Results of the phase 2 ZUMA-12 trial suggest that axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor (CAR) T-cell therapy approved to treat certain types of lymphoma, also shows promise as a treatment for another group of lymphoma patients – those with high-risk large B-cell lymphoma (LBCL) who failed two rounds of standard chemoimmunotherapy. In fact, a study author said, first-line treatment with this therapy could help usher some patients toward a cure.

The results appeared March 21, 2022, in Nature Medicine.

“The high efficacy with manageable safety profile suggest that further evaluation of axi-cel in first-line setting in patients with high-risk LBCL is warranted in a randomized, phase 3 trial comparing it to standard chemoimmunotherapy,” study lead author Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

According to Dr. Neelapu, “patients with high-risk LBCL include those with high-intermediate or high International Prognostic Index score and those with certain molecular subtypes such as double- or triple-hit lymphoma. These patients have lower response rates and lower progression-free and overall survival with standard chemoimmunotherapy.”

Treatment of these patients can be especially challenging because they are underrepresented in clinical research, hematologist Michael Dickinson, MBBS, of the Peter MacCallum Cancer Center in Melbourne, said in an interview. “They often have disease that requires urgent treatment, so there is no time to recruit them into trials. A feature of ZUMA-12 is that it allowed patients to be recruited after short exposure to chemotherapy, which means that higher-risk patients could successfully be recruited into the trial.”

Axi-cel is already Food and Drug Administration approved for treatment of relapsed or refractory LBCL after 2 or more lines of systemic therapy plus relapsed or refractory follicular lymphoma, also after two or more lines of systemic therapy, Dr. Neelapu said.

For this study, researchers administered the treatment to 40 subjects with high-risk disease from 2019-2020 (median age, 61 years; 68% male; 95% at disease stage III or IV).

The researchers reported that 78% of 37 patients in the primary efficacy analysis reached complete response rate (95% confidence interval, 62-90); the median time to first complete response rate was 30 days (range, 27-207). About 89% of these subjects reached the secondary endpoint of objective response rate (95% CI, 75-97); the median time to first objective response was 29 days (range, 27-207).

At a median follow-up of 15.9 months, 73% were still in objective response.

“This is quite remarkable,” Dr. Neelapu said. “The durability of more than 70% is far higher than what would be expected with standard chemoimmunotherapy in these patients – under 40% durability with standard chemoimmunotherapy. Also, axi-cel induces durable responses in about 40% of patients in second- and third-line setting. However, when used as part of first-line therapy in this study, durable responses were observed in more than 70% of patients, suggesting that the efficacy of axi-cel may be much higher when used in first-line setting.”

Dr. Neelapu added: “Although the follow-up is short, it is highly likely that the majority of the patients with ongoing response beyond 1 year will likely be cured of their lymphoma.”

As for side effects, no treatment-related grade 5 events occurred, but 18 patients (45%) experienced serious adverse events. Grade 3 or higher cytokine release syndrome occurred in three patients (8%) and nine experienced neurologic events (23%).

“The majority of the higher-grade adverse events observed were due to cytopenias, which were expected due to the conditioning therapy,” Dr. Neelapu said. “Such cytopenias would also have been expected if these patients had received standard chemoimmunotherapy.”

Six patients (15%) died, 4 of progressive disease after going forward to other therapies.

As for cost, Dr. Neelapu said it should be similar to that of axi-cel as an FDA-approved third-line therapy. Axi-cel is highly expensive. Research has suggested that CAR T-cell therapy can boost costs beyond standard chemotherapy by $350,000-$490,000 with gains of 2-8 years of life (J Med Econ. Jan-Dec 2021;24[1]:458-68).

The study was funded by Kite. The authors reported various disclosures.

Results of the phase 2 ZUMA-12 trial suggest that axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor (CAR) T-cell therapy approved to treat certain types of lymphoma, also shows promise as a treatment for another group of lymphoma patients – those with high-risk large B-cell lymphoma (LBCL) who failed two rounds of standard chemoimmunotherapy. In fact, a study author said, first-line treatment with this therapy could help usher some patients toward a cure.

The results appeared March 21, 2022, in Nature Medicine.

“The high efficacy with manageable safety profile suggest that further evaluation of axi-cel in first-line setting in patients with high-risk LBCL is warranted in a randomized, phase 3 trial comparing it to standard chemoimmunotherapy,” study lead author Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

According to Dr. Neelapu, “patients with high-risk LBCL include those with high-intermediate or high International Prognostic Index score and those with certain molecular subtypes such as double- or triple-hit lymphoma. These patients have lower response rates and lower progression-free and overall survival with standard chemoimmunotherapy.”

Treatment of these patients can be especially challenging because they are underrepresented in clinical research, hematologist Michael Dickinson, MBBS, of the Peter MacCallum Cancer Center in Melbourne, said in an interview. “They often have disease that requires urgent treatment, so there is no time to recruit them into trials. A feature of ZUMA-12 is that it allowed patients to be recruited after short exposure to chemotherapy, which means that higher-risk patients could successfully be recruited into the trial.”

Axi-cel is already Food and Drug Administration approved for treatment of relapsed or refractory LBCL after 2 or more lines of systemic therapy plus relapsed or refractory follicular lymphoma, also after two or more lines of systemic therapy, Dr. Neelapu said.

For this study, researchers administered the treatment to 40 subjects with high-risk disease from 2019-2020 (median age, 61 years; 68% male; 95% at disease stage III or IV).

The researchers reported that 78% of 37 patients in the primary efficacy analysis reached complete response rate (95% confidence interval, 62-90); the median time to first complete response rate was 30 days (range, 27-207). About 89% of these subjects reached the secondary endpoint of objective response rate (95% CI, 75-97); the median time to first objective response was 29 days (range, 27-207).

At a median follow-up of 15.9 months, 73% were still in objective response.

“This is quite remarkable,” Dr. Neelapu said. “The durability of more than 70% is far higher than what would be expected with standard chemoimmunotherapy in these patients – under 40% durability with standard chemoimmunotherapy. Also, axi-cel induces durable responses in about 40% of patients in second- and third-line setting. However, when used as part of first-line therapy in this study, durable responses were observed in more than 70% of patients, suggesting that the efficacy of axi-cel may be much higher when used in first-line setting.”

Dr. Neelapu added: “Although the follow-up is short, it is highly likely that the majority of the patients with ongoing response beyond 1 year will likely be cured of their lymphoma.”

As for side effects, no treatment-related grade 5 events occurred, but 18 patients (45%) experienced serious adverse events. Grade 3 or higher cytokine release syndrome occurred in three patients (8%) and nine experienced neurologic events (23%).

“The majority of the higher-grade adverse events observed were due to cytopenias, which were expected due to the conditioning therapy,” Dr. Neelapu said. “Such cytopenias would also have been expected if these patients had received standard chemoimmunotherapy.”

Six patients (15%) died, 4 of progressive disease after going forward to other therapies.

As for cost, Dr. Neelapu said it should be similar to that of axi-cel as an FDA-approved third-line therapy. Axi-cel is highly expensive. Research has suggested that CAR T-cell therapy can boost costs beyond standard chemotherapy by $350,000-$490,000 with gains of 2-8 years of life (J Med Econ. Jan-Dec 2021;24[1]:458-68).

The study was funded by Kite. The authors reported various disclosures.

Results of the phase 2 ZUMA-12 trial suggest that axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor (CAR) T-cell therapy approved to treat certain types of lymphoma, also shows promise as a treatment for another group of lymphoma patients – those with high-risk large B-cell lymphoma (LBCL) who failed two rounds of standard chemoimmunotherapy. In fact, a study author said, first-line treatment with this therapy could help usher some patients toward a cure.

The results appeared March 21, 2022, in Nature Medicine.

“The high efficacy with manageable safety profile suggest that further evaluation of axi-cel in first-line setting in patients with high-risk LBCL is warranted in a randomized, phase 3 trial comparing it to standard chemoimmunotherapy,” study lead author Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

According to Dr. Neelapu, “patients with high-risk LBCL include those with high-intermediate or high International Prognostic Index score and those with certain molecular subtypes such as double- or triple-hit lymphoma. These patients have lower response rates and lower progression-free and overall survival with standard chemoimmunotherapy.”

Treatment of these patients can be especially challenging because they are underrepresented in clinical research, hematologist Michael Dickinson, MBBS, of the Peter MacCallum Cancer Center in Melbourne, said in an interview. “They often have disease that requires urgent treatment, so there is no time to recruit them into trials. A feature of ZUMA-12 is that it allowed patients to be recruited after short exposure to chemotherapy, which means that higher-risk patients could successfully be recruited into the trial.”

Axi-cel is already Food and Drug Administration approved for treatment of relapsed or refractory LBCL after 2 or more lines of systemic therapy plus relapsed or refractory follicular lymphoma, also after two or more lines of systemic therapy, Dr. Neelapu said.

For this study, researchers administered the treatment to 40 subjects with high-risk disease from 2019-2020 (median age, 61 years; 68% male; 95% at disease stage III or IV).

The researchers reported that 78% of 37 patients in the primary efficacy analysis reached complete response rate (95% confidence interval, 62-90); the median time to first complete response rate was 30 days (range, 27-207). About 89% of these subjects reached the secondary endpoint of objective response rate (95% CI, 75-97); the median time to first objective response was 29 days (range, 27-207).

At a median follow-up of 15.9 months, 73% were still in objective response.

“This is quite remarkable,” Dr. Neelapu said. “The durability of more than 70% is far higher than what would be expected with standard chemoimmunotherapy in these patients – under 40% durability with standard chemoimmunotherapy. Also, axi-cel induces durable responses in about 40% of patients in second- and third-line setting. However, when used as part of first-line therapy in this study, durable responses were observed in more than 70% of patients, suggesting that the efficacy of axi-cel may be much higher when used in first-line setting.”

Dr. Neelapu added: “Although the follow-up is short, it is highly likely that the majority of the patients with ongoing response beyond 1 year will likely be cured of their lymphoma.”

As for side effects, no treatment-related grade 5 events occurred, but 18 patients (45%) experienced serious adverse events. Grade 3 or higher cytokine release syndrome occurred in three patients (8%) and nine experienced neurologic events (23%).

“The majority of the higher-grade adverse events observed were due to cytopenias, which were expected due to the conditioning therapy,” Dr. Neelapu said. “Such cytopenias would also have been expected if these patients had received standard chemoimmunotherapy.”

Six patients (15%) died, 4 of progressive disease after going forward to other therapies.

As for cost, Dr. Neelapu said it should be similar to that of axi-cel as an FDA-approved third-line therapy. Axi-cel is highly expensive. Research has suggested that CAR T-cell therapy can boost costs beyond standard chemotherapy by $350,000-$490,000 with gains of 2-8 years of life (J Med Econ. Jan-Dec 2021;24[1]:458-68).

The study was funded by Kite. The authors reported various disclosures.

An intervention with extra virgin olive oil in a pilot study of 22 patients significantly improved biomarkers for early stage chronic lymphocytic leukemia (CLL).

Olive oil is a major component of the Mediterranean diet, and olive phenols have been shown to convey antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects by modulating various molecular pathways, Andrea Paola Rojas Gil, PhD, of the University of Peloponnese, Tripoli, Greece, and colleagues wrote.

In most patients, CLL is incurable, but those at the early stages do not need immediate therapy and may benefit from an intervention to prevent disease progression, the authors wrote. Previous research suggested that dietary intervention exerts a salutary effect on early CLL, and in vitro studies suggested that oleocanthal, a component of extra virgin olive oil, induced anticancer activity.

In a study published in Frontiers in Oncology, the researchers enrolled adults with early stage CLL who had not undergone chemotherapy or other treatment. All patients adhered to a Mediterranean-style diet.

After a washout period of 9-12 months, the researchers randomized 22 patients to extra virgin olive oil high in oleocanthal and oleacein (high OC/OL-EVOO). Patients in the intervention group consumed 40 mL/day of high OC/OL-EVOO before meals. Their average age was 71 years; 10 were women and 12 were men.

The primary outcomes included changes in hematological, biochemical, and apoptotic markers. After 6 months, patients in the intervention group showed a statistically significant reduction in white blood cells and lymphocyte count, compared with measurements taken 3 months before the intervention. The WBC decrease was greatest among patients with the highest WBC levels at baseline.

As for biochemical markers, the researchers observed a significant decrease in glucose levels during the intervention, but no significant effects on metabolic indexes or renal function.

After 3 months and also after 6 months of the olive oil intervention, patients showed a significant increase in the apoptotic markers ccK18 and Apo1-Fas (P ≤ .05 for both), as well as an increase in the cell cycle negative regulator p21. The dietary intervention also was associated with significant decreases in expression of the antiapoptotic protein survivin and in cyclin D, a positive cell cycle regulator protein.

Further, patients who had a high ccK18 level at baseline showed a significantly greater increase in ccK18 after the intervention, compared with those with lower ccK18 at baseline (P = .001).

Notably, “a negative correlation of the WBC at the end of the dietary intervention with the fluctuation of the protein expression of the apoptotic marker ccK18 (final – initial) was observed,” the researchers wrote in their discussion.

The study findings were limited by several factors including the small sample size, short intervention time, and pilot design, the researchers said. Other limitations include the possible effect of other unmeasured properties of olive oil.

However, the results reflect previous studies showing the benefits of a Mediterranean-type diet, and they represent the first clinical trial to indicate possible beneficial effects from oleocanthal and oleacein on the progression of CLL. Therefore, the authors concluded, the study is worthy of a large, multicenter trial.
 

Pilot data merit more research

In an interview, corresponding author Prokopios Magiatis, PhD, noted that CLL is “the most commonly diagnosed adult leukemia in Western countries and is responsible for about one in four cases of all leukemias.” CLL remains incurable in most patients, and ways to delay disease progression are needed.

“Oleocanthal is the active ingredient of early harvest olive oil with proven anticancer activities in vitro and in vivo,” Dr. Magiatis explained. “For this reason, it was a unique challenge to investigate the anticancer activity of this compound for the first time in humans through the dietary consumption of specifically selected olive oil.” He expressed surprise at the beneficial effects of high-oleocanthal olive oil, not only to the white blood cells, but also to glucose levels.

“It seems that oleocanthal can activate mechanisms related to the apoptosis of cancer cells, and also mechanisms related to blood glucose regulation without affecting any normal cells of the body,” he said. “All anticancer drugs usually have severe side effects, however the administration of 25 mg of oleocanthal through the dietary consumption of olive oil did not present any harmful effects for at least 6 months of everyday use.

“The addition of naturally produced high-oleocanthal olive oil in the diet of early-stage CLL patients at a dose of three tablespoons per day [40 mL] is a practice that may lower the cancerous white blood cells of the patients without any risk,” said Dr. Magiatis. “High-oleocanthal early-harvest olive oil has been consumed for centuries, and may be the key of longevity of several Mediterranean populations.

“In our study, the number of the white blood cells returned back to the number it was one year before the initiation of the study; this clearly shows that it could be a significant factor for the delay of the progress of the disease,” he said.

The current trial was a pilot study in one hospital with only 22 patients for 6 months, said Dr. Magiatis. “We are currently preparing the expansion of the study to other hospitals and other countries, and we aim to include at least 100 patients for at least 1 year, to validate the already-obtained beneficial results.”

The clinical trial is supported by the nonprofit organization World Olive Center for Health, he added.

The current study received no outside funding. The researchers had no financial conflicts to disclose.

An intervention with extra virgin olive oil in a pilot study of 22 patients significantly improved biomarkers for early stage chronic lymphocytic leukemia (CLL).

Olive oil is a major component of the Mediterranean diet, and olive phenols have been shown to convey antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects by modulating various molecular pathways, Andrea Paola Rojas Gil, PhD, of the University of Peloponnese, Tripoli, Greece, and colleagues wrote.

In most patients, CLL is incurable, but those at the early stages do not need immediate therapy and may benefit from an intervention to prevent disease progression, the authors wrote. Previous research suggested that dietary intervention exerts a salutary effect on early CLL, and in vitro studies suggested that oleocanthal, a component of extra virgin olive oil, induced anticancer activity.

In a study published in Frontiers in Oncology, the researchers enrolled adults with early stage CLL who had not undergone chemotherapy or other treatment. All patients adhered to a Mediterranean-style diet.

After a washout period of 9-12 months, the researchers randomized 22 patients to extra virgin olive oil high in oleocanthal and oleacein (high OC/OL-EVOO). Patients in the intervention group consumed 40 mL/day of high OC/OL-EVOO before meals. Their average age was 71 years; 10 were women and 12 were men.

The primary outcomes included changes in hematological, biochemical, and apoptotic markers. After 6 months, patients in the intervention group showed a statistically significant reduction in white blood cells and lymphocyte count, compared with measurements taken 3 months before the intervention. The WBC decrease was greatest among patients with the highest WBC levels at baseline.

As for biochemical markers, the researchers observed a significant decrease in glucose levels during the intervention, but no significant effects on metabolic indexes or renal function.

After 3 months and also after 6 months of the olive oil intervention, patients showed a significant increase in the apoptotic markers ccK18 and Apo1-Fas (P ≤ .05 for both), as well as an increase in the cell cycle negative regulator p21. The dietary intervention also was associated with significant decreases in expression of the antiapoptotic protein survivin and in cyclin D, a positive cell cycle regulator protein.

Further, patients who had a high ccK18 level at baseline showed a significantly greater increase in ccK18 after the intervention, compared with those with lower ccK18 at baseline (P = .001).

Notably, “a negative correlation of the WBC at the end of the dietary intervention with the fluctuation of the protein expression of the apoptotic marker ccK18 (final – initial) was observed,” the researchers wrote in their discussion.

The study findings were limited by several factors including the small sample size, short intervention time, and pilot design, the researchers said. Other limitations include the possible effect of other unmeasured properties of olive oil.

However, the results reflect previous studies showing the benefits of a Mediterranean-type diet, and they represent the first clinical trial to indicate possible beneficial effects from oleocanthal and oleacein on the progression of CLL. Therefore, the authors concluded, the study is worthy of a large, multicenter trial.
 

Pilot data merit more research

In an interview, corresponding author Prokopios Magiatis, PhD, noted that CLL is “the most commonly diagnosed adult leukemia in Western countries and is responsible for about one in four cases of all leukemias.” CLL remains incurable in most patients, and ways to delay disease progression are needed.

“Oleocanthal is the active ingredient of early harvest olive oil with proven anticancer activities in vitro and in vivo,” Dr. Magiatis explained. “For this reason, it was a unique challenge to investigate the anticancer activity of this compound for the first time in humans through the dietary consumption of specifically selected olive oil.” He expressed surprise at the beneficial effects of high-oleocanthal olive oil, not only to the white blood cells, but also to glucose levels.

“It seems that oleocanthal can activate mechanisms related to the apoptosis of cancer cells, and also mechanisms related to blood glucose regulation without affecting any normal cells of the body,” he said. “All anticancer drugs usually have severe side effects, however the administration of 25 mg of oleocanthal through the dietary consumption of olive oil did not present any harmful effects for at least 6 months of everyday use.

“The addition of naturally produced high-oleocanthal olive oil in the diet of early-stage CLL patients at a dose of three tablespoons per day [40 mL] is a practice that may lower the cancerous white blood cells of the patients without any risk,” said Dr. Magiatis. “High-oleocanthal early-harvest olive oil has been consumed for centuries, and may be the key of longevity of several Mediterranean populations.

“In our study, the number of the white blood cells returned back to the number it was one year before the initiation of the study; this clearly shows that it could be a significant factor for the delay of the progress of the disease,” he said.

The current trial was a pilot study in one hospital with only 22 patients for 6 months, said Dr. Magiatis. “We are currently preparing the expansion of the study to other hospitals and other countries, and we aim to include at least 100 patients for at least 1 year, to validate the already-obtained beneficial results.”

The clinical trial is supported by the nonprofit organization World Olive Center for Health, he added.

The current study received no outside funding. The researchers had no financial conflicts to disclose.

An intervention with extra virgin olive oil in a pilot study of 22 patients significantly improved biomarkers for early stage chronic lymphocytic leukemia (CLL).

Olive oil is a major component of the Mediterranean diet, and olive phenols have been shown to convey antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects by modulating various molecular pathways, Andrea Paola Rojas Gil, PhD, of the University of Peloponnese, Tripoli, Greece, and colleagues wrote.

In most patients, CLL is incurable, but those at the early stages do not need immediate therapy and may benefit from an intervention to prevent disease progression, the authors wrote. Previous research suggested that dietary intervention exerts a salutary effect on early CLL, and in vitro studies suggested that oleocanthal, a component of extra virgin olive oil, induced anticancer activity.

In a study published in Frontiers in Oncology, the researchers enrolled adults with early stage CLL who had not undergone chemotherapy or other treatment. All patients adhered to a Mediterranean-style diet.

After a washout period of 9-12 months, the researchers randomized 22 patients to extra virgin olive oil high in oleocanthal and oleacein (high OC/OL-EVOO). Patients in the intervention group consumed 40 mL/day of high OC/OL-EVOO before meals. Their average age was 71 years; 10 were women and 12 were men.

The primary outcomes included changes in hematological, biochemical, and apoptotic markers. After 6 months, patients in the intervention group showed a statistically significant reduction in white blood cells and lymphocyte count, compared with measurements taken 3 months before the intervention. The WBC decrease was greatest among patients with the highest WBC levels at baseline.

As for biochemical markers, the researchers observed a significant decrease in glucose levels during the intervention, but no significant effects on metabolic indexes or renal function.

After 3 months and also after 6 months of the olive oil intervention, patients showed a significant increase in the apoptotic markers ccK18 and Apo1-Fas (P ≤ .05 for both), as well as an increase in the cell cycle negative regulator p21. The dietary intervention also was associated with significant decreases in expression of the antiapoptotic protein survivin and in cyclin D, a positive cell cycle regulator protein.

Further, patients who had a high ccK18 level at baseline showed a significantly greater increase in ccK18 after the intervention, compared with those with lower ccK18 at baseline (P = .001).

Notably, “a negative correlation of the WBC at the end of the dietary intervention with the fluctuation of the protein expression of the apoptotic marker ccK18 (final – initial) was observed,” the researchers wrote in their discussion.

The study findings were limited by several factors including the small sample size, short intervention time, and pilot design, the researchers said. Other limitations include the possible effect of other unmeasured properties of olive oil.

However, the results reflect previous studies showing the benefits of a Mediterranean-type diet, and they represent the first clinical trial to indicate possible beneficial effects from oleocanthal and oleacein on the progression of CLL. Therefore, the authors concluded, the study is worthy of a large, multicenter trial.
 

Pilot data merit more research

In an interview, corresponding author Prokopios Magiatis, PhD, noted that CLL is “the most commonly diagnosed adult leukemia in Western countries and is responsible for about one in four cases of all leukemias.” CLL remains incurable in most patients, and ways to delay disease progression are needed.

“Oleocanthal is the active ingredient of early harvest olive oil with proven anticancer activities in vitro and in vivo,” Dr. Magiatis explained. “For this reason, it was a unique challenge to investigate the anticancer activity of this compound for the first time in humans through the dietary consumption of specifically selected olive oil.” He expressed surprise at the beneficial effects of high-oleocanthal olive oil, not only to the white blood cells, but also to glucose levels.

“It seems that oleocanthal can activate mechanisms related to the apoptosis of cancer cells, and also mechanisms related to blood glucose regulation without affecting any normal cells of the body,” he said. “All anticancer drugs usually have severe side effects, however the administration of 25 mg of oleocanthal through the dietary consumption of olive oil did not present any harmful effects for at least 6 months of everyday use.

“The addition of naturally produced high-oleocanthal olive oil in the diet of early-stage CLL patients at a dose of three tablespoons per day [40 mL] is a practice that may lower the cancerous white blood cells of the patients without any risk,” said Dr. Magiatis. “High-oleocanthal early-harvest olive oil has been consumed for centuries, and may be the key of longevity of several Mediterranean populations.

“In our study, the number of the white blood cells returned back to the number it was one year before the initiation of the study; this clearly shows that it could be a significant factor for the delay of the progress of the disease,” he said.

The current trial was a pilot study in one hospital with only 22 patients for 6 months, said Dr. Magiatis. “We are currently preparing the expansion of the study to other hospitals and other countries, and we aim to include at least 100 patients for at least 1 year, to validate the already-obtained beneficial results.”

The clinical trial is supported by the nonprofit organization World Olive Center for Health, he added.

The current study received no outside funding. The researchers had no financial conflicts to disclose.

For patients with psoriatic arthritis (PsA) whose condition doesn’t respond adequately to methotrexate, addition of the tumor necrosis factor (TNF) inhibitor adalimumab increased the likelihood of achieving minimum disease activity (MDA), compared with escalation of MTX dose, according to results from a phase 4, open-label study.

The new study is one of only a few to compare treatment protocols in a field that has seen new therapeutic options become available in recent years. That lack of evidence can leave patients and physicians uncertain about the next step if the initial results of treatment are disappointing.

“There are some gaps in our database and our understanding of psoriatic arthritis, compared to rheumatoid arthritis, where we have had many more studies over the years,” Arthur Kavanaugh, MD, told this news organization when asked to comment on the study.

The trial provides one answer, at least. “There was a clear-cut signal that it made more sense to add adalimumab at that early juncture where a person is not quite doing well enough on methotrexate to satisfy our goal of getting the patient to low disease activity. It gives us as clinicians some ammunition to speak to our insurance formulary people on this side of the Atlantic, or [for] people in the U.K. to go to their local regulatory board that approves medicines and be able to show them some actual practically derived evidence about this very common question that comes up in practice,” senior and corresponding author Philip Mease, MD, said in an interview. The study was published online in The Lancet Rheumatology.

“When a clinician and patient are making the decision to move on from methotrexate monotherapy, either because of lack of efficacy or safety issues, tolerability issues, it makes most sense to add on a biologic medication such as a TNF inhibitor at that juncture, rather than intensifying methotrexate therapy,” said Dr. Mease, who is director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health and a clinical professor at the University of Washington, both in Seattle.

Physicians may be tempted to bump up the dose for patients who can tolerate MTX and who may be showing some improvement, but the new study should prompt a different strategy if MDA isn’t achieved, according to Oliver FitzGerald, MD, a professor at the Conway Institute for Biomolecular Research at University College Dublin, who was asked to comment on the study. “This study clearly shows that the early addition of adalimumab is the better choice, and it would change practice. That being said, there are clearly some patients who do respond sufficiently to increasing methotrexate, and it would be useful to be able to predict which patients might do that.” He added that the study focused on adalimumab and that the results might not apply to other biologics.

The study should encourage use of a quantitative treat-to-target measure like MDA, which is a composite measure of patient perspectives, Dr. Mease said. The American College of Rheumatology and National Psoriasis Foundation and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have recommended the use of MDA as a treat-to-target measure for PsA. The ACR and NPF recommend TNF inhibitors as first-line treatment, and GRAPPA includes it as a first-line option, whereas the European Alliance of Associations for Rheumatology recommends MTX only in the first line.

The study also suggests that there is value to using adalimumab on a weekly basis if an every-other-week schedule doesn’t produce the desired results. This strategy hasn’t been examined in PsA or even RA, according to Dr. Kavanaugh, who is a professor of medicine at the University of California, San Diego. “It did look like raising the dose might be an option for patients who are on every other week and are not doing quite as well as we would have hoped.”

The CONTROL study was a phase 4, two-part, open-label study. It included 245 patients in 14 countries who did not have MDA with MTX. In the first part of the study, patients were randomly assigned to receive weekly 15 mg MTX along with 40 mg adalimumab every other week, or escalation of MTX dose to 20-25 mg/week. MTX could be administered orally or intravenously. After 16 weeks (part 1), for patients who achieved MDA, current therapy was maintained or modified; for patients who did not achieve MDA, therapy was escalated over the following 16 weeks by giving adalimumab every week in the combination group or by adding adalimumab every other week in the MTX escalation arm.

Overall, 95% of the MTX plus adalimumab group completed part 1, as did 90% of the MTX escalation group. A total of 41% of the adalimumab group achieved MDA at 16 weeks versus 13% of the MTX group (P < .0001). The result held after accounting for sex and the interaction between sex and treatment (odds ratio, 4.6; 95% confidence interval, 2.4-8.9).

Among patients who achieved MDA at 16 weeks, 80% in the adalimumab group continued to have MDA at 32 weeks even after MTX had been withdrawn. Of those in the MTX escalation group, 67% continued to have MDA at 32 weeks with continued escalation of MTX.

Of the patients in the MTX escalation group who did not respond, 55% reached MDA following introduction of adalimumab every other week. Of those who did not respond to adalimumab, 30% reached MDA after switching to weekly adalimumab doses.

The study was open label, and patients who received adalimumab may have expected some improvement; that could have skewed the findings, Dr. Kavanaugh said. “I think that’s an important consideration as we interpret the data. The people who got the MTX arm probably had less of an expectation that they were going to do much better than those who switched to the adalimumab, as did the doctors taking care of them.”

The CONTROL study was funded by AbbVie. Dr. Mease has received research grants, consulted for, or received speaker honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB. Dr. FitzGerald has received grant support and honoraria from AbbVie. Dr. Kavanaugh has received research support from or consulted for AbbVie, Janssen, Pfizer, Lilly, Novartis, and UCB.

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

For patients with psoriatic arthritis (PsA) whose condition doesn’t respond adequately to methotrexate, addition of the tumor necrosis factor (TNF) inhibitor adalimumab increased the likelihood of achieving minimum disease activity (MDA), compared with escalation of MTX dose, according to results from a phase 4, open-label study.

The new study is one of only a few to compare treatment protocols in a field that has seen new therapeutic options become available in recent years. That lack of evidence can leave patients and physicians uncertain about the next step if the initial results of treatment are disappointing.

“There are some gaps in our database and our understanding of psoriatic arthritis, compared to rheumatoid arthritis, where we have had many more studies over the years,” Arthur Kavanaugh, MD, told this news organization when asked to comment on the study.

The trial provides one answer, at least. “There was a clear-cut signal that it made more sense to add adalimumab at that early juncture where a person is not quite doing well enough on methotrexate to satisfy our goal of getting the patient to low disease activity. It gives us as clinicians some ammunition to speak to our insurance formulary people on this side of the Atlantic, or [for] people in the U.K. to go to their local regulatory board that approves medicines and be able to show them some actual practically derived evidence about this very common question that comes up in practice,” senior and corresponding author Philip Mease, MD, said in an interview. The study was published online in The Lancet Rheumatology.

“When a clinician and patient are making the decision to move on from methotrexate monotherapy, either because of lack of efficacy or safety issues, tolerability issues, it makes most sense to add on a biologic medication such as a TNF inhibitor at that juncture, rather than intensifying methotrexate therapy,” said Dr. Mease, who is director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health and a clinical professor at the University of Washington, both in Seattle.

Physicians may be tempted to bump up the dose for patients who can tolerate MTX and who may be showing some improvement, but the new study should prompt a different strategy if MDA isn’t achieved, according to Oliver FitzGerald, MD, a professor at the Conway Institute for Biomolecular Research at University College Dublin, who was asked to comment on the study. “This study clearly shows that the early addition of adalimumab is the better choice, and it would change practice. That being said, there are clearly some patients who do respond sufficiently to increasing methotrexate, and it would be useful to be able to predict which patients might do that.” He added that the study focused on adalimumab and that the results might not apply to other biologics.

The study should encourage use of a quantitative treat-to-target measure like MDA, which is a composite measure of patient perspectives, Dr. Mease said. The American College of Rheumatology and National Psoriasis Foundation and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have recommended the use of MDA as a treat-to-target measure for PsA. The ACR and NPF recommend TNF inhibitors as first-line treatment, and GRAPPA includes it as a first-line option, whereas the European Alliance of Associations for Rheumatology recommends MTX only in the first line.

The study also suggests that there is value to using adalimumab on a weekly basis if an every-other-week schedule doesn’t produce the desired results. This strategy hasn’t been examined in PsA or even RA, according to Dr. Kavanaugh, who is a professor of medicine at the University of California, San Diego. “It did look like raising the dose might be an option for patients who are on every other week and are not doing quite as well as we would have hoped.”

The CONTROL study was a phase 4, two-part, open-label study. It included 245 patients in 14 countries who did not have MDA with MTX. In the first part of the study, patients were randomly assigned to receive weekly 15 mg MTX along with 40 mg adalimumab every other week, or escalation of MTX dose to 20-25 mg/week. MTX could be administered orally or intravenously. After 16 weeks (part 1), for patients who achieved MDA, current therapy was maintained or modified; for patients who did not achieve MDA, therapy was escalated over the following 16 weeks by giving adalimumab every week in the combination group or by adding adalimumab every other week in the MTX escalation arm.

Overall, 95% of the MTX plus adalimumab group completed part 1, as did 90% of the MTX escalation group. A total of 41% of the adalimumab group achieved MDA at 16 weeks versus 13% of the MTX group (P < .0001). The result held after accounting for sex and the interaction between sex and treatment (odds ratio, 4.6; 95% confidence interval, 2.4-8.9).

Among patients who achieved MDA at 16 weeks, 80% in the adalimumab group continued to have MDA at 32 weeks even after MTX had been withdrawn. Of those in the MTX escalation group, 67% continued to have MDA at 32 weeks with continued escalation of MTX.

Of the patients in the MTX escalation group who did not respond, 55% reached MDA following introduction of adalimumab every other week. Of those who did not respond to adalimumab, 30% reached MDA after switching to weekly adalimumab doses.

The study was open label, and patients who received adalimumab may have expected some improvement; that could have skewed the findings, Dr. Kavanaugh said. “I think that’s an important consideration as we interpret the data. The people who got the MTX arm probably had less of an expectation that they were going to do much better than those who switched to the adalimumab, as did the doctors taking care of them.”

The CONTROL study was funded by AbbVie. Dr. Mease has received research grants, consulted for, or received speaker honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB. Dr. FitzGerald has received grant support and honoraria from AbbVie. Dr. Kavanaugh has received research support from or consulted for AbbVie, Janssen, Pfizer, Lilly, Novartis, and UCB.

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

For patients with psoriatic arthritis (PsA) whose condition doesn’t respond adequately to methotrexate, addition of the tumor necrosis factor (TNF) inhibitor adalimumab increased the likelihood of achieving minimum disease activity (MDA), compared with escalation of MTX dose, according to results from a phase 4, open-label study.

The new study is one of only a few to compare treatment protocols in a field that has seen new therapeutic options become available in recent years. That lack of evidence can leave patients and physicians uncertain about the next step if the initial results of treatment are disappointing.

“There are some gaps in our database and our understanding of psoriatic arthritis, compared to rheumatoid arthritis, where we have had many more studies over the years,” Arthur Kavanaugh, MD, told this news organization when asked to comment on the study.

The trial provides one answer, at least. “There was a clear-cut signal that it made more sense to add adalimumab at that early juncture where a person is not quite doing well enough on methotrexate to satisfy our goal of getting the patient to low disease activity. It gives us as clinicians some ammunition to speak to our insurance formulary people on this side of the Atlantic, or [for] people in the U.K. to go to their local regulatory board that approves medicines and be able to show them some actual practically derived evidence about this very common question that comes up in practice,” senior and corresponding author Philip Mease, MD, said in an interview. The study was published online in The Lancet Rheumatology.

“When a clinician and patient are making the decision to move on from methotrexate monotherapy, either because of lack of efficacy or safety issues, tolerability issues, it makes most sense to add on a biologic medication such as a TNF inhibitor at that juncture, rather than intensifying methotrexate therapy,” said Dr. Mease, who is director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health and a clinical professor at the University of Washington, both in Seattle.

Physicians may be tempted to bump up the dose for patients who can tolerate MTX and who may be showing some improvement, but the new study should prompt a different strategy if MDA isn’t achieved, according to Oliver FitzGerald, MD, a professor at the Conway Institute for Biomolecular Research at University College Dublin, who was asked to comment on the study. “This study clearly shows that the early addition of adalimumab is the better choice, and it would change practice. That being said, there are clearly some patients who do respond sufficiently to increasing methotrexate, and it would be useful to be able to predict which patients might do that.” He added that the study focused on adalimumab and that the results might not apply to other biologics.

The study should encourage use of a quantitative treat-to-target measure like MDA, which is a composite measure of patient perspectives, Dr. Mease said. The American College of Rheumatology and National Psoriasis Foundation and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have recommended the use of MDA as a treat-to-target measure for PsA. The ACR and NPF recommend TNF inhibitors as first-line treatment, and GRAPPA includes it as a first-line option, whereas the European Alliance of Associations for Rheumatology recommends MTX only in the first line.

The study also suggests that there is value to using adalimumab on a weekly basis if an every-other-week schedule doesn’t produce the desired results. This strategy hasn’t been examined in PsA or even RA, according to Dr. Kavanaugh, who is a professor of medicine at the University of California, San Diego. “It did look like raising the dose might be an option for patients who are on every other week and are not doing quite as well as we would have hoped.”

The CONTROL study was a phase 4, two-part, open-label study. It included 245 patients in 14 countries who did not have MDA with MTX. In the first part of the study, patients were randomly assigned to receive weekly 15 mg MTX along with 40 mg adalimumab every other week, or escalation of MTX dose to 20-25 mg/week. MTX could be administered orally or intravenously. After 16 weeks (part 1), for patients who achieved MDA, current therapy was maintained or modified; for patients who did not achieve MDA, therapy was escalated over the following 16 weeks by giving adalimumab every week in the combination group or by adding adalimumab every other week in the MTX escalation arm.

Overall, 95% of the MTX plus adalimumab group completed part 1, as did 90% of the MTX escalation group. A total of 41% of the adalimumab group achieved MDA at 16 weeks versus 13% of the MTX group (P < .0001). The result held after accounting for sex and the interaction between sex and treatment (odds ratio, 4.6; 95% confidence interval, 2.4-8.9).

Among patients who achieved MDA at 16 weeks, 80% in the adalimumab group continued to have MDA at 32 weeks even after MTX had been withdrawn. Of those in the MTX escalation group, 67% continued to have MDA at 32 weeks with continued escalation of MTX.

Of the patients in the MTX escalation group who did not respond, 55% reached MDA following introduction of adalimumab every other week. Of those who did not respond to adalimumab, 30% reached MDA after switching to weekly adalimumab doses.

The study was open label, and patients who received adalimumab may have expected some improvement; that could have skewed the findings, Dr. Kavanaugh said. “I think that’s an important consideration as we interpret the data. The people who got the MTX arm probably had less of an expectation that they were going to do much better than those who switched to the adalimumab, as did the doctors taking care of them.”

The CONTROL study was funded by AbbVie. Dr. Mease has received research grants, consulted for, or received speaker honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB. Dr. FitzGerald has received grant support and honoraria from AbbVie. Dr. Kavanaugh has received research support from or consulted for AbbVie, Janssen, Pfizer, Lilly, Novartis, and UCB.

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

After the excitement and the well-deserved celebrations of matching in a gastroenterology fellowship program, a whole new set of unanswered questions and worries can start forming in a first-year fellow’s mind. “I made it, but now what? How do I learn a whole new career skill like endoscopy? Is my GI knowledge solid and wide enough to manage patients and answer the medical team consult? How will I keep up with my reading and learning with a busy fellowship schedule? How do I balance growth in clinical knowledge, endoscopy, and research? Can I integrate ‘life’ alongside a busy fellowship?” All of these questions and more can be overwhelming to answer in the beginning. The following guide is designed to help you through this transition and navigate the various aspects of first-year fellowship. 

First-year goals

It is important to keep in mind that you have 3 full years to become a well-rounded, highly skilled, and knowledgeable gastroenterologist and endoscopist. So, set realistic goals and expectations for your first year, but be mindful that this year also lays the solid foundations of who you will become as a clinician, educator, or researcher.

One of the main goals of fellowship is to learn and implement evidence-based medicine in the diagnosis and management of GI conditions, as well as to learn endoscopic skills and ethics, all while keeping the patient (as a whole person) at the center of what you do. According to a recently published article by Bollipo and colleagues,¹ the overall growth as a gastroenterologist not only depends on acquisition of knowledge but also involves cultivating teamwork, communication, situational awareness, compassion, leadership, and situational awareness. Beyond your medical education, your professional growth is also dependent on intentionally working towards acquiring the following skills:

1. Manage your time efficiently and prioritize your daily tasks

2. Become a consultant: effectively communicate with others, teach, lead, and delegate as appropriate

3. Work as a team with colleagues, faculty, and endoscopy staff

4. Develop critical thinking, give and receive constructive feedback, and understand your skills, limitations, and growth potential

5. Identify mentors and potential niche area

6. Start building your professional network and your reputation

7. Get involved in national GI societies

Consults

Mindset

Shifting gear from residency to fellowship involves a shifting of your clinical mindset too, going from being part of a primary care team responsible for all aspects of a patient’s medical care, to that of a consulting team focused on a patient’s GI condition. It is important to find the right balance of refraining from micromanaging non-GI comorbidities while being fully aware of their impact on your diagnostic and therapeutic approach to the GI condition.

Let’s face it, you will not always get “exciting and interesting GI cases” consults, and on a busy day some consultations might feel unnecessary and frustrating to you. Remember that what seems obvious to you, based on your focused GI knowledge, might not be so simple to the primary team. In addition, every consult is an opportunity to improve your approach to patient care, as well as an opportunity to learn and teach others, from medical students to residents. So, always be professional and respectful when you pick up the phone, and build positive collaborative bridges between you and the medical or surgical consulting teams. Be the GI fellow others are not reluctant to call for help, and better, be the one who communicates GI pearls along the way, inspires others to join the field of gastroenterology, and positively represent the GI division.
 

Triage

When you answer your consult page, ask the primary team what specific question they have for you and/or what is the main GI complaint or test abnormality the patient has. This will help you assess the urgency and the complexity of the consult, and hence allow you to prioritize each consult (which one you need to see first and give the attending a heads-up), assign (or not) a rotating medical resident or student to the consult, tailor your preliminary recommendations to the primary team, and anticipate the need for a procedure. When you anticipate a procedure, assess its (semi-)urgency to get the process ready for same day or a bedside procedure by getting information on the patient’s vitals, basic labs, significant acute comorbidities, and supportive therapies in place. In other words, by judiciously obtaining key information from the primary team, you can efficiently triage the consults and keep your day organized and manageable (for the most part). Learn to divide and conquer the tasks of the day: split inpatient endoscopy and consults with your cofellows, assign appropriate consults and follow-ups to residents or students rotating on the GI service, and properly communicate with the primary team a plan of care (even a preliminary one) to avoid recurrent pages and interruptions. Some days the number or urgency of the consults and the required multitasking can be overwhelming: stop, breathe, and ask for help from your co-fellows and your attending. Remember, this is a fellowship, not a solo-ship and your program is here to support your work and growth.

Communication

Timely and efficient communication, between you and the different stakeholders, is crucial to provide optimal patient care and minimize the risk of “things falling through the cracks”. Convey to the primary team your recommendations and plan of care clearly, and use direct verbal communication (not just a note in the chart) when managing complex or urgent situations. Obtain information regarding current patient level of care (i.e., ICU), isolation precautions, and cardiac devices (i.e., left ventricular assist device). Keep the dialogue open with your attending about acutely ill patients and potentially urgent procedures. Inform the endoscopy suite early that you are adding a procedure on the same day, and communicate anticipated needs (such as intubation, fluoroscopy room, pediatric scope, stent). Using a “closed-loop” communication structure can ensure that your recommendations are received and implemented appropriately.² 

Time management and structure

Having a structured routine to your day, in what seems to be a chaotic process of juggling different duties and being in different locations at once, will ensure that you efficiently complete your tasks in a timely manner. Find what works best for you, taking into account the challenges and resources available to you, such as the number of fellows and other trainees on the GI consult service, the average number of consults per day and their acuity, the availability of inpatient protocols for specific clinical situations (GI bleed, acute severe ulcerative colitis, etc.), and the time and style preferences of the rounding attending. We suggest the following schedule on a consult day: Round early in the morning and leave a note in the chart and/or communicate with the team key information, then review with the rotating trainees the patients they are following and personally reassess some patients as needed. Inform the endoscopy suite of the same day procedures and let your attending know of any issues that require immediate attention. Take your team and head to radiology and review the imaging studies on your patients. Learn and teach key points in diagnosis and therapeutic approach as you move through your day from the inpatient floors to the hallways. Divide consults during the day with your team and agree on a time to touch base. Review your patient list at the end of the day and assess which patients the GI service no longer need to follow and communicate that clearly to the primary team along with the appropriate outpatient GI care follow-up. Let the endoscopy suite know of any procedures you are adding for the next day along with their degree of urgency to allow the charge nurse to prioritize cases. When you leave the hospital, be intentional with your free time: Read about the GI conditions you have encountered, enjoy some fun relaxing time, and rest!

Call

Know your call environment and your emergency cart

Familiarize yourself with the locations where you could potentially perform an emergent case (i.e., the ICU, ED, operating room) and the relevant points of contact (such as the charge nurse, the anesthesia team, the on-call tech team) for overnight or weekend cases. Whether or not you have an endoscopy support team on call, learn to set up the emergency cart, find and check your equipment, and troubleshoot technical issues by soliciting an “in-service” from senior fellows or the endoscopy technical support staff. Before heading to an urgent case, double check that you have your “bleeder” or “food impaction” tools. For food impaction, consider obtaining rat tooth forceps, snares, Roth nets, and an overtube. For bleeding cases, obtain a therapeutic upper endoscope, hemostatic clips, clear caps, injection needles, epinephrine, HemosprayTM, banding kits, and the appropriate electrocautery/thermal set up.



What is an emergency?

Consults that require your immediate attention include food impactions, acute biliary conditions leading to septic shock, and hemodynamically unstable GI bleeds, especially variceal bleeds. Remember that patients who are hemodynamically unstable require adequate resuscitation before proceeding with any endoscopic intervention. Assess the need for intubation, the timing of the procedure, and the most optimal location to perform the procedure, depending on the time and acuity of the patients’ presentation, how they respond to resuscitation measures, and the resources and preferences of your institution.

 

The overnight ‘nonemergent’ call

Non-emergent consults can be addressed the next day, after reviewing the clinical information provided by the consulting team and the patient’s EMR to ensure no urgent measures are needed. Overnight call may include patient phone calls, from inquiries about colon prep (so familiarize yourself with the different prep instructions and how to troubleshoot prep difficulties) to GI symptoms that you will need to triage to either the ED or to an outpatient follow-up. Document all phone encounters in the EMR and route your note to the appropriate clinician and nurse or administrative assistant for follow-up.

The five E’s of endoscopy

Endoscopy training is a large component of a GI fellowship and can create achievement anxiety in many first-year fellows seeking the cecum! But there is more to endoscopy than technical skills: It is as important to adequately evaluate clinical situations, understand the indications and potential limitations and complications of the procedure, and assess how it will impact the management of the patient. And no, you don’t have to be a video gamer to be a good endoscopist; and yes, you will be able to regularly complete a colonoscopy before the end of your first year!



Evaluation

In order to improve your endoscopic skills, it is important to honestly assess your areas of proficiency and improvement and to welcome real-time constructive feedback from your teaching attending about your endoscopic skills range. Consider meeting regularly with your attending to discuss your short-term and long-term endoscopic goals and how to enhance your skills. This practice demonstrates responsibility, credibility, and accountability amongst your peers as well as a genuine commitment to your growth as an endoscopist.



Efficiency

In addition to focusing on the quality of your endoscopy, learn to be efficient in the pre- and postprocedure time flow. This entails any step from properly explaining the procedure to patients before they come to the endoscopy suite, making sure the needed endoscopy equipment and tools are available in your room, completing your personal setup (i.e., gowning up, setting up your bed/monitor height, testing your endoscope) even before time out, to discharging the patient and communicating key findings and plan of care to the primary team. Depending on the acuity of the procedure and patient’s comorbidities, certain procedures may need to be performed or completed by a more efficient and experienced senior fellow or attending; don’t let this situation trigger passive frustration in you, but rather use it as an active and engaging opportunity to learn.



Expectations

You (and all the other neighborhood kids) didn’t learn to ride a bike without falling, struggling, needing help, and practicing over and over again, and it goes the same when learning to scope as a first-year fellow. Keep this in mind to lessen frustration, set realistic expectations, and be patient with yourself and celebrate all the small victories. Set tangible goals with your attending prior to procedural days/rotations so they can help you hone in and perfect the desired endoscopy skills. 



Ergonomics

In a recent study, endoscopy-related injury (ERI) was reported to occur in up to 75% of gastroenterologists.³ While your primary focus might be reaching the cecum, it is as crucial for you to learn how to prevent ERI to ensure your long term health and continued success in procedures.



Excellence over quantity

Your main focus as a trainee is to learn how to provide effective, efficient, and safe care to patients, including in endoscopy. The quality of the endoscopy you perform is much more important than the total number of procedures you do. Thus, it is key to take each procedure as a complete learning opportunity to perform a thorough evaluation, improve your technical skills, interpret the findings, and develop a therapeutic plan.

Work-life balance and burnout 

Fellowship is a marathon and not a sprint, so you need to slow down after a busy workday and care for yourself and enjoy time with loved ones. The cognitive, physical, mental, and emotional demands for first-year fellows are arguably the highest during GI training and can lead to burnout. Signs of burnout include emotional exhaustion, loss of empathy, fatigue, depersonalization and detachment, and feelings of personal inadequacy.⁴ Antiburnout measures include respecting basic healthy life hygiene (eat and sleep well, regular physical activity), having a hobby, practicing meditation, avoiding taking work home, and having a healthy social network.⁵ Remember that your cofellows whom you share common experiences with are not only your colleagues but can also be your friends and your social support. If you are a parent juggling work and family, remember to ask for help from your peers if you need it and have an open discussion with your attending to find practical solutions to your schedule.

Professional growth in the field of gastroenterology

Becoming a successful gastroenterologist and endoscopist involves going above the “I” and into the inclusive “we.” Building collegial and professional relationships early on with different stakeholders will set you up for success during and beyond your fellowship.

Building relationships

Developing genuine collegial and collaborative relationships with cofellows and faculty will positively impact your wellness during fellowship but also build the foundation of your professional network necessary to your career growth. Be inclusive of your cofellows in your research projects and publications, and support and amplify their work as much as you amplify your own. Your cofellows or attendings are likely to be the ones to help you find the right job, invite you to speak at grand rounds, or sit on a GI committee and promote your postfellowship professional growth.

Mentorship, being an educator and role model

It is important to identify and seek out mentors, within or outside your fellowship program or institution, who can not only guide you in your career choices but also open doors for you and sponsor you to advance your career. On the other hand, you too can be a role model, mentor, and sponsor to medical residents and students interested in the field of GI. Teach others in didactic settings or on the consult service, include trainees in quality improvement projects and publications, and lead by example.

Research

Most academic GI programs have a baseline requirement of research. Choose and devise a project you can realistically complete despite your busy first-year schedule: expand on a residency research project, focus on a specific simple question triggered by a clinical situation you encountered, proceed with a retrospective chart review or quality improvement project, and include other fellows and trainees to divide tasks. Alternatively, devise a specific timeline with a research mentor to complete a larger research project during your three years of fellowship.

Involvement in GI societies/committees

Become a member of one (or all) of the national GI societies that align with your interests. Membership gives you access not only to peer-reviewed scientific articles and guidelines but also to fellow-focused programs, committees’ opportunities, early career research grants, and mentorship.^6-10

Summary

The first year of a GI fellowship lays the foundation for your next 3 years: Be mindful of how you can optimize the opportunities at hand to learn, teach, build a solid reputation, and grow your professional network. But also remember you have 3 full years to accomplish all your goals, so be patient, pace yourself, and include others in your journey. Judiciously use the many resources within your program and GI societies to help you achieve your goals, reach out to others to overcome difficulties and barriers, and dedicate time to care for your personal health and growth. This is what a true comprehensive and healthy fellowship is all about!

 

Dr. Advani is with the division of gastroenterology and hepatology, Stony Brook (N.Y.) University Hospital. Dr. Saeed is with the division of gastroenterology and hepatology, University of Kentucky, Lexington. Dr. Charabaty is with the division of gastroenterology, Johns Hopkins University, Baltimore, and Johns Hopkins–Sibley Memorial Hospital, Washington. Dr. Advani and Dr. Saeed have no conflicts to disclose. Dr. Charabaty disclosed ties to AbbVie, Janssen, Takeda, Pfizer, and Bristol-Myers Squibb and is founder of @MondayNightIBD, and cofounder of Scrubs & Heels.

References

1. Bollipo S. Gastroenterology. 2020 Nov;159(5):1648-52.

2. Adams MA et al. Gastroenterology. 2014 Jan 1;146(1):5-9.

3. Pawa S et al. Am J Gastroenterol. 2021 Mar 1;116(3):530-8.

4. DeCross AJ. Gastroenterology. 2020 Jan 1;158(1):32-5.

5. Burke C et al. Am J Gastroenterol. 2017 Oct 1;112:S593-4.

6. Fellows Resources under Fellows & Early Career. American Gastroenterological Association. https://gastro.org/fellows-and-early-career/training-resources/fellows-resources/.

7. Trainee Courses and Events. American College of Gastroenterology. https://gi.org/trainees/trainee-courses-and-events/.

8. Trainee Resources. American Association for the Study of Liver Diseases.  https://www.aasld.org/membership/hepatology-associates/trainee-resources.

9. First Year Fellows Courses under Education. American Society of Gastrointestinal Endoscopy. https://www.asge.org/home/education/advanced-education-training/first-year-fellow-(fyf)-courses.

10. Annual GI Fellow Summer Course Presentations. New York Society for Gastrointestinal Endoscopy. https://www.nysge.org/annual%20gi%20fellows%20summer%20course.

After the excitement and the well-deserved celebrations of matching in a gastroenterology fellowship program, a whole new set of unanswered questions and worries can start forming in a first-year fellow’s mind. “I made it, but now what? How do I learn a whole new career skill like endoscopy? Is my GI knowledge solid and wide enough to manage patients and answer the medical team consult? How will I keep up with my reading and learning with a busy fellowship schedule? How do I balance growth in clinical knowledge, endoscopy, and research? Can I integrate ‘life’ alongside a busy fellowship?” All of these questions and more can be overwhelming to answer in the beginning. The following guide is designed to help you through this transition and navigate the various aspects of first-year fellowship. 

First-year goals

It is important to keep in mind that you have 3 full years to become a well-rounded, highly skilled, and knowledgeable gastroenterologist and endoscopist. So, set realistic goals and expectations for your first year, but be mindful that this year also lays the solid foundations of who you will become as a clinician, educator, or researcher.

One of the main goals of fellowship is to learn and implement evidence-based medicine in the diagnosis and management of GI conditions, as well as to learn endoscopic skills and ethics, all while keeping the patient (as a whole person) at the center of what you do. According to a recently published article by Bollipo and colleagues,¹ the overall growth as a gastroenterologist not only depends on acquisition of knowledge but also involves cultivating teamwork, communication, situational awareness, compassion, leadership, and situational awareness. Beyond your medical education, your professional growth is also dependent on intentionally working towards acquiring the following skills:

1. Manage your time efficiently and prioritize your daily tasks

2. Become a consultant: effectively communicate with others, teach, lead, and delegate as appropriate

3. Work as a team with colleagues, faculty, and endoscopy staff

4. Develop critical thinking, give and receive constructive feedback, and understand your skills, limitations, and growth potential

5. Identify mentors and potential niche area

6. Start building your professional network and your reputation

7. Get involved in national GI societies

Consults

Mindset

Shifting gear from residency to fellowship involves a shifting of your clinical mindset too, going from being part of a primary care team responsible for all aspects of a patient’s medical care, to that of a consulting team focused on a patient’s GI condition. It is important to find the right balance of refraining from micromanaging non-GI comorbidities while being fully aware of their impact on your diagnostic and therapeutic approach to the GI condition.

Let’s face it, you will not always get “exciting and interesting GI cases” consults, and on a busy day some consultations might feel unnecessary and frustrating to you. Remember that what seems obvious to you, based on your focused GI knowledge, might not be so simple to the primary team. In addition, every consult is an opportunity to improve your approach to patient care, as well as an opportunity to learn and teach others, from medical students to residents. So, always be professional and respectful when you pick up the phone, and build positive collaborative bridges between you and the medical or surgical consulting teams. Be the GI fellow others are not reluctant to call for help, and better, be the one who communicates GI pearls along the way, inspires others to join the field of gastroenterology, and positively represent the GI division.
 

Triage

When you answer your consult page, ask the primary team what specific question they have for you and/or what is the main GI complaint or test abnormality the patient has. This will help you assess the urgency and the complexity of the consult, and hence allow you to prioritize each consult (which one you need to see first and give the attending a heads-up), assign (or not) a rotating medical resident or student to the consult, tailor your preliminary recommendations to the primary team, and anticipate the need for a procedure. When you anticipate a procedure, assess its (semi-)urgency to get the process ready for same day or a bedside procedure by getting information on the patient’s vitals, basic labs, significant acute comorbidities, and supportive therapies in place. In other words, by judiciously obtaining key information from the primary team, you can efficiently triage the consults and keep your day organized and manageable (for the most part). Learn to divide and conquer the tasks of the day: split inpatient endoscopy and consults with your cofellows, assign appropriate consults and follow-ups to residents or students rotating on the GI service, and properly communicate with the primary team a plan of care (even a preliminary one) to avoid recurrent pages and interruptions. Some days the number or urgency of the consults and the required multitasking can be overwhelming: stop, breathe, and ask for help from your co-fellows and your attending. Remember, this is a fellowship, not a solo-ship and your program is here to support your work and growth.

Communication

Timely and efficient communication, between you and the different stakeholders, is crucial to provide optimal patient care and minimize the risk of “things falling through the cracks”. Convey to the primary team your recommendations and plan of care clearly, and use direct verbal communication (not just a note in the chart) when managing complex or urgent situations. Obtain information regarding current patient level of care (i.e., ICU), isolation precautions, and cardiac devices (i.e., left ventricular assist device). Keep the dialogue open with your attending about acutely ill patients and potentially urgent procedures. Inform the endoscopy suite early that you are adding a procedure on the same day, and communicate anticipated needs (such as intubation, fluoroscopy room, pediatric scope, stent). Using a “closed-loop” communication structure can ensure that your recommendations are received and implemented appropriately.² 

Time management and structure

Having a structured routine to your day, in what seems to be a chaotic process of juggling different duties and being in different locations at once, will ensure that you efficiently complete your tasks in a timely manner. Find what works best for you, taking into account the challenges and resources available to you, such as the number of fellows and other trainees on the GI consult service, the average number of consults per day and their acuity, the availability of inpatient protocols for specific clinical situations (GI bleed, acute severe ulcerative colitis, etc.), and the time and style preferences of the rounding attending. We suggest the following schedule on a consult day: Round early in the morning and leave a note in the chart and/or communicate with the team key information, then review with the rotating trainees the patients they are following and personally reassess some patients as needed. Inform the endoscopy suite of the same day procedures and let your attending know of any issues that require immediate attention. Take your team and head to radiology and review the imaging studies on your patients. Learn and teach key points in diagnosis and therapeutic approach as you move through your day from the inpatient floors to the hallways. Divide consults during the day with your team and agree on a time to touch base. Review your patient list at the end of the day and assess which patients the GI service no longer need to follow and communicate that clearly to the primary team along with the appropriate outpatient GI care follow-up. Let the endoscopy suite know of any procedures you are adding for the next day along with their degree of urgency to allow the charge nurse to prioritize cases. When you leave the hospital, be intentional with your free time: Read about the GI conditions you have encountered, enjoy some fun relaxing time, and rest!

Call

Know your call environment and your emergency cart

Familiarize yourself with the locations where you could potentially perform an emergent case (i.e., the ICU, ED, operating room) and the relevant points of contact (such as the charge nurse, the anesthesia team, the on-call tech team) for overnight or weekend cases. Whether or not you have an endoscopy support team on call, learn to set up the emergency cart, find and check your equipment, and troubleshoot technical issues by soliciting an “in-service” from senior fellows or the endoscopy technical support staff. Before heading to an urgent case, double check that you have your “bleeder” or “food impaction” tools. For food impaction, consider obtaining rat tooth forceps, snares, Roth nets, and an overtube. For bleeding cases, obtain a therapeutic upper endoscope, hemostatic clips, clear caps, injection needles, epinephrine, HemosprayTM, banding kits, and the appropriate electrocautery/thermal set up.



What is an emergency?

Consults that require your immediate attention include food impactions, acute biliary conditions leading to septic shock, and hemodynamically unstable GI bleeds, especially variceal bleeds. Remember that patients who are hemodynamically unstable require adequate resuscitation before proceeding with any endoscopic intervention. Assess the need for intubation, the timing of the procedure, and the most optimal location to perform the procedure, depending on the time and acuity of the patients’ presentation, how they respond to resuscitation measures, and the resources and preferences of your institution.

 

The overnight ‘nonemergent’ call

Non-emergent consults can be addressed the next day, after reviewing the clinical information provided by the consulting team and the patient’s EMR to ensure no urgent measures are needed. Overnight call may include patient phone calls, from inquiries about colon prep (so familiarize yourself with the different prep instructions and how to troubleshoot prep difficulties) to GI symptoms that you will need to triage to either the ED or to an outpatient follow-up. Document all phone encounters in the EMR and route your note to the appropriate clinician and nurse or administrative assistant for follow-up.

The five E’s of endoscopy

Endoscopy training is a large component of a GI fellowship and can create achievement anxiety in many first-year fellows seeking the cecum! But there is more to endoscopy than technical skills: It is as important to adequately evaluate clinical situations, understand the indications and potential limitations and complications of the procedure, and assess how it will impact the management of the patient. And no, you don’t have to be a video gamer to be a good endoscopist; and yes, you will be able to regularly complete a colonoscopy before the end of your first year!



Evaluation

In order to improve your endoscopic skills, it is important to honestly assess your areas of proficiency and improvement and to welcome real-time constructive feedback from your teaching attending about your endoscopic skills range. Consider meeting regularly with your attending to discuss your short-term and long-term endoscopic goals and how to enhance your skills. This practice demonstrates responsibility, credibility, and accountability amongst your peers as well as a genuine commitment to your growth as an endoscopist.



Efficiency

In addition to focusing on the quality of your endoscopy, learn to be efficient in the pre- and postprocedure time flow. This entails any step from properly explaining the procedure to patients before they come to the endoscopy suite, making sure the needed endoscopy equipment and tools are available in your room, completing your personal setup (i.e., gowning up, setting up your bed/monitor height, testing your endoscope) even before time out, to discharging the patient and communicating key findings and plan of care to the primary team. Depending on the acuity of the procedure and patient’s comorbidities, certain procedures may need to be performed or completed by a more efficient and experienced senior fellow or attending; don’t let this situation trigger passive frustration in you, but rather use it as an active and engaging opportunity to learn.



Expectations

You (and all the other neighborhood kids) didn’t learn to ride a bike without falling, struggling, needing help, and practicing over and over again, and it goes the same when learning to scope as a first-year fellow. Keep this in mind to lessen frustration, set realistic expectations, and be patient with yourself and celebrate all the small victories. Set tangible goals with your attending prior to procedural days/rotations so they can help you hone in and perfect the desired endoscopy skills. 



Ergonomics

In a recent study, endoscopy-related injury (ERI) was reported to occur in up to 75% of gastroenterologists.³ While your primary focus might be reaching the cecum, it is as crucial for you to learn how to prevent ERI to ensure your long term health and continued success in procedures.



Excellence over quantity

Your main focus as a trainee is to learn how to provide effective, efficient, and safe care to patients, including in endoscopy. The quality of the endoscopy you perform is much more important than the total number of procedures you do. Thus, it is key to take each procedure as a complete learning opportunity to perform a thorough evaluation, improve your technical skills, interpret the findings, and develop a therapeutic plan.

Work-life balance and burnout 

Fellowship is a marathon and not a sprint, so you need to slow down after a busy workday and care for yourself and enjoy time with loved ones. The cognitive, physical, mental, and emotional demands for first-year fellows are arguably the highest during GI training and can lead to burnout. Signs of burnout include emotional exhaustion, loss of empathy, fatigue, depersonalization and detachment, and feelings of personal inadequacy.⁴ Antiburnout measures include respecting basic healthy life hygiene (eat and sleep well, regular physical activity), having a hobby, practicing meditation, avoiding taking work home, and having a healthy social network.⁵ Remember that your cofellows whom you share common experiences with are not only your colleagues but can also be your friends and your social support. If you are a parent juggling work and family, remember to ask for help from your peers if you need it and have an open discussion with your attending to find practical solutions to your schedule.

Professional growth in the field of gastroenterology

Becoming a successful gastroenterologist and endoscopist involves going above the “I” and into the inclusive “we.” Building collegial and professional relationships early on with different stakeholders will set you up for success during and beyond your fellowship.

Building relationships

Developing genuine collegial and collaborative relationships with cofellows and faculty will positively impact your wellness during fellowship but also build the foundation of your professional network necessary to your career growth. Be inclusive of your cofellows in your research projects and publications, and support and amplify their work as much as you amplify your own. Your cofellows or attendings are likely to be the ones to help you find the right job, invite you to speak at grand rounds, or sit on a GI committee and promote your postfellowship professional growth.

Mentorship, being an educator and role model

It is important to identify and seek out mentors, within or outside your fellowship program or institution, who can not only guide you in your career choices but also open doors for you and sponsor you to advance your career. On the other hand, you too can be a role model, mentor, and sponsor to medical residents and students interested in the field of GI. Teach others in didactic settings or on the consult service, include trainees in quality improvement projects and publications, and lead by example.

Research

Most academic GI programs have a baseline requirement of research. Choose and devise a project you can realistically complete despite your busy first-year schedule: expand on a residency research project, focus on a specific simple question triggered by a clinical situation you encountered, proceed with a retrospective chart review or quality improvement project, and include other fellows and trainees to divide tasks. Alternatively, devise a specific timeline with a research mentor to complete a larger research project during your three years of fellowship.

Involvement in GI societies/committees

Become a member of one (or all) of the national GI societies that align with your interests. Membership gives you access not only to peer-reviewed scientific articles and guidelines but also to fellow-focused programs, committees’ opportunities, early career research grants, and mentorship.^6-10

Summary

The first year of a GI fellowship lays the foundation for your next 3 years: Be mindful of how you can optimize the opportunities at hand to learn, teach, build a solid reputation, and grow your professional network. But also remember you have 3 full years to accomplish all your goals, so be patient, pace yourself, and include others in your journey. Judiciously use the many resources within your program and GI societies to help you achieve your goals, reach out to others to overcome difficulties and barriers, and dedicate time to care for your personal health and growth. This is what a true comprehensive and healthy fellowship is all about!

 

Dr. Advani is with the division of gastroenterology and hepatology, Stony Brook (N.Y.) University Hospital. Dr. Saeed is with the division of gastroenterology and hepatology, University of Kentucky, Lexington. Dr. Charabaty is with the division of gastroenterology, Johns Hopkins University, Baltimore, and Johns Hopkins–Sibley Memorial Hospital, Washington. Dr. Advani and Dr. Saeed have no conflicts to disclose. Dr. Charabaty disclosed ties to AbbVie, Janssen, Takeda, Pfizer, and Bristol-Myers Squibb and is founder of @MondayNightIBD, and cofounder of Scrubs & Heels.

References

1. Bollipo S. Gastroenterology. 2020 Nov;159(5):1648-52.

2. Adams MA et al. Gastroenterology. 2014 Jan 1;146(1):5-9.

3. Pawa S et al. Am J Gastroenterol. 2021 Mar 1;116(3):530-8.

4. DeCross AJ. Gastroenterology. 2020 Jan 1;158(1):32-5.

5. Burke C et al. Am J Gastroenterol. 2017 Oct 1;112:S593-4.

6. Fellows Resources under Fellows & Early Career. American Gastroenterological Association. https://gastro.org/fellows-and-early-career/training-resources/fellows-resources/.

7. Trainee Courses and Events. American College of Gastroenterology. https://gi.org/trainees/trainee-courses-and-events/.

8. Trainee Resources. American Association for the Study of Liver Diseases.  https://www.aasld.org/membership/hepatology-associates/trainee-resources.

9. First Year Fellows Courses under Education. American Society of Gastrointestinal Endoscopy. https://www.asge.org/home/education/advanced-education-training/first-year-fellow-(fyf)-courses.

10. Annual GI Fellow Summer Course Presentations. New York Society for Gastrointestinal Endoscopy. https://www.nysge.org/annual%20gi%20fellows%20summer%20course.

After the excitement and the well-deserved celebrations of matching in a gastroenterology fellowship program, a whole new set of unanswered questions and worries can start forming in a first-year fellow’s mind. “I made it, but now what? How do I learn a whole new career skill like endoscopy? Is my GI knowledge solid and wide enough to manage patients and answer the medical team consult? How will I keep up with my reading and learning with a busy fellowship schedule? How do I balance growth in clinical knowledge, endoscopy, and research? Can I integrate ‘life’ alongside a busy fellowship?” All of these questions and more can be overwhelming to answer in the beginning. The following guide is designed to help you through this transition and navigate the various aspects of first-year fellowship. 

First-year goals

It is important to keep in mind that you have 3 full years to become a well-rounded, highly skilled, and knowledgeable gastroenterologist and endoscopist. So, set realistic goals and expectations for your first year, but be mindful that this year also lays the solid foundations of who you will become as a clinician, educator, or researcher.

One of the main goals of fellowship is to learn and implement evidence-based medicine in the diagnosis and management of GI conditions, as well as to learn endoscopic skills and ethics, all while keeping the patient (as a whole person) at the center of what you do. According to a recently published article by Bollipo and colleagues,¹ the overall growth as a gastroenterologist not only depends on acquisition of knowledge but also involves cultivating teamwork, communication, situational awareness, compassion, leadership, and situational awareness. Beyond your medical education, your professional growth is also dependent on intentionally working towards acquiring the following skills:

1. Manage your time efficiently and prioritize your daily tasks

2. Become a consultant: effectively communicate with others, teach, lead, and delegate as appropriate

3. Work as a team with colleagues, faculty, and endoscopy staff

4. Develop critical thinking, give and receive constructive feedback, and understand your skills, limitations, and growth potential

5. Identify mentors and potential niche area

6. Start building your professional network and your reputation

7. Get involved in national GI societies

Consults

Mindset

Shifting gear from residency to fellowship involves a shifting of your clinical mindset too, going from being part of a primary care team responsible for all aspects of a patient’s medical care, to that of a consulting team focused on a patient’s GI condition. It is important to find the right balance of refraining from micromanaging non-GI comorbidities while being fully aware of their impact on your diagnostic and therapeutic approach to the GI condition.

Let’s face it, you will not always get “exciting and interesting GI cases” consults, and on a busy day some consultations might feel unnecessary and frustrating to you. Remember that what seems obvious to you, based on your focused GI knowledge, might not be so simple to the primary team. In addition, every consult is an opportunity to improve your approach to patient care, as well as an opportunity to learn and teach others, from medical students to residents. So, always be professional and respectful when you pick up the phone, and build positive collaborative bridges between you and the medical or surgical consulting teams. Be the GI fellow others are not reluctant to call for help, and better, be the one who communicates GI pearls along the way, inspires others to join the field of gastroenterology, and positively represent the GI division.
 

Triage

When you answer your consult page, ask the primary team what specific question they have for you and/or what is the main GI complaint or test abnormality the patient has. This will help you assess the urgency and the complexity of the consult, and hence allow you to prioritize each consult (which one you need to see first and give the attending a heads-up), assign (or not) a rotating medical resident or student to the consult, tailor your preliminary recommendations to the primary team, and anticipate the need for a procedure. When you anticipate a procedure, assess its (semi-)urgency to get the process ready for same day or a bedside procedure by getting information on the patient’s vitals, basic labs, significant acute comorbidities, and supportive therapies in place. In other words, by judiciously obtaining key information from the primary team, you can efficiently triage the consults and keep your day organized and manageable (for the most part). Learn to divide and conquer the tasks of the day: split inpatient endoscopy and consults with your cofellows, assign appropriate consults and follow-ups to residents or students rotating on the GI service, and properly communicate with the primary team a plan of care (even a preliminary one) to avoid recurrent pages and interruptions. Some days the number or urgency of the consults and the required multitasking can be overwhelming: stop, breathe, and ask for help from your co-fellows and your attending. Remember, this is a fellowship, not a solo-ship and your program is here to support your work and growth.

Communication

Timely and efficient communication, between you and the different stakeholders, is crucial to provide optimal patient care and minimize the risk of “things falling through the cracks”. Convey to the primary team your recommendations and plan of care clearly, and use direct verbal communication (not just a note in the chart) when managing complex or urgent situations. Obtain information regarding current patient level of care (i.e., ICU), isolation precautions, and cardiac devices (i.e., left ventricular assist device). Keep the dialogue open with your attending about acutely ill patients and potentially urgent procedures. Inform the endoscopy suite early that you are adding a procedure on the same day, and communicate anticipated needs (such as intubation, fluoroscopy room, pediatric scope, stent). Using a “closed-loop” communication structure can ensure that your recommendations are received and implemented appropriately.² 

Time management and structure

Having a structured routine to your day, in what seems to be a chaotic process of juggling different duties and being in different locations at once, will ensure that you efficiently complete your tasks in a timely manner. Find what works best for you, taking into account the challenges and resources available to you, such as the number of fellows and other trainees on the GI consult service, the average number of consults per day and their acuity, the availability of inpatient protocols for specific clinical situations (GI bleed, acute severe ulcerative colitis, etc.), and the time and style preferences of the rounding attending. We suggest the following schedule on a consult day: Round early in the morning and leave a note in the chart and/or communicate with the team key information, then review with the rotating trainees the patients they are following and personally reassess some patients as needed. Inform the endoscopy suite of the same day procedures and let your attending know of any issues that require immediate attention. Take your team and head to radiology and review the imaging studies on your patients. Learn and teach key points in diagnosis and therapeutic approach as you move through your day from the inpatient floors to the hallways. Divide consults during the day with your team and agree on a time to touch base. Review your patient list at the end of the day and assess which patients the GI service no longer need to follow and communicate that clearly to the primary team along with the appropriate outpatient GI care follow-up. Let the endoscopy suite know of any procedures you are adding for the next day along with their degree of urgency to allow the charge nurse to prioritize cases. When you leave the hospital, be intentional with your free time: Read about the GI conditions you have encountered, enjoy some fun relaxing time, and rest!

Call

Know your call environment and your emergency cart

Familiarize yourself with the locations where you could potentially perform an emergent case (i.e., the ICU, ED, operating room) and the relevant points of contact (such as the charge nurse, the anesthesia team, the on-call tech team) for overnight or weekend cases. Whether or not you have an endoscopy support team on call, learn to set up the emergency cart, find and check your equipment, and troubleshoot technical issues by soliciting an “in-service” from senior fellows or the endoscopy technical support staff. Before heading to an urgent case, double check that you have your “bleeder” or “food impaction” tools. For food impaction, consider obtaining rat tooth forceps, snares, Roth nets, and an overtube. For bleeding cases, obtain a therapeutic upper endoscope, hemostatic clips, clear caps, injection needles, epinephrine, HemosprayTM, banding kits, and the appropriate electrocautery/thermal set up.



What is an emergency?

Consults that require your immediate attention include food impactions, acute biliary conditions leading to septic shock, and hemodynamically unstable GI bleeds, especially variceal bleeds. Remember that patients who are hemodynamically unstable require adequate resuscitation before proceeding with any endoscopic intervention. Assess the need for intubation, the timing of the procedure, and the most optimal location to perform the procedure, depending on the time and acuity of the patients’ presentation, how they respond to resuscitation measures, and the resources and preferences of your institution.

 

The overnight ‘nonemergent’ call

Non-emergent consults can be addressed the next day, after reviewing the clinical information provided by the consulting team and the patient’s EMR to ensure no urgent measures are needed. Overnight call may include patient phone calls, from inquiries about colon prep (so familiarize yourself with the different prep instructions and how to troubleshoot prep difficulties) to GI symptoms that you will need to triage to either the ED or to an outpatient follow-up. Document all phone encounters in the EMR and route your note to the appropriate clinician and nurse or administrative assistant for follow-up.

The five E’s of endoscopy

Endoscopy training is a large component of a GI fellowship and can create achievement anxiety in many first-year fellows seeking the cecum! But there is more to endoscopy than technical skills: It is as important to adequately evaluate clinical situations, understand the indications and potential limitations and complications of the procedure, and assess how it will impact the management of the patient. And no, you don’t have to be a video gamer to be a good endoscopist; and yes, you will be able to regularly complete a colonoscopy before the end of your first year!



Evaluation

In order to improve your endoscopic skills, it is important to honestly assess your areas of proficiency and improvement and to welcome real-time constructive feedback from your teaching attending about your endoscopic skills range. Consider meeting regularly with your attending to discuss your short-term and long-term endoscopic goals and how to enhance your skills. This practice demonstrates responsibility, credibility, and accountability amongst your peers as well as a genuine commitment to your growth as an endoscopist.



Efficiency

In addition to focusing on the quality of your endoscopy, learn to be efficient in the pre- and postprocedure time flow. This entails any step from properly explaining the procedure to patients before they come to the endoscopy suite, making sure the needed endoscopy equipment and tools are available in your room, completing your personal setup (i.e., gowning up, setting up your bed/monitor height, testing your endoscope) even before time out, to discharging the patient and communicating key findings and plan of care to the primary team. Depending on the acuity of the procedure and patient’s comorbidities, certain procedures may need to be performed or completed by a more efficient and experienced senior fellow or attending; don’t let this situation trigger passive frustration in you, but rather use it as an active and engaging opportunity to learn.



Expectations

You (and all the other neighborhood kids) didn’t learn to ride a bike without falling, struggling, needing help, and practicing over and over again, and it goes the same when learning to scope as a first-year fellow. Keep this in mind to lessen frustration, set realistic expectations, and be patient with yourself and celebrate all the small victories. Set tangible goals with your attending prior to procedural days/rotations so they can help you hone in and perfect the desired endoscopy skills. 



Ergonomics

In a recent study, endoscopy-related injury (ERI) was reported to occur in up to 75% of gastroenterologists.³ While your primary focus might be reaching the cecum, it is as crucial for you to learn how to prevent ERI to ensure your long term health and continued success in procedures.



Excellence over quantity

Your main focus as a trainee is to learn how to provide effective, efficient, and safe care to patients, including in endoscopy. The quality of the endoscopy you perform is much more important than the total number of procedures you do. Thus, it is key to take each procedure as a complete learning opportunity to perform a thorough evaluation, improve your technical skills, interpret the findings, and develop a therapeutic plan.

Work-life balance and burnout 

Fellowship is a marathon and not a sprint, so you need to slow down after a busy workday and care for yourself and enjoy time with loved ones. The cognitive, physical, mental, and emotional demands for first-year fellows are arguably the highest during GI training and can lead to burnout. Signs of burnout include emotional exhaustion, loss of empathy, fatigue, depersonalization and detachment, and feelings of personal inadequacy.⁴ Antiburnout measures include respecting basic healthy life hygiene (eat and sleep well, regular physical activity), having a hobby, practicing meditation, avoiding taking work home, and having a healthy social network.⁵ Remember that your cofellows whom you share common experiences with are not only your colleagues but can also be your friends and your social support. If you are a parent juggling work and family, remember to ask for help from your peers if you need it and have an open discussion with your attending to find practical solutions to your schedule.

Professional growth in the field of gastroenterology

Becoming a successful gastroenterologist and endoscopist involves going above the “I” and into the inclusive “we.” Building collegial and professional relationships early on with different stakeholders will set you up for success during and beyond your fellowship.

Building relationships

Developing genuine collegial and collaborative relationships with cofellows and faculty will positively impact your wellness during fellowship but also build the foundation of your professional network necessary to your career growth. Be inclusive of your cofellows in your research projects and publications, and support and amplify their work as much as you amplify your own. Your cofellows or attendings are likely to be the ones to help you find the right job, invite you to speak at grand rounds, or sit on a GI committee and promote your postfellowship professional growth.

Mentorship, being an educator and role model

It is important to identify and seek out mentors, within or outside your fellowship program or institution, who can not only guide you in your career choices but also open doors for you and sponsor you to advance your career. On the other hand, you too can be a role model, mentor, and sponsor to medical residents and students interested in the field of GI. Teach others in didactic settings or on the consult service, include trainees in quality improvement projects and publications, and lead by example.

Research

Most academic GI programs have a baseline requirement of research. Choose and devise a project you can realistically complete despite your busy first-year schedule: expand on a residency research project, focus on a specific simple question triggered by a clinical situation you encountered, proceed with a retrospective chart review or quality improvement project, and include other fellows and trainees to divide tasks. Alternatively, devise a specific timeline with a research mentor to complete a larger research project during your three years of fellowship.

Involvement in GI societies/committees

Become a member of one (or all) of the national GI societies that align with your interests. Membership gives you access not only to peer-reviewed scientific articles and guidelines but also to fellow-focused programs, committees’ opportunities, early career research grants, and mentorship.^6-10

Summary

The first year of a GI fellowship lays the foundation for your next 3 years: Be mindful of how you can optimize the opportunities at hand to learn, teach, build a solid reputation, and grow your professional network. But also remember you have 3 full years to accomplish all your goals, so be patient, pace yourself, and include others in your journey. Judiciously use the many resources within your program and GI societies to help you achieve your goals, reach out to others to overcome difficulties and barriers, and dedicate time to care for your personal health and growth. This is what a true comprehensive and healthy fellowship is all about!

 

Dr. Advani is with the division of gastroenterology and hepatology, Stony Brook (N.Y.) University Hospital. Dr. Saeed is with the division of gastroenterology and hepatology, University of Kentucky, Lexington. Dr. Charabaty is with the division of gastroenterology, Johns Hopkins University, Baltimore, and Johns Hopkins–Sibley Memorial Hospital, Washington. Dr. Advani and Dr. Saeed have no conflicts to disclose. Dr. Charabaty disclosed ties to AbbVie, Janssen, Takeda, Pfizer, and Bristol-Myers Squibb and is founder of @MondayNightIBD, and cofounder of Scrubs & Heels.

References

1. Bollipo S. Gastroenterology. 2020 Nov;159(5):1648-52.

2. Adams MA et al. Gastroenterology. 2014 Jan 1;146(1):5-9.

3. Pawa S et al. Am J Gastroenterol. 2021 Mar 1;116(3):530-8.

4. DeCross AJ. Gastroenterology. 2020 Jan 1;158(1):32-5.

5. Burke C et al. Am J Gastroenterol. 2017 Oct 1;112:S593-4.

6. Fellows Resources under Fellows & Early Career. American Gastroenterological Association. https://gastro.org/fellows-and-early-career/training-resources/fellows-resources/.

7. Trainee Courses and Events. American College of Gastroenterology. https://gi.org/trainees/trainee-courses-and-events/.

8. Trainee Resources. American Association for the Study of Liver Diseases.  https://www.aasld.org/membership/hepatology-associates/trainee-resources.

9. First Year Fellows Courses under Education. American Society of Gastrointestinal Endoscopy. https://www.asge.org/home/education/advanced-education-training/first-year-fellow-(fyf)-courses.

10. Annual GI Fellow Summer Course Presentations. New York Society for Gastrointestinal Endoscopy. https://www.nysge.org/annual%20gi%20fellows%20summer%20course.

The incremental step test is a highly reliable measure of exercise capacity in patients with moderate to severe asthma, based on data from 50 individuals.

Asthma patients often limit their physical exercise to avoid respiratory symptoms, which creates a downward spiral of reduced exercise capacity and ability to perform activities of daily living, wrote Renata Cléia Claudino Barbosa of the University of Sao Paulo and colleagues. “However, exercise training has been shown to be an important adjunctive therapy for asthma treatment that improves exercise capacity and health-related quality of life,” they wrote.

Step tests have been identified as a simpler, less costly alternative to cardiopulmonary exercise tests to measure exercise capacity in patients with chronic obstructive pulmonary disease, but their effectiveness for asthma patients has not investigated, the researchers said.

In a study published in Pulmonology, the researchers recruited 50 adults with moderate or severe asthma during routine care at a university hospital. The participants had been clinically stable for at least 6 months, with no hospitalizations, emergency care, or medication changes in the past 30 days. All participants received short-acting and long-acting bronchodilators and inhaled corticosteroids. The patients ranged in age from 18 to 60 years, with body mass index measures from 20 kg/m² to 40 kg/m².

Participants were randomized to tests on 2 nonconsecutive days at least 48 hours apart. On the first day, patients completed asthma control questionnaires and lung function tests, then performed either a cardiopulmonary exercise test (CPET) or two incremental step tests (IST-1 and IST-2). On the second day, they performed the other test. Participants were instructed to use bronchodilators 15 minutes before each test.

The step test involved stepping up and down on a 20-cm high wooden bench.

Overall, the peak oxygen uptakes were 27.6 mL/kg per minute for the CPET, 22.3 mL/kg per minute for the first IST, and 23.3 mL/kg per minute for the second IST.

“The IST with better performance regarding the peak VO₂ value was called the best IST (b-IST),” and these values were used for validity and interpretability analyses, the researchers wrote.

In a reliability analysis, the intraclass correlation coefficient (ICC) was 0.93, the measurement error was 2.5%, and the construct validity for peak VO₂ was significantly more reliable than the CPET (P < 0.001), the researchers said. The ICC for total number of steps was 0.88.

Notably, “the present study also demonstrated that IST is not interchangeable with the CPET since the subjects with moderate to severe asthma did not reach the maximal exercise capacity,” the researchers said. However, “we believe that the IST is superior to walking tests in subjects with asthma because it is an activity that requires greater ventilation in a subject’s daily life,” they said.

The study findings were limited by several factors including the relatively small study population and the small number of male patients, which may limit generalizability to males with asthma or other asthma endotypes, the researchers said. However, the results were strengthened by the randomized design, and support the value of the IST as a cost-effective option for assessing exercise capacity, preferably with two step tests to minimize the learning effect, they said. Additional research is needed to determine whether IST can assess responsiveness to pharmacological and nonpharmalogical treatments in asthma patients, they noted.

The study was supported by the Sao Paulo Research Foundation, Conselho Nacional de Pesquisa, and Coordination of Improvement of Higher Level Personnel--Brazil. The researchers had no financial conflicts to disclose.

The incremental step test is a highly reliable measure of exercise capacity in patients with moderate to severe asthma, based on data from 50 individuals.

Asthma patients often limit their physical exercise to avoid respiratory symptoms, which creates a downward spiral of reduced exercise capacity and ability to perform activities of daily living, wrote Renata Cléia Claudino Barbosa of the University of Sao Paulo and colleagues. “However, exercise training has been shown to be an important adjunctive therapy for asthma treatment that improves exercise capacity and health-related quality of life,” they wrote.

Step tests have been identified as a simpler, less costly alternative to cardiopulmonary exercise tests to measure exercise capacity in patients with chronic obstructive pulmonary disease, but their effectiveness for asthma patients has not investigated, the researchers said.

In a study published in Pulmonology, the researchers recruited 50 adults with moderate or severe asthma during routine care at a university hospital. The participants had been clinically stable for at least 6 months, with no hospitalizations, emergency care, or medication changes in the past 30 days. All participants received short-acting and long-acting bronchodilators and inhaled corticosteroids. The patients ranged in age from 18 to 60 years, with body mass index measures from 20 kg/m² to 40 kg/m².

Participants were randomized to tests on 2 nonconsecutive days at least 48 hours apart. On the first day, patients completed asthma control questionnaires and lung function tests, then performed either a cardiopulmonary exercise test (CPET) or two incremental step tests (IST-1 and IST-2). On the second day, they performed the other test. Participants were instructed to use bronchodilators 15 minutes before each test.

The step test involved stepping up and down on a 20-cm high wooden bench.

Overall, the peak oxygen uptakes were 27.6 mL/kg per minute for the CPET, 22.3 mL/kg per minute for the first IST, and 23.3 mL/kg per minute for the second IST.

“The IST with better performance regarding the peak VO₂ value was called the best IST (b-IST),” and these values were used for validity and interpretability analyses, the researchers wrote.

In a reliability analysis, the intraclass correlation coefficient (ICC) was 0.93, the measurement error was 2.5%, and the construct validity for peak VO₂ was significantly more reliable than the CPET (P < 0.001), the researchers said. The ICC for total number of steps was 0.88.

Notably, “the present study also demonstrated that IST is not interchangeable with the CPET since the subjects with moderate to severe asthma did not reach the maximal exercise capacity,” the researchers said. However, “we believe that the IST is superior to walking tests in subjects with asthma because it is an activity that requires greater ventilation in a subject’s daily life,” they said.

The study findings were limited by several factors including the relatively small study population and the small number of male patients, which may limit generalizability to males with asthma or other asthma endotypes, the researchers said. However, the results were strengthened by the randomized design, and support the value of the IST as a cost-effective option for assessing exercise capacity, preferably with two step tests to minimize the learning effect, they said. Additional research is needed to determine whether IST can assess responsiveness to pharmacological and nonpharmalogical treatments in asthma patients, they noted.

The study was supported by the Sao Paulo Research Foundation, Conselho Nacional de Pesquisa, and Coordination of Improvement of Higher Level Personnel--Brazil. The researchers had no financial conflicts to disclose.

The incremental step test is a highly reliable measure of exercise capacity in patients with moderate to severe asthma, based on data from 50 individuals.

Asthma patients often limit their physical exercise to avoid respiratory symptoms, which creates a downward spiral of reduced exercise capacity and ability to perform activities of daily living, wrote Renata Cléia Claudino Barbosa of the University of Sao Paulo and colleagues. “However, exercise training has been shown to be an important adjunctive therapy for asthma treatment that improves exercise capacity and health-related quality of life,” they wrote.

Step tests have been identified as a simpler, less costly alternative to cardiopulmonary exercise tests to measure exercise capacity in patients with chronic obstructive pulmonary disease, but their effectiveness for asthma patients has not investigated, the researchers said.

In a study published in Pulmonology, the researchers recruited 50 adults with moderate or severe asthma during routine care at a university hospital. The participants had been clinically stable for at least 6 months, with no hospitalizations, emergency care, or medication changes in the past 30 days. All participants received short-acting and long-acting bronchodilators and inhaled corticosteroids. The patients ranged in age from 18 to 60 years, with body mass index measures from 20 kg/m² to 40 kg/m².

Participants were randomized to tests on 2 nonconsecutive days at least 48 hours apart. On the first day, patients completed asthma control questionnaires and lung function tests, then performed either a cardiopulmonary exercise test (CPET) or two incremental step tests (IST-1 and IST-2). On the second day, they performed the other test. Participants were instructed to use bronchodilators 15 minutes before each test.

The step test involved stepping up and down on a 20-cm high wooden bench.

Overall, the peak oxygen uptakes were 27.6 mL/kg per minute for the CPET, 22.3 mL/kg per minute for the first IST, and 23.3 mL/kg per minute for the second IST.

“The IST with better performance regarding the peak VO₂ value was called the best IST (b-IST),” and these values were used for validity and interpretability analyses, the researchers wrote.

In a reliability analysis, the intraclass correlation coefficient (ICC) was 0.93, the measurement error was 2.5%, and the construct validity for peak VO₂ was significantly more reliable than the CPET (P < 0.001), the researchers said. The ICC for total number of steps was 0.88.

Notably, “the present study also demonstrated that IST is not interchangeable with the CPET since the subjects with moderate to severe asthma did not reach the maximal exercise capacity,” the researchers said. However, “we believe that the IST is superior to walking tests in subjects with asthma because it is an activity that requires greater ventilation in a subject’s daily life,” they said.

The study findings were limited by several factors including the relatively small study population and the small number of male patients, which may limit generalizability to males with asthma or other asthma endotypes, the researchers said. However, the results were strengthened by the randomized design, and support the value of the IST as a cost-effective option for assessing exercise capacity, preferably with two step tests to minimize the learning effect, they said. Additional research is needed to determine whether IST can assess responsiveness to pharmacological and nonpharmalogical treatments in asthma patients, they noted.

The study was supported by the Sao Paulo Research Foundation, Conselho Nacional de Pesquisa, and Coordination of Improvement of Higher Level Personnel--Brazil. The researchers had no financial conflicts to disclose.

Mrs. Jones is a 44-year-old woman who has struggled with her weight. She has a body mass index (BMI) of 35 kg/m² and hypertension requiring daily medication. She has tried various diets over the years and has never been able to exercise consistently. She desperately wants to lose weight to improve her confidence and to avoid developing diabetes and dialysis that her parents required. She has considered weight loss surgery but is afraid after her best friend died following uterine fibroid surgery. She saw a billboard that advertised a new weight loss procedure without surgery. She looked up the procedure, found Dr. Indo on the university medical center’s website, and booked an appointment. Dr. Indo talked about performing an incisionless procedure done with an endoscope through her mouth. It would make her stomach into a tube to reduce the amount of food she could eat as well as prevent some absorption of food in her intestines. When Mrs. Jones asked how many of these the doctor had performed, Dr. Indo remarked she personally had done “several” in the past few years including training. Dr. Indo reassured Mrs. Jones that the procedure has been performed hundreds of times around the country and has been shown to be safe. Dr. Indo also explained that studies were still ongoing, including possibly at the university medical center, but that she had never personally seen any serious complications or death, and only one patient she knew of converted to a traditional bariatric surgery.

Obesity is a large international public health problem, with the World Health Organization estimating that there are 600 million obese adults worldwide.¹ Bariatric surgery has been an effective way to improve complications related to obesity and quality of life. Endoscopic approaches to bariatric surgery have appeared since at least the late 1980s and, similarly to their traditional surgical counterparts, work in two main categories: restrictive or malabsorptive.¹ Restrictive endoscopic bariatric therapies (EBTs) include intragastric balloons (IGB) that are filled with saline or gas to decrease intragastric luminal size, endoscopic sleeve gastroplasty that makes full-thickness plications of the gastric wall to tubularize the stomach like a sleeve gastrectomy, and AspireAssist where patients use a percutaneous gastrostomy to remove part of an ingested meal.¹ Malabsorptive procedures include bypass sleeves that use a stentlike device to bypass absorption of food in the duodenum and proximal jejunum, the incisionless magnetic anastomosis system (IMAS) that creates a gastrojejunal bypass for diverting absorption, and duodenal mucosal resurfacing (DMR) that ablates the duodenal mucosa.^1,2

The benefits of EBTs over traditional bariatric surgery are that they have a lower risk profile, there is limited anatomic alternation, and they are potentially reversible.¹ Although no formal guidelines exist in the United States for the use of EBTs, the American Society for Gastrointestinal Endoscopy (ASGE) preliminary recommendations describe EBTs as applicable for patients who have failed lifestyle interventions and have BMIs between 30 and 45.¹ While some of these techniques were first described in the 1980s, many individual companies and devices still do not have Food and Drug Administration approval and some have even had approval withdrawn. While traditional bariatric surgery may have complication rates up to 17%, EBTs are not without complications.¹ Endoscopic barriers can migrate and occlude, cause pancreatitis, cause liver abscesses from biliary occlusion, and more severely cause GI bleeding and perforations.¹ Many EBTs are also temporary treatments with IGBs and barrier bypasses placed only for 6-12 months.1 While there have been some studies looking at individual outcomes of the various EBTs, large prospective research trials looking at safety and efficacy, especially when comparing EBT to traditional bariatric surgery or in combination, are lacking.

Continued innovation in medicine and technology is critical to improving patient care. New innovations in medicine have allowed us to treat more disease, save lives, reduce complications, and better care for patients. But what exactly is innovation and when does it become research? The landmark Belmont Report in 1979 distinguishes research from innovative therapy, calling research “an activity designed to test a hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge.”³ Patients in research thus bear the risks while others stand to benefit. The report affirms then that routine medical practice involves interventions designed specifically to benefit the individual patient. The European Association for Endoscopic Surgery defines innovations as any “significant modification of a standard technique, a new application of or new indication for an established technique, or an alternative combination of an established technique with another therapeutic modality.”⁴ As such, innovations should eventually be formally studied with institutional review board (IRB) approval and protocols to establish safety and efficacy. Another complicating factor is that there is no FDA approval for surgical and procedural techniques as there is for medications and certain devices. Therefore, no robust regulatory mechanisms exist to ensure patient safety and benefit. Further complicating matters is that innovative procedures often start as modifications of techniques and are often done regularly to fit specific situations – for example, an additional stitch in a different location or in a different orientation to what is done in the standard fashion. However, true innovations should be distinguished from these modifications. Perhaps then another way to think about the two is to splinter them into three types of activity: research, routine accepted practice, and innovative medicine.⁵

Dr. Williams is a general surgery resident at the University of Chicago and a fellow at the MacLean Center for clinical medical ethics. Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics, vice chairman for ethics, professional development, and wellness, and chief of endocrine surgery, department of surgery, and the associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago. The authors have no conflicts to disclose.

References

1. Goyal H et al. Ther Adv Gastrointest Endosc. 2021;14. doi: 10.1177/2631774520984627.

2. Machytka E et al. Gastrointestinal Endosc. 2017;86(5):904-12. doi: 10.1016/j.gie.2017.07.009.

3. Eastwood GL. J Gastroenterol Hepatol (Australia). 2015;30(S1):8-11. doi: 10.1111/jgh.12755.

4. Neugebauer EAM et al. Surg Endosc. 2010;24(7):1594-1615. doi: 10.1007/s00464-009-0818-3.

5. Eaton, ML and Kennedy, DL. Innovation in Medical Technology: Ethical Issues and Challenges. Baltimore: Johns Hopkins University Press, 2007.

6. Angelos P. Ann Thorac Surg. 2019;108(6):1611-2. doi: 10.1016/j.athoracsur.2019.08.010.

7. Angelos P. Virtual Mentor. 2011;13(1):6-9. doi: 10.1001/virtualmentor.2011.13.1.ccas1-1101.

Mrs. Jones is a 44-year-old woman who has struggled with her weight. She has a body mass index (BMI) of 35 kg/m² and hypertension requiring daily medication. She has tried various diets over the years and has never been able to exercise consistently. She desperately wants to lose weight to improve her confidence and to avoid developing diabetes and dialysis that her parents required. She has considered weight loss surgery but is afraid after her best friend died following uterine fibroid surgery. She saw a billboard that advertised a new weight loss procedure without surgery. She looked up the procedure, found Dr. Indo on the university medical center’s website, and booked an appointment. Dr. Indo talked about performing an incisionless procedure done with an endoscope through her mouth. It would make her stomach into a tube to reduce the amount of food she could eat as well as prevent some absorption of food in her intestines. When Mrs. Jones asked how many of these the doctor had performed, Dr. Indo remarked she personally had done “several” in the past few years including training. Dr. Indo reassured Mrs. Jones that the procedure has been performed hundreds of times around the country and has been shown to be safe. Dr. Indo also explained that studies were still ongoing, including possibly at the university medical center, but that she had never personally seen any serious complications or death, and only one patient she knew of converted to a traditional bariatric surgery.

Obesity is a large international public health problem, with the World Health Organization estimating that there are 600 million obese adults worldwide.¹ Bariatric surgery has been an effective way to improve complications related to obesity and quality of life. Endoscopic approaches to bariatric surgery have appeared since at least the late 1980s and, similarly to their traditional surgical counterparts, work in two main categories: restrictive or malabsorptive.¹ Restrictive endoscopic bariatric therapies (EBTs) include intragastric balloons (IGB) that are filled with saline or gas to decrease intragastric luminal size, endoscopic sleeve gastroplasty that makes full-thickness plications of the gastric wall to tubularize the stomach like a sleeve gastrectomy, and AspireAssist where patients use a percutaneous gastrostomy to remove part of an ingested meal.¹ Malabsorptive procedures include bypass sleeves that use a stentlike device to bypass absorption of food in the duodenum and proximal jejunum, the incisionless magnetic anastomosis system (IMAS) that creates a gastrojejunal bypass for diverting absorption, and duodenal mucosal resurfacing (DMR) that ablates the duodenal mucosa.^1,2

The benefits of EBTs over traditional bariatric surgery are that they have a lower risk profile, there is limited anatomic alternation, and they are potentially reversible.¹ Although no formal guidelines exist in the United States for the use of EBTs, the American Society for Gastrointestinal Endoscopy (ASGE) preliminary recommendations describe EBTs as applicable for patients who have failed lifestyle interventions and have BMIs between 30 and 45.¹ While some of these techniques were first described in the 1980s, many individual companies and devices still do not have Food and Drug Administration approval and some have even had approval withdrawn. While traditional bariatric surgery may have complication rates up to 17%, EBTs are not without complications.¹ Endoscopic barriers can migrate and occlude, cause pancreatitis, cause liver abscesses from biliary occlusion, and more severely cause GI bleeding and perforations.¹ Many EBTs are also temporary treatments with IGBs and barrier bypasses placed only for 6-12 months.1 While there have been some studies looking at individual outcomes of the various EBTs, large prospective research trials looking at safety and efficacy, especially when comparing EBT to traditional bariatric surgery or in combination, are lacking.

Continued innovation in medicine and technology is critical to improving patient care. New innovations in medicine have allowed us to treat more disease, save lives, reduce complications, and better care for patients. But what exactly is innovation and when does it become research? The landmark Belmont Report in 1979 distinguishes research from innovative therapy, calling research “an activity designed to test a hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge.”³ Patients in research thus bear the risks while others stand to benefit. The report affirms then that routine medical practice involves interventions designed specifically to benefit the individual patient. The European Association for Endoscopic Surgery defines innovations as any “significant modification of a standard technique, a new application of or new indication for an established technique, or an alternative combination of an established technique with another therapeutic modality.”⁴ As such, innovations should eventually be formally studied with institutional review board (IRB) approval and protocols to establish safety and efficacy. Another complicating factor is that there is no FDA approval for surgical and procedural techniques as there is for medications and certain devices. Therefore, no robust regulatory mechanisms exist to ensure patient safety and benefit. Further complicating matters is that innovative procedures often start as modifications of techniques and are often done regularly to fit specific situations – for example, an additional stitch in a different location or in a different orientation to what is done in the standard fashion. However, true innovations should be distinguished from these modifications. Perhaps then another way to think about the two is to splinter them into three types of activity: research, routine accepted practice, and innovative medicine.⁵

Dr. Williams is a general surgery resident at the University of Chicago and a fellow at the MacLean Center for clinical medical ethics. Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics, vice chairman for ethics, professional development, and wellness, and chief of endocrine surgery, department of surgery, and the associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago. The authors have no conflicts to disclose.

References

1. Goyal H et al. Ther Adv Gastrointest Endosc. 2021;14. doi: 10.1177/2631774520984627.

2. Machytka E et al. Gastrointestinal Endosc. 2017;86(5):904-12. doi: 10.1016/j.gie.2017.07.009.

3. Eastwood GL. J Gastroenterol Hepatol (Australia). 2015;30(S1):8-11. doi: 10.1111/jgh.12755.

4. Neugebauer EAM et al. Surg Endosc. 2010;24(7):1594-1615. doi: 10.1007/s00464-009-0818-3.

5. Eaton, ML and Kennedy, DL. Innovation in Medical Technology: Ethical Issues and Challenges. Baltimore: Johns Hopkins University Press, 2007.

6. Angelos P. Ann Thorac Surg. 2019;108(6):1611-2. doi: 10.1016/j.athoracsur.2019.08.010.

7. Angelos P. Virtual Mentor. 2011;13(1):6-9. doi: 10.1001/virtualmentor.2011.13.1.ccas1-1101.

Mrs. Jones is a 44-year-old woman who has struggled with her weight. She has a body mass index (BMI) of 35 kg/m² and hypertension requiring daily medication. She has tried various diets over the years and has never been able to exercise consistently. She desperately wants to lose weight to improve her confidence and to avoid developing diabetes and dialysis that her parents required. She has considered weight loss surgery but is afraid after her best friend died following uterine fibroid surgery. She saw a billboard that advertised a new weight loss procedure without surgery. She looked up the procedure, found Dr. Indo on the university medical center’s website, and booked an appointment. Dr. Indo talked about performing an incisionless procedure done with an endoscope through her mouth. It would make her stomach into a tube to reduce the amount of food she could eat as well as prevent some absorption of food in her intestines. When Mrs. Jones asked how many of these the doctor had performed, Dr. Indo remarked she personally had done “several” in the past few years including training. Dr. Indo reassured Mrs. Jones that the procedure has been performed hundreds of times around the country and has been shown to be safe. Dr. Indo also explained that studies were still ongoing, including possibly at the university medical center, but that she had never personally seen any serious complications or death, and only one patient she knew of converted to a traditional bariatric surgery.

Obesity is a large international public health problem, with the World Health Organization estimating that there are 600 million obese adults worldwide.¹ Bariatric surgery has been an effective way to improve complications related to obesity and quality of life. Endoscopic approaches to bariatric surgery have appeared since at least the late 1980s and, similarly to their traditional surgical counterparts, work in two main categories: restrictive or malabsorptive.¹ Restrictive endoscopic bariatric therapies (EBTs) include intragastric balloons (IGB) that are filled with saline or gas to decrease intragastric luminal size, endoscopic sleeve gastroplasty that makes full-thickness plications of the gastric wall to tubularize the stomach like a sleeve gastrectomy, and AspireAssist where patients use a percutaneous gastrostomy to remove part of an ingested meal.¹ Malabsorptive procedures include bypass sleeves that use a stentlike device to bypass absorption of food in the duodenum and proximal jejunum, the incisionless magnetic anastomosis system (IMAS) that creates a gastrojejunal bypass for diverting absorption, and duodenal mucosal resurfacing (DMR) that ablates the duodenal mucosa.^1,2

The benefits of EBTs over traditional bariatric surgery are that they have a lower risk profile, there is limited anatomic alternation, and they are potentially reversible.¹ Although no formal guidelines exist in the United States for the use of EBTs, the American Society for Gastrointestinal Endoscopy (ASGE) preliminary recommendations describe EBTs as applicable for patients who have failed lifestyle interventions and have BMIs between 30 and 45.¹ While some of these techniques were first described in the 1980s, many individual companies and devices still do not have Food and Drug Administration approval and some have even had approval withdrawn. While traditional bariatric surgery may have complication rates up to 17%, EBTs are not without complications.¹ Endoscopic barriers can migrate and occlude, cause pancreatitis, cause liver abscesses from biliary occlusion, and more severely cause GI bleeding and perforations.¹ Many EBTs are also temporary treatments with IGBs and barrier bypasses placed only for 6-12 months.1 While there have been some studies looking at individual outcomes of the various EBTs, large prospective research trials looking at safety and efficacy, especially when comparing EBT to traditional bariatric surgery or in combination, are lacking.

Continued innovation in medicine and technology is critical to improving patient care. New innovations in medicine have allowed us to treat more disease, save lives, reduce complications, and better care for patients. But what exactly is innovation and when does it become research? The landmark Belmont Report in 1979 distinguishes research from innovative therapy, calling research “an activity designed to test a hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge.”³ Patients in research thus bear the risks while others stand to benefit. The report affirms then that routine medical practice involves interventions designed specifically to benefit the individual patient. The European Association for Endoscopic Surgery defines innovations as any “significant modification of a standard technique, a new application of or new indication for an established technique, or an alternative combination of an established technique with another therapeutic modality.”⁴ As such, innovations should eventually be formally studied with institutional review board (IRB) approval and protocols to establish safety and efficacy. Another complicating factor is that there is no FDA approval for surgical and procedural techniques as there is for medications and certain devices. Therefore, no robust regulatory mechanisms exist to ensure patient safety and benefit. Further complicating matters is that innovative procedures often start as modifications of techniques and are often done regularly to fit specific situations – for example, an additional stitch in a different location or in a different orientation to what is done in the standard fashion. However, true innovations should be distinguished from these modifications. Perhaps then another way to think about the two is to splinter them into three types of activity: research, routine accepted practice, and innovative medicine.⁵

Dr. Williams is a general surgery resident at the University of Chicago and a fellow at the MacLean Center for clinical medical ethics. Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics, vice chairman for ethics, professional development, and wellness, and chief of endocrine surgery, department of surgery, and the associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago. The authors have no conflicts to disclose.

References

1. Goyal H et al. Ther Adv Gastrointest Endosc. 2021;14. doi: 10.1177/2631774520984627.

2. Machytka E et al. Gastrointestinal Endosc. 2017;86(5):904-12. doi: 10.1016/j.gie.2017.07.009.

3. Eastwood GL. J Gastroenterol Hepatol (Australia). 2015;30(S1):8-11. doi: 10.1111/jgh.12755.

4. Neugebauer EAM et al. Surg Endosc. 2010;24(7):1594-1615. doi: 10.1007/s00464-009-0818-3.

5. Eaton, ML and Kennedy, DL. Innovation in Medical Technology: Ethical Issues and Challenges. Baltimore: Johns Hopkins University Press, 2007.

6. Angelos P. Ann Thorac Surg. 2019;108(6):1611-2. doi: 10.1016/j.athoracsur.2019.08.010.

7. Angelos P. Virtual Mentor. 2011;13(1):6-9. doi: 10.1001/virtualmentor.2011.13.1.ccas1-1101.

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

Received income in an amount equal to or greater than $250 from: Actelion

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

Received income in an amount equal to or greater than $250 from: Actelion

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

Received income in an amount equal to or greater than $250 from: Actelion

Aerosolized hydrogen peroxide (aHP) can significantly reduce Clostridioides difficile infection (CDI) and is an effective disinfection system, suggests a study published in the American Journal of Infection Control.

C. difficile is the most common cause of health care–associated infection and increasingly occurs outside acute care hospitals. CDI symptoms can range from mild diarrhea to life-threatening colitis and sepsis, sometimes requiring urgent colon removal.

The Centers for Disease Control and Prevention has reported that, in the United States, 223,900 people required hospitalization for CDI and at least 12,800 died in 2017. Because of its large toll, CDI is grouped with antimicrobial-resistant “threat” organisms that often accompany it. People older than age 65 are at particular risk for disease, and at least 20% of patients experience recurrence.

In health care facilities, C. difficile is transmitted by bacterial spores that readily contaminate surfaces in patients’ rooms, from handrails to bedside tables to light switches and knobs. The spores are resistant to disinfectants, and rooms are often cleaned with bleach solutions. But those bleach fumes are irritating and may cause bronchospasm for patients with asthma or chronic obstructive pulmonary disease, and so alternative cleaning agents are needed.

In a retrospective study of an acute-care facility in Philadelphia, researchers compared the incidence of health care–associated CDI (HA-CDI) at the facility before and after adding aHP to other infection control practices. The aHP process produces an aerosolized dry-mist fog that contains a specified percentage of hydrogen peroxide. The fog is used after the room has been physically cleaned, settling on exposed surfaces and killing any remaining C. difficile spores.

The aHP mixture also contains 0.01% ionic silver. The study lead was Christopher L. Truitt, PhD, of Wayland Baptist University. Dr. Truitt told this news organization that hydrogen peroxide affects the endospore layer of the C. difficile organism and allows the “ionic silver to get into the cell and is shown to bind to enzymes and inactivate those inside the cell and actually improve the efficacy.”

Asked whether it’s the silver or the peroxide that disinfects, Dr. Truitt replied: “I can’t answer that. We don’t know if it’s the silver or the hydrogen peroxide. The commercially available chemical that’s used in that machine is a proprietary set-up ... with EPA approval as a sporicidal.”

In the baseline 27-month period, the hospital tallied 120 HA-CDI cases. After aHP was introduced, they counted just 72 cases over 33 months, a 41% decrease in the facility’s HA-CDI rate, from 4.6 per 10,000 patient-days to 2.7 per 10,000 patient-days (P < .001).

There was also a progressive decrease in hospital-onset CDI even after aHP was introduced, from 5.4 per 10,000 patient-days in 2015 to 1.4 per 10,000 patient-days in 2019.

Yoav Golan, MD, of Tufts University, Boston, told this news organization there were two major study limitations. “One is the fact that they did not control for other interventions that may have an effect on C. difficile: antibiotic stewardship and infection control,” he explained. This limitation was noted by the study authors and may explain the continued decline in infections after the introduction of aHP. The other limitation was not using a crossover study design.

“I would argue that they should have provided a little more information about their own practices in their own hospital when it comes to intensification of infection control [and] when it comes to a stewardship and changes that they’ve made to antibiotic usage,” Dr. Golan continued. “The description of changes over time and those practices would have allowed us to better understand the impact of the hydrogen peroxide intervention.”

Despite his criticisms, Dr. Golan concluded: “I think that the study is important. I think their intervention is unique in a way that they’ve been using an aerosolizing system that’s using a relatively high concentration of hydrogen peroxide. I think that there’s enough in this paper to suggest that using such a system may have an impact on the environment, and through that, on dissemination.”

Dr. Truitt added that a next step would be to compare aHP with ultraviolet light, which is commonly used to disinfect hospital rooms.

Dr. Truitt is chief science officer at Infection Controls, dba Germblast, a proprietary service that uses cold-mist hydrogen peroxide and other modalities to disinfect surfaces. Dr. Golan has reported being a consultant for Merck, Seres Therapeutics, Vedanta Biosciences, and Ferring Pharmaceuticals.

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

Aerosolized hydrogen peroxide (aHP) can significantly reduce Clostridioides difficile infection (CDI) and is an effective disinfection system, suggests a study published in the American Journal of Infection Control.

C. difficile is the most common cause of health care–associated infection and increasingly occurs outside acute care hospitals. CDI symptoms can range from mild diarrhea to life-threatening colitis and sepsis, sometimes requiring urgent colon removal.

The Centers for Disease Control and Prevention has reported that, in the United States, 223,900 people required hospitalization for CDI and at least 12,800 died in 2017. Because of its large toll, CDI is grouped with antimicrobial-resistant “threat” organisms that often accompany it. People older than age 65 are at particular risk for disease, and at least 20% of patients experience recurrence.

In health care facilities, C. difficile is transmitted by bacterial spores that readily contaminate surfaces in patients’ rooms, from handrails to bedside tables to light switches and knobs. The spores are resistant to disinfectants, and rooms are often cleaned with bleach solutions. But those bleach fumes are irritating and may cause bronchospasm for patients with asthma or chronic obstructive pulmonary disease, and so alternative cleaning agents are needed.

In a retrospective study of an acute-care facility in Philadelphia, researchers compared the incidence of health care–associated CDI (HA-CDI) at the facility before and after adding aHP to other infection control practices. The aHP process produces an aerosolized dry-mist fog that contains a specified percentage of hydrogen peroxide. The fog is used after the room has been physically cleaned, settling on exposed surfaces and killing any remaining C. difficile spores.

The aHP mixture also contains 0.01% ionic silver. The study lead was Christopher L. Truitt, PhD, of Wayland Baptist University. Dr. Truitt told this news organization that hydrogen peroxide affects the endospore layer of the C. difficile organism and allows the “ionic silver to get into the cell and is shown to bind to enzymes and inactivate those inside the cell and actually improve the efficacy.”

Asked whether it’s the silver or the peroxide that disinfects, Dr. Truitt replied: “I can’t answer that. We don’t know if it’s the silver or the hydrogen peroxide. The commercially available chemical that’s used in that machine is a proprietary set-up ... with EPA approval as a sporicidal.”

In the baseline 27-month period, the hospital tallied 120 HA-CDI cases. After aHP was introduced, they counted just 72 cases over 33 months, a 41% decrease in the facility’s HA-CDI rate, from 4.6 per 10,000 patient-days to 2.7 per 10,000 patient-days (P < .001).

There was also a progressive decrease in hospital-onset CDI even after aHP was introduced, from 5.4 per 10,000 patient-days in 2015 to 1.4 per 10,000 patient-days in 2019.

Yoav Golan, MD, of Tufts University, Boston, told this news organization there were two major study limitations. “One is the fact that they did not control for other interventions that may have an effect on C. difficile: antibiotic stewardship and infection control,” he explained. This limitation was noted by the study authors and may explain the continued decline in infections after the introduction of aHP. The other limitation was not using a crossover study design.

“I would argue that they should have provided a little more information about their own practices in their own hospital when it comes to intensification of infection control [and] when it comes to a stewardship and changes that they’ve made to antibiotic usage,” Dr. Golan continued. “The description of changes over time and those practices would have allowed us to better understand the impact of the hydrogen peroxide intervention.”

Despite his criticisms, Dr. Golan concluded: “I think that the study is important. I think their intervention is unique in a way that they’ve been using an aerosolizing system that’s using a relatively high concentration of hydrogen peroxide. I think that there’s enough in this paper to suggest that using such a system may have an impact on the environment, and through that, on dissemination.”

Dr. Truitt added that a next step would be to compare aHP with ultraviolet light, which is commonly used to disinfect hospital rooms.

Dr. Truitt is chief science officer at Infection Controls, dba Germblast, a proprietary service that uses cold-mist hydrogen peroxide and other modalities to disinfect surfaces. Dr. Golan has reported being a consultant for Merck, Seres Therapeutics, Vedanta Biosciences, and Ferring Pharmaceuticals.

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

Aerosolized hydrogen peroxide (aHP) can significantly reduce Clostridioides difficile infection (CDI) and is an effective disinfection system, suggests a study published in the American Journal of Infection Control.

C. difficile is the most common cause of health care–associated infection and increasingly occurs outside acute care hospitals. CDI symptoms can range from mild diarrhea to life-threatening colitis and sepsis, sometimes requiring urgent colon removal.

The Centers for Disease Control and Prevention has reported that, in the United States, 223,900 people required hospitalization for CDI and at least 12,800 died in 2017. Because of its large toll, CDI is grouped with antimicrobial-resistant “threat” organisms that often accompany it. People older than age 65 are at particular risk for disease, and at least 20% of patients experience recurrence.

In health care facilities, C. difficile is transmitted by bacterial spores that readily contaminate surfaces in patients’ rooms, from handrails to bedside tables to light switches and knobs. The spores are resistant to disinfectants, and rooms are often cleaned with bleach solutions. But those bleach fumes are irritating and may cause bronchospasm for patients with asthma or chronic obstructive pulmonary disease, and so alternative cleaning agents are needed.

In a retrospective study of an acute-care facility in Philadelphia, researchers compared the incidence of health care–associated CDI (HA-CDI) at the facility before and after adding aHP to other infection control practices. The aHP process produces an aerosolized dry-mist fog that contains a specified percentage of hydrogen peroxide. The fog is used after the room has been physically cleaned, settling on exposed surfaces and killing any remaining C. difficile spores.

The aHP mixture also contains 0.01% ionic silver. The study lead was Christopher L. Truitt, PhD, of Wayland Baptist University. Dr. Truitt told this news organization that hydrogen peroxide affects the endospore layer of the C. difficile organism and allows the “ionic silver to get into the cell and is shown to bind to enzymes and inactivate those inside the cell and actually improve the efficacy.”

Asked whether it’s the silver or the peroxide that disinfects, Dr. Truitt replied: “I can’t answer that. We don’t know if it’s the silver or the hydrogen peroxide. The commercially available chemical that’s used in that machine is a proprietary set-up ... with EPA approval as a sporicidal.”

In the baseline 27-month period, the hospital tallied 120 HA-CDI cases. After aHP was introduced, they counted just 72 cases over 33 months, a 41% decrease in the facility’s HA-CDI rate, from 4.6 per 10,000 patient-days to 2.7 per 10,000 patient-days (P < .001).

There was also a progressive decrease in hospital-onset CDI even after aHP was introduced, from 5.4 per 10,000 patient-days in 2015 to 1.4 per 10,000 patient-days in 2019.

Yoav Golan, MD, of Tufts University, Boston, told this news organization there were two major study limitations. “One is the fact that they did not control for other interventions that may have an effect on C. difficile: antibiotic stewardship and infection control,” he explained. This limitation was noted by the study authors and may explain the continued decline in infections after the introduction of aHP. The other limitation was not using a crossover study design.

“I would argue that they should have provided a little more information about their own practices in their own hospital when it comes to intensification of infection control [and] when it comes to a stewardship and changes that they’ve made to antibiotic usage,” Dr. Golan continued. “The description of changes over time and those practices would have allowed us to better understand the impact of the hydrogen peroxide intervention.”

Despite his criticisms, Dr. Golan concluded: “I think that the study is important. I think their intervention is unique in a way that they’ve been using an aerosolizing system that’s using a relatively high concentration of hydrogen peroxide. I think that there’s enough in this paper to suggest that using such a system may have an impact on the environment, and through that, on dissemination.”

Dr. Truitt added that a next step would be to compare aHP with ultraviolet light, which is commonly used to disinfect hospital rooms.

Dr. Truitt is chief science officer at Infection Controls, dba Germblast, a proprietary service that uses cold-mist hydrogen peroxide and other modalities to disinfect surfaces. Dr. Golan has reported being a consultant for Merck, Seres Therapeutics, Vedanta Biosciences, and Ferring Pharmaceuticals.

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

COVID-19 patients who are successfully weaned off a ventilator may take days, or even weeks, to regain consciousness, especially those who experienced episodes of hypoxemia while intubated, a new study shows.

“As we started to see the first patients waking up after successful COVID-19 ICU treatments, we also encountered many patients who remained comatose for days and weeks and then regained consciousness to become fully oriented,” co-senior investigator Nicholas Schiff, MD, with NewYork-Presbyterian/Weill Cornell Medical Center, says in a news release.

The findings have immediate implications regarding life-sustaining therapies for unresponsive COVID-19 patients, the investigators note.

“In critical care medicine, one of our main tasks is to advise families about planning in the event a patient does not regain consciousness,” said co-senior author Jan Claassen, MD, with New York-Presbyterian/Columbia University Irving Medical Center. 

“Our findings suggest that for patients with severe COVID, the decision to withdraw life support shouldn’t be based solely on prolonged periods of unconsciousness, as these patients may eventually recover,” Dr. Claassen adds.

The study was published online March 7 in Annals of Neurology.
 

Slow road back

The researchers examined 795 intubated patients with severe COVID-19 at three medical centers in New York during the first wave of the pandemic (March-July 2020). All patients had impaired consciousness (Glasgow Coma Scale [GCS] motor score less than 6) on day 7 of intubation.

A total of 571 patients (72%) survived and regained consciousness.

The median time to recovery of consciousness was 30 days. One-quarter of the patients recovered consciousness 10 days or longer after they stopped receiving ventilator support and 10% took 23 days or longer to recover.

Time to recovery of consciousness was associated with hypoxemia. The hazard ratio was 0.56 (95% confidence interval, 0.46-0.68) with arterial partial pressure of oxygen (PaO2) less than or equal to 55 mm Hg and 0.88 (95% CI, 0.85-0.91) with a PaO2 less than or equal to 70 mm Hg.

Each additional day of hypoxemia decreased the odds of recovery of consciousness after accounting for confounding factors including sedation.

These findings were confirmed among patients without any imaging evidence of structural brain injury and in a non-overlapping cohort of 427 patients from the second wave of the pandemic (October-April 2021).

“These findings provide us with more accurate information to guide families who are deciding whether to continue life-sustaining therapy in unconscious COVID-19 patients,” co-senior author Brian Edlow, MD, with Massachusetts General Hospital and Harvard Medical School in Boston, says in the news release.

“Encouragingly,” adds Dr. Claassen, “our study shows that the vast majority of unconscious COVID patients recover consciousness, but it is important to consider that we did not look at the quality of recovery. That’s something that should be the focus of long-term follow-up studies.”

The study was supported by the James S. McDonnell Foundation (JSMF). Dr. Schiff, Dr. Claassen, and Dr. Edlow have disclosed no relevant financial relationships.

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

COVID-19 patients who are successfully weaned off a ventilator may take days, or even weeks, to regain consciousness, especially those who experienced episodes of hypoxemia while intubated, a new study shows.

“As we started to see the first patients waking up after successful COVID-19 ICU treatments, we also encountered many patients who remained comatose for days and weeks and then regained consciousness to become fully oriented,” co-senior investigator Nicholas Schiff, MD, with NewYork-Presbyterian/Weill Cornell Medical Center, says in a news release.

The findings have immediate implications regarding life-sustaining therapies for unresponsive COVID-19 patients, the investigators note.

“In critical care medicine, one of our main tasks is to advise families about planning in the event a patient does not regain consciousness,” said co-senior author Jan Claassen, MD, with New York-Presbyterian/Columbia University Irving Medical Center. 

“Our findings suggest that for patients with severe COVID, the decision to withdraw life support shouldn’t be based solely on prolonged periods of unconsciousness, as these patients may eventually recover,” Dr. Claassen adds.

The study was published online March 7 in Annals of Neurology.
 

Slow road back

The researchers examined 795 intubated patients with severe COVID-19 at three medical centers in New York during the first wave of the pandemic (March-July 2020). All patients had impaired consciousness (Glasgow Coma Scale [GCS] motor score less than 6) on day 7 of intubation.

A total of 571 patients (72%) survived and regained consciousness.

The median time to recovery of consciousness was 30 days. One-quarter of the patients recovered consciousness 10 days or longer after they stopped receiving ventilator support and 10% took 23 days or longer to recover.

Time to recovery of consciousness was associated with hypoxemia. The hazard ratio was 0.56 (95% confidence interval, 0.46-0.68) with arterial partial pressure of oxygen (PaO2) less than or equal to 55 mm Hg and 0.88 (95% CI, 0.85-0.91) with a PaO2 less than or equal to 70 mm Hg.

Each additional day of hypoxemia decreased the odds of recovery of consciousness after accounting for confounding factors including sedation.

These findings were confirmed among patients without any imaging evidence of structural brain injury and in a non-overlapping cohort of 427 patients from the second wave of the pandemic (October-April 2021).

“These findings provide us with more accurate information to guide families who are deciding whether to continue life-sustaining therapy in unconscious COVID-19 patients,” co-senior author Brian Edlow, MD, with Massachusetts General Hospital and Harvard Medical School in Boston, says in the news release.

“Encouragingly,” adds Dr. Claassen, “our study shows that the vast majority of unconscious COVID patients recover consciousness, but it is important to consider that we did not look at the quality of recovery. That’s something that should be the focus of long-term follow-up studies.”

The study was supported by the James S. McDonnell Foundation (JSMF). Dr. Schiff, Dr. Claassen, and Dr. Edlow have disclosed no relevant financial relationships.

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

COVID-19 patients who are successfully weaned off a ventilator may take days, or even weeks, to regain consciousness, especially those who experienced episodes of hypoxemia while intubated, a new study shows.

“As we started to see the first patients waking up after successful COVID-19 ICU treatments, we also encountered many patients who remained comatose for days and weeks and then regained consciousness to become fully oriented,” co-senior investigator Nicholas Schiff, MD, with NewYork-Presbyterian/Weill Cornell Medical Center, says in a news release.

The findings have immediate implications regarding life-sustaining therapies for unresponsive COVID-19 patients, the investigators note.

“In critical care medicine, one of our main tasks is to advise families about planning in the event a patient does not regain consciousness,” said co-senior author Jan Claassen, MD, with New York-Presbyterian/Columbia University Irving Medical Center. 

“Our findings suggest that for patients with severe COVID, the decision to withdraw life support shouldn’t be based solely on prolonged periods of unconsciousness, as these patients may eventually recover,” Dr. Claassen adds.

The study was published online March 7 in Annals of Neurology.
 

Slow road back

The researchers examined 795 intubated patients with severe COVID-19 at three medical centers in New York during the first wave of the pandemic (March-July 2020). All patients had impaired consciousness (Glasgow Coma Scale [GCS] motor score less than 6) on day 7 of intubation.

A total of 571 patients (72%) survived and regained consciousness.

The median time to recovery of consciousness was 30 days. One-quarter of the patients recovered consciousness 10 days or longer after they stopped receiving ventilator support and 10% took 23 days or longer to recover.

Time to recovery of consciousness was associated with hypoxemia. The hazard ratio was 0.56 (95% confidence interval, 0.46-0.68) with arterial partial pressure of oxygen (PaO2) less than or equal to 55 mm Hg and 0.88 (95% CI, 0.85-0.91) with a PaO2 less than or equal to 70 mm Hg.

Each additional day of hypoxemia decreased the odds of recovery of consciousness after accounting for confounding factors including sedation.

These findings were confirmed among patients without any imaging evidence of structural brain injury and in a non-overlapping cohort of 427 patients from the second wave of the pandemic (October-April 2021).

“These findings provide us with more accurate information to guide families who are deciding whether to continue life-sustaining therapy in unconscious COVID-19 patients,” co-senior author Brian Edlow, MD, with Massachusetts General Hospital and Harvard Medical School in Boston, says in the news release.

“Encouragingly,” adds Dr. Claassen, “our study shows that the vast majority of unconscious COVID patients recover consciousness, but it is important to consider that we did not look at the quality of recovery. That’s something that should be the focus of long-term follow-up studies.”

The study was supported by the James S. McDonnell Foundation (JSMF). Dr. Schiff, Dr. Claassen, and Dr. Edlow have disclosed no relevant financial relationships.

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

Over the past decade, data have suggested that antiretroviral therapy (ART) may be associated with an increased risk for adverse pregnancy outcomes, namely, preterm birth (PTB). But a combination of methodologic challenges, demographic gaps, and spotty clinical data has left the question unresolved, especially for pregnant women with HIV who reside in developed countries.

“Given that a lot of the emerging data has come out of resource-limited settings where patient and clinical characteristics are different from developed world settings like the United States, we felt that this was an important question to address,” Kartik Venkatesh, MD, PhD, a high-risk obstetrician and perinatal epidemiologist at the Ohio State Wexner Medical Center, Columbus, told this news organization.

In a prospective cohort study of U.S. women with or at risk for HIV, Dr. Venkatesh and his colleagues found that ART exposure (including highly active antiretroviral therapy [HAART]) was associated with as much as an 80% decline in the likelihood of PTB (defined as birth less than 34 weeks). The study was published in HIV Medicine.
 

24 years of data analyzed

Dr. Venkatesh and his team analyzed self-reported birth data of women with singleton live-born pregnancies enrolled in the ongoing, multicenter, prospective observational Women’s Interagency HIV Study (WIHS) from Oct. 1, 1995, to March 31, 2019.

“We first looked at women with HIV versus without HIV, [who were] matched on many clinical and sociodemographic characteristics and at similarly high risk of some of these obstetrical outcomes like PTB,” explained Dr. Venkatesh. “We then looked at the relative impact of antiretroviral therapy amongst women living with HIV compared to no antiretroviral therapy.”

ART regimens were classified as none, monotherapy, dual therapy, or HAART. (HAART was defined as more than three antiretrovirals, including at least one protease inhibitor [PI], nonnucleoside reverse transcriptase inhibitor, integrase inhibitor, or entry inhibitor.) In this cohort, for 63.5% of women receiving ART, therapy was initiated before pregnancy (mean duration of HAART, 6 years), and most were virally suppressed.

Among the 4,944 women assessed in the WIHS trial, 74% (3,646) had HIV. In total, 383 women had 488 singleton deliveries, including 218 women with HIV (272 deliveries) and 165 without HIV (216 deliveries). Sociodemographics in both cohorts were well matched. For most participants, the mean age was 40-41 years at delivery, most were non-Hispanic Black persons, and the mean pregnancy body mass index was greater than or equal to 29 kg/m2. Of the women with HIV, 33% had chronic hypertension; of those without HIV, 42.1% had chronic hypertension; 4.7% and 5.0%, respectively, had pregestational diabetes.

The findings showed that PTB risk less than 34 weeks was similar between women with (10%) and without (8%) HIV (adjusted risk ratio, 1.30; 95% confidence interval, 0.74-2.31). Among deliveries to women with HIV who were receiving ART, PTB risk less than 34 weeks was lower with HAART (7%), compared with not receiving ART (26%) (aRR, 0.19), as well as with monotherapy or dual therapy (3% vs. no ART) (aRR, 0.12). Notably, 67% of deliveries to women receiving HAART included a PI-containing regimen, but these women were not significantly more likely to have a PTB less than 34 weeks, compared with women taking non-PI HAART regimens (aRR, 2.61; 95% CI, 0.65-10.59). Results were similar for secondary outcomes (PTB less than 28 weeks, less than 37 weeks).
 

Filling in the gaps toward the safest regimen

“This study spans 25 years, so it covers a lot of the history of HIV in pregnancy and is reassuring around using ART in pregnancy,” Shahin Lockman, MD, told this news organization. Dr. Lockman is an associate professor of infectious diseases at Brigham and Women’s Hospital and a co-PI of the Botswana Clinical Trials Unit at the Botswana Harvard AIDS Institute Partnership. She was not involved in the study. “One of the worst things for a mother and for pregnancy outcomes, for the fetus and baby’s health and development, is uncontrolled maternal HIV,’’ she said.

Dr. Lockman also noted potential confounders that drive poor birth outcomes in Southern African women, compared with U.S. women, making comparisons between this and other observational studies difficult. Still, she said that the question is not whether women should be receiving treatment but whether or not there are differences between antiretroviral regimens.

“One of the areas that we did not go deeper into was the subtype of antiretroviral therapy, given the relatively small study numbers [did not] allow us to do a robust analysis,” Dr. Venkatesh said.

Rather, he emphasized that the findings might lend more weight to speculation that immunologic characteristics associated with HIV status and immunotherapy – such as low CD4 cell counts prior to delivery, or duration of HIV infection – may be important drivers of adverse birth outcomes among women with HIV taking ART.

And at least in this cohort, many of these characteristics were similar between the treatment groups.

Both researchers agree that the findings – while reassuring – highlight the importance of collecting robust obstetric and safety data as part of prospective databases of individuals living with HIV, not only in resource-limited settings but also among the domestic U.S. population.

“We’ve learned a lot over the last 10 years,” Dr. Lockman said. “Some regimens (like lopinavir/ritonavir or nevirapine) are associated with significantly worse birth outcomes, whereas efavirenz doesn’t seem to be, or less so, and dolutegravir seems to be associated with even better outcomes. So, I think that where we are moving is to regimens that are the safest.”

Moving forward, Dr. Venkatesh explained, not only should researchers focus on exploring which antiretrovirals are safest in this context but also if the use of preexposure prophylaxis during conception periods affects birth outcomes.

Dr. Venkatesh and Dr. Lockman report no relevant financial relationships.

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

Over the past decade, data have suggested that antiretroviral therapy (ART) may be associated with an increased risk for adverse pregnancy outcomes, namely, preterm birth (PTB). But a combination of methodologic challenges, demographic gaps, and spotty clinical data has left the question unresolved, especially for pregnant women with HIV who reside in developed countries.

“Given that a lot of the emerging data has come out of resource-limited settings where patient and clinical characteristics are different from developed world settings like the United States, we felt that this was an important question to address,” Kartik Venkatesh, MD, PhD, a high-risk obstetrician and perinatal epidemiologist at the Ohio State Wexner Medical Center, Columbus, told this news organization.

In a prospective cohort study of U.S. women with or at risk for HIV, Dr. Venkatesh and his colleagues found that ART exposure (including highly active antiretroviral therapy [HAART]) was associated with as much as an 80% decline in the likelihood of PTB (defined as birth less than 34 weeks). The study was published in HIV Medicine.
 

24 years of data analyzed

Dr. Venkatesh and his team analyzed self-reported birth data of women with singleton live-born pregnancies enrolled in the ongoing, multicenter, prospective observational Women’s Interagency HIV Study (WIHS) from Oct. 1, 1995, to March 31, 2019.

“We first looked at women with HIV versus without HIV, [who were] matched on many clinical and sociodemographic characteristics and at similarly high risk of some of these obstetrical outcomes like PTB,” explained Dr. Venkatesh. “We then looked at the relative impact of antiretroviral therapy amongst women living with HIV compared to no antiretroviral therapy.”

ART regimens were classified as none, monotherapy, dual therapy, or HAART. (HAART was defined as more than three antiretrovirals, including at least one protease inhibitor [PI], nonnucleoside reverse transcriptase inhibitor, integrase inhibitor, or entry inhibitor.) In this cohort, for 63.5% of women receiving ART, therapy was initiated before pregnancy (mean duration of HAART, 6 years), and most were virally suppressed.

Among the 4,944 women assessed in the WIHS trial, 74% (3,646) had HIV. In total, 383 women had 488 singleton deliveries, including 218 women with HIV (272 deliveries) and 165 without HIV (216 deliveries). Sociodemographics in both cohorts were well matched. For most participants, the mean age was 40-41 years at delivery, most were non-Hispanic Black persons, and the mean pregnancy body mass index was greater than or equal to 29 kg/m2. Of the women with HIV, 33% had chronic hypertension; of those without HIV, 42.1% had chronic hypertension; 4.7% and 5.0%, respectively, had pregestational diabetes.

The findings showed that PTB risk less than 34 weeks was similar between women with (10%) and without (8%) HIV (adjusted risk ratio, 1.30; 95% confidence interval, 0.74-2.31). Among deliveries to women with HIV who were receiving ART, PTB risk less than 34 weeks was lower with HAART (7%), compared with not receiving ART (26%) (aRR, 0.19), as well as with monotherapy or dual therapy (3% vs. no ART) (aRR, 0.12). Notably, 67% of deliveries to women receiving HAART included a PI-containing regimen, but these women were not significantly more likely to have a PTB less than 34 weeks, compared with women taking non-PI HAART regimens (aRR, 2.61; 95% CI, 0.65-10.59). Results were similar for secondary outcomes (PTB less than 28 weeks, less than 37 weeks).
 

Filling in the gaps toward the safest regimen

“This study spans 25 years, so it covers a lot of the history of HIV in pregnancy and is reassuring around using ART in pregnancy,” Shahin Lockman, MD, told this news organization. Dr. Lockman is an associate professor of infectious diseases at Brigham and Women’s Hospital and a co-PI of the Botswana Clinical Trials Unit at the Botswana Harvard AIDS Institute Partnership. She was not involved in the study. “One of the worst things for a mother and for pregnancy outcomes, for the fetus and baby’s health and development, is uncontrolled maternal HIV,’’ she said.

Dr. Lockman also noted potential confounders that drive poor birth outcomes in Southern African women, compared with U.S. women, making comparisons between this and other observational studies difficult. Still, she said that the question is not whether women should be receiving treatment but whether or not there are differences between antiretroviral regimens.

“One of the areas that we did not go deeper into was the subtype of antiretroviral therapy, given the relatively small study numbers [did not] allow us to do a robust analysis,” Dr. Venkatesh said.

Rather, he emphasized that the findings might lend more weight to speculation that immunologic characteristics associated with HIV status and immunotherapy – such as low CD4 cell counts prior to delivery, or duration of HIV infection – may be important drivers of adverse birth outcomes among women with HIV taking ART.

And at least in this cohort, many of these characteristics were similar between the treatment groups.

Both researchers agree that the findings – while reassuring – highlight the importance of collecting robust obstetric and safety data as part of prospective databases of individuals living with HIV, not only in resource-limited settings but also among the domestic U.S. population.

“We’ve learned a lot over the last 10 years,” Dr. Lockman said. “Some regimens (like lopinavir/ritonavir or nevirapine) are associated with significantly worse birth outcomes, whereas efavirenz doesn’t seem to be, or less so, and dolutegravir seems to be associated with even better outcomes. So, I think that where we are moving is to regimens that are the safest.”

Moving forward, Dr. Venkatesh explained, not only should researchers focus on exploring which antiretrovirals are safest in this context but also if the use of preexposure prophylaxis during conception periods affects birth outcomes.

Dr. Venkatesh and Dr. Lockman report no relevant financial relationships.

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

Over the past decade, data have suggested that antiretroviral therapy (ART) may be associated with an increased risk for adverse pregnancy outcomes, namely, preterm birth (PTB). But a combination of methodologic challenges, demographic gaps, and spotty clinical data has left the question unresolved, especially for pregnant women with HIV who reside in developed countries.

“Given that a lot of the emerging data has come out of resource-limited settings where patient and clinical characteristics are different from developed world settings like the United States, we felt that this was an important question to address,” Kartik Venkatesh, MD, PhD, a high-risk obstetrician and perinatal epidemiologist at the Ohio State Wexner Medical Center, Columbus, told this news organization.

In a prospective cohort study of U.S. women with or at risk for HIV, Dr. Venkatesh and his colleagues found that ART exposure (including highly active antiretroviral therapy [HAART]) was associated with as much as an 80% decline in the likelihood of PTB (defined as birth less than 34 weeks). The study was published in HIV Medicine.
 

24 years of data analyzed

Dr. Venkatesh and his team analyzed self-reported birth data of women with singleton live-born pregnancies enrolled in the ongoing, multicenter, prospective observational Women’s Interagency HIV Study (WIHS) from Oct. 1, 1995, to March 31, 2019.

“We first looked at women with HIV versus without HIV, [who were] matched on many clinical and sociodemographic characteristics and at similarly high risk of some of these obstetrical outcomes like PTB,” explained Dr. Venkatesh. “We then looked at the relative impact of antiretroviral therapy amongst women living with HIV compared to no antiretroviral therapy.”

ART regimens were classified as none, monotherapy, dual therapy, or HAART. (HAART was defined as more than three antiretrovirals, including at least one protease inhibitor [PI], nonnucleoside reverse transcriptase inhibitor, integrase inhibitor, or entry inhibitor.) In this cohort, for 63.5% of women receiving ART, therapy was initiated before pregnancy (mean duration of HAART, 6 years), and most were virally suppressed.

Among the 4,944 women assessed in the WIHS trial, 74% (3,646) had HIV. In total, 383 women had 488 singleton deliveries, including 218 women with HIV (272 deliveries) and 165 without HIV (216 deliveries). Sociodemographics in both cohorts were well matched. For most participants, the mean age was 40-41 years at delivery, most were non-Hispanic Black persons, and the mean pregnancy body mass index was greater than or equal to 29 kg/m2. Of the women with HIV, 33% had chronic hypertension; of those without HIV, 42.1% had chronic hypertension; 4.7% and 5.0%, respectively, had pregestational diabetes.

The findings showed that PTB risk less than 34 weeks was similar between women with (10%) and without (8%) HIV (adjusted risk ratio, 1.30; 95% confidence interval, 0.74-2.31). Among deliveries to women with HIV who were receiving ART, PTB risk less than 34 weeks was lower with HAART (7%), compared with not receiving ART (26%) (aRR, 0.19), as well as with monotherapy or dual therapy (3% vs. no ART) (aRR, 0.12). Notably, 67% of deliveries to women receiving HAART included a PI-containing regimen, but these women were not significantly more likely to have a PTB less than 34 weeks, compared with women taking non-PI HAART regimens (aRR, 2.61; 95% CI, 0.65-10.59). Results were similar for secondary outcomes (PTB less than 28 weeks, less than 37 weeks).
 

Filling in the gaps toward the safest regimen

“This study spans 25 years, so it covers a lot of the history of HIV in pregnancy and is reassuring around using ART in pregnancy,” Shahin Lockman, MD, told this news organization. Dr. Lockman is an associate professor of infectious diseases at Brigham and Women’s Hospital and a co-PI of the Botswana Clinical Trials Unit at the Botswana Harvard AIDS Institute Partnership. She was not involved in the study. “One of the worst things for a mother and for pregnancy outcomes, for the fetus and baby’s health and development, is uncontrolled maternal HIV,’’ she said.

Dr. Lockman also noted potential confounders that drive poor birth outcomes in Southern African women, compared with U.S. women, making comparisons between this and other observational studies difficult. Still, she said that the question is not whether women should be receiving treatment but whether or not there are differences between antiretroviral regimens.

“One of the areas that we did not go deeper into was the subtype of antiretroviral therapy, given the relatively small study numbers [did not] allow us to do a robust analysis,” Dr. Venkatesh said.

Rather, he emphasized that the findings might lend more weight to speculation that immunologic characteristics associated with HIV status and immunotherapy – such as low CD4 cell counts prior to delivery, or duration of HIV infection – may be important drivers of adverse birth outcomes among women with HIV taking ART.

And at least in this cohort, many of these characteristics were similar between the treatment groups.

Both researchers agree that the findings – while reassuring – highlight the importance of collecting robust obstetric and safety data as part of prospective databases of individuals living with HIV, not only in resource-limited settings but also among the domestic U.S. population.

“We’ve learned a lot over the last 10 years,” Dr. Lockman said. “Some regimens (like lopinavir/ritonavir or nevirapine) are associated with significantly worse birth outcomes, whereas efavirenz doesn’t seem to be, or less so, and dolutegravir seems to be associated with even better outcomes. So, I think that where we are moving is to regimens that are the safest.”

Moving forward, Dr. Venkatesh explained, not only should researchers focus on exploring which antiretrovirals are safest in this context but also if the use of preexposure prophylaxis during conception periods affects birth outcomes.

Dr. Venkatesh and Dr. Lockman report no relevant financial relationships.

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