We’ve still got some work to do before we can say with authority whether concurrent neoadjuvant chemotherapy and immunotherapy is better than concurrent adjuvant chemotherapy with immunotherapy for non–small cell lung cancer (NSCLC). While there has been some notable progress in this area, we need phase 3 trials that compare the two therapeutic approaches.

Investigators reporting at the 2022 annual meeting of American Society of Clinical Oncology focused primarily on neoadjuvant treatment, which I’ll address here.

In the randomized, phase 2 NADIM II clinical trial reported at the meeting, researchers expanded on the results of NADIM published in 2020 in the Lancet Oncology and in May 2022 in the Journal of Clinical Oncology along with CheckMate 816 results published in the New England Journal of Medicine.

In each of these three studies, researchers compared nivolumab plus chemotherapy versus chemotherapy alone (abstract 8501) as a neoadjuvant treatment for resectable stage IIIA NSCLC. In the study reported at ASCO 2022, patients with resectable clinical stage IIIA-B (per American Joint Committee on Cancer 8th edition) NSCLC and no known EGFR/ALK alterations, were randomized to receive preoperative nivolumab plus chemotherapy (paclitaxel and carboplatin; n = 57) or chemotherapy (n = 29) alone followed by surgery.

The primary endpoint was pathological complete response (pCR); secondary endpoints included major pathological response, safety and tolerability, impact on surgical issues such as delayed or canceled surgeries or length of hospital stay, overall survival and progression free survival. The pCR rate was 36.8% in the neoadjuvant nivolumab plus chemotherapy arm and 6.9% in the chemotherapy alone arm. (P = .0068). 25% of patients on the nivolumab plus chemo arm had grade 3-4 adverse events, compared with 10.3% in the control arm. 93% of patients on the nivolumab plus chemo arm underwent definitive surgery whereas 69.0% of the patients on the chemo alone arm had definitive surgery. (P = .008)
 

What else did we learn about neoadjuvant treatment at the meeting?

Investigators looking at the optimal number of neoadjuvant cycles (abstract 8500) found that three cycles of sintilimab (an investigational PD-1 inhibitor) produced a numerically higher major pathological response rate, compared with two cycles (when given in concert with platinum-doublet chemotherapy). And, neoadjuvant chemoradiotherapy does not result in significant survival benefits when compared with neoadjuvant chemotherapy alone (abstract 8503).

Of course, when it comes to resectable NSCLC, the goal of treatment is to increase the cure rate and improve survival. No randomized studies have reported yet on overall survival, probably because they are too immature. Instead, disease-free survival (DFS) or event-free survival (EFS) are often used as surrogate endpoints. Since none of the studies reported at ASCO reported on DFS or EFS, we need to look elsewhere. CheckMate 816 was a phase 3 study which randomized patients with stages IB-IIIA NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy or neoadjuvant platinum-based chemotherapy alone, followed by resection. The median EFS was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone (P = .005). The percentage of patients with a pCR was 24.0% and 2.2%, respectively (P < .001).

We all know one has to be careful when doing cross-trial comparisons as these studies differ by the percentage of patients with various stages of disease, the type of immunotherapy and chemotherapy used, etc. However, I think we can agree that neoadjuvant chemoimmunotherapy results in better outcomes than chemotherapy alone.

Of course, resectable NSCLC is, by definition, resectable. And traditionally, resection is followed by adjuvant chemotherapy to eradicate micrometastases. Unfortunately, the current standard of care for completely resected early-stage NSCLC (stage I [tumor ≥ 4 cm] to IIIA) involves adjuvant platinum-based combination chemotherapy which results in only a modest 4%-5% improvement in survival versus observation.

Given these modest results, as in the neoadjuvant space, investigators have looked at the benefit of adding immunotherapy to adjuvant chemotherapy. One such study has been reported. IMpower 010 randomly assigned patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA NSCLC, whose tumor cells expressed at least 1% PD-L1, to receive adjuvant atezolizumab or best supportive care after adjuvant platinum-based chemotherapy. In the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells, 3-year DFS rates were 60% and 48% in the atezolizumab and best supportive care arms, respectively (hazard ratio, 0·66 P =·.0039). In all patients in the stage II-IIIA population, the 3-year DFS rates were 56% in the atezolizumab group and 49% in the best supportive care group, (HR, 0.79; P = .020).

KEYNOTE-091, reported at the 2021 annual meeting of the European Society for Medical Oncology, randomized early-stage NSCLC patients following complete resection and adjuvant chemotherapy to pembrolizumab or placebo. Median DFS for the overall population was 53.6 months for patients in the pembro arm versus 42 months in the placebo arm (HR, 0.76; P = .0014). Interestingly, the benefit was not seen in patients with PD-L1 with at least 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm (HR, 0.82; P = .14). Although the contradictory results of PD-L1 as a biomarker is puzzling, I think we can agree that the addition of immunotherapy following adjuvant chemotherapy improves outcomes compared to adjuvant chemotherapy alone.
 

What to do when a patient presents with resectable disease?

Cross-trial comparisons are fraught with danger. Until we have a phase 3 study comparing concurrent neoadjuvant chemo/immunotherapy with concurrent adjuvant chemo/immunotherapy, I do not think we can answer the question “which is better?” However, there are some caveats to keep in mind when deciding on which approach to recommend to our patients: First, neoadjuvant treatment requires biomarker testing to ensure the patient does not have EGFR or ALK mutations. This will necessitate a delay in the operation. Will patients be willing to wait? Will the surgeon? Or, would patients prefer to proceed with surgery while the results are pending? Yes, neoadjuvant therapy gives you information regarding the pCR rate, but does that help you in subsequent management of the patient? We do not know.

Secondly, the two adjuvant studies used adjuvant chemotherapy followed by adjuvant immunotherapy, as contrasted to the neoadjuvant study which used concurrent chemo/immunotherapy. Given the longer duration of treatment in postoperative sequential adjuvant studies, there tends to be more drop off because of patients being unwilling or unfit postoperatively to receive long courses of therapy. In IMpower 010, 1,269 patients completed adjuvant chemotherapy; 1,005 were randomized, and of the 507 assigned to the atezolizumab/chemo group, only 323 completed treatment.

Finally, we must beware of using neoadjuvant chemo/immunotherapy to “down-stage” a patient. KEYNOTE-091 included patients with IIIA disease and no benefit to adjuvant chemotherapy followed by immunotherapy was found in this subgroup of patients, which leads me to wonder if these patients were appropriately selected as surgical candidates. In the NADIM II trials, 9 of 29 patients on the neoadjuvant chemotherapy were not resected.

So, many questions remain. In addition to the ones we’ve raised, there is a clear and immediate need for predictive and prognostic biomarkers. In the NADIM II trial, PD-L1 expression was a predictive biomarker of response. The pCR rate for patients with a PD-L1 tumor expression of less than 1%, 1%-49%, and 50% or higher was 15%, 41.7%, and 61.1%, respectively. However, in KEYNOTE-091, the benefit was not seen in patients with PD-L1 of at least than 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm.

Another possible biomarker: circulating tumor DNA. In the first NADIM study, three low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and overall survival (HR, 0.20 and HR, 0.07, respectively). Although clinical response did not predict survival outcomes, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and overall survival (HR, 0.26 and HR0.04, respectively). Similarly, in CheckMate 816, clearance of ctDNA was associated with longer EFS in patients with ctDNA clearance than in those without ctDNA clearance in both the nivolumab/chemotherapy group (HR, 0.60) and the chemotherapy-alone group (HR, 0.63).

Hopefully, ASCO 2023 will provide more answers.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

We’ve still got some work to do before we can say with authority whether concurrent neoadjuvant chemotherapy and immunotherapy is better than concurrent adjuvant chemotherapy with immunotherapy for non–small cell lung cancer (NSCLC). While there has been some notable progress in this area, we need phase 3 trials that compare the two therapeutic approaches.

Investigators reporting at the 2022 annual meeting of American Society of Clinical Oncology focused primarily on neoadjuvant treatment, which I’ll address here.

In the randomized, phase 2 NADIM II clinical trial reported at the meeting, researchers expanded on the results of NADIM published in 2020 in the Lancet Oncology and in May 2022 in the Journal of Clinical Oncology along with CheckMate 816 results published in the New England Journal of Medicine.

In each of these three studies, researchers compared nivolumab plus chemotherapy versus chemotherapy alone (abstract 8501) as a neoadjuvant treatment for resectable stage IIIA NSCLC. In the study reported at ASCO 2022, patients with resectable clinical stage IIIA-B (per American Joint Committee on Cancer 8th edition) NSCLC and no known EGFR/ALK alterations, were randomized to receive preoperative nivolumab plus chemotherapy (paclitaxel and carboplatin; n = 57) or chemotherapy (n = 29) alone followed by surgery.

The primary endpoint was pathological complete response (pCR); secondary endpoints included major pathological response, safety and tolerability, impact on surgical issues such as delayed or canceled surgeries or length of hospital stay, overall survival and progression free survival. The pCR rate was 36.8% in the neoadjuvant nivolumab plus chemotherapy arm and 6.9% in the chemotherapy alone arm. (P = .0068). 25% of patients on the nivolumab plus chemo arm had grade 3-4 adverse events, compared with 10.3% in the control arm. 93% of patients on the nivolumab plus chemo arm underwent definitive surgery whereas 69.0% of the patients on the chemo alone arm had definitive surgery. (P = .008)
 

What else did we learn about neoadjuvant treatment at the meeting?

Investigators looking at the optimal number of neoadjuvant cycles (abstract 8500) found that three cycles of sintilimab (an investigational PD-1 inhibitor) produced a numerically higher major pathological response rate, compared with two cycles (when given in concert with platinum-doublet chemotherapy). And, neoadjuvant chemoradiotherapy does not result in significant survival benefits when compared with neoadjuvant chemotherapy alone (abstract 8503).

Of course, when it comes to resectable NSCLC, the goal of treatment is to increase the cure rate and improve survival. No randomized studies have reported yet on overall survival, probably because they are too immature. Instead, disease-free survival (DFS) or event-free survival (EFS) are often used as surrogate endpoints. Since none of the studies reported at ASCO reported on DFS or EFS, we need to look elsewhere. CheckMate 816 was a phase 3 study which randomized patients with stages IB-IIIA NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy or neoadjuvant platinum-based chemotherapy alone, followed by resection. The median EFS was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone (P = .005). The percentage of patients with a pCR was 24.0% and 2.2%, respectively (P < .001).

We all know one has to be careful when doing cross-trial comparisons as these studies differ by the percentage of patients with various stages of disease, the type of immunotherapy and chemotherapy used, etc. However, I think we can agree that neoadjuvant chemoimmunotherapy results in better outcomes than chemotherapy alone.

Of course, resectable NSCLC is, by definition, resectable. And traditionally, resection is followed by adjuvant chemotherapy to eradicate micrometastases. Unfortunately, the current standard of care for completely resected early-stage NSCLC (stage I [tumor ≥ 4 cm] to IIIA) involves adjuvant platinum-based combination chemotherapy which results in only a modest 4%-5% improvement in survival versus observation.

Given these modest results, as in the neoadjuvant space, investigators have looked at the benefit of adding immunotherapy to adjuvant chemotherapy. One such study has been reported. IMpower 010 randomly assigned patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA NSCLC, whose tumor cells expressed at least 1% PD-L1, to receive adjuvant atezolizumab or best supportive care after adjuvant platinum-based chemotherapy. In the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells, 3-year DFS rates were 60% and 48% in the atezolizumab and best supportive care arms, respectively (hazard ratio, 0·66 P =·.0039). In all patients in the stage II-IIIA population, the 3-year DFS rates were 56% in the atezolizumab group and 49% in the best supportive care group, (HR, 0.79; P = .020).

KEYNOTE-091, reported at the 2021 annual meeting of the European Society for Medical Oncology, randomized early-stage NSCLC patients following complete resection and adjuvant chemotherapy to pembrolizumab or placebo. Median DFS for the overall population was 53.6 months for patients in the pembro arm versus 42 months in the placebo arm (HR, 0.76; P = .0014). Interestingly, the benefit was not seen in patients with PD-L1 with at least 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm (HR, 0.82; P = .14). Although the contradictory results of PD-L1 as a biomarker is puzzling, I think we can agree that the addition of immunotherapy following adjuvant chemotherapy improves outcomes compared to adjuvant chemotherapy alone.
 

What to do when a patient presents with resectable disease?

Cross-trial comparisons are fraught with danger. Until we have a phase 3 study comparing concurrent neoadjuvant chemo/immunotherapy with concurrent adjuvant chemo/immunotherapy, I do not think we can answer the question “which is better?” However, there are some caveats to keep in mind when deciding on which approach to recommend to our patients: First, neoadjuvant treatment requires biomarker testing to ensure the patient does not have EGFR or ALK mutations. This will necessitate a delay in the operation. Will patients be willing to wait? Will the surgeon? Or, would patients prefer to proceed with surgery while the results are pending? Yes, neoadjuvant therapy gives you information regarding the pCR rate, but does that help you in subsequent management of the patient? We do not know.

Secondly, the two adjuvant studies used adjuvant chemotherapy followed by adjuvant immunotherapy, as contrasted to the neoadjuvant study which used concurrent chemo/immunotherapy. Given the longer duration of treatment in postoperative sequential adjuvant studies, there tends to be more drop off because of patients being unwilling or unfit postoperatively to receive long courses of therapy. In IMpower 010, 1,269 patients completed adjuvant chemotherapy; 1,005 were randomized, and of the 507 assigned to the atezolizumab/chemo group, only 323 completed treatment.

Finally, we must beware of using neoadjuvant chemo/immunotherapy to “down-stage” a patient. KEYNOTE-091 included patients with IIIA disease and no benefit to adjuvant chemotherapy followed by immunotherapy was found in this subgroup of patients, which leads me to wonder if these patients were appropriately selected as surgical candidates. In the NADIM II trials, 9 of 29 patients on the neoadjuvant chemotherapy were not resected.

So, many questions remain. In addition to the ones we’ve raised, there is a clear and immediate need for predictive and prognostic biomarkers. In the NADIM II trial, PD-L1 expression was a predictive biomarker of response. The pCR rate for patients with a PD-L1 tumor expression of less than 1%, 1%-49%, and 50% or higher was 15%, 41.7%, and 61.1%, respectively. However, in KEYNOTE-091, the benefit was not seen in patients with PD-L1 of at least than 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm.

Another possible biomarker: circulating tumor DNA. In the first NADIM study, three low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and overall survival (HR, 0.20 and HR, 0.07, respectively). Although clinical response did not predict survival outcomes, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and overall survival (HR, 0.26 and HR0.04, respectively). Similarly, in CheckMate 816, clearance of ctDNA was associated with longer EFS in patients with ctDNA clearance than in those without ctDNA clearance in both the nivolumab/chemotherapy group (HR, 0.60) and the chemotherapy-alone group (HR, 0.63).

Hopefully, ASCO 2023 will provide more answers.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

We’ve still got some work to do before we can say with authority whether concurrent neoadjuvant chemotherapy and immunotherapy is better than concurrent adjuvant chemotherapy with immunotherapy for non–small cell lung cancer (NSCLC). While there has been some notable progress in this area, we need phase 3 trials that compare the two therapeutic approaches.

Investigators reporting at the 2022 annual meeting of American Society of Clinical Oncology focused primarily on neoadjuvant treatment, which I’ll address here.

In the randomized, phase 2 NADIM II clinical trial reported at the meeting, researchers expanded on the results of NADIM published in 2020 in the Lancet Oncology and in May 2022 in the Journal of Clinical Oncology along with CheckMate 816 results published in the New England Journal of Medicine.

In each of these three studies, researchers compared nivolumab plus chemotherapy versus chemotherapy alone (abstract 8501) as a neoadjuvant treatment for resectable stage IIIA NSCLC. In the study reported at ASCO 2022, patients with resectable clinical stage IIIA-B (per American Joint Committee on Cancer 8th edition) NSCLC and no known EGFR/ALK alterations, were randomized to receive preoperative nivolumab plus chemotherapy (paclitaxel and carboplatin; n = 57) or chemotherapy (n = 29) alone followed by surgery.

The primary endpoint was pathological complete response (pCR); secondary endpoints included major pathological response, safety and tolerability, impact on surgical issues such as delayed or canceled surgeries or length of hospital stay, overall survival and progression free survival. The pCR rate was 36.8% in the neoadjuvant nivolumab plus chemotherapy arm and 6.9% in the chemotherapy alone arm. (P = .0068). 25% of patients on the nivolumab plus chemo arm had grade 3-4 adverse events, compared with 10.3% in the control arm. 93% of patients on the nivolumab plus chemo arm underwent definitive surgery whereas 69.0% of the patients on the chemo alone arm had definitive surgery. (P = .008)
 

What else did we learn about neoadjuvant treatment at the meeting?

Investigators looking at the optimal number of neoadjuvant cycles (abstract 8500) found that three cycles of sintilimab (an investigational PD-1 inhibitor) produced a numerically higher major pathological response rate, compared with two cycles (when given in concert with platinum-doublet chemotherapy). And, neoadjuvant chemoradiotherapy does not result in significant survival benefits when compared with neoadjuvant chemotherapy alone (abstract 8503).

Of course, when it comes to resectable NSCLC, the goal of treatment is to increase the cure rate and improve survival. No randomized studies have reported yet on overall survival, probably because they are too immature. Instead, disease-free survival (DFS) or event-free survival (EFS) are often used as surrogate endpoints. Since none of the studies reported at ASCO reported on DFS or EFS, we need to look elsewhere. CheckMate 816 was a phase 3 study which randomized patients with stages IB-IIIA NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy or neoadjuvant platinum-based chemotherapy alone, followed by resection. The median EFS was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone (P = .005). The percentage of patients with a pCR was 24.0% and 2.2%, respectively (P < .001).

We all know one has to be careful when doing cross-trial comparisons as these studies differ by the percentage of patients with various stages of disease, the type of immunotherapy and chemotherapy used, etc. However, I think we can agree that neoadjuvant chemoimmunotherapy results in better outcomes than chemotherapy alone.

Of course, resectable NSCLC is, by definition, resectable. And traditionally, resection is followed by adjuvant chemotherapy to eradicate micrometastases. Unfortunately, the current standard of care for completely resected early-stage NSCLC (stage I [tumor ≥ 4 cm] to IIIA) involves adjuvant platinum-based combination chemotherapy which results in only a modest 4%-5% improvement in survival versus observation.

Given these modest results, as in the neoadjuvant space, investigators have looked at the benefit of adding immunotherapy to adjuvant chemotherapy. One such study has been reported. IMpower 010 randomly assigned patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA NSCLC, whose tumor cells expressed at least 1% PD-L1, to receive adjuvant atezolizumab or best supportive care after adjuvant platinum-based chemotherapy. In the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells, 3-year DFS rates were 60% and 48% in the atezolizumab and best supportive care arms, respectively (hazard ratio, 0·66 P =·.0039). In all patients in the stage II-IIIA population, the 3-year DFS rates were 56% in the atezolizumab group and 49% in the best supportive care group, (HR, 0.79; P = .020).

KEYNOTE-091, reported at the 2021 annual meeting of the European Society for Medical Oncology, randomized early-stage NSCLC patients following complete resection and adjuvant chemotherapy to pembrolizumab or placebo. Median DFS for the overall population was 53.6 months for patients in the pembro arm versus 42 months in the placebo arm (HR, 0.76; P = .0014). Interestingly, the benefit was not seen in patients with PD-L1 with at least 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm (HR, 0.82; P = .14). Although the contradictory results of PD-L1 as a biomarker is puzzling, I think we can agree that the addition of immunotherapy following adjuvant chemotherapy improves outcomes compared to adjuvant chemotherapy alone.
 

What to do when a patient presents with resectable disease?

Cross-trial comparisons are fraught with danger. Until we have a phase 3 study comparing concurrent neoadjuvant chemo/immunotherapy with concurrent adjuvant chemo/immunotherapy, I do not think we can answer the question “which is better?” However, there are some caveats to keep in mind when deciding on which approach to recommend to our patients: First, neoadjuvant treatment requires biomarker testing to ensure the patient does not have EGFR or ALK mutations. This will necessitate a delay in the operation. Will patients be willing to wait? Will the surgeon? Or, would patients prefer to proceed with surgery while the results are pending? Yes, neoadjuvant therapy gives you information regarding the pCR rate, but does that help you in subsequent management of the patient? We do not know.

Secondly, the two adjuvant studies used adjuvant chemotherapy followed by adjuvant immunotherapy, as contrasted to the neoadjuvant study which used concurrent chemo/immunotherapy. Given the longer duration of treatment in postoperative sequential adjuvant studies, there tends to be more drop off because of patients being unwilling or unfit postoperatively to receive long courses of therapy. In IMpower 010, 1,269 patients completed adjuvant chemotherapy; 1,005 were randomized, and of the 507 assigned to the atezolizumab/chemo group, only 323 completed treatment.

Finally, we must beware of using neoadjuvant chemo/immunotherapy to “down-stage” a patient. KEYNOTE-091 included patients with IIIA disease and no benefit to adjuvant chemotherapy followed by immunotherapy was found in this subgroup of patients, which leads me to wonder if these patients were appropriately selected as surgical candidates. In the NADIM II trials, 9 of 29 patients on the neoadjuvant chemotherapy were not resected.

So, many questions remain. In addition to the ones we’ve raised, there is a clear and immediate need for predictive and prognostic biomarkers. In the NADIM II trial, PD-L1 expression was a predictive biomarker of response. The pCR rate for patients with a PD-L1 tumor expression of less than 1%, 1%-49%, and 50% or higher was 15%, 41.7%, and 61.1%, respectively. However, in KEYNOTE-091, the benefit was not seen in patients with PD-L1 of at least than 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm.

Another possible biomarker: circulating tumor DNA. In the first NADIM study, three low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and overall survival (HR, 0.20 and HR, 0.07, respectively). Although clinical response did not predict survival outcomes, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and overall survival (HR, 0.26 and HR0.04, respectively). Similarly, in CheckMate 816, clearance of ctDNA was associated with longer EFS in patients with ctDNA clearance than in those without ctDNA clearance in both the nivolumab/chemotherapy group (HR, 0.60) and the chemotherapy-alone group (HR, 0.63).

Hopefully, ASCO 2023 will provide more answers.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

The country’s top medical organizations condemned the overturning of Roe v. Wade, saying the removal of federal protections for women to access abortion services marks a “dark day.”

“It is unfathomable. It is unfair. It is wrong,” said the President of the American College of Obstetricians and Gynecologists (ACOG) Iffath Abbasi Hoskins, MD.

“Today is a very dark day in health care. It is a dark day, indeed, for the tens of millions of patients who have suddenly and unfairly lost access to safe legal and evidence-based abortion care,” Dr. Hoskins said at a press conference June 24 sponsored by ACOG. 

“It is dark for the thousands of clinicians who now, instead of focusing on providing health care to their patients, have to live with the threats of legal, civil, and even professional penalties,” Dr. Hoskins added.

ACOG has 62,000 members and is the leading group of doctors that provides obstetric and gynecologic care.
 

Dilemma for some doctors?

“I’d like to take a moment to talk about the future of the medical profession,” said ACOG Chief Executive Officer Maureen G. Phipps, MD, MPH. “[The] decision is, as Dr. Hoskins clearly said, a tragic one for our patients in states across the country, but the harm does not end there.”

Dr. Phipps described overturning Roe v. Wade as “the boldest act of legislative interference that we have seen in this country. It will allow state legislators to tell physicians what care they can and cannot provide to their patients.”

“It will leave physicians looking over our shoulders, wondering if a patient is in enough of a crisis to permit an exception to a law,” Dr. Phipps added. “This is an affront to all that drew my colleagues and me into medicine.”

Although the impact on doctor training remains to be seen, she said 44% of ob.gyn. residents are trained in states now empowered to ban abortions.

The effect of the Supreme Court decision on miscarriage management is another unknown.

“It’s going to be very difficult for us, the clinicians, to manage miscarriage,” Dr. Hoskins said. “Many miscarriages could be what we call ‘incomplete’ in the beginning,” where there is still a heartbeat and the patient is cramping and/or bleeding.

In that instance, Dr. Hoskins said, clinicians may be thinking that they have to wait.

“They may be needing to get additional opinions, whether it’s a legal opinion ... or another medical opinion.”

“It’s going to have a devastating effect on every aspect of a woman’s health care, including if she is spontaneously miscarrying,” Dr. Hoskins predicted.

Physician protect thyself?

To what extent doctors can shield themselves from potential prosecution “is a hard question to answer,” Molly Meegan, JD, ACOG’s chief legal officer and general counsel, said.

Ms. Meegan recommended members speak to the risk managers at their individual institutions for guidance.

“It is a real patchwork [of laws] out there, she said. “And that patchwork itself is a danger to people as they seek essential reproductive health care.”

Also, she added, “If a doctor can’t tell what the law is at the time they’re trying to provide the care, it has a terribly chilling effect on medical care.”

Another potential threat to doctors in states that still allow abortion services is action from a neighboring state.

“We are going to be advocating very strongly that states do not have extra-territorial jurisdiction to reach beyond the edges of their state.”

The worry is if a doctor in New Mexico, where abortion is legal, performs an abortion for a person from Texas, where it will soon be illegal, is then prosecuted by Texas, for example.
 

Medication abortion

Asked about any potential effects on medication abortions, ACOG’s Jen Villavicencio, MD, said it remains to be seen.

“Certainly many of the laws that we have seen, including trigger ban laws, encompass medication abortion,” she said. Several states have these so-called trigger laws, which put into effect laws passed to ban abortion in case Roe was overturned.

This means, she said, that any abortion option, whether it’s procedural or medication, could be and will be banned in some of these states.

Ms. Meegan added that ACOG will continue to support access to medication abortion and that it should be decided by the U.S. Food and Drug Administration and not individual states.
 

Maternal mortality may rise

“Maternal mortality in and of itself is a very difficult topic,” Dr. Hoskins said, but [the] decision amplifies the implications. “I think of the patients who will have to manage severe complications and mental health challenges while they are carrying a pregnancy that they are forced to carry.”

“I also think of the patients who need to end their pregnancies in order to save their own lives,” Dr. Hoskins added.

Dr. Hoskins said the United States already has a high maternal mortality rate. This new law, she added, could force women into higher-risk situations if they experience high blood pressure, preeclampsia, or bleeding after the birth of the baby.
 

Growing inequality possible?

“The grievous inequities that exist in this country will grow and expand unchecked without safe access to legal abortion,” Dr. Phipps said.

She noted that women, based on location, will continue “to have protected access to safe evidence-based abortion. Others will have the means and resources and opportunities to secure the care.”

But the same may not be true for women in underserved or disadvantaged communities, Dr. Phipps added.
 

American Medical Association

ACOG was not the only group to react. “The American Medical Association is deeply disturbed by the U.S. Supreme Court’s decision to overturn nearly a half century of precedent protecting patients’ right to critical reproductive health care,” President Jack Resneck Jr., MD, said in a statement.

The decision represents “an egregious allowance of government intrusion into the medical examination room, a direct attack on the practice of medicine and the patient-physician relationship, and a brazen violation of patients’ rights to evidence-based reproductive health services.”

American Academy of Family Physicians

“The American Academy of Family Physicians is disappointed and disheartened by the Supreme Court’s decision to strike down longstanding protections afforded by Roe v. Wade and Planned Parenthood v. Casey,” President Sterling N. Ransone Jr., MD, said in a statement.

The organization has 127,600 physician and medical student members.

“This decision negatively impacts our practices and our patients by undermining the patient-physician relationship and potentially criminalizing evidence-based medical care,” added Dr. Ransone.
 

American College of Physicians

“A patient’s decision about whether to continue a pregnancy should be a private decision made in consultation with a physician or other health care professional, without interference from the government,” President Ryan D. Mire, MD, said in a statement. “We strongly oppose medically unnecessary government restrictions on any health care services,” added Dr. Mire on behalf of the group’s 161,000 members.

American Academy of Pediatrics

“This decision carries grave consequences for our adolescent patients, who already face many more barriers than adults in accessing comprehensive reproductive health care services and abortion care,” President Moira Szilagyi, MD, PhD, said in a statement. 

“In the wake of this ruling, the American Academy of Pediatrics will continue to support our chapters as states consider policies affecting access to abortion care, and pediatricians will continue to support our patients,” Dr. Szilagyi added.
 

American Public Health Association

The court’s decision “is a catastrophic judicial failure that will reverberate differently in each state and portends to jeopardize the health and lives of all Americans,” Executive Director Georges C. Benjamin, MD, said in a statement.

American Urogynecologic Society

“The American Urogynecologic Society opposes any ruling that restricts a person’s access to health care and criminalizes the practice of medicine,” the group said in a statement. “This ruling ultimately poses a serious threat to the patient-provider relationship and subsequent decisionmaking necessary to ensure optimal outcomes for patients. As practitioners, we should be free to provide what is in the best interest of our patients.”

A version of this article first appeared on Medscape.com.

The country’s top medical organizations condemned the overturning of Roe v. Wade, saying the removal of federal protections for women to access abortion services marks a “dark day.”

“It is unfathomable. It is unfair. It is wrong,” said the President of the American College of Obstetricians and Gynecologists (ACOG) Iffath Abbasi Hoskins, MD.

“Today is a very dark day in health care. It is a dark day, indeed, for the tens of millions of patients who have suddenly and unfairly lost access to safe legal and evidence-based abortion care,” Dr. Hoskins said at a press conference June 24 sponsored by ACOG. 

“It is dark for the thousands of clinicians who now, instead of focusing on providing health care to their patients, have to live with the threats of legal, civil, and even professional penalties,” Dr. Hoskins added.

ACOG has 62,000 members and is the leading group of doctors that provides obstetric and gynecologic care.
 

Dilemma for some doctors?

“I’d like to take a moment to talk about the future of the medical profession,” said ACOG Chief Executive Officer Maureen G. Phipps, MD, MPH. “[The] decision is, as Dr. Hoskins clearly said, a tragic one for our patients in states across the country, but the harm does not end there.”

Dr. Phipps described overturning Roe v. Wade as “the boldest act of legislative interference that we have seen in this country. It will allow state legislators to tell physicians what care they can and cannot provide to their patients.”

“It will leave physicians looking over our shoulders, wondering if a patient is in enough of a crisis to permit an exception to a law,” Dr. Phipps added. “This is an affront to all that drew my colleagues and me into medicine.”

Although the impact on doctor training remains to be seen, she said 44% of ob.gyn. residents are trained in states now empowered to ban abortions.

The effect of the Supreme Court decision on miscarriage management is another unknown.

“It’s going to be very difficult for us, the clinicians, to manage miscarriage,” Dr. Hoskins said. “Many miscarriages could be what we call ‘incomplete’ in the beginning,” where there is still a heartbeat and the patient is cramping and/or bleeding.

In that instance, Dr. Hoskins said, clinicians may be thinking that they have to wait.

“They may be needing to get additional opinions, whether it’s a legal opinion ... or another medical opinion.”

“It’s going to have a devastating effect on every aspect of a woman’s health care, including if she is spontaneously miscarrying,” Dr. Hoskins predicted.

Physician protect thyself?

To what extent doctors can shield themselves from potential prosecution “is a hard question to answer,” Molly Meegan, JD, ACOG’s chief legal officer and general counsel, said.

Ms. Meegan recommended members speak to the risk managers at their individual institutions for guidance.

“It is a real patchwork [of laws] out there, she said. “And that patchwork itself is a danger to people as they seek essential reproductive health care.”

Also, she added, “If a doctor can’t tell what the law is at the time they’re trying to provide the care, it has a terribly chilling effect on medical care.”

Another potential threat to doctors in states that still allow abortion services is action from a neighboring state.

“We are going to be advocating very strongly that states do not have extra-territorial jurisdiction to reach beyond the edges of their state.”

The worry is if a doctor in New Mexico, where abortion is legal, performs an abortion for a person from Texas, where it will soon be illegal, is then prosecuted by Texas, for example.
 

Medication abortion

Asked about any potential effects on medication abortions, ACOG’s Jen Villavicencio, MD, said it remains to be seen.

“Certainly many of the laws that we have seen, including trigger ban laws, encompass medication abortion,” she said. Several states have these so-called trigger laws, which put into effect laws passed to ban abortion in case Roe was overturned.

This means, she said, that any abortion option, whether it’s procedural or medication, could be and will be banned in some of these states.

Ms. Meegan added that ACOG will continue to support access to medication abortion and that it should be decided by the U.S. Food and Drug Administration and not individual states.
 

Maternal mortality may rise

“Maternal mortality in and of itself is a very difficult topic,” Dr. Hoskins said, but [the] decision amplifies the implications. “I think of the patients who will have to manage severe complications and mental health challenges while they are carrying a pregnancy that they are forced to carry.”

“I also think of the patients who need to end their pregnancies in order to save their own lives,” Dr. Hoskins added.

Dr. Hoskins said the United States already has a high maternal mortality rate. This new law, she added, could force women into higher-risk situations if they experience high blood pressure, preeclampsia, or bleeding after the birth of the baby.
 

Growing inequality possible?

“The grievous inequities that exist in this country will grow and expand unchecked without safe access to legal abortion,” Dr. Phipps said.

She noted that women, based on location, will continue “to have protected access to safe evidence-based abortion. Others will have the means and resources and opportunities to secure the care.”

But the same may not be true for women in underserved or disadvantaged communities, Dr. Phipps added.
 

American Medical Association

ACOG was not the only group to react. “The American Medical Association is deeply disturbed by the U.S. Supreme Court’s decision to overturn nearly a half century of precedent protecting patients’ right to critical reproductive health care,” President Jack Resneck Jr., MD, said in a statement.

The decision represents “an egregious allowance of government intrusion into the medical examination room, a direct attack on the practice of medicine and the patient-physician relationship, and a brazen violation of patients’ rights to evidence-based reproductive health services.”

American Academy of Family Physicians

“The American Academy of Family Physicians is disappointed and disheartened by the Supreme Court’s decision to strike down longstanding protections afforded by Roe v. Wade and Planned Parenthood v. Casey,” President Sterling N. Ransone Jr., MD, said in a statement.

The organization has 127,600 physician and medical student members.

“This decision negatively impacts our practices and our patients by undermining the patient-physician relationship and potentially criminalizing evidence-based medical care,” added Dr. Ransone.
 

American College of Physicians

“A patient’s decision about whether to continue a pregnancy should be a private decision made in consultation with a physician or other health care professional, without interference from the government,” President Ryan D. Mire, MD, said in a statement. “We strongly oppose medically unnecessary government restrictions on any health care services,” added Dr. Mire on behalf of the group’s 161,000 members.

American Academy of Pediatrics

“This decision carries grave consequences for our adolescent patients, who already face many more barriers than adults in accessing comprehensive reproductive health care services and abortion care,” President Moira Szilagyi, MD, PhD, said in a statement. 

“In the wake of this ruling, the American Academy of Pediatrics will continue to support our chapters as states consider policies affecting access to abortion care, and pediatricians will continue to support our patients,” Dr. Szilagyi added.
 

American Public Health Association

The court’s decision “is a catastrophic judicial failure that will reverberate differently in each state and portends to jeopardize the health and lives of all Americans,” Executive Director Georges C. Benjamin, MD, said in a statement.

American Urogynecologic Society

“The American Urogynecologic Society opposes any ruling that restricts a person’s access to health care and criminalizes the practice of medicine,” the group said in a statement. “This ruling ultimately poses a serious threat to the patient-provider relationship and subsequent decisionmaking necessary to ensure optimal outcomes for patients. As practitioners, we should be free to provide what is in the best interest of our patients.”

A version of this article first appeared on Medscape.com.

The country’s top medical organizations condemned the overturning of Roe v. Wade, saying the removal of federal protections for women to access abortion services marks a “dark day.”

“It is unfathomable. It is unfair. It is wrong,” said the President of the American College of Obstetricians and Gynecologists (ACOG) Iffath Abbasi Hoskins, MD.

“Today is a very dark day in health care. It is a dark day, indeed, for the tens of millions of patients who have suddenly and unfairly lost access to safe legal and evidence-based abortion care,” Dr. Hoskins said at a press conference June 24 sponsored by ACOG. 

“It is dark for the thousands of clinicians who now, instead of focusing on providing health care to their patients, have to live with the threats of legal, civil, and even professional penalties,” Dr. Hoskins added.

ACOG has 62,000 members and is the leading group of doctors that provides obstetric and gynecologic care.
 

Dilemma for some doctors?

“I’d like to take a moment to talk about the future of the medical profession,” said ACOG Chief Executive Officer Maureen G. Phipps, MD, MPH. “[The] decision is, as Dr. Hoskins clearly said, a tragic one for our patients in states across the country, but the harm does not end there.”

Dr. Phipps described overturning Roe v. Wade as “the boldest act of legislative interference that we have seen in this country. It will allow state legislators to tell physicians what care they can and cannot provide to their patients.”

“It will leave physicians looking over our shoulders, wondering if a patient is in enough of a crisis to permit an exception to a law,” Dr. Phipps added. “This is an affront to all that drew my colleagues and me into medicine.”

Although the impact on doctor training remains to be seen, she said 44% of ob.gyn. residents are trained in states now empowered to ban abortions.

The effect of the Supreme Court decision on miscarriage management is another unknown.

“It’s going to be very difficult for us, the clinicians, to manage miscarriage,” Dr. Hoskins said. “Many miscarriages could be what we call ‘incomplete’ in the beginning,” where there is still a heartbeat and the patient is cramping and/or bleeding.

In that instance, Dr. Hoskins said, clinicians may be thinking that they have to wait.

“They may be needing to get additional opinions, whether it’s a legal opinion ... or another medical opinion.”

“It’s going to have a devastating effect on every aspect of a woman’s health care, including if she is spontaneously miscarrying,” Dr. Hoskins predicted.

Physician protect thyself?

To what extent doctors can shield themselves from potential prosecution “is a hard question to answer,” Molly Meegan, JD, ACOG’s chief legal officer and general counsel, said.

Ms. Meegan recommended members speak to the risk managers at their individual institutions for guidance.

“It is a real patchwork [of laws] out there, she said. “And that patchwork itself is a danger to people as they seek essential reproductive health care.”

Also, she added, “If a doctor can’t tell what the law is at the time they’re trying to provide the care, it has a terribly chilling effect on medical care.”

Another potential threat to doctors in states that still allow abortion services is action from a neighboring state.

“We are going to be advocating very strongly that states do not have extra-territorial jurisdiction to reach beyond the edges of their state.”

The worry is if a doctor in New Mexico, where abortion is legal, performs an abortion for a person from Texas, where it will soon be illegal, is then prosecuted by Texas, for example.
 

Medication abortion

Asked about any potential effects on medication abortions, ACOG’s Jen Villavicencio, MD, said it remains to be seen.

“Certainly many of the laws that we have seen, including trigger ban laws, encompass medication abortion,” she said. Several states have these so-called trigger laws, which put into effect laws passed to ban abortion in case Roe was overturned.

This means, she said, that any abortion option, whether it’s procedural or medication, could be and will be banned in some of these states.

Ms. Meegan added that ACOG will continue to support access to medication abortion and that it should be decided by the U.S. Food and Drug Administration and not individual states.
 

Maternal mortality may rise

“Maternal mortality in and of itself is a very difficult topic,” Dr. Hoskins said, but [the] decision amplifies the implications. “I think of the patients who will have to manage severe complications and mental health challenges while they are carrying a pregnancy that they are forced to carry.”

“I also think of the patients who need to end their pregnancies in order to save their own lives,” Dr. Hoskins added.

Dr. Hoskins said the United States already has a high maternal mortality rate. This new law, she added, could force women into higher-risk situations if they experience high blood pressure, preeclampsia, or bleeding after the birth of the baby.
 

Growing inequality possible?

“The grievous inequities that exist in this country will grow and expand unchecked without safe access to legal abortion,” Dr. Phipps said.

She noted that women, based on location, will continue “to have protected access to safe evidence-based abortion. Others will have the means and resources and opportunities to secure the care.”

But the same may not be true for women in underserved or disadvantaged communities, Dr. Phipps added.
 

American Medical Association

ACOG was not the only group to react. “The American Medical Association is deeply disturbed by the U.S. Supreme Court’s decision to overturn nearly a half century of precedent protecting patients’ right to critical reproductive health care,” President Jack Resneck Jr., MD, said in a statement.

The decision represents “an egregious allowance of government intrusion into the medical examination room, a direct attack on the practice of medicine and the patient-physician relationship, and a brazen violation of patients’ rights to evidence-based reproductive health services.”

American Academy of Family Physicians

“The American Academy of Family Physicians is disappointed and disheartened by the Supreme Court’s decision to strike down longstanding protections afforded by Roe v. Wade and Planned Parenthood v. Casey,” President Sterling N. Ransone Jr., MD, said in a statement.

The organization has 127,600 physician and medical student members.

“This decision negatively impacts our practices and our patients by undermining the patient-physician relationship and potentially criminalizing evidence-based medical care,” added Dr. Ransone.
 

American College of Physicians

“A patient’s decision about whether to continue a pregnancy should be a private decision made in consultation with a physician or other health care professional, without interference from the government,” President Ryan D. Mire, MD, said in a statement. “We strongly oppose medically unnecessary government restrictions on any health care services,” added Dr. Mire on behalf of the group’s 161,000 members.

American Academy of Pediatrics

“This decision carries grave consequences for our adolescent patients, who already face many more barriers than adults in accessing comprehensive reproductive health care services and abortion care,” President Moira Szilagyi, MD, PhD, said in a statement. 

“In the wake of this ruling, the American Academy of Pediatrics will continue to support our chapters as states consider policies affecting access to abortion care, and pediatricians will continue to support our patients,” Dr. Szilagyi added.
 

American Public Health Association

The court’s decision “is a catastrophic judicial failure that will reverberate differently in each state and portends to jeopardize the health and lives of all Americans,” Executive Director Georges C. Benjamin, MD, said in a statement.

American Urogynecologic Society

“The American Urogynecologic Society opposes any ruling that restricts a person’s access to health care and criminalizes the practice of medicine,” the group said in a statement. “This ruling ultimately poses a serious threat to the patient-provider relationship and subsequent decisionmaking necessary to ensure optimal outcomes for patients. As practitioners, we should be free to provide what is in the best interest of our patients.”

A version of this article first appeared on Medscape.com.

Most GI physicians will tell you that we didn’t get where we are without help along the way. Each of us can point to one – or in most cases, several – specific mentors who provided invaluable guidance when we were in medical school, fellowship, and starting our careers. This is true for gastroenterologists across the spectrum, whether they chose careers in private practice, academic medicine, or within a hospital system.

The leadership at Atlanta Gastroenterology Associates, where I practice, has always recognized the importance of mentorship and its role in developing fulfilling careers for its physicians and a healthy practice culture in which people feel valued and supported. But only recently have we begun to create a formalized program to ensure that everyone has access to mentors.

When I started my career, formalized programs for mentorship did not exist. While I reached out to various doctors in my office and the senior partners throughout the practice, not everyone is comfortable proactively reaching out to ask practice leadership for help and guidance. And as independent GI practices continue to get bigger, there may not be as many opportunities to interact with senior leadership or executives, which means new associates could be left to “cold call” potential mentors by phone or email.
 

New associates face many challenges

When I was an associate, the path to partnership looked much different than it does in our practice now, and it definitely varies from practice to practice. In our practice, physicians remain associates for 2-3 years before they have the option to become a partner. As they work diligently to provide the best care to patients, new associates face many challenges, like learning how to build a practice and interact with referring physicians, understanding the process to become a partner, and figuring out how to juggle other commitments, such as the balance between work and home life.

Then there are things like buying a home, getting life and disability insurance, and understanding the financial planning aspects of being a business owner. For those whose group model requires buying into the practice to become a partner, medical school doesn’t teach you how to analyze the return on an investment. Providing access to people who have this experience through a mentorship program can help associates be more prepared to become partners, and hopefully be happier and more successful while doing so.

Formalizing a mentorship program

The mentorship program at Atlanta Gastroenterology Associates matches new physicians with a partner-level mentor with whom they are encouraged to meet monthly. We’ve even provided a budget so that mentees and mentors can meet for dinner or coffee and get to know each other better.

The program starts with a meeting of volunteer partners and associates, who then rank their preferred choices for potential mentors. This helps to ensure that the associates are able get to know the mentors a little bit and decide who might be the best fit for their needs. This is also important for new associates who don’t feel comfortable proactively searching for a mentor as they’re able to provide a list of partners they think would be the best match for them.

Each associate is then assigned a partner-level mentor who is responsible for guiding them and providing education around not only clinical care, but also business, marketing, health policy, and all the other critical components of running a successful private practice. Our program specifically pairs mentors and mentees who do not work in the same location. We wanted the mentors to be paired with associates they are not interacting with daily, to ensure our associates get exposed to different perspectives.

As a group, program participants get together every quarter – twice a year in person, and twice virtually. One of the in-person meetings brings together the mentors and mentees with C-suite executives to meet and network with the practice leadership. We organized the program this way because otherwise, most associates wouldn’t get many opportunities to interact with the CEO, chief medical officer, or chief operating officer in any capacity, let alone in a small gathering where they can engage on a personal level.

The second in-person meeting is a dinner with the mentors and mentees, along with their significant others. We understand that all our physicians have responsibilities outside of work, and bringing families together helps provide new associates with a network of support for questions that aren’t work-related. For associates who are not from Atlanta, this can be especially helpful in figuring out housing, schools, and other aspects of work/life balance.

The other two virtual meetings include the C-suite executives and our physician executive board. We develop specific agenda topics related to a career in private practice and provide a forum for the associates to ask practice leadership questions about challenges they may face on their path to becoming a partner.

At the end of each year, we survey the current program participants to see what was successful and what can be improved for the next cohort of incoming associates. So far, the feedback we’ve received from the mentors and mentees has been overwhelmingly positive.
 

Mentorship benefits the entire practice

As groups continue to grow, more practices may begin to formalize their mentorship programs, particularly those who see the merit they provide in helping recruit and retain valuable associates. To supplement our internal mentorship program, we’ve also started reaching out to local fellowship programs to provide resources to fellows who are considering private practice.

Even though about half of gastroenterology fellows choose independent GI, many aren’t educated about what it means to choose a career in private practice. Our outreach to provide information at the fellowship level is aimed at giving early career physicians an opportunity to know the benefits and challenges associated with private practice. Furthermore, we strive to educate fellows about the resources that are available to guide them through not only joining a group, but also having a successful career.

Leaders of independent GI groups need physicians who want the practice to succeed. Medical school trains physicians to take care of patients but falls short on training physicians to run a business. And building good, strong businesses makes sure that the next generation of leaders are prepared to take over.

Supporting the next generation of practice leaders helps current leadership make changes that will ensure practice sustainability. Often, associates are at the forefront of new technologies, both in terms of patient care, and in terms of practice management, communications, marketing, and advertising. As times change, having associates who are engaged and excited will help any practice be positioned positively for whatever the future holds.
 

What to look for in joining a practice

Ideally, people should start looking for mentors when they’re looking for a residency program. Joining a practice isn’t much different. If you’re an early career physician who is considering private practice, find an independent GI physician who can tell you about their experiences. And when you’re interviewing with practices, be sure to ask questions about how the group approaches mentorship. If a practice doesn’t have a formal mentorship program, it doesn’t mean it’s an environment where mentorship relationships won’t flourish. In many practices, informal mentorship programs are very successful.

Ask questions about how the practice provides or supports mentorship. Does the practice leadership make themselves available as mentors? Does the practice expect new physicians to find and nurture mentorship relations on their own? Ask about the path to becoming a partner and who is available to discuss challenges, concerns, or any questions that arise.

Independent GI practices are partnerships that seek to provide high-quality care at a lower cost to our community. Strengthening and sustaining that partnership requires us to take the time and continuously invest in the future of new physicians who will go on to serve our community as partner physicians retire. By formalizing a mentorship program, we’re hoping to make it easier for our mentors and mentees to create productive partnerships that will strengthen our group, and ultimately independent gastroenterology overall.

Dr. Sonenshine is a practicing gastroenterologist at Atlanta Gastroenterology Associates, and a partner in United Digestive. He previously served as the chair of communications as a member of the Executive Committee of the Digestive Health Physicians Association. Dr. Sonenshine has no conflicts to declare.

Most GI physicians will tell you that we didn’t get where we are without help along the way. Each of us can point to one – or in most cases, several – specific mentors who provided invaluable guidance when we were in medical school, fellowship, and starting our careers. This is true for gastroenterologists across the spectrum, whether they chose careers in private practice, academic medicine, or within a hospital system.

The leadership at Atlanta Gastroenterology Associates, where I practice, has always recognized the importance of mentorship and its role in developing fulfilling careers for its physicians and a healthy practice culture in which people feel valued and supported. But only recently have we begun to create a formalized program to ensure that everyone has access to mentors.

When I started my career, formalized programs for mentorship did not exist. While I reached out to various doctors in my office and the senior partners throughout the practice, not everyone is comfortable proactively reaching out to ask practice leadership for help and guidance. And as independent GI practices continue to get bigger, there may not be as many opportunities to interact with senior leadership or executives, which means new associates could be left to “cold call” potential mentors by phone or email.
 

New associates face many challenges

When I was an associate, the path to partnership looked much different than it does in our practice now, and it definitely varies from practice to practice. In our practice, physicians remain associates for 2-3 years before they have the option to become a partner. As they work diligently to provide the best care to patients, new associates face many challenges, like learning how to build a practice and interact with referring physicians, understanding the process to become a partner, and figuring out how to juggle other commitments, such as the balance between work and home life.

Then there are things like buying a home, getting life and disability insurance, and understanding the financial planning aspects of being a business owner. For those whose group model requires buying into the practice to become a partner, medical school doesn’t teach you how to analyze the return on an investment. Providing access to people who have this experience through a mentorship program can help associates be more prepared to become partners, and hopefully be happier and more successful while doing so.

Formalizing a mentorship program

The mentorship program at Atlanta Gastroenterology Associates matches new physicians with a partner-level mentor with whom they are encouraged to meet monthly. We’ve even provided a budget so that mentees and mentors can meet for dinner or coffee and get to know each other better.

The program starts with a meeting of volunteer partners and associates, who then rank their preferred choices for potential mentors. This helps to ensure that the associates are able get to know the mentors a little bit and decide who might be the best fit for their needs. This is also important for new associates who don’t feel comfortable proactively searching for a mentor as they’re able to provide a list of partners they think would be the best match for them.

Each associate is then assigned a partner-level mentor who is responsible for guiding them and providing education around not only clinical care, but also business, marketing, health policy, and all the other critical components of running a successful private practice. Our program specifically pairs mentors and mentees who do not work in the same location. We wanted the mentors to be paired with associates they are not interacting with daily, to ensure our associates get exposed to different perspectives.

As a group, program participants get together every quarter – twice a year in person, and twice virtually. One of the in-person meetings brings together the mentors and mentees with C-suite executives to meet and network with the practice leadership. We organized the program this way because otherwise, most associates wouldn’t get many opportunities to interact with the CEO, chief medical officer, or chief operating officer in any capacity, let alone in a small gathering where they can engage on a personal level.

The second in-person meeting is a dinner with the mentors and mentees, along with their significant others. We understand that all our physicians have responsibilities outside of work, and bringing families together helps provide new associates with a network of support for questions that aren’t work-related. For associates who are not from Atlanta, this can be especially helpful in figuring out housing, schools, and other aspects of work/life balance.

The other two virtual meetings include the C-suite executives and our physician executive board. We develop specific agenda topics related to a career in private practice and provide a forum for the associates to ask practice leadership questions about challenges they may face on their path to becoming a partner.

At the end of each year, we survey the current program participants to see what was successful and what can be improved for the next cohort of incoming associates. So far, the feedback we’ve received from the mentors and mentees has been overwhelmingly positive.
 

Mentorship benefits the entire practice

As groups continue to grow, more practices may begin to formalize their mentorship programs, particularly those who see the merit they provide in helping recruit and retain valuable associates. To supplement our internal mentorship program, we’ve also started reaching out to local fellowship programs to provide resources to fellows who are considering private practice.

Even though about half of gastroenterology fellows choose independent GI, many aren’t educated about what it means to choose a career in private practice. Our outreach to provide information at the fellowship level is aimed at giving early career physicians an opportunity to know the benefits and challenges associated with private practice. Furthermore, we strive to educate fellows about the resources that are available to guide them through not only joining a group, but also having a successful career.

Leaders of independent GI groups need physicians who want the practice to succeed. Medical school trains physicians to take care of patients but falls short on training physicians to run a business. And building good, strong businesses makes sure that the next generation of leaders are prepared to take over.

Supporting the next generation of practice leaders helps current leadership make changes that will ensure practice sustainability. Often, associates are at the forefront of new technologies, both in terms of patient care, and in terms of practice management, communications, marketing, and advertising. As times change, having associates who are engaged and excited will help any practice be positioned positively for whatever the future holds.
 

What to look for in joining a practice

Ideally, people should start looking for mentors when they’re looking for a residency program. Joining a practice isn’t much different. If you’re an early career physician who is considering private practice, find an independent GI physician who can tell you about their experiences. And when you’re interviewing with practices, be sure to ask questions about how the group approaches mentorship. If a practice doesn’t have a formal mentorship program, it doesn’t mean it’s an environment where mentorship relationships won’t flourish. In many practices, informal mentorship programs are very successful.

Ask questions about how the practice provides or supports mentorship. Does the practice leadership make themselves available as mentors? Does the practice expect new physicians to find and nurture mentorship relations on their own? Ask about the path to becoming a partner and who is available to discuss challenges, concerns, or any questions that arise.

Independent GI practices are partnerships that seek to provide high-quality care at a lower cost to our community. Strengthening and sustaining that partnership requires us to take the time and continuously invest in the future of new physicians who will go on to serve our community as partner physicians retire. By formalizing a mentorship program, we’re hoping to make it easier for our mentors and mentees to create productive partnerships that will strengthen our group, and ultimately independent gastroenterology overall.

Dr. Sonenshine is a practicing gastroenterologist at Atlanta Gastroenterology Associates, and a partner in United Digestive. He previously served as the chair of communications as a member of the Executive Committee of the Digestive Health Physicians Association. Dr. Sonenshine has no conflicts to declare.

Most GI physicians will tell you that we didn’t get where we are without help along the way. Each of us can point to one – or in most cases, several – specific mentors who provided invaluable guidance when we were in medical school, fellowship, and starting our careers. This is true for gastroenterologists across the spectrum, whether they chose careers in private practice, academic medicine, or within a hospital system.

The leadership at Atlanta Gastroenterology Associates, where I practice, has always recognized the importance of mentorship and its role in developing fulfilling careers for its physicians and a healthy practice culture in which people feel valued and supported. But only recently have we begun to create a formalized program to ensure that everyone has access to mentors.

When I started my career, formalized programs for mentorship did not exist. While I reached out to various doctors in my office and the senior partners throughout the practice, not everyone is comfortable proactively reaching out to ask practice leadership for help and guidance. And as independent GI practices continue to get bigger, there may not be as many opportunities to interact with senior leadership or executives, which means new associates could be left to “cold call” potential mentors by phone or email.
 

New associates face many challenges

When I was an associate, the path to partnership looked much different than it does in our practice now, and it definitely varies from practice to practice. In our practice, physicians remain associates for 2-3 years before they have the option to become a partner. As they work diligently to provide the best care to patients, new associates face many challenges, like learning how to build a practice and interact with referring physicians, understanding the process to become a partner, and figuring out how to juggle other commitments, such as the balance between work and home life.

Then there are things like buying a home, getting life and disability insurance, and understanding the financial planning aspects of being a business owner. For those whose group model requires buying into the practice to become a partner, medical school doesn’t teach you how to analyze the return on an investment. Providing access to people who have this experience through a mentorship program can help associates be more prepared to become partners, and hopefully be happier and more successful while doing so.

Formalizing a mentorship program

The mentorship program at Atlanta Gastroenterology Associates matches new physicians with a partner-level mentor with whom they are encouraged to meet monthly. We’ve even provided a budget so that mentees and mentors can meet for dinner or coffee and get to know each other better.

The program starts with a meeting of volunteer partners and associates, who then rank their preferred choices for potential mentors. This helps to ensure that the associates are able get to know the mentors a little bit and decide who might be the best fit for their needs. This is also important for new associates who don’t feel comfortable proactively searching for a mentor as they’re able to provide a list of partners they think would be the best match for them.

Each associate is then assigned a partner-level mentor who is responsible for guiding them and providing education around not only clinical care, but also business, marketing, health policy, and all the other critical components of running a successful private practice. Our program specifically pairs mentors and mentees who do not work in the same location. We wanted the mentors to be paired with associates they are not interacting with daily, to ensure our associates get exposed to different perspectives.

As a group, program participants get together every quarter – twice a year in person, and twice virtually. One of the in-person meetings brings together the mentors and mentees with C-suite executives to meet and network with the practice leadership. We organized the program this way because otherwise, most associates wouldn’t get many opportunities to interact with the CEO, chief medical officer, or chief operating officer in any capacity, let alone in a small gathering where they can engage on a personal level.

The second in-person meeting is a dinner with the mentors and mentees, along with their significant others. We understand that all our physicians have responsibilities outside of work, and bringing families together helps provide new associates with a network of support for questions that aren’t work-related. For associates who are not from Atlanta, this can be especially helpful in figuring out housing, schools, and other aspects of work/life balance.

The other two virtual meetings include the C-suite executives and our physician executive board. We develop specific agenda topics related to a career in private practice and provide a forum for the associates to ask practice leadership questions about challenges they may face on their path to becoming a partner.

At the end of each year, we survey the current program participants to see what was successful and what can be improved for the next cohort of incoming associates. So far, the feedback we’ve received from the mentors and mentees has been overwhelmingly positive.
 

Mentorship benefits the entire practice

As groups continue to grow, more practices may begin to formalize their mentorship programs, particularly those who see the merit they provide in helping recruit and retain valuable associates. To supplement our internal mentorship program, we’ve also started reaching out to local fellowship programs to provide resources to fellows who are considering private practice.

Even though about half of gastroenterology fellows choose independent GI, many aren’t educated about what it means to choose a career in private practice. Our outreach to provide information at the fellowship level is aimed at giving early career physicians an opportunity to know the benefits and challenges associated with private practice. Furthermore, we strive to educate fellows about the resources that are available to guide them through not only joining a group, but also having a successful career.

Leaders of independent GI groups need physicians who want the practice to succeed. Medical school trains physicians to take care of patients but falls short on training physicians to run a business. And building good, strong businesses makes sure that the next generation of leaders are prepared to take over.

Supporting the next generation of practice leaders helps current leadership make changes that will ensure practice sustainability. Often, associates are at the forefront of new technologies, both in terms of patient care, and in terms of practice management, communications, marketing, and advertising. As times change, having associates who are engaged and excited will help any practice be positioned positively for whatever the future holds.
 

What to look for in joining a practice

Ideally, people should start looking for mentors when they’re looking for a residency program. Joining a practice isn’t much different. If you’re an early career physician who is considering private practice, find an independent GI physician who can tell you about their experiences. And when you’re interviewing with practices, be sure to ask questions about how the group approaches mentorship. If a practice doesn’t have a formal mentorship program, it doesn’t mean it’s an environment where mentorship relationships won’t flourish. In many practices, informal mentorship programs are very successful.

Ask questions about how the practice provides or supports mentorship. Does the practice leadership make themselves available as mentors? Does the practice expect new physicians to find and nurture mentorship relations on their own? Ask about the path to becoming a partner and who is available to discuss challenges, concerns, or any questions that arise.

Independent GI practices are partnerships that seek to provide high-quality care at a lower cost to our community. Strengthening and sustaining that partnership requires us to take the time and continuously invest in the future of new physicians who will go on to serve our community as partner physicians retire. By formalizing a mentorship program, we’re hoping to make it easier for our mentors and mentees to create productive partnerships that will strengthen our group, and ultimately independent gastroenterology overall.

Dr. Sonenshine is a practicing gastroenterologist at Atlanta Gastroenterology Associates, and a partner in United Digestive. He previously served as the chair of communications as a member of the Executive Committee of the Digestive Health Physicians Association. Dr. Sonenshine has no conflicts to declare.

Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.

Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.

“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.

tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.

The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
 

First study of its kind

Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.

Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.

“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.

Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.

The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.

Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.

In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.

A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.

The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.

The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.

The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.

The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.

Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.

This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.

Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
 

Encouraging results offer new hope

Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.

“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”

“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.

“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.

“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.

A version of this article first appeared on Medscape.com.

Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.

Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.

“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.

tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.

The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
 

First study of its kind

Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.

Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.

“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.

Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.

The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.

Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.

In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.

A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.

The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.

The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.

The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.

The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.

Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.

This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.

Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
 

Encouraging results offer new hope

Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.

“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”

“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.

“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.

“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.

A version of this article first appeared on Medscape.com.

Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.

Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.

“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.

tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.

The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
 

First study of its kind

Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.

Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.

“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.

Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.

The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.

Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.

In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.

A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.

The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.

The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.

The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.

The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.

Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.

This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.

Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
 

Encouraging results offer new hope

Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.

“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”

“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.

“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.

“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.

A version of this article first appeared on Medscape.com.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Acupuncture deep needling provides significant, long-term relief from chronic tension type headache (TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.

At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.

“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.

The findings were published online in Neurology.
 

Deqi sensation key

TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.

Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.

To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.

The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.

The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.

At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).

Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.

Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.

Only four patients reported adverse effects, all of which were mild and none requiring treatment.

Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.

“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
 

Deeper understanding?

Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.

“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.

However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.

“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.

The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.

“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.

Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Acupuncture deep needling provides significant, long-term relief from chronic tension type headache (TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.

At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.

“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.

The findings were published online in Neurology.
 

Deqi sensation key

TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.

Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.

To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.

The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.

The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.

At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).

Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.

Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.

Only four patients reported adverse effects, all of which were mild and none requiring treatment.

Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.

“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
 

Deeper understanding?

Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.

“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.

However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.

“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.

The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.

“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.

Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Acupuncture deep needling provides significant, long-term relief from chronic tension type headache (TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.

At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.

“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.

The findings were published online in Neurology.
 

Deqi sensation key

TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.

Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.

To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.

The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.

The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.

At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).

Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.

Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.

Only four patients reported adverse effects, all of which were mild and none requiring treatment.

Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.

“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
 

Deeper understanding?

Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.

“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.

However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.

“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.

The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.

“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.

Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Infertility, pregnancy loss, and stillbirth increased women’s later risk of both nonfatal and fatal stroke, based on data from more than 600,000 women.

“To date, multiple studies have generated an expanding body of evidence on the association between pregnancy complications (e.g., gestational diabetes and preeclampsia) and the long-term risk of stroke, but studies on associations with infertility, miscarriage, or stillbirth have produced mixed evidence,” Chen Liang, a PhD candidate at the University of Queensland, Brisbane, Australia, and colleagues wrote.

In a study published in the BMJ, the researchers reviewed data from eight observational cohort studies across seven countries (Australia, China, Japan, the Netherlands, Sweden, the United Kingdom, and the United States). The participants were part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium established in 2021. Most observational studies included in the analysis began between 1990 and 2000.

The study population included 618,851 women aged 32-73 years at baseline for whom data on infertility, miscarriage, or stillbirth, were available. The primary outcome was the association of infertility, recurrent miscarriage, and stillbirth with risk of first fatal or nonfatal stroke, and the results were further stratified by subtype. Stroke was identified through self-reports, linked hospital data, national patient registers, or death registry data. Baseline was defined as the first incidence of infertility, miscarriage, or stillbirth. The exception was the National Survey of Health and Development, a British birth cohort started in 1946, that collected data retrospectively.

The median follow-up period was 13 years for nonfatal stroke and 9.4 years for fatal stroke.

Overall, 17.2%, 16.6%, and 4.6% of the women experienced infertility, miscarriage, and stillbirth, respectively.

Women with a history of infertility had a significantly higher nonfatal stroke risk, compared with those without infertility (hazard ratio, 1.14). Further analysis by stroke subtypes showed an increased association between miscarriage and ischemic stroke (HR, 1.15).

Those with a history of miscarriage also had an increased risk of nonfatal stroke, compared with those without miscarriages (HR, 1.11). In the miscarriage group, the risk of stroke increased with the number of miscarriages, with adjusted HRs of 1.07, 1.12, and 1.35 for women with one, two, and three or more miscarriages, respectively. When stratified by stroke subtype, women with three or more miscarriages were more likely than women with no miscarriages to experience ischemic and hemorrhagic nonfatal strokes.

Associations were similar between miscarriage history and fatal stroke risk. Women with one, two, and three or more miscarriages had increased risk of fatal stroke, compared with those with no miscarriages (aHR, 1.08, 1.26, and 1.82, respectively, and women with three or more miscarriages had a higher risk of ischemic and hemorrhagic stroke (aHR, 1.83 and 1.84, respectively).

Women with a history of stillbirth had an approximately 31% increased risk of nonfatal stroke, compared with those with no history of stillbirth, with aHRs similar for single and recurrent stillbirths (1.32 and 1.29, respectively). Ischemic nonfatal stroke risk was higher in women with any stillbirth, compared with those without stillbirth (aHR, 1.77). Fatal stroke risk also was higher in women with any stillbirth, compared with those without, and this risk increased with the number of stillbirths (HR, 0.97 and HR, 1.26 for those with one stillbirth and two or more, respectively).

“The increased risk of stroke associated with infertility or recurrent stillbirths was mainly driven by a single subtype of stroke (nonfatal ischemic stroke or fatal hemorrhagic stroke, respectively), whereas the risk of stroke associated with recurrent miscarriages was driven by both subtypes,” the researchers wrote.

The researchers cited endothelial dysfunction as a potential underlying mechanism for increased stroke risk associated with pregnancy complications. “Endothelial dysfunction might lead to pregnancy loss through placentation-related defects, persist after a complicated pregnancy, and contribute to the development of stroke through reduced vasodilation, proinflammatory status, and prothrombic properties,” and that history of recurrent pregnancy loss might be a female-specific risk factor for stroke.

To mitigate this risk, they advised early monitoring of women with a history of recurrent miscarriages and stillbirths for stroke risk factors such as high blood pressure, blood sugar levels, and lipid levels.

The study findings were limited by several factors including the use of questionnaires to collect information on infertility, miscarriage, and stillbirth, and the potential variation in definitions of infertility, miscarriage, and stillbirth across the included studies, and a lack of data on the effect of different causes or treatments based on reproductive histories, the researchers noted. Other limitations include incomplete data on stroke subtypes and inability to adjust for all covariates such as thyroid disorders and endometriosis. However, the results were strengthened by the large study size and geographically and racially diverse population, extend the current knowledge on associations between infertility, miscarriage, and stillbirth with stroke, and highlight the need for more research on underlying mechanisms.
 

Data support gender-specific stroke risk stratification

“Studies that seek to understand gender differences and disparities in adverse outcomes, such as stroke risk, are extremely important given that women historically were excluded from research studies,” Catherine M. Albright, MD, of the University of Washington, Seattle, said in an interview. “By doing these studies, we are able to better risk stratify people in order to better predict and modify risks,” added Dr. Albright, who was not involved in the current study.

“It is well known than adverse pregnancy outcomes such as hypertension in pregnancy, fetal growth restriction, and preterm birth, lead to increased risk of cardiovascular disease and stroke later in life, so the general findings of an association between other adverse reproductive and pregnancy outcomes leads to increased stroke risk are not surprising,” she said.

“The take-home message is that outcomes for pregnancy really do provide a window to future health,” said Dr. Albright. “For clinicians, especially non-ob.gyns., knowing a complete pregnancy history for any new patient is important and can help risk-stratify patients, especially as we continue to gain knowledge like what is shown in this study.”

However, “this study did not evaluate why individual patients may have had infertility, recurrent pregnancy loss, or stillbirth, so research to look further into this association to determine if there is an underlying medical condition that could be treated and therefore possibly reduce both pregnancy complications and future stroke risks would be important,” Dr. Albright noted.

The study was supported by the Australian National Health and Medical Research Council Centres of Research Excellence; one corresponding author was supported by an Australian National Health and Medical Research Council Investigator grant. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

A new artificial intelligence (AI) system can help expert endoscopists improve their colonoscopies, a new study indicates.

Endoscopists using the computer program SKOUT (Iterative Scopes) achieved a 27% better detection rate of adenomas per colonoscopy, compared with endoscopists working without computer assistance, said lead author Aasma Shaukat, MD, MPH, director of outcomes research in the division of gastroenterology and hepatology at New York University.

The study showed that AI colonoscopy systems can work in a routine population of U.S. patients, Dr. Shaukat said in an interview.

“As gastroenterologists, we are very excited,” she said.

The study was published online in Gastroenterology and was presented at the annual Digestive Disease^® Week.

Previous research has shown that experienced endoscopists miss many polyps. To improve their detection rate, multiple companies have used machine learning to develop algorithms to identify suspicious areas.

“Once the computer sees the polyp, it puts a bounding box around it,” said Dr. Shaukat. “It draws the attention of the endoscopist to it. It assists the endoscopist but doesn’t replace the endoscopist.”

The Food and Drug Administration has approved two such systems: EndoScreener (Wision AI) and GI Genius (Cosmo Pharmaceuticals).

The SKOUT algorithm was trained on 3,616 full-length colonoscopy procedure videos from multiple centers. In bench testing, it achieved a 93.5% polyp-level true positive rate and a 2.3% false positive rate.
 

Randomized trial pits AI against standard procedure

To see how well the system works in the clinic, Dr. Shaukat and colleagues recruited 22 U.S. board-certified gastroenterologists from five academic and community centers. The gastroenterologists all had a minimum adenoma detection rate of 25%, defined as the number of colonoscopies in which at least one adenoma is found, divided by the number of colonoscopies performed. All the gastroenterologists had performed a minimum of 1,000 colonoscopy procedures.

The researchers randomly assigned 682 patients to undergo colonoscopy with the SKOUT and 677 to undergo colonoscopy using the standard procedure. The patients were aged 40 years or older and were scheduled for either screening or surveillance.

The endoscopists who received computer assistance detected 1.05 adenomas per colonoscopy versus 0.83 for those who did not have computer assistance, a statistically significant difference.

The proportion of resections with clinically significant histology was 71.7% with standard colonoscopies versus 67.4% with computer-assisted colonoscopies. This fell within the 14% margin that the researchers had set to show noninferiority for the computer system.

“The important thing is not just detecting all polyps but the polyps we care about, which are adenomas, and doing so without increasing the false positive rate,” said Dr. Shaukat.

The adenoma detection rate was 43.9% for the standard procedure and 47.8% for the computer-assisted procedure. This difference was not statistically significant, but Dr. Shaukat argued that the adenoma detection rate is not the best measure of success, because endoscopists sometimes stop looking for polyps once they find one.

The overall sessile serrated lesion detection rate for the standard colonoscopies was 16.0% versus 12.6% for the computer-assisted colonoscopies, which also was not statistically significant.
 

Next steps

This study is important because it was a large, multicenter trial in the United States, said Omer Ahmad, BSc, MBBS, MRCP, a gastroenterologist and clinical researcher at University College London, who was not involved in the study. Most of the trials of AI have been in China or Europe. “It was very important just to see this replicated in the U.S. population.”

The average procedure time was 15.41 minutes for the standard colonoscopies versus 15.82 minutes for the computer-assisted colonoscopies, which was not statistically different.

“It is important to note that the studies so far suggest that false positives do not have a significant impact on workflow,” said Dr. Ahmad.

The next crucial step in evaluating AI colonoscopy will be to track the effects over the long term, said Dr. Shaukat.

“As these technologies get approved and we see them in practice, we need to see that it’s leading to some outcome, like reduced colon cancer,” she said.

That also may be necessary before payers in the United States are willing to pay the additional cost for this technology, she added.

In the meantime, Dr. Ahmad said computer assistance is improving his own colonoscopies.

“I have found the systems have spotted some polyps that I may have otherwise missed,” he said. “There is a false positive rate, but for me, it doesn’t distract from my workflow.”

He believes the systems will be particularly helpful in improving the performance of less-skilled endoscopists.

He is also looking forward to systems that can help complete the reports needed at the end of each colonoscopy. “Most of us dislike having to write a laborious report and having to code everything at the end of the procedure,” he said.

The study was funded by Iterative Scopes. Dr. Shaukat reported having received research funding to her institution for the current study from Iterative Scopes and consulting fees from Freenome and Medtronic. Dr. Ahmad reports receiving speaker fees from the Canadian Association of Gastroenterology/Medtronic.

A version of this article first appeared on Medscape.com.

A new artificial intelligence (AI) system can help expert endoscopists improve their colonoscopies, a new study indicates.

Endoscopists using the computer program SKOUT (Iterative Scopes) achieved a 27% better detection rate of adenomas per colonoscopy, compared with endoscopists working without computer assistance, said lead author Aasma Shaukat, MD, MPH, director of outcomes research in the division of gastroenterology and hepatology at New York University.

The study showed that AI colonoscopy systems can work in a routine population of U.S. patients, Dr. Shaukat said in an interview.

“As gastroenterologists, we are very excited,” she said.

The study was published online in Gastroenterology and was presented at the annual Digestive Disease^® Week.

Previous research has shown that experienced endoscopists miss many polyps. To improve their detection rate, multiple companies have used machine learning to develop algorithms to identify suspicious areas.

“Once the computer sees the polyp, it puts a bounding box around it,” said Dr. Shaukat. “It draws the attention of the endoscopist to it. It assists the endoscopist but doesn’t replace the endoscopist.”

The Food and Drug Administration has approved two such systems: EndoScreener (Wision AI) and GI Genius (Cosmo Pharmaceuticals).

The SKOUT algorithm was trained on 3,616 full-length colonoscopy procedure videos from multiple centers. In bench testing, it achieved a 93.5% polyp-level true positive rate and a 2.3% false positive rate.
 

Randomized trial pits AI against standard procedure

To see how well the system works in the clinic, Dr. Shaukat and colleagues recruited 22 U.S. board-certified gastroenterologists from five academic and community centers. The gastroenterologists all had a minimum adenoma detection rate of 25%, defined as the number of colonoscopies in which at least one adenoma is found, divided by the number of colonoscopies performed. All the gastroenterologists had performed a minimum of 1,000 colonoscopy procedures.

The researchers randomly assigned 682 patients to undergo colonoscopy with the SKOUT and 677 to undergo colonoscopy using the standard procedure. The patients were aged 40 years or older and were scheduled for either screening or surveillance.

The endoscopists who received computer assistance detected 1.05 adenomas per colonoscopy versus 0.83 for those who did not have computer assistance, a statistically significant difference.

The proportion of resections with clinically significant histology was 71.7% with standard colonoscopies versus 67.4% with computer-assisted colonoscopies. This fell within the 14% margin that the researchers had set to show noninferiority for the computer system.

“The important thing is not just detecting all polyps but the polyps we care about, which are adenomas, and doing so without increasing the false positive rate,” said Dr. Shaukat.

The adenoma detection rate was 43.9% for the standard procedure and 47.8% for the computer-assisted procedure. This difference was not statistically significant, but Dr. Shaukat argued that the adenoma detection rate is not the best measure of success, because endoscopists sometimes stop looking for polyps once they find one.

The overall sessile serrated lesion detection rate for the standard colonoscopies was 16.0% versus 12.6% for the computer-assisted colonoscopies, which also was not statistically significant.
 

Next steps

This study is important because it was a large, multicenter trial in the United States, said Omer Ahmad, BSc, MBBS, MRCP, a gastroenterologist and clinical researcher at University College London, who was not involved in the study. Most of the trials of AI have been in China or Europe. “It was very important just to see this replicated in the U.S. population.”

The average procedure time was 15.41 minutes for the standard colonoscopies versus 15.82 minutes for the computer-assisted colonoscopies, which was not statistically different.

“It is important to note that the studies so far suggest that false positives do not have a significant impact on workflow,” said Dr. Ahmad.

The next crucial step in evaluating AI colonoscopy will be to track the effects over the long term, said Dr. Shaukat.

“As these technologies get approved and we see them in practice, we need to see that it’s leading to some outcome, like reduced colon cancer,” she said.

That also may be necessary before payers in the United States are willing to pay the additional cost for this technology, she added.

In the meantime, Dr. Ahmad said computer assistance is improving his own colonoscopies.

“I have found the systems have spotted some polyps that I may have otherwise missed,” he said. “There is a false positive rate, but for me, it doesn’t distract from my workflow.”

He believes the systems will be particularly helpful in improving the performance of less-skilled endoscopists.

He is also looking forward to systems that can help complete the reports needed at the end of each colonoscopy. “Most of us dislike having to write a laborious report and having to code everything at the end of the procedure,” he said.

The study was funded by Iterative Scopes. Dr. Shaukat reported having received research funding to her institution for the current study from Iterative Scopes and consulting fees from Freenome and Medtronic. Dr. Ahmad reports receiving speaker fees from the Canadian Association of Gastroenterology/Medtronic.

A version of this article first appeared on Medscape.com.

A new artificial intelligence (AI) system can help expert endoscopists improve their colonoscopies, a new study indicates.

Endoscopists using the computer program SKOUT (Iterative Scopes) achieved a 27% better detection rate of adenomas per colonoscopy, compared with endoscopists working without computer assistance, said lead author Aasma Shaukat, MD, MPH, director of outcomes research in the division of gastroenterology and hepatology at New York University.

The study showed that AI colonoscopy systems can work in a routine population of U.S. patients, Dr. Shaukat said in an interview.

“As gastroenterologists, we are very excited,” she said.

The study was published online in Gastroenterology and was presented at the annual Digestive Disease^® Week.

Previous research has shown that experienced endoscopists miss many polyps. To improve their detection rate, multiple companies have used machine learning to develop algorithms to identify suspicious areas.

“Once the computer sees the polyp, it puts a bounding box around it,” said Dr. Shaukat. “It draws the attention of the endoscopist to it. It assists the endoscopist but doesn’t replace the endoscopist.”

The Food and Drug Administration has approved two such systems: EndoScreener (Wision AI) and GI Genius (Cosmo Pharmaceuticals).

The SKOUT algorithm was trained on 3,616 full-length colonoscopy procedure videos from multiple centers. In bench testing, it achieved a 93.5% polyp-level true positive rate and a 2.3% false positive rate.
 

Randomized trial pits AI against standard procedure

To see how well the system works in the clinic, Dr. Shaukat and colleagues recruited 22 U.S. board-certified gastroenterologists from five academic and community centers. The gastroenterologists all had a minimum adenoma detection rate of 25%, defined as the number of colonoscopies in which at least one adenoma is found, divided by the number of colonoscopies performed. All the gastroenterologists had performed a minimum of 1,000 colonoscopy procedures.

The researchers randomly assigned 682 patients to undergo colonoscopy with the SKOUT and 677 to undergo colonoscopy using the standard procedure. The patients were aged 40 years or older and were scheduled for either screening or surveillance.

The endoscopists who received computer assistance detected 1.05 adenomas per colonoscopy versus 0.83 for those who did not have computer assistance, a statistically significant difference.

The proportion of resections with clinically significant histology was 71.7% with standard colonoscopies versus 67.4% with computer-assisted colonoscopies. This fell within the 14% margin that the researchers had set to show noninferiority for the computer system.

“The important thing is not just detecting all polyps but the polyps we care about, which are adenomas, and doing so without increasing the false positive rate,” said Dr. Shaukat.

The adenoma detection rate was 43.9% for the standard procedure and 47.8% for the computer-assisted procedure. This difference was not statistically significant, but Dr. Shaukat argued that the adenoma detection rate is not the best measure of success, because endoscopists sometimes stop looking for polyps once they find one.

The overall sessile serrated lesion detection rate for the standard colonoscopies was 16.0% versus 12.6% for the computer-assisted colonoscopies, which also was not statistically significant.
 

Next steps

This study is important because it was a large, multicenter trial in the United States, said Omer Ahmad, BSc, MBBS, MRCP, a gastroenterologist and clinical researcher at University College London, who was not involved in the study. Most of the trials of AI have been in China or Europe. “It was very important just to see this replicated in the U.S. population.”

The average procedure time was 15.41 minutes for the standard colonoscopies versus 15.82 minutes for the computer-assisted colonoscopies, which was not statistically different.

“It is important to note that the studies so far suggest that false positives do not have a significant impact on workflow,” said Dr. Ahmad.

The next crucial step in evaluating AI colonoscopy will be to track the effects over the long term, said Dr. Shaukat.

“As these technologies get approved and we see them in practice, we need to see that it’s leading to some outcome, like reduced colon cancer,” she said.

That also may be necessary before payers in the United States are willing to pay the additional cost for this technology, she added.

In the meantime, Dr. Ahmad said computer assistance is improving his own colonoscopies.

“I have found the systems have spotted some polyps that I may have otherwise missed,” he said. “There is a false positive rate, but for me, it doesn’t distract from my workflow.”

He believes the systems will be particularly helpful in improving the performance of less-skilled endoscopists.

He is also looking forward to systems that can help complete the reports needed at the end of each colonoscopy. “Most of us dislike having to write a laborious report and having to code everything at the end of the procedure,” he said.

The study was funded by Iterative Scopes. Dr. Shaukat reported having received research funding to her institution for the current study from Iterative Scopes and consulting fees from Freenome and Medtronic. Dr. Ahmad reports receiving speaker fees from the Canadian Association of Gastroenterology/Medtronic.

A version of this article first appeared on Medscape.com.

HP-3070, an asenapine transdermal system, is superior to placebo in reducing schizophrenia-associated hostility, results of a phase 3 study show.

The results suggest that these effects are at least partially independent of general antipsychotic effects or effects on sedation or akathisia.

“It’s important not to assume that antipsychotics decrease hostility by having people feel more sedated and that the only way to treat someone hostile is by sedating them,” lead investigator Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences, New York Medical College, Valhalla, told this news organization.

“Our findings suggest that transdermal asenapine has a specific antihostility effect in patients with schizophrenia,” he added.

A complex disorder

“Patients with schizophrenia are known to potentially exhibit aggressive, hostile behavior, especially during the acute phase of the illness, thus making effective management critical,” the authors write.

Dr. Citrome said schizophrenia is a complex condition that consists of five different symptom domains. These include positive (hallucinations, delusions), negative (amotivation, apathy), disorganization (cognitive symptoms), depression/anxiety, and excitability/hostility symptoms.

“These five domains are more or less independent of each other, in terms of treatment effects,” he noted.

Dr. Citrome has long been interested in the activity of antipsychotics and their impact on these various symptoms – particularly hostility – and recently published a review focusing on the impact of an array of antipsychotics on this symptom domain.

“What struck me here is that this is a transdermal system, a patch,” Dr. Citrome said. “None of the sedation that would ordinarily be associated with a sublingual asenapine would be present here.”

Dr. Citrome wanted to investigate whether the transdermal system would have an impact on hostility because, if so, “it would support the notion that hostility is an independent treatment target in schizophrenia.”

To investigate, Dr. Citrome and co-authors analyzed data from the pivotal HP-3070 phase 3 randomized, double-blind, placebo-controlled study of adults with schizophrenia who were randomly selected to receive either HP-3070 7.6 mg/24h, HP-3070 3.8 mg/24h, or placebo for 6 weeks.

The trial found that once-daily applications of HP-3070 demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores after 2-3 weeks of treatment, with the improvements sustained through week 6.

The current study was a post hoc analysis focusing specifically on 442 patients with hostility and agitation (defined as PANSS hostility item score > 1).

The outcome was the least-squares mean (LSM) changes in the PANSS hostility item. They also analyzed PANSS–Excited Component (PANSS-EC) from baseline to week 6 in all study participants. Findings were adjusted for the presence of somnolence or akathisia.

Demographic and baseline disease characteristics were “balanced” between the HP-3070–6.6-mg and the HP-3070–3.8-mg groups (n = 151 and n = 147, respectively) and the placebo group (n = 144) in the intent-to-treat analysis, with a mean (standard deviation) age of between 41.5 and 42.3 (11.6-11.9) years. Roughly three-quarters of participants were White, and most participants had a mean duration of between 15 and 16 years since diagnosis.
 

Independent effect

At week 6, the LSM mean change from baseline (CFB) in the PANSS hostility score was superior in both treatment groups at 6 weeks, compared with placebo (7.6 mg/24 hr: CFB, –0.4; 95% confidence interval, –0.6 to –0.2; P  < .001; 3.8 mg/24 hr: CFB, –0.3; 95% CI, –0.6 to –0.1; P < .01).

The findings remained significant, even after the researchers adjusted for covariates.

For all patients, regardless of baseline PANSS hostility item score, PANSS-EC week 6 LSM CFB was greater in both treatment groups compared with placebo (7.6 mg/24 hr: CFB, –1.1; 95% CI, –1.9 to –0.4; P < .01; 3.8 mg/24 hr: CFB, –1.3; 95% CI, –2.0 to –0.6; P  < .001).

Patients with a PANSS hostility score > 1 at baseline in both treatment groups also showed significant improvement in PANSS-EC score, compared with the placebo, beginning at week 2 and continuing through week 6.

“These effects of HP-3070 treatment on the PANSS hostility item score remained, even after adjustment for confounding variables, suggesting that the effect of HP-3070 on reducing symptoms of hostility may at be at least partially independent of general antipsychotic effects on hallucinations or delusions or the presence or absence of relevant medication-induced adverse effects, such as sedation or akathisia,” the authors comment.

They note that a limitation of the study is that it was conducted post hoc. In addition, the mean baseline PANSS hostility score was “low,” even among those with a score > 1, “translating to a severity level of minimal to mild,” which “limits the generalizability” of the analysis.
 

Important treatment target

Commenting on the study, Rifaat El-Mallakh, MD, MS, director of the Mood Disorders Research Program, department of psychiatry and behavioral sciences, University of Louisville (Ky.) School of Medicine, said, “aggression and hostility may exhibit themselves as symptoms of a psychotic illness or independent of psychosis and are an important treatment target.”

Dr. El-Mallakh, who was not involved with the study, said the “most effective anti-aggression medicine is clozapine.” He believes that it is this effect that “gives clozapine its stellar reputation,” rather than its antipsychotic effect.

“Of importance, the anti-aggression effect of clozapine is independent of its antipsychotic effect, which is an important point because if the behavior is rooted in psychosis, then successful treatment of psychosis with any agent should reduce aggression.”

The researchers “demonstrated that the effect was independent of psychosis” but because the study only recruited people with schizophrenia, the researchers “could not examine to see if the effect is independent of diagnosis,” Dr. El-Mallakh said.

“It is important to consider aggression/hostility as an independent behavior in pharmacologic studies, because it probably has its own biochemistry and neuroanatomy,” he added.

This study was funded by Hisamitsu Pharmaceutical. Dr. Citrome has received nonfinancial support from Hisamitsu Pharmaceutical and personal fees from Noven Pharmaceuticals during the conduct of the study; personal fees from numerous companies and organizations; and one-off ad hoc consulting for medical education companies such as Medscape, NACCME, NEI, Vindico, and universities and professional organizations/societies outside the submitted work. He has stocks and received royalties from numerous companies and organizations. Dr. El-Mallakh is a speaker for Noven, as well as Indivior, Intracellular, Janssen, Lundbeck, Otsuka, Sunovion, and Teva.

A version of this article first appeared on Medscape.com.

HP-3070, an asenapine transdermal system, is superior to placebo in reducing schizophrenia-associated hostility, results of a phase 3 study show.

The results suggest that these effects are at least partially independent of general antipsychotic effects or effects on sedation or akathisia.

“It’s important not to assume that antipsychotics decrease hostility by having people feel more sedated and that the only way to treat someone hostile is by sedating them,” lead investigator Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences, New York Medical College, Valhalla, told this news organization.

“Our findings suggest that transdermal asenapine has a specific antihostility effect in patients with schizophrenia,” he added.

A complex disorder

“Patients with schizophrenia are known to potentially exhibit aggressive, hostile behavior, especially during the acute phase of the illness, thus making effective management critical,” the authors write.

Dr. Citrome said schizophrenia is a complex condition that consists of five different symptom domains. These include positive (hallucinations, delusions), negative (amotivation, apathy), disorganization (cognitive symptoms), depression/anxiety, and excitability/hostility symptoms.

“These five domains are more or less independent of each other, in terms of treatment effects,” he noted.

Dr. Citrome has long been interested in the activity of antipsychotics and their impact on these various symptoms – particularly hostility – and recently published a review focusing on the impact of an array of antipsychotics on this symptom domain.

“What struck me here is that this is a transdermal system, a patch,” Dr. Citrome said. “None of the sedation that would ordinarily be associated with a sublingual asenapine would be present here.”

Dr. Citrome wanted to investigate whether the transdermal system would have an impact on hostility because, if so, “it would support the notion that hostility is an independent treatment target in schizophrenia.”

To investigate, Dr. Citrome and co-authors analyzed data from the pivotal HP-3070 phase 3 randomized, double-blind, placebo-controlled study of adults with schizophrenia who were randomly selected to receive either HP-3070 7.6 mg/24h, HP-3070 3.8 mg/24h, or placebo for 6 weeks.

The trial found that once-daily applications of HP-3070 demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores after 2-3 weeks of treatment, with the improvements sustained through week 6.

The current study was a post hoc analysis focusing specifically on 442 patients with hostility and agitation (defined as PANSS hostility item score > 1).

The outcome was the least-squares mean (LSM) changes in the PANSS hostility item. They also analyzed PANSS–Excited Component (PANSS-EC) from baseline to week 6 in all study participants. Findings were adjusted for the presence of somnolence or akathisia.

Demographic and baseline disease characteristics were “balanced” between the HP-3070–6.6-mg and the HP-3070–3.8-mg groups (n = 151 and n = 147, respectively) and the placebo group (n = 144) in the intent-to-treat analysis, with a mean (standard deviation) age of between 41.5 and 42.3 (11.6-11.9) years. Roughly three-quarters of participants were White, and most participants had a mean duration of between 15 and 16 years since diagnosis.
 

Independent effect

At week 6, the LSM mean change from baseline (CFB) in the PANSS hostility score was superior in both treatment groups at 6 weeks, compared with placebo (7.6 mg/24 hr: CFB, –0.4; 95% confidence interval, –0.6 to –0.2; P  < .001; 3.8 mg/24 hr: CFB, –0.3; 95% CI, –0.6 to –0.1; P < .01).

The findings remained significant, even after the researchers adjusted for covariates.

For all patients, regardless of baseline PANSS hostility item score, PANSS-EC week 6 LSM CFB was greater in both treatment groups compared with placebo (7.6 mg/24 hr: CFB, –1.1; 95% CI, –1.9 to –0.4; P < .01; 3.8 mg/24 hr: CFB, –1.3; 95% CI, –2.0 to –0.6; P  < .001).

Patients with a PANSS hostility score > 1 at baseline in both treatment groups also showed significant improvement in PANSS-EC score, compared with the placebo, beginning at week 2 and continuing through week 6.

“These effects of HP-3070 treatment on the PANSS hostility item score remained, even after adjustment for confounding variables, suggesting that the effect of HP-3070 on reducing symptoms of hostility may at be at least partially independent of general antipsychotic effects on hallucinations or delusions or the presence or absence of relevant medication-induced adverse effects, such as sedation or akathisia,” the authors comment.

They note that a limitation of the study is that it was conducted post hoc. In addition, the mean baseline PANSS hostility score was “low,” even among those with a score > 1, “translating to a severity level of minimal to mild,” which “limits the generalizability” of the analysis.
 

Important treatment target

Commenting on the study, Rifaat El-Mallakh, MD, MS, director of the Mood Disorders Research Program, department of psychiatry and behavioral sciences, University of Louisville (Ky.) School of Medicine, said, “aggression and hostility may exhibit themselves as symptoms of a psychotic illness or independent of psychosis and are an important treatment target.”

Dr. El-Mallakh, who was not involved with the study, said the “most effective anti-aggression medicine is clozapine.” He believes that it is this effect that “gives clozapine its stellar reputation,” rather than its antipsychotic effect.

“Of importance, the anti-aggression effect of clozapine is independent of its antipsychotic effect, which is an important point because if the behavior is rooted in psychosis, then successful treatment of psychosis with any agent should reduce aggression.”

The researchers “demonstrated that the effect was independent of psychosis” but because the study only recruited people with schizophrenia, the researchers “could not examine to see if the effect is independent of diagnosis,” Dr. El-Mallakh said.

“It is important to consider aggression/hostility as an independent behavior in pharmacologic studies, because it probably has its own biochemistry and neuroanatomy,” he added.

This study was funded by Hisamitsu Pharmaceutical. Dr. Citrome has received nonfinancial support from Hisamitsu Pharmaceutical and personal fees from Noven Pharmaceuticals during the conduct of the study; personal fees from numerous companies and organizations; and one-off ad hoc consulting for medical education companies such as Medscape, NACCME, NEI, Vindico, and universities and professional organizations/societies outside the submitted work. He has stocks and received royalties from numerous companies and organizations. Dr. El-Mallakh is a speaker for Noven, as well as Indivior, Intracellular, Janssen, Lundbeck, Otsuka, Sunovion, and Teva.

A version of this article first appeared on Medscape.com.

HP-3070, an asenapine transdermal system, is superior to placebo in reducing schizophrenia-associated hostility, results of a phase 3 study show.

The results suggest that these effects are at least partially independent of general antipsychotic effects or effects on sedation or akathisia.

“It’s important not to assume that antipsychotics decrease hostility by having people feel more sedated and that the only way to treat someone hostile is by sedating them,” lead investigator Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences, New York Medical College, Valhalla, told this news organization.

“Our findings suggest that transdermal asenapine has a specific antihostility effect in patients with schizophrenia,” he added.

A complex disorder

“Patients with schizophrenia are known to potentially exhibit aggressive, hostile behavior, especially during the acute phase of the illness, thus making effective management critical,” the authors write.

Dr. Citrome said schizophrenia is a complex condition that consists of five different symptom domains. These include positive (hallucinations, delusions), negative (amotivation, apathy), disorganization (cognitive symptoms), depression/anxiety, and excitability/hostility symptoms.

“These five domains are more or less independent of each other, in terms of treatment effects,” he noted.

Dr. Citrome has long been interested in the activity of antipsychotics and their impact on these various symptoms – particularly hostility – and recently published a review focusing on the impact of an array of antipsychotics on this symptom domain.

“What struck me here is that this is a transdermal system, a patch,” Dr. Citrome said. “None of the sedation that would ordinarily be associated with a sublingual asenapine would be present here.”

Dr. Citrome wanted to investigate whether the transdermal system would have an impact on hostility because, if so, “it would support the notion that hostility is an independent treatment target in schizophrenia.”

To investigate, Dr. Citrome and co-authors analyzed data from the pivotal HP-3070 phase 3 randomized, double-blind, placebo-controlled study of adults with schizophrenia who were randomly selected to receive either HP-3070 7.6 mg/24h, HP-3070 3.8 mg/24h, or placebo for 6 weeks.

The trial found that once-daily applications of HP-3070 demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores after 2-3 weeks of treatment, with the improvements sustained through week 6.

The current study was a post hoc analysis focusing specifically on 442 patients with hostility and agitation (defined as PANSS hostility item score > 1).

The outcome was the least-squares mean (LSM) changes in the PANSS hostility item. They also analyzed PANSS–Excited Component (PANSS-EC) from baseline to week 6 in all study participants. Findings were adjusted for the presence of somnolence or akathisia.

Demographic and baseline disease characteristics were “balanced” between the HP-3070–6.6-mg and the HP-3070–3.8-mg groups (n = 151 and n = 147, respectively) and the placebo group (n = 144) in the intent-to-treat analysis, with a mean (standard deviation) age of between 41.5 and 42.3 (11.6-11.9) years. Roughly three-quarters of participants were White, and most participants had a mean duration of between 15 and 16 years since diagnosis.
 

Independent effect

At week 6, the LSM mean change from baseline (CFB) in the PANSS hostility score was superior in both treatment groups at 6 weeks, compared with placebo (7.6 mg/24 hr: CFB, –0.4; 95% confidence interval, –0.6 to –0.2; P  < .001; 3.8 mg/24 hr: CFB, –0.3; 95% CI, –0.6 to –0.1; P < .01).

The findings remained significant, even after the researchers adjusted for covariates.

For all patients, regardless of baseline PANSS hostility item score, PANSS-EC week 6 LSM CFB was greater in both treatment groups compared with placebo (7.6 mg/24 hr: CFB, –1.1; 95% CI, –1.9 to –0.4; P < .01; 3.8 mg/24 hr: CFB, –1.3; 95% CI, –2.0 to –0.6; P  < .001).

Patients with a PANSS hostility score > 1 at baseline in both treatment groups also showed significant improvement in PANSS-EC score, compared with the placebo, beginning at week 2 and continuing through week 6.

“These effects of HP-3070 treatment on the PANSS hostility item score remained, even after adjustment for confounding variables, suggesting that the effect of HP-3070 on reducing symptoms of hostility may at be at least partially independent of general antipsychotic effects on hallucinations or delusions or the presence or absence of relevant medication-induced adverse effects, such as sedation or akathisia,” the authors comment.

They note that a limitation of the study is that it was conducted post hoc. In addition, the mean baseline PANSS hostility score was “low,” even among those with a score > 1, “translating to a severity level of minimal to mild,” which “limits the generalizability” of the analysis.
 

Important treatment target

Commenting on the study, Rifaat El-Mallakh, MD, MS, director of the Mood Disorders Research Program, department of psychiatry and behavioral sciences, University of Louisville (Ky.) School of Medicine, said, “aggression and hostility may exhibit themselves as symptoms of a psychotic illness or independent of psychosis and are an important treatment target.”

Dr. El-Mallakh, who was not involved with the study, said the “most effective anti-aggression medicine is clozapine.” He believes that it is this effect that “gives clozapine its stellar reputation,” rather than its antipsychotic effect.

“Of importance, the anti-aggression effect of clozapine is independent of its antipsychotic effect, which is an important point because if the behavior is rooted in psychosis, then successful treatment of psychosis with any agent should reduce aggression.”

The researchers “demonstrated that the effect was independent of psychosis” but because the study only recruited people with schizophrenia, the researchers “could not examine to see if the effect is independent of diagnosis,” Dr. El-Mallakh said.

“It is important to consider aggression/hostility as an independent behavior in pharmacologic studies, because it probably has its own biochemistry and neuroanatomy,” he added.

This study was funded by Hisamitsu Pharmaceutical. Dr. Citrome has received nonfinancial support from Hisamitsu Pharmaceutical and personal fees from Noven Pharmaceuticals during the conduct of the study; personal fees from numerous companies and organizations; and one-off ad hoc consulting for medical education companies such as Medscape, NACCME, NEI, Vindico, and universities and professional organizations/societies outside the submitted work. He has stocks and received royalties from numerous companies and organizations. Dr. El-Mallakh is a speaker for Noven, as well as Indivior, Intracellular, Janssen, Lundbeck, Otsuka, Sunovion, and Teva.

A version of this article first appeared on Medscape.com.

Infants who were introduced to a low-protein diet – high in fruit, vegetables, and roots – ate more fruits and vegetables at 12 and 18 months of age, compared with those who ate a conventional diet, in a new study.

The “Nordic diet” has shown health benefits in children and adults, but has not been studied in infants, said Ulrica Johansson, MD, of Umeå (Sweden) University, in a presentation on the study at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

A healthy and sustainable diet early in life could have a significant impact on future health, Dr. Johansson said in an interview.

Dr. Johansson and colleagues aimed to investigate the effect of a Nordic diet in infants aged 4-18 months in the OTIS trial. All infants were breastfed or formula-fed at baseline.
 

Study methods and results

A total of 250 infants aged 4-6 months were randomized to consuming a Nordic diet or a conventional diet. Those in the Nordic group received exposures to Nordic foods and flavors, including Nordic fruit, berries, vegetables, and roots. Those in the conventional group received baby food products that followed the current Swedish dietary recommendations for infants. The researchers collected data on dietary intake, biomarkers, and growth from baseline up to 18 months of age.

Notably, acceptance of all the flavors in the Nordic diet was high, including those with sour or bitter taste, such as cranberry and white radish, Dr. Johansson said in her presentation. Food refusals were few, and did not differ among the Nordic food offerings.

At both 12- and 18-month follow-ups, infants in the Nordic group consumed 42%-45% more fruits and vegetables compared with those in the conventional group (P < .001). Plasma folate levels also were significantly higher in the Nordic group compared with in the conventional group, at both 12 months and 18 months (P < .001 and P < .003, respectively).

The daily mean protein intake ranged from 17% to 29% lower in the Nordic group compared with in the conventional group, at both 12 months and 18 months. The intake of protein in terms of g/kg of body weight was significantly lower in the Nordic group, at both time points. Lower protein intake was confirmed by blood urea nitrogen measurements.

The protein intake in the Nordic group still fell within the safe level recommended for healthy growth in young children by the World Health Organization, noted Dr. Johansson, and no significant differences were observed in growth between the groups. Total energy intake, iron status, and duration of breastfeeding also remained similar between the groups throughout the study period.

Parents received support from research nurses via social media and monthly clinic visits, which she believes contributed to the success of the intervention, she said.
 

Nordic diet offers feasible encouragement of healthy eating

The key message for clinicians, and for parents of young children, is that “the protein-reduced, Nordic diet is both feasible and safe for infants’ growth, nutritional requirements, and development during the complementary feeding period,” Dr. Johansson said in an interview. “Thus, it may serve as a healthy and environmentally sustainable diet alternative for infants and their parents in the future.”

“Nordic foods are feasible to use when exposing infants to a variety of flavors so that healthy food preferences can be established early in life; Nordic berries and some root vegetables are preferable when introducing bitter and sour tastes during the sensitive period,” she added.

“Multicomponent interventions with long-term follow-up are required to advance the field of child nutrition research,” Dr. Johansson emphasized. Home-based interventions are lacking, and “more studies are needed to bridge the gap in research between the transfer period from baby food to family food at 1-2 years of age.”

Large, randomized controlled studies of Nordic diet during infancy and later childhood are needed as well, said Dr. Johansson. “The long-term effects of the Nordic diet during this highly dynamic period of childhood need continued follow-up to school age to give indications of any lasting health effects,” and the researchers plan to follow the current study population at 7 years of age.

Findings reinforce need for better nutrition

Previous research documents concern for childhood obesity associated with higher intake of protein, fats and overall calories in infancy, said Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview. “The inclusion of high-calorie, high-fat foods contributes to obesity in all children, so focusing on intake of fruits and vegetables is extremely important early in life,” she said.

A key barrier to the widespread use of a Nordic-type diet is that and vegetables tend to be more expensive than other foods and may not be readily available to all families, especially lower income families, Dr. Haut added.

However, for primary care clinicians, the current study reinforces the need to encourage the intake of fruits and vegetables at all ages, beginning in infancy, she said.

Looking ahead, “there is still limited information in the literature about the ideal recommended daily protein, except for increased amounts needed for preterm infants, early infancy, and during periods of healing,” Dr. Haut emphasized. “Some controls for this study were not included in the abstract, such as monitoring what foods were given to the infants in the conventional group. Parent and caregiver interpretation of recommendations can be highly variable,” she noted. Also, “The activity levels of late infancy and toddlers can vary in terms of energy usage, especially when crawling, walking, running and other exercise-related activities begin. These factors were not readily available in the abstract/study,” she said.  

The OTIS trial was sponsored by Semper. Dr. Johansson had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News.

Infants who were introduced to a low-protein diet – high in fruit, vegetables, and roots – ate more fruits and vegetables at 12 and 18 months of age, compared with those who ate a conventional diet, in a new study.

The “Nordic diet” has shown health benefits in children and adults, but has not been studied in infants, said Ulrica Johansson, MD, of Umeå (Sweden) University, in a presentation on the study at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

A healthy and sustainable diet early in life could have a significant impact on future health, Dr. Johansson said in an interview.

Dr. Johansson and colleagues aimed to investigate the effect of a Nordic diet in infants aged 4-18 months in the OTIS trial. All infants were breastfed or formula-fed at baseline.
 

Study methods and results

A total of 250 infants aged 4-6 months were randomized to consuming a Nordic diet or a conventional diet. Those in the Nordic group received exposures to Nordic foods and flavors, including Nordic fruit, berries, vegetables, and roots. Those in the conventional group received baby food products that followed the current Swedish dietary recommendations for infants. The researchers collected data on dietary intake, biomarkers, and growth from baseline up to 18 months of age.

Notably, acceptance of all the flavors in the Nordic diet was high, including those with sour or bitter taste, such as cranberry and white radish, Dr. Johansson said in her presentation. Food refusals were few, and did not differ among the Nordic food offerings.

At both 12- and 18-month follow-ups, infants in the Nordic group consumed 42%-45% more fruits and vegetables compared with those in the conventional group (P < .001). Plasma folate levels also were significantly higher in the Nordic group compared with in the conventional group, at both 12 months and 18 months (P < .001 and P < .003, respectively).

The daily mean protein intake ranged from 17% to 29% lower in the Nordic group compared with in the conventional group, at both 12 months and 18 months. The intake of protein in terms of g/kg of body weight was significantly lower in the Nordic group, at both time points. Lower protein intake was confirmed by blood urea nitrogen measurements.

The protein intake in the Nordic group still fell within the safe level recommended for healthy growth in young children by the World Health Organization, noted Dr. Johansson, and no significant differences were observed in growth between the groups. Total energy intake, iron status, and duration of breastfeeding also remained similar between the groups throughout the study period.

Parents received support from research nurses via social media and monthly clinic visits, which she believes contributed to the success of the intervention, she said.
 

Nordic diet offers feasible encouragement of healthy eating

The key message for clinicians, and for parents of young children, is that “the protein-reduced, Nordic diet is both feasible and safe for infants’ growth, nutritional requirements, and development during the complementary feeding period,” Dr. Johansson said in an interview. “Thus, it may serve as a healthy and environmentally sustainable diet alternative for infants and their parents in the future.”

“Nordic foods are feasible to use when exposing infants to a variety of flavors so that healthy food preferences can be established early in life; Nordic berries and some root vegetables are preferable when introducing bitter and sour tastes during the sensitive period,” she added.

“Multicomponent interventions with long-term follow-up are required to advance the field of child nutrition research,” Dr. Johansson emphasized. Home-based interventions are lacking, and “more studies are needed to bridge the gap in research between the transfer period from baby food to family food at 1-2 years of age.”

Large, randomized controlled studies of Nordic diet during infancy and later childhood are needed as well, said Dr. Johansson. “The long-term effects of the Nordic diet during this highly dynamic period of childhood need continued follow-up to school age to give indications of any lasting health effects,” and the researchers plan to follow the current study population at 7 years of age.

Findings reinforce need for better nutrition

Previous research documents concern for childhood obesity associated with higher intake of protein, fats and overall calories in infancy, said Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview. “The inclusion of high-calorie, high-fat foods contributes to obesity in all children, so focusing on intake of fruits and vegetables is extremely important early in life,” she said.

A key barrier to the widespread use of a Nordic-type diet is that and vegetables tend to be more expensive than other foods and may not be readily available to all families, especially lower income families, Dr. Haut added.

However, for primary care clinicians, the current study reinforces the need to encourage the intake of fruits and vegetables at all ages, beginning in infancy, she said.

Looking ahead, “there is still limited information in the literature about the ideal recommended daily protein, except for increased amounts needed for preterm infants, early infancy, and during periods of healing,” Dr. Haut emphasized. “Some controls for this study were not included in the abstract, such as monitoring what foods were given to the infants in the conventional group. Parent and caregiver interpretation of recommendations can be highly variable,” she noted. Also, “The activity levels of late infancy and toddlers can vary in terms of energy usage, especially when crawling, walking, running and other exercise-related activities begin. These factors were not readily available in the abstract/study,” she said.  

The OTIS trial was sponsored by Semper. Dr. Johansson had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News.

Infants who were introduced to a low-protein diet – high in fruit, vegetables, and roots – ate more fruits and vegetables at 12 and 18 months of age, compared with those who ate a conventional diet, in a new study.

The “Nordic diet” has shown health benefits in children and adults, but has not been studied in infants, said Ulrica Johansson, MD, of Umeå (Sweden) University, in a presentation on the study at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

A healthy and sustainable diet early in life could have a significant impact on future health, Dr. Johansson said in an interview.

Dr. Johansson and colleagues aimed to investigate the effect of a Nordic diet in infants aged 4-18 months in the OTIS trial. All infants were breastfed or formula-fed at baseline.
 

Study methods and results

A total of 250 infants aged 4-6 months were randomized to consuming a Nordic diet or a conventional diet. Those in the Nordic group received exposures to Nordic foods and flavors, including Nordic fruit, berries, vegetables, and roots. Those in the conventional group received baby food products that followed the current Swedish dietary recommendations for infants. The researchers collected data on dietary intake, biomarkers, and growth from baseline up to 18 months of age.

Notably, acceptance of all the flavors in the Nordic diet was high, including those with sour or bitter taste, such as cranberry and white radish, Dr. Johansson said in her presentation. Food refusals were few, and did not differ among the Nordic food offerings.

At both 12- and 18-month follow-ups, infants in the Nordic group consumed 42%-45% more fruits and vegetables compared with those in the conventional group (P < .001). Plasma folate levels also were significantly higher in the Nordic group compared with in the conventional group, at both 12 months and 18 months (P < .001 and P < .003, respectively).

The daily mean protein intake ranged from 17% to 29% lower in the Nordic group compared with in the conventional group, at both 12 months and 18 months. The intake of protein in terms of g/kg of body weight was significantly lower in the Nordic group, at both time points. Lower protein intake was confirmed by blood urea nitrogen measurements.

The protein intake in the Nordic group still fell within the safe level recommended for healthy growth in young children by the World Health Organization, noted Dr. Johansson, and no significant differences were observed in growth between the groups. Total energy intake, iron status, and duration of breastfeeding also remained similar between the groups throughout the study period.

Parents received support from research nurses via social media and monthly clinic visits, which she believes contributed to the success of the intervention, she said.
 

Nordic diet offers feasible encouragement of healthy eating

The key message for clinicians, and for parents of young children, is that “the protein-reduced, Nordic diet is both feasible and safe for infants’ growth, nutritional requirements, and development during the complementary feeding period,” Dr. Johansson said in an interview. “Thus, it may serve as a healthy and environmentally sustainable diet alternative for infants and their parents in the future.”

“Nordic foods are feasible to use when exposing infants to a variety of flavors so that healthy food preferences can be established early in life; Nordic berries and some root vegetables are preferable when introducing bitter and sour tastes during the sensitive period,” she added.

“Multicomponent interventions with long-term follow-up are required to advance the field of child nutrition research,” Dr. Johansson emphasized. Home-based interventions are lacking, and “more studies are needed to bridge the gap in research between the transfer period from baby food to family food at 1-2 years of age.”

Large, randomized controlled studies of Nordic diet during infancy and later childhood are needed as well, said Dr. Johansson. “The long-term effects of the Nordic diet during this highly dynamic period of childhood need continued follow-up to school age to give indications of any lasting health effects,” and the researchers plan to follow the current study population at 7 years of age.

Findings reinforce need for better nutrition

Previous research documents concern for childhood obesity associated with higher intake of protein, fats and overall calories in infancy, said Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview. “The inclusion of high-calorie, high-fat foods contributes to obesity in all children, so focusing on intake of fruits and vegetables is extremely important early in life,” she said.

A key barrier to the widespread use of a Nordic-type diet is that and vegetables tend to be more expensive than other foods and may not be readily available to all families, especially lower income families, Dr. Haut added.

However, for primary care clinicians, the current study reinforces the need to encourage the intake of fruits and vegetables at all ages, beginning in infancy, she said.

Looking ahead, “there is still limited information in the literature about the ideal recommended daily protein, except for increased amounts needed for preterm infants, early infancy, and during periods of healing,” Dr. Haut emphasized. “Some controls for this study were not included in the abstract, such as monitoring what foods were given to the infants in the conventional group. Parent and caregiver interpretation of recommendations can be highly variable,” she noted. Also, “The activity levels of late infancy and toddlers can vary in terms of energy usage, especially when crawling, walking, running and other exercise-related activities begin. These factors were not readily available in the abstract/study,” she said.  

The OTIS trial was sponsored by Semper. Dr. Johansson had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News.