other factors that are implicated in the observed trends, according to Dr. Lal. He suggested that decreasing reimbursement for the performance of these procedures, better clinical management of risk factors, and advances in medical therapy. He cited a physician survey that showed a growing preference for medical management over invasive procedures in patients with high-grade stenosis and indicated that this last factor might be a particularly important driver of the decline in revascularization referrals for asymptomatic carotid disease.

The degree to which these Medicare data are representative of overall trends in the United States is unclear, but Dr. Lal called for further work to understand the forces that these data suggest are driving the changing patterns of carotid revascularization.

NEW YORK – The rates of carotid artery revascularization with either endarterectomy or stenting declined precipitously over a recent 15-year period, at least among Medicare fee-for-service beneficiaries, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

A reduction in carotid endarterectomies (CEA) largely accounted for the decline during 1999-2014 although there was a cumulative decline in all carotid revascularization procedures when rates of CEA and stenting were combined, according to Brajesh K. Lal, MD, professor of surgery, University of Maryland Medical System, Baltimore.

In 1999, when enthusiasm for CEA appears to have peaked, 81,306 patients received this procedure, but a steady decline was observed until 2014, when 36,325 patients were being treated annually in the Medicare database. When calculated as endarterectomies per 100,000 beneficiaries, the rate declined from 298 to 128 (57%; P less than .001) over this 15-year period.

The number of stenting procedures had not reached its peak in 1999, when 10,416 were performed. Rather, the number performed annually nearly doubled to, 22.865 by 2006. However, it then began to decline and reached 10,208 by 2014, which was slightly fewer than in 1999, according to Dr. Lal.

These trends have been observed even though outcomes are getting better, at least for CEA, according to Dr. Lal. From the same pool of data, there was a 31% (1.1% vs. 1.6%) reduction from 1999 to 2014 in mortality at 30 days following CEA. For a composite of ischemic stroke and all-cause mortality, the rate fell 29.5% (3.1% vs. 4.4%). Both reductions were called statistically significant by Dr. Lal.

The improvements in CEA outcomes were observed even though “the treated patients got sicker when looking at comorbidities and risk factors, particularly hypertension, renal insufficiency, and diabetes,” Dr. Lal said.

Outcomes also improved among patients undergoing carotid stenting in general, although the patterns were described as “more complex.” In general, there was steady improvement on outcomes during 1999-2006, but there was no further gain and some lost ground during 2006-2014. For example, ischemic stroke or death fell from 7.0% in 1999 to 4.8% in 2006, but it had climbed back to 7.0% by 2014 with no net change when the first and last year were compared.

However, with risk adjustment, there was a reduction in in-hospital mortality (1.13% vs. 2.78%) over the study period for patients undergoing carotid stenting, according to Dr. Lal, who said this reached statistical significance. Like the CEA group, there was more comorbidity among those treated with stenting at the end, relative to the early part of the study period.

In the stenting group, patients with symptomatic carotid disease rose from 14.4% in 1999 to 25.9% in 2014. This tracks with Medicare policy, which required patients after 2005 to have symptomatic disease for reimbursement, according to Dr. Lal. Prior to 2005, reimbursement was granted for patients participating in clinical trials only.

The rates of carotid revascularization are not evenly distributed geographically in the United States, according to the Medicare data. Endarterectomy in particular has been more common in the south and Midwest than on either coast. This was true in 1999 and remained so in 2014. The distribution was similar for stenting, although it was also relatively common in the southwest in the early part of the study period.

In the beginning of the study, the increased rate of stenting might have contributed to the decline in endarterectomy, but there are several other factors that are implicated in the observed trends, according to Dr. Lal. He suggested that decreasing reimbursement for the performance of these procedures, better clinical management of risk factors, and advances in medical therapy. He cited a physician survey that showed a growing preference for medical management over invasive procedures in patients with high-grade stenosis and indicated that this last factor might be a particularly important driver of the decline in revascularization referrals for asymptomatic carotid disease.

The degree to which these Medicare data are representative of overall trends in the United States is unclear, but Dr. Lal called for further work to understand the forces that these data suggest are driving the changing patterns of carotid revascularization.

NEW YORK – The rates of carotid artery revascularization with either endarterectomy or stenting declined precipitously over a recent 15-year period, at least among Medicare fee-for-service beneficiaries, according to data presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

A reduction in carotid endarterectomies (CEA) largely accounted for the decline during 1999-2014 although there was a cumulative decline in all carotid revascularization procedures when rates of CEA and stenting were combined, according to Brajesh K. Lal, MD, professor of surgery, University of Maryland Medical System, Baltimore.

In 1999, when enthusiasm for CEA appears to have peaked, 81,306 patients received this procedure, but a steady decline was observed until 2014, when 36,325 patients were being treated annually in the Medicare database. When calculated as endarterectomies per 100,000 beneficiaries, the rate declined from 298 to 128 (57%; P less than .001) over this 15-year period.

The number of stenting procedures had not reached its peak in 1999, when 10,416 were performed. Rather, the number performed annually nearly doubled to, 22.865 by 2006. However, it then began to decline and reached 10,208 by 2014, which was slightly fewer than in 1999, according to Dr. Lal.

These trends have been observed even though outcomes are getting better, at least for CEA, according to Dr. Lal. From the same pool of data, there was a 31% (1.1% vs. 1.6%) reduction from 1999 to 2014 in mortality at 30 days following CEA. For a composite of ischemic stroke and all-cause mortality, the rate fell 29.5% (3.1% vs. 4.4%). Both reductions were called statistically significant by Dr. Lal.

The improvements in CEA outcomes were observed even though “the treated patients got sicker when looking at comorbidities and risk factors, particularly hypertension, renal insufficiency, and diabetes,” Dr. Lal said.

Outcomes also improved among patients undergoing carotid stenting in general, although the patterns were described as “more complex.” In general, there was steady improvement on outcomes during 1999-2006, but there was no further gain and some lost ground during 2006-2014. For example, ischemic stroke or death fell from 7.0% in 1999 to 4.8% in 2006, but it had climbed back to 7.0% by 2014 with no net change when the first and last year were compared.

However, with risk adjustment, there was a reduction in in-hospital mortality (1.13% vs. 2.78%) over the study period for patients undergoing carotid stenting, according to Dr. Lal, who said this reached statistical significance. Like the CEA group, there was more comorbidity among those treated with stenting at the end, relative to the early part of the study period.

In the stenting group, patients with symptomatic carotid disease rose from 14.4% in 1999 to 25.9% in 2014. This tracks with Medicare policy, which required patients after 2005 to have symptomatic disease for reimbursement, according to Dr. Lal. Prior to 2005, reimbursement was granted for patients participating in clinical trials only.

The rates of carotid revascularization are not evenly distributed geographically in the United States, according to the Medicare data. Endarterectomy in particular has been more common in the south and Midwest than on either coast. This was true in 1999 and remained so in 2014. The distribution was similar for stenting, although it was also relatively common in the southwest in the early part of the study period.

In the beginning of the study, the increased rate of stenting might have contributed to the decline in endarterectomy, but there are several other factors that are implicated in the observed trends, according to Dr. Lal. He suggested that decreasing reimbursement for the performance of these procedures, better clinical management of risk factors, and advances in medical therapy. He cited a physician survey that showed a growing preference for medical management over invasive procedures in patients with high-grade stenosis and indicated that this last factor might be a particularly important driver of the decline in revascularization referrals for asymptomatic carotid disease.

The degree to which these Medicare data are representative of overall trends in the United States is unclear, but Dr. Lal called for further work to understand the forces that these data suggest are driving the changing patterns of carotid revascularization.

In the years since I last wrote about addressing patients’ complaints, the issues that prompt them have only grown, both in number and complexity. More than ever, it seems impossible to construct any sort of template for consistent, mutually satisfactory resolutions of such disputes.

But it is possible, and it’s not as complex as it appears, once you realize what the vast majority of complaints have in common: Expectations have not been met. Sometimes it’s your fault, sometimes the patient’s, and often a bit of both, but either way, the result is the same: You have an unhappy patient, and you must deal with it.

Why, you might ask? Is the expenditure of time and effort necessary to resolve complaints really worth it? Absolutely, because the old cliché is true: A satisfied patient will refer five new patients, but a dissatisfied one will chase away twenty or more. Besides, if the complaint is significant, and you decline to resolve it, the patient is likely to find someone who will; and chances are you won’t like the choice, or the venue – or the resolution.

As such, this is not a job you should delegate. Unless the complaint is trivial or purely administrative, you should address it yourself. It’s what you would want if you were the complainant, and it’s often too important to trust to a subordinate.

I have distilled this unpleasant duty down to a three-part strategy:

• Discover which expectations went unmet, and why.
• Agree on a solution.
• Learn from the experience, to prevent similar future complaints.

Of course, the easiest way to deal with complaints is to prevent as many as possible in the first place. Take the time to explain all treatments and procedures, and their most likely outcomes. Nip unrealistic expectations in the bud. Make it clear (preferably in writing) that reputable practitioners cannot guarantee perfect results. And, of course, document everything you have explained. Documentation is like garlic: There is no such thing as too much of it.

Of course, despite your best efforts at prevention, there will always be complaints, and handling them is a skill set worth honing, especially the one most of us do poorly: listening to the complaint.

Before you can resolve a problem you have to know what it is, and this is precisely the wrong time to make assumptions or jump to conclusions. So listen to the entire complaint without interrupting, defending, or justifying. Angry patients don’t care why the problem occurred, and they are not interested in your side of the story. This is not about you, so listen and understand.

As you listen, the unmet expectations will become clear. When the patient is finished, I like to summarize the complaint in that context: “So if I understand you correctly, you expected ‘X’ to happen, but ‘Y’ happened instead.” If I’m wrong, I modify my summary until the patient agrees that I understand the issue.

Once you know the problem, you can talk about a solution. The patient usually has one in mind – additional treatment, a referral elsewhere, a fee adjustment, or sometimes simply an apology. Consider it.

If the patient’s solution is reasonable, by all means, agree to it; if it is unreasonable, try to offer a reasonable alternative. The temptation here is to think more about protecting yourself than making the patient happy, but that often leads to bigger problems. Don’t be defensive. Again, this is not about you.

I am often asked if a refund is a reasonable option. Some patients (and lawyers) will interpret a refund as a tacit admission of guilt, so I generally try to avoid them. However, canceling a small fee or copay for an angry patient can be an expedient solution (particularly if it is still unpaid), and in my opinion, looks exactly like what it is: an honest effort to rectify the situation. But in general, additional materials or services, at reduced or waived fees, are a better alternative than refunding money.

Once you have arrived at a mutually satisfactory solution, again, document everything but consider reserving a “private” chart area for such documentation (unless it is a bona fide clinical issue), so that it won’t go out to referrers and other third parties with copies of your clinical notes. Also, consider having the patient sign off on the documentation, acknowledging that the complaint has been resolved.

Finally, always try to learn something from the experience. Ask yourself what you can do (or avoid doing) next time, and how you might prevent similar unrealistic expectations in a future situation.

Above all, never take complaints personally – even when they are personal. It’s always worth reminding yourself that no matter how hard you try, you will never please everyone.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

In the years since I last wrote about addressing patients’ complaints, the issues that prompt them have only grown, both in number and complexity. More than ever, it seems impossible to construct any sort of template for consistent, mutually satisfactory resolutions of such disputes.

But it is possible, and it’s not as complex as it appears, once you realize what the vast majority of complaints have in common: Expectations have not been met. Sometimes it’s your fault, sometimes the patient’s, and often a bit of both, but either way, the result is the same: You have an unhappy patient, and you must deal with it.

Why, you might ask? Is the expenditure of time and effort necessary to resolve complaints really worth it? Absolutely, because the old cliché is true: A satisfied patient will refer five new patients, but a dissatisfied one will chase away twenty or more. Besides, if the complaint is significant, and you decline to resolve it, the patient is likely to find someone who will; and chances are you won’t like the choice, or the venue – or the resolution.

As such, this is not a job you should delegate. Unless the complaint is trivial or purely administrative, you should address it yourself. It’s what you would want if you were the complainant, and it’s often too important to trust to a subordinate.

I have distilled this unpleasant duty down to a three-part strategy:

• Discover which expectations went unmet, and why.
• Agree on a solution.
• Learn from the experience, to prevent similar future complaints.

Of course, the easiest way to deal with complaints is to prevent as many as possible in the first place. Take the time to explain all treatments and procedures, and their most likely outcomes. Nip unrealistic expectations in the bud. Make it clear (preferably in writing) that reputable practitioners cannot guarantee perfect results. And, of course, document everything you have explained. Documentation is like garlic: There is no such thing as too much of it.

Of course, despite your best efforts at prevention, there will always be complaints, and handling them is a skill set worth honing, especially the one most of us do poorly: listening to the complaint.

Before you can resolve a problem you have to know what it is, and this is precisely the wrong time to make assumptions or jump to conclusions. So listen to the entire complaint without interrupting, defending, or justifying. Angry patients don’t care why the problem occurred, and they are not interested in your side of the story. This is not about you, so listen and understand.

As you listen, the unmet expectations will become clear. When the patient is finished, I like to summarize the complaint in that context: “So if I understand you correctly, you expected ‘X’ to happen, but ‘Y’ happened instead.” If I’m wrong, I modify my summary until the patient agrees that I understand the issue.

Once you know the problem, you can talk about a solution. The patient usually has one in mind – additional treatment, a referral elsewhere, a fee adjustment, or sometimes simply an apology. Consider it.

If the patient’s solution is reasonable, by all means, agree to it; if it is unreasonable, try to offer a reasonable alternative. The temptation here is to think more about protecting yourself than making the patient happy, but that often leads to bigger problems. Don’t be defensive. Again, this is not about you.

I am often asked if a refund is a reasonable option. Some patients (and lawyers) will interpret a refund as a tacit admission of guilt, so I generally try to avoid them. However, canceling a small fee or copay for an angry patient can be an expedient solution (particularly if it is still unpaid), and in my opinion, looks exactly like what it is: an honest effort to rectify the situation. But in general, additional materials or services, at reduced or waived fees, are a better alternative than refunding money.

Once you have arrived at a mutually satisfactory solution, again, document everything but consider reserving a “private” chart area for such documentation (unless it is a bona fide clinical issue), so that it won’t go out to referrers and other third parties with copies of your clinical notes. Also, consider having the patient sign off on the documentation, acknowledging that the complaint has been resolved.

Finally, always try to learn something from the experience. Ask yourself what you can do (or avoid doing) next time, and how you might prevent similar unrealistic expectations in a future situation.

Above all, never take complaints personally – even when they are personal. It’s always worth reminding yourself that no matter how hard you try, you will never please everyone.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

In the years since I last wrote about addressing patients’ complaints, the issues that prompt them have only grown, both in number and complexity. More than ever, it seems impossible to construct any sort of template for consistent, mutually satisfactory resolutions of such disputes.

But it is possible, and it’s not as complex as it appears, once you realize what the vast majority of complaints have in common: Expectations have not been met. Sometimes it’s your fault, sometimes the patient’s, and often a bit of both, but either way, the result is the same: You have an unhappy patient, and you must deal with it.

Why, you might ask? Is the expenditure of time and effort necessary to resolve complaints really worth it? Absolutely, because the old cliché is true: A satisfied patient will refer five new patients, but a dissatisfied one will chase away twenty or more. Besides, if the complaint is significant, and you decline to resolve it, the patient is likely to find someone who will; and chances are you won’t like the choice, or the venue – or the resolution.

As such, this is not a job you should delegate. Unless the complaint is trivial or purely administrative, you should address it yourself. It’s what you would want if you were the complainant, and it’s often too important to trust to a subordinate.

I have distilled this unpleasant duty down to a three-part strategy:

• Discover which expectations went unmet, and why.
• Agree on a solution.
• Learn from the experience, to prevent similar future complaints.

Of course, the easiest way to deal with complaints is to prevent as many as possible in the first place. Take the time to explain all treatments and procedures, and their most likely outcomes. Nip unrealistic expectations in the bud. Make it clear (preferably in writing) that reputable practitioners cannot guarantee perfect results. And, of course, document everything you have explained. Documentation is like garlic: There is no such thing as too much of it.

Of course, despite your best efforts at prevention, there will always be complaints, and handling them is a skill set worth honing, especially the one most of us do poorly: listening to the complaint.

Before you can resolve a problem you have to know what it is, and this is precisely the wrong time to make assumptions or jump to conclusions. So listen to the entire complaint without interrupting, defending, or justifying. Angry patients don’t care why the problem occurred, and they are not interested in your side of the story. This is not about you, so listen and understand.

As you listen, the unmet expectations will become clear. When the patient is finished, I like to summarize the complaint in that context: “So if I understand you correctly, you expected ‘X’ to happen, but ‘Y’ happened instead.” If I’m wrong, I modify my summary until the patient agrees that I understand the issue.

Once you know the problem, you can talk about a solution. The patient usually has one in mind – additional treatment, a referral elsewhere, a fee adjustment, or sometimes simply an apology. Consider it.

If the patient’s solution is reasonable, by all means, agree to it; if it is unreasonable, try to offer a reasonable alternative. The temptation here is to think more about protecting yourself than making the patient happy, but that often leads to bigger problems. Don’t be defensive. Again, this is not about you.

I am often asked if a refund is a reasonable option. Some patients (and lawyers) will interpret a refund as a tacit admission of guilt, so I generally try to avoid them. However, canceling a small fee or copay for an angry patient can be an expedient solution (particularly if it is still unpaid), and in my opinion, looks exactly like what it is: an honest effort to rectify the situation. But in general, additional materials or services, at reduced or waived fees, are a better alternative than refunding money.

Once you have arrived at a mutually satisfactory solution, again, document everything but consider reserving a “private” chart area for such documentation (unless it is a bona fide clinical issue), so that it won’t go out to referrers and other third parties with copies of your clinical notes. Also, consider having the patient sign off on the documentation, acknowledging that the complaint has been resolved.

Finally, always try to learn something from the experience. Ask yourself what you can do (or avoid doing) next time, and how you might prevent similar unrealistic expectations in a future situation.

Above all, never take complaints personally – even when they are personal. It’s always worth reminding yourself that no matter how hard you try, you will never please everyone.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

SAN ANTONIO – Younger breast cancer patients who undergo unilateral or bilateral mastectomy report lower breast satisfaction and poorer psychosocial and sexual well-being than counterparts who undergo breast-conserving surgery, finds a cross-sectional cohort study presented by lead investigator Laura S. Dominici, MD, FACS, at the San Antonio Breast Cancer Symposium.

The 560 women studied had a mean age of 37 years and had completed the BREAST-Q questionnaire a median of 5.8 years after their breast cancer diagnosis. Results showed that the mean score for satisfaction with breasts was 65.5 with breast-conserving surgery, 59.3 with unilateral mastectomy, and 60.4 with bilateral mastectomy (P = .008). The mastectomy groups also had poorer scores for psychosocial well-being (P less than .001) and sexual well-being (P less than .001), but not physical well-being. Most of the differences remained significant in meta-analysis. In a video interview, Dr. Dominici, of Dana-Farber Cancer Institute, Boston, discussed worry and anxiety about recurrence and second cancers as drivers of choosing mastectomy, generalizability of the study’s findings, and strategies for incorporating this new information into counseling and shared decision making.

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SAN ANTONIO – Younger breast cancer patients who undergo unilateral or bilateral mastectomy report lower breast satisfaction and poorer psychosocial and sexual well-being than counterparts who undergo breast-conserving surgery, finds a cross-sectional cohort study presented by lead investigator Laura S. Dominici, MD, FACS, at the San Antonio Breast Cancer Symposium.

The 560 women studied had a mean age of 37 years and had completed the BREAST-Q questionnaire a median of 5.8 years after their breast cancer diagnosis. Results showed that the mean score for satisfaction with breasts was 65.5 with breast-conserving surgery, 59.3 with unilateral mastectomy, and 60.4 with bilateral mastectomy (P = .008). The mastectomy groups also had poorer scores for psychosocial well-being (P less than .001) and sexual well-being (P less than .001), but not physical well-being. Most of the differences remained significant in meta-analysis. In a video interview, Dr. Dominici, of Dana-Farber Cancer Institute, Boston, discussed worry and anxiety about recurrence and second cancers as drivers of choosing mastectomy, generalizability of the study’s findings, and strategies for incorporating this new information into counseling and shared decision making.

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SAN ANTONIO – Younger breast cancer patients who undergo unilateral or bilateral mastectomy report lower breast satisfaction and poorer psychosocial and sexual well-being than counterparts who undergo breast-conserving surgery, finds a cross-sectional cohort study presented by lead investigator Laura S. Dominici, MD, FACS, at the San Antonio Breast Cancer Symposium.

The 560 women studied had a mean age of 37 years and had completed the BREAST-Q questionnaire a median of 5.8 years after their breast cancer diagnosis. Results showed that the mean score for satisfaction with breasts was 65.5 with breast-conserving surgery, 59.3 with unilateral mastectomy, and 60.4 with bilateral mastectomy (P = .008). The mastectomy groups also had poorer scores for psychosocial well-being (P less than .001) and sexual well-being (P less than .001), but not physical well-being. Most of the differences remained significant in meta-analysis. In a video interview, Dr. Dominici, of Dana-Farber Cancer Institute, Boston, discussed worry and anxiety about recurrence and second cancers as drivers of choosing mastectomy, generalizability of the study’s findings, and strategies for incorporating this new information into counseling and shared decision making.

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.

Susan London/MDedge News

“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”

The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.

“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”

“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”

For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.

Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.

Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.

Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.

The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.

Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).

Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.

“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.

SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.

BERLIN – Among a host of potential risk factors for multiple sclerosis (MS), one emerging risk factor – dietary sodium – has accumulating evidence, bolstered by new imaging techniques and emerging research about the mediating effect of the gut microbiome.

Georges Lievre / Fotolia.com

“The word is still out on salt – there’s still some work to do; we are not where we stand with smoking or obesity” and the association with MS, said Ralf Linker, MD, speaking at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

For all potential emerging risk factors for MS, there’s an attractive hypothesis and, often, epidemiologic data, Dr. Linker said. “There are probably good [epidemiologic] data in multiple sclerosis for vitamin D, smoking, obesity, and probably also alcohol,” he said. “The therapeutic consequence, however, is much less clear, the best example of that being, of course, vitamin D.”

“The attractive risk factor is not enough to be a hypothesis, although some people seem to believe that nowadays,” said Dr. Linker, chair of the department of neurology at Friedrich-Alexander University, Erlangen, Germany. “Probably it’s better to start with some basic science and some experimental data to get an idea of the mechanism.”

“Today, we need clear associations with clear markers, well-defined cohorts, and proper epidemiological data telling us whether this is a real risk factor. ... If you look at the clinicians – and there are many among us in the room here – your ultimate goal, of course, is to use this as an intervention.”

For salt intake, there’s a clear overlap between high salt consumption in Westernized diets and increasing incidence of MS. The association also holds for many other autoimmune diseases, Dr. Linker added.

“The next step is experimental evidence,” Dr. Linker said. In a rodent model of experimental autoimmune encephalomyelitis (EAE), rats with high salt intake had a worse clinical course, compared with control rats fed a usual diet (Nature. 2013 Apr 25;496[7446]:518-22).

“There were a lot of follow-up studies on that,” with identification of multiple immune cells that are up- or down-regulated via distinct pathways in a high-salt environment, Dr. Linker said.

[email protected]

SOURCE: Linker R. ECTRIMS 2018, Scientific Session 7.

BERLIN – Among a host of potential risk factors for multiple sclerosis (MS), one emerging risk factor – dietary sodium – has accumulating evidence, bolstered by new imaging techniques and emerging research about the mediating effect of the gut microbiome.

Georges Lievre / Fotolia.com

“The word is still out on salt – there’s still some work to do; we are not where we stand with smoking or obesity” and the association with MS, said Ralf Linker, MD, speaking at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

For all potential emerging risk factors for MS, there’s an attractive hypothesis and, often, epidemiologic data, Dr. Linker said. “There are probably good [epidemiologic] data in multiple sclerosis for vitamin D, smoking, obesity, and probably also alcohol,” he said. “The therapeutic consequence, however, is much less clear, the best example of that being, of course, vitamin D.”

“The attractive risk factor is not enough to be a hypothesis, although some people seem to believe that nowadays,” said Dr. Linker, chair of the department of neurology at Friedrich-Alexander University, Erlangen, Germany. “Probably it’s better to start with some basic science and some experimental data to get an idea of the mechanism.”

“Today, we need clear associations with clear markers, well-defined cohorts, and proper epidemiological data telling us whether this is a real risk factor. ... If you look at the clinicians – and there are many among us in the room here – your ultimate goal, of course, is to use this as an intervention.”

For salt intake, there’s a clear overlap between high salt consumption in Westernized diets and increasing incidence of MS. The association also holds for many other autoimmune diseases, Dr. Linker added.

“The next step is experimental evidence,” Dr. Linker said. In a rodent model of experimental autoimmune encephalomyelitis (EAE), rats with high salt intake had a worse clinical course, compared with control rats fed a usual diet (Nature. 2013 Apr 25;496[7446]:518-22).

“There were a lot of follow-up studies on that,” with identification of multiple immune cells that are up- or down-regulated via distinct pathways in a high-salt environment, Dr. Linker said.

[email protected]

SOURCE: Linker R. ECTRIMS 2018, Scientific Session 7.

BERLIN – Among a host of potential risk factors for multiple sclerosis (MS), one emerging risk factor – dietary sodium – has accumulating evidence, bolstered by new imaging techniques and emerging research about the mediating effect of the gut microbiome.

Georges Lievre / Fotolia.com

“The word is still out on salt – there’s still some work to do; we are not where we stand with smoking or obesity” and the association with MS, said Ralf Linker, MD, speaking at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

For all potential emerging risk factors for MS, there’s an attractive hypothesis and, often, epidemiologic data, Dr. Linker said. “There are probably good [epidemiologic] data in multiple sclerosis for vitamin D, smoking, obesity, and probably also alcohol,” he said. “The therapeutic consequence, however, is much less clear, the best example of that being, of course, vitamin D.”

“The attractive risk factor is not enough to be a hypothesis, although some people seem to believe that nowadays,” said Dr. Linker, chair of the department of neurology at Friedrich-Alexander University, Erlangen, Germany. “Probably it’s better to start with some basic science and some experimental data to get an idea of the mechanism.”

“Today, we need clear associations with clear markers, well-defined cohorts, and proper epidemiological data telling us whether this is a real risk factor. ... If you look at the clinicians – and there are many among us in the room here – your ultimate goal, of course, is to use this as an intervention.”

For salt intake, there’s a clear overlap between high salt consumption in Westernized diets and increasing incidence of MS. The association also holds for many other autoimmune diseases, Dr. Linker added.

“The next step is experimental evidence,” Dr. Linker said. In a rodent model of experimental autoimmune encephalomyelitis (EAE), rats with high salt intake had a worse clinical course, compared with control rats fed a usual diet (Nature. 2013 Apr 25;496[7446]:518-22).

“There were a lot of follow-up studies on that,” with identification of multiple immune cells that are up- or down-regulated via distinct pathways in a high-salt environment, Dr. Linker said.

[email protected]

SOURCE: Linker R. ECTRIMS 2018, Scientific Session 7.

LOS ANGELES – On any given day, type “statins” in the subject line of your favorite search engine and many results are likely to focus on risks: some based on science, others not so much.

Doug Brunk/MDedge News

“There is all kind of misinformation that are preventing people from taking statins,” Joshua W. Knowles, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The most important side effects of statins are the increased lifespan and decreased risk of heart attacks, but that’s not what our patients are telling us. One of the things that is true is that statins do seem to increase the risk of diabetes. This only emerged after many years and it’s gotten a lot of press.”

In 2016, Dr. Knowles, a cardiologist at the Stanford (Calif.) Center for Inherited Cardiovascular Disease, coauthored a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) randomized controlled trials (Am J Cardiol 2016;118[9]:1275-81). The authors found that statins particularly increase the risk of type 2 diabetes in those with prediabetes and insulin resistance. “That’s a risk group that we are all treating,” he said. “But that still doesn’t answer the question as to why this happens. Is this because statins increase insulin resistance, because they decrease beta cell function, or because they increase insulin clearance rate?”

In an effort to find out, Dr. Knowles and his colleagues have launched a clinical trial entitled “Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling” (NCT 02437084). Candidates do not have diabetes, yet qualify for statin therapy because they have a greater than 7.5% risk of cardiovascular disease over 10 years. To date, the researchers have enrolled 74 patients: 42 to the insulin-sensitive group (defined as having an LDL above 130 mg/dL and a triglyceride level below 150 mg/dL) and 11 to the insulin-resistant group (defined as having an LDL of 130 mg/dL or greater and a triglyceride level of 150 mg/dL or greater). Dr. Knowles said that about two-thirds of patients have been recruited and that full results are expected in late 2019.

At baseline, subjects underwent the insulin suppression test, the graded glucose infusion test, metabolic characterization, and integrated personal omics profiling (iPOP), a monitoring method. After 3 months of atorvastatin therapy 40 mg/day, the researchers repeated these measures and compared the results between groups. “Basically we were looking for changes in insulin resistance, secretion, and clearance between those groups over time,” said Dr. Knowles, who is the study’s principal investigator.

Of the 74 subjects, 13 decided that they did not want to participate and 6 are still undergoing baseline tests. In all, 55 started statin therapy, and 2 have dropped out. This left 42 in the low-triglyceride group and 11 in the high-triglyceride group.

The average age of the 52 individuals who have completed the study so far is 61 years, 30 are male, 35 are non-Hispanic white, their mean body mass index was 27.9 kg/m², and their mean blood pressure was 127/79 mm Hg. By the end of statin therapy, body mass index did not change, but total cholesterol fell from a median of 234 mg/dL to a median of 150 mg/dL, triglycerides fell from a median of 109 mg/dL to a median of 78 mg/dL, LDL cholesterol fell from a median of 153 mg/dL to a median of 71 mg/dL, and mean high-sensitivity C-reactive protein dropped from a median of 1.2 mg/L to a median of 0.8 mg/L. All differences were statistically significant.

Fasting glucose levels have been completed on only 35 patients. “Two-hour glucose is going up, but it’s not yet significant, and on the oral glucose tolerance test, the curves are separating slightly but are not yet significant,” Dr. Knowles said.

On average, insulin resistance among the 35 patients worsened slightly, from 156 mg/dL before statin therapy to 170 mg/dL after initiation. “This is nominally significant (P = 0.03), and we’ll have to see if this holds up over time,” he said. The researchers also observed that statin use was associated with slight decreases in insulin secretion and clearance. Dr. Knowles emphasized that these are preliminary results and need to be further validated.

The study is funded by the Doris Duke Charitable Foundation. Dr. Knowles reported having no disclosures.

[email protected]

LOS ANGELES – On any given day, type “statins” in the subject line of your favorite search engine and many results are likely to focus on risks: some based on science, others not so much.

Doug Brunk/MDedge News

“There is all kind of misinformation that are preventing people from taking statins,” Joshua W. Knowles, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The most important side effects of statins are the increased lifespan and decreased risk of heart attacks, but that’s not what our patients are telling us. One of the things that is true is that statins do seem to increase the risk of diabetes. This only emerged after many years and it’s gotten a lot of press.”

In 2016, Dr. Knowles, a cardiologist at the Stanford (Calif.) Center for Inherited Cardiovascular Disease, coauthored a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) randomized controlled trials (Am J Cardiol 2016;118[9]:1275-81). The authors found that statins particularly increase the risk of type 2 diabetes in those with prediabetes and insulin resistance. “That’s a risk group that we are all treating,” he said. “But that still doesn’t answer the question as to why this happens. Is this because statins increase insulin resistance, because they decrease beta cell function, or because they increase insulin clearance rate?”

In an effort to find out, Dr. Knowles and his colleagues have launched a clinical trial entitled “Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling” (NCT 02437084). Candidates do not have diabetes, yet qualify for statin therapy because they have a greater than 7.5% risk of cardiovascular disease over 10 years. To date, the researchers have enrolled 74 patients: 42 to the insulin-sensitive group (defined as having an LDL above 130 mg/dL and a triglyceride level below 150 mg/dL) and 11 to the insulin-resistant group (defined as having an LDL of 130 mg/dL or greater and a triglyceride level of 150 mg/dL or greater). Dr. Knowles said that about two-thirds of patients have been recruited and that full results are expected in late 2019.

At baseline, subjects underwent the insulin suppression test, the graded glucose infusion test, metabolic characterization, and integrated personal omics profiling (iPOP), a monitoring method. After 3 months of atorvastatin therapy 40 mg/day, the researchers repeated these measures and compared the results between groups. “Basically we were looking for changes in insulin resistance, secretion, and clearance between those groups over time,” said Dr. Knowles, who is the study’s principal investigator.

Of the 74 subjects, 13 decided that they did not want to participate and 6 are still undergoing baseline tests. In all, 55 started statin therapy, and 2 have dropped out. This left 42 in the low-triglyceride group and 11 in the high-triglyceride group.

The average age of the 52 individuals who have completed the study so far is 61 years, 30 are male, 35 are non-Hispanic white, their mean body mass index was 27.9 kg/m², and their mean blood pressure was 127/79 mm Hg. By the end of statin therapy, body mass index did not change, but total cholesterol fell from a median of 234 mg/dL to a median of 150 mg/dL, triglycerides fell from a median of 109 mg/dL to a median of 78 mg/dL, LDL cholesterol fell from a median of 153 mg/dL to a median of 71 mg/dL, and mean high-sensitivity C-reactive protein dropped from a median of 1.2 mg/L to a median of 0.8 mg/L. All differences were statistically significant.

Fasting glucose levels have been completed on only 35 patients. “Two-hour glucose is going up, but it’s not yet significant, and on the oral glucose tolerance test, the curves are separating slightly but are not yet significant,” Dr. Knowles said.

On average, insulin resistance among the 35 patients worsened slightly, from 156 mg/dL before statin therapy to 170 mg/dL after initiation. “This is nominally significant (P = 0.03), and we’ll have to see if this holds up over time,” he said. The researchers also observed that statin use was associated with slight decreases in insulin secretion and clearance. Dr. Knowles emphasized that these are preliminary results and need to be further validated.

The study is funded by the Doris Duke Charitable Foundation. Dr. Knowles reported having no disclosures.

[email protected]

LOS ANGELES – On any given day, type “statins” in the subject line of your favorite search engine and many results are likely to focus on risks: some based on science, others not so much.

Doug Brunk/MDedge News

“There is all kind of misinformation that are preventing people from taking statins,” Joshua W. Knowles, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The most important side effects of statins are the increased lifespan and decreased risk of heart attacks, but that’s not what our patients are telling us. One of the things that is true is that statins do seem to increase the risk of diabetes. This only emerged after many years and it’s gotten a lot of press.”

In 2016, Dr. Knowles, a cardiologist at the Stanford (Calif.) Center for Inherited Cardiovascular Disease, coauthored a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) randomized controlled trials (Am J Cardiol 2016;118[9]:1275-81). The authors found that statins particularly increase the risk of type 2 diabetes in those with prediabetes and insulin resistance. “That’s a risk group that we are all treating,” he said. “But that still doesn’t answer the question as to why this happens. Is this because statins increase insulin resistance, because they decrease beta cell function, or because they increase insulin clearance rate?”

In an effort to find out, Dr. Knowles and his colleagues have launched a clinical trial entitled “Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling” (NCT 02437084). Candidates do not have diabetes, yet qualify for statin therapy because they have a greater than 7.5% risk of cardiovascular disease over 10 years. To date, the researchers have enrolled 74 patients: 42 to the insulin-sensitive group (defined as having an LDL above 130 mg/dL and a triglyceride level below 150 mg/dL) and 11 to the insulin-resistant group (defined as having an LDL of 130 mg/dL or greater and a triglyceride level of 150 mg/dL or greater). Dr. Knowles said that about two-thirds of patients have been recruited and that full results are expected in late 2019.

At baseline, subjects underwent the insulin suppression test, the graded glucose infusion test, metabolic characterization, and integrated personal omics profiling (iPOP), a monitoring method. After 3 months of atorvastatin therapy 40 mg/day, the researchers repeated these measures and compared the results between groups. “Basically we were looking for changes in insulin resistance, secretion, and clearance between those groups over time,” said Dr. Knowles, who is the study’s principal investigator.

Of the 74 subjects, 13 decided that they did not want to participate and 6 are still undergoing baseline tests. In all, 55 started statin therapy, and 2 have dropped out. This left 42 in the low-triglyceride group and 11 in the high-triglyceride group.

The average age of the 52 individuals who have completed the study so far is 61 years, 30 are male, 35 are non-Hispanic white, their mean body mass index was 27.9 kg/m², and their mean blood pressure was 127/79 mm Hg. By the end of statin therapy, body mass index did not change, but total cholesterol fell from a median of 234 mg/dL to a median of 150 mg/dL, triglycerides fell from a median of 109 mg/dL to a median of 78 mg/dL, LDL cholesterol fell from a median of 153 mg/dL to a median of 71 mg/dL, and mean high-sensitivity C-reactive protein dropped from a median of 1.2 mg/L to a median of 0.8 mg/L. All differences were statistically significant.

Fasting glucose levels have been completed on only 35 patients. “Two-hour glucose is going up, but it’s not yet significant, and on the oral glucose tolerance test, the curves are separating slightly but are not yet significant,” Dr. Knowles said.

On average, insulin resistance among the 35 patients worsened slightly, from 156 mg/dL before statin therapy to 170 mg/dL after initiation. “This is nominally significant (P = 0.03), and we’ll have to see if this holds up over time,” he said. The researchers also observed that statin use was associated with slight decreases in insulin secretion and clearance. Dr. Knowles emphasized that these are preliminary results and need to be further validated.

The study is funded by the Doris Duke Charitable Foundation. Dr. Knowles reported having no disclosures.

[email protected]