Image from NHS

Children born to mothers who underwent fertility treatments have an increased risk of developing pediatric neoplasms, according to research published in the American Journal of Obstetrics & Gynecology.

The study showed an increased risk of malignancies and benign tumors among children conceived after fertility treatments.

However, the risk of leukemias and lymphomas among these children was not significantly different from the risk among children who were conceived spontaneously.

The study was a population-based cohort analysis of babies born between 1991 and 2013 at Soroka University Medical Center in Beer-Sheva, Israel, with follow-up to age 18.

Of the 242,187 newborn infants in the study, 237,863 (98.3%) were conceived spontaneously, 2603 (1.1%) were conceived after in vitro fertilization (IVF), and 1721 (0.7%) were conceived after ovulation induction (OI) treatments.

During a median follow-up of 10.55 years, there were 1498 neoplasms reported, including 1074 benign tumors and 429 malignancies.

The rate of neoplasms per 10,000 children was 61.85 for the entire study cohort, 111.41 for the IVF group, 110.40 for the OI group, and 60.96 for the spontaneous conception group (P<0.001 for the comparison between spontaneous conception and both types of fertility treatments).

The rate of benign tumors per 10,000 children was 44.35 for the entire study cohort, 84.51 for the IVF group, 69.73 for the OI group, and 43.72 for the spontaneous conception group (P=0.002).

The rate of malignancies per 10,000 children was 17.71 for the entire study cohort, 26.89 for the IVF group, 40.67 for the OI group, and 17.44 for the spontaneous conception group (P=0.038).

The rate of leukemia per 10,000 children was 3.72 for the entire study cohort (n=90 leukemia cases total), 0 for the IVF group (n=0), 5.81 for the OI group (n=1), and 3.74 for the spontaneous conception group (n=89, P=0.56).

The rate of lymphoma per 10,000 children was 2.27 for the entire study cohort (n=55), 7.68 for the IVF group (n=2), 0 for the OI group (n=0), and 2.23 for the spontaneous conception group (n=53, P=0.15).

The researchers said the association between fertility treatments and total pediatric neoplasms or total malignancies remained significant in analyses controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age.

For any fertility treatment, the adjusted hazard ratio (aHR) for all neoplasms was 1.97, and the aHR for all malignancies was 1.96.

For IVF, the aHR was 2.48 for all neoplasms and 1.89 for all malignancies. For OI, the aHR was 1.51 for all neoplasms and 2.03 for all malignancies.

“The research concludes that the association between IVF and total pediatric neoplasms and malignancies is significant,” said study author Eyal Sheiner, MD, PhD, of Ben-Gurion University of the Negev in Beer-Sheva, Israel.

“With increasing numbers of offspring conceived after fertility treatments, it is important to follow up on their health.”

Image from NHS

Children born to mothers who underwent fertility treatments have an increased risk of developing pediatric neoplasms, according to research published in the American Journal of Obstetrics & Gynecology.

The study showed an increased risk of malignancies and benign tumors among children conceived after fertility treatments.

However, the risk of leukemias and lymphomas among these children was not significantly different from the risk among children who were conceived spontaneously.

The study was a population-based cohort analysis of babies born between 1991 and 2013 at Soroka University Medical Center in Beer-Sheva, Israel, with follow-up to age 18.

Of the 242,187 newborn infants in the study, 237,863 (98.3%) were conceived spontaneously, 2603 (1.1%) were conceived after in vitro fertilization (IVF), and 1721 (0.7%) were conceived after ovulation induction (OI) treatments.

During a median follow-up of 10.55 years, there were 1498 neoplasms reported, including 1074 benign tumors and 429 malignancies.

The rate of neoplasms per 10,000 children was 61.85 for the entire study cohort, 111.41 for the IVF group, 110.40 for the OI group, and 60.96 for the spontaneous conception group (P<0.001 for the comparison between spontaneous conception and both types of fertility treatments).

The rate of benign tumors per 10,000 children was 44.35 for the entire study cohort, 84.51 for the IVF group, 69.73 for the OI group, and 43.72 for the spontaneous conception group (P=0.002).

The rate of malignancies per 10,000 children was 17.71 for the entire study cohort, 26.89 for the IVF group, 40.67 for the OI group, and 17.44 for the spontaneous conception group (P=0.038).

The rate of leukemia per 10,000 children was 3.72 for the entire study cohort (n=90 leukemia cases total), 0 for the IVF group (n=0), 5.81 for the OI group (n=1), and 3.74 for the spontaneous conception group (n=89, P=0.56).

The rate of lymphoma per 10,000 children was 2.27 for the entire study cohort (n=55), 7.68 for the IVF group (n=2), 0 for the OI group (n=0), and 2.23 for the spontaneous conception group (n=53, P=0.15).

The researchers said the association between fertility treatments and total pediatric neoplasms or total malignancies remained significant in analyses controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age.

For any fertility treatment, the adjusted hazard ratio (aHR) for all neoplasms was 1.97, and the aHR for all malignancies was 1.96.

For IVF, the aHR was 2.48 for all neoplasms and 1.89 for all malignancies. For OI, the aHR was 1.51 for all neoplasms and 2.03 for all malignancies.

“The research concludes that the association between IVF and total pediatric neoplasms and malignancies is significant,” said study author Eyal Sheiner, MD, PhD, of Ben-Gurion University of the Negev in Beer-Sheva, Israel.

“With increasing numbers of offspring conceived after fertility treatments, it is important to follow up on their health.”

Image from NHS

Children born to mothers who underwent fertility treatments have an increased risk of developing pediatric neoplasms, according to research published in the American Journal of Obstetrics & Gynecology.

The study showed an increased risk of malignancies and benign tumors among children conceived after fertility treatments.

However, the risk of leukemias and lymphomas among these children was not significantly different from the risk among children who were conceived spontaneously.

The study was a population-based cohort analysis of babies born between 1991 and 2013 at Soroka University Medical Center in Beer-Sheva, Israel, with follow-up to age 18.

Of the 242,187 newborn infants in the study, 237,863 (98.3%) were conceived spontaneously, 2603 (1.1%) were conceived after in vitro fertilization (IVF), and 1721 (0.7%) were conceived after ovulation induction (OI) treatments.

During a median follow-up of 10.55 years, there were 1498 neoplasms reported, including 1074 benign tumors and 429 malignancies.

The rate of neoplasms per 10,000 children was 61.85 for the entire study cohort, 111.41 for the IVF group, 110.40 for the OI group, and 60.96 for the spontaneous conception group (P<0.001 for the comparison between spontaneous conception and both types of fertility treatments).

The rate of benign tumors per 10,000 children was 44.35 for the entire study cohort, 84.51 for the IVF group, 69.73 for the OI group, and 43.72 for the spontaneous conception group (P=0.002).

The rate of malignancies per 10,000 children was 17.71 for the entire study cohort, 26.89 for the IVF group, 40.67 for the OI group, and 17.44 for the spontaneous conception group (P=0.038).

The rate of leukemia per 10,000 children was 3.72 for the entire study cohort (n=90 leukemia cases total), 0 for the IVF group (n=0), 5.81 for the OI group (n=1), and 3.74 for the spontaneous conception group (n=89, P=0.56).

The rate of lymphoma per 10,000 children was 2.27 for the entire study cohort (n=55), 7.68 for the IVF group (n=2), 0 for the OI group (n=0), and 2.23 for the spontaneous conception group (n=53, P=0.15).

The researchers said the association between fertility treatments and total pediatric neoplasms or total malignancies remained significant in analyses controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age.

For any fertility treatment, the adjusted hazard ratio (aHR) for all neoplasms was 1.97, and the aHR for all malignancies was 1.96.

For IVF, the aHR was 2.48 for all neoplasms and 1.89 for all malignancies. For OI, the aHR was 1.51 for all neoplasms and 2.03 for all malignancies.

“The research concludes that the association between IVF and total pediatric neoplasms and malignancies is significant,” said study author Eyal Sheiner, MD, PhD, of Ben-Gurion University of the Negev in Beer-Sheva, Israel.

“With increasing numbers of offspring conceived after fertility treatments, it is important to follow up on their health.”

Photo by Nina Matthews

Treatment with tranexamic acid (TXA) should become the frontline response to major bleeding after childbirth, according to researchers.

Results of a global study showed that TXA can reduce death due to bleeding in women with post-partum hemorrhage, particularly when the drug is given early.

TXA reduced deaths from bleeding by 19% overall and by 31% when patients received TXA within 3 hours of giving birth.

In addition, there was no significant difference in adverse events for women who received TXA and those who received placebo.

Researchers reported these results in The Lancet.

Funds to support the drug and placebo costs in the run-in phase of the trial were provided by Pfizer. The trial was also funded by the London School of Hygiene & Tropical Medicine, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

The trial included 20,060 mothers, age 16 and older, who were treated at 193 hospitals in 21 countries.

All of the women had a clinical diagnosis of post-partum hemorrhage—defined as a blood loss of more than 500 ml within 24 hours of giving birth—after a vaginal birth or caesarean section.

The women were randomized to receive either 1 g of intravenous TXA (n=10,051) or matching placebo (n=10,009) in addition to standard care. The patients could receive a second dose of TXA or placebo if their bleeding continued after 30 minutes or stopped and restarted within 24 hours of the first dose.

The patients and their caregivers were blinded to randomization.

Results

In the final analysis, there were 10,036 women in the TXA arm and 9985 in the placebo arm.

TXA significantly reduced the risk of death from bleeding. The incidence of death from bleeding was 1.5% (n=155) among women who received TXA and 1.9% (n=191) in the placebo group. The risk ratio (RR) was 0.81 (P=0.045).

The incidence of death due to bleeding was 1.2% (n=89) among women who received TXA within 3 hours of giving birth and 1.7% (n=127) among women who received placebo within the same time period. The RR was 0.69 (P=0.008).

There was no significant difference between the treatment groups for other causes of death, and there was no significant difference in the use of hysterectomy.

Likewise, there was no significant difference between the treatment groups when it came to the composite endpoint of death from all causes or hysterectomy within 42 days of giving birth. This endpoint occurred in 5.3% (n=534) of patients in the TXA group and 5.6% (n=546) of those in the placebo group. The RR was 0.97 (P=0.65).

There was no significant difference between the treatment groups in the use of blood products. Fifty-four percent of patients in each group received blood transfusions. Among women who received transfusions, there was no significant difference in the mean number of units received.

On the other hand, there was a significant reduction in laparotomy to control bleeding for patients who received TXA (0.8%, n=82) compared to placebo (1.3%, n=127), with an RR of 0.64 (P=0.002).

There was no significant difference between the treatment groups (TXA and placebo, respectively) with regard to thromboembolic events (0.3% vs 0.3%), renal failure (1.3% vs 1.2%), cardiac failure (1.1% vs 1.2%), respiratory failure (1.1% vs 1.2%), hepatic failure (0.3% vs 0.3%), sepsis (1.8% vs 1.9%), or seizure (0.3% vs 0.4%).

And there was no significant difference between the treatment groups in quality of life measures, such as pain/discomfort, anxiety/depression, and mobility.

“We now have important evidence that the early use of tranexamic acid can save women’s lives and ensure more children grow up with a mother,” said study author Haleema Shakur, of the London School of Hygiene & Tropical Medicine in the UK.

“[TXA is] safe, affordable, and easy to administer, and we hope that doctors will use it as early as possible following the onset of severe bleeding after childbirth.”

Current World Health Organization guidelines recommend the use of TXA in post-partum hemorrhage as a treatment option if uterotonics fail to control the bleeding or if the bleeding is thought to be due to trauma.

Photo by Nina Matthews

Treatment with tranexamic acid (TXA) should become the frontline response to major bleeding after childbirth, according to researchers.

Results of a global study showed that TXA can reduce death due to bleeding in women with post-partum hemorrhage, particularly when the drug is given early.

TXA reduced deaths from bleeding by 19% overall and by 31% when patients received TXA within 3 hours of giving birth.

In addition, there was no significant difference in adverse events for women who received TXA and those who received placebo.

Researchers reported these results in The Lancet.

Funds to support the drug and placebo costs in the run-in phase of the trial were provided by Pfizer. The trial was also funded by the London School of Hygiene & Tropical Medicine, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

The trial included 20,060 mothers, age 16 and older, who were treated at 193 hospitals in 21 countries.

All of the women had a clinical diagnosis of post-partum hemorrhage—defined as a blood loss of more than 500 ml within 24 hours of giving birth—after a vaginal birth or caesarean section.

The women were randomized to receive either 1 g of intravenous TXA (n=10,051) or matching placebo (n=10,009) in addition to standard care. The patients could receive a second dose of TXA or placebo if their bleeding continued after 30 minutes or stopped and restarted within 24 hours of the first dose.

The patients and their caregivers were blinded to randomization.

Results

In the final analysis, there were 10,036 women in the TXA arm and 9985 in the placebo arm.

TXA significantly reduced the risk of death from bleeding. The incidence of death from bleeding was 1.5% (n=155) among women who received TXA and 1.9% (n=191) in the placebo group. The risk ratio (RR) was 0.81 (P=0.045).

The incidence of death due to bleeding was 1.2% (n=89) among women who received TXA within 3 hours of giving birth and 1.7% (n=127) among women who received placebo within the same time period. The RR was 0.69 (P=0.008).

There was no significant difference between the treatment groups for other causes of death, and there was no significant difference in the use of hysterectomy.

Likewise, there was no significant difference between the treatment groups when it came to the composite endpoint of death from all causes or hysterectomy within 42 days of giving birth. This endpoint occurred in 5.3% (n=534) of patients in the TXA group and 5.6% (n=546) of those in the placebo group. The RR was 0.97 (P=0.65).

There was no significant difference between the treatment groups in the use of blood products. Fifty-four percent of patients in each group received blood transfusions. Among women who received transfusions, there was no significant difference in the mean number of units received.

On the other hand, there was a significant reduction in laparotomy to control bleeding for patients who received TXA (0.8%, n=82) compared to placebo (1.3%, n=127), with an RR of 0.64 (P=0.002).

There was no significant difference between the treatment groups (TXA and placebo, respectively) with regard to thromboembolic events (0.3% vs 0.3%), renal failure (1.3% vs 1.2%), cardiac failure (1.1% vs 1.2%), respiratory failure (1.1% vs 1.2%), hepatic failure (0.3% vs 0.3%), sepsis (1.8% vs 1.9%), or seizure (0.3% vs 0.4%).

And there was no significant difference between the treatment groups in quality of life measures, such as pain/discomfort, anxiety/depression, and mobility.

“We now have important evidence that the early use of tranexamic acid can save women’s lives and ensure more children grow up with a mother,” said study author Haleema Shakur, of the London School of Hygiene & Tropical Medicine in the UK.

“[TXA is] safe, affordable, and easy to administer, and we hope that doctors will use it as early as possible following the onset of severe bleeding after childbirth.”

Current World Health Organization guidelines recommend the use of TXA in post-partum hemorrhage as a treatment option if uterotonics fail to control the bleeding or if the bleeding is thought to be due to trauma.

Photo by Nina Matthews

Treatment with tranexamic acid (TXA) should become the frontline response to major bleeding after childbirth, according to researchers.

Results of a global study showed that TXA can reduce death due to bleeding in women with post-partum hemorrhage, particularly when the drug is given early.

TXA reduced deaths from bleeding by 19% overall and by 31% when patients received TXA within 3 hours of giving birth.

In addition, there was no significant difference in adverse events for women who received TXA and those who received placebo.

Researchers reported these results in The Lancet.

Funds to support the drug and placebo costs in the run-in phase of the trial were provided by Pfizer. The trial was also funded by the London School of Hygiene & Tropical Medicine, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

The trial included 20,060 mothers, age 16 and older, who were treated at 193 hospitals in 21 countries.

All of the women had a clinical diagnosis of post-partum hemorrhage—defined as a blood loss of more than 500 ml within 24 hours of giving birth—after a vaginal birth or caesarean section.

The women were randomized to receive either 1 g of intravenous TXA (n=10,051) or matching placebo (n=10,009) in addition to standard care. The patients could receive a second dose of TXA or placebo if their bleeding continued after 30 minutes or stopped and restarted within 24 hours of the first dose.

The patients and their caregivers were blinded to randomization.

Results

In the final analysis, there were 10,036 women in the TXA arm and 9985 in the placebo arm.

TXA significantly reduced the risk of death from bleeding. The incidence of death from bleeding was 1.5% (n=155) among women who received TXA and 1.9% (n=191) in the placebo group. The risk ratio (RR) was 0.81 (P=0.045).

The incidence of death due to bleeding was 1.2% (n=89) among women who received TXA within 3 hours of giving birth and 1.7% (n=127) among women who received placebo within the same time period. The RR was 0.69 (P=0.008).

There was no significant difference between the treatment groups for other causes of death, and there was no significant difference in the use of hysterectomy.

Likewise, there was no significant difference between the treatment groups when it came to the composite endpoint of death from all causes or hysterectomy within 42 days of giving birth. This endpoint occurred in 5.3% (n=534) of patients in the TXA group and 5.6% (n=546) of those in the placebo group. The RR was 0.97 (P=0.65).

There was no significant difference between the treatment groups in the use of blood products. Fifty-four percent of patients in each group received blood transfusions. Among women who received transfusions, there was no significant difference in the mean number of units received.

On the other hand, there was a significant reduction in laparotomy to control bleeding for patients who received TXA (0.8%, n=82) compared to placebo (1.3%, n=127), with an RR of 0.64 (P=0.002).

There was no significant difference between the treatment groups (TXA and placebo, respectively) with regard to thromboembolic events (0.3% vs 0.3%), renal failure (1.3% vs 1.2%), cardiac failure (1.1% vs 1.2%), respiratory failure (1.1% vs 1.2%), hepatic failure (0.3% vs 0.3%), sepsis (1.8% vs 1.9%), or seizure (0.3% vs 0.4%).

And there was no significant difference between the treatment groups in quality of life measures, such as pain/discomfort, anxiety/depression, and mobility.

“We now have important evidence that the early use of tranexamic acid can save women’s lives and ensure more children grow up with a mother,” said study author Haleema Shakur, of the London School of Hygiene & Tropical Medicine in the UK.

“[TXA is] safe, affordable, and easy to administer, and we hope that doctors will use it as early as possible following the onset of severe bleeding after childbirth.”

Current World Health Organization guidelines recommend the use of TXA in post-partum hemorrhage as a treatment option if uterotonics fail to control the bleeding or if the bleeding is thought to be due to trauma.

Drug vials

A managed access program is making the histone deacetylase inhibitor belinostat (Beleodaq®) available to patients in Europe who have relapsed or refractory peripheral T-cell lymphoma (PTCL).

The program allows physicians to request belinostat for individual PTCL patients who have no alternative treatment options.

This enables patients to use belinostat ahead of a potential European approval. There are currently no approved treatments for PTCL in Europe.

The program will provide access to belinostat for patients in the UK, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.

The managed access program was made possible via an agreement between Onxeo, the company developing belinostat, and Clinigen Group plc., a company focused on providing access to medicines.

Healthcare professionals can obtain details about the belinostat managed access program by calling a Clinigen representative at +44 (0) 1283 44 347 or emailing [email protected].

Drug vials

A managed access program is making the histone deacetylase inhibitor belinostat (Beleodaq®) available to patients in Europe who have relapsed or refractory peripheral T-cell lymphoma (PTCL).

The program allows physicians to request belinostat for individual PTCL patients who have no alternative treatment options.

This enables patients to use belinostat ahead of a potential European approval. There are currently no approved treatments for PTCL in Europe.

The program will provide access to belinostat for patients in the UK, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.

The managed access program was made possible via an agreement between Onxeo, the company developing belinostat, and Clinigen Group plc., a company focused on providing access to medicines.

Healthcare professionals can obtain details about the belinostat managed access program by calling a Clinigen representative at +44 (0) 1283 44 347 or emailing [email protected].

Drug vials

A managed access program is making the histone deacetylase inhibitor belinostat (Beleodaq®) available to patients in Europe who have relapsed or refractory peripheral T-cell lymphoma (PTCL).

The program allows physicians to request belinostat for individual PTCL patients who have no alternative treatment options.

This enables patients to use belinostat ahead of a potential European approval. There are currently no approved treatments for PTCL in Europe.

The program will provide access to belinostat for patients in the UK, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.

The managed access program was made possible via an agreement between Onxeo, the company developing belinostat, and Clinigen Group plc., a company focused on providing access to medicines.

Healthcare professionals can obtain details about the belinostat managed access program by calling a Clinigen representative at +44 (0) 1283 44 347 or emailing [email protected].

Polytechnic Institute

Researchers have reported that tablets made from dried leaves of the Artemisia annua plant were able to cure malaria in 18 critically ill patients in a clinic in Africa.

When standard malaria medications failed to help the patients, the attending physician at the clinic acted under the compassionate use doctrine and prescribed the unapproved therapy, known as dried-leaf Artemisia (DLA).

Within 5 days, all 18 patients had fully recovered, with lab tests showing no parasites in their blood.

Details on this small trial were published in Phytomedicine.

The trial included 18 patients in the North Kivu province of the Democratic Republic of Congo who showed symptoms of malaria and were originally treated with artemisinin-based combination therapy (ACT).

The patients, who ranged in age from 14 months to 60 years, did not respond to ACT and lapsed into severe malaria.

Seven of the patients had anemia, 6 had convulsions, and 4 had vomiting and diarrhea. One patient, a 5-year-old child, became comatose.

All of the patients were then treated with intravenous artesunate, but they showed no improvement.

As a last resort, doctors turned to DLA. After 5 days of treatment with DLA tablets, all 18 patients fully recovered. Tests showed they had no parasites remaining in their blood.

The researchers said the DLA tablets were well-tolerated, as there were no side effects observed.

“These 18 patients were dying,” said study author Pamela Weathers, PhD, of Worcester Polytechnic Institute in Massachusetts.

“So to see 100% recover, even the child who had lapsed into a coma, was just amazing. It’s a small study, but the results are powerful.”

Dr Weathers noted that more than 100 other drug-resistant patients have been successfully treated with DLA tablets.

She said the superior performance of DLA in comparison to ACT, as well as DLA’s ability to kill drug-resistant parasites and avoid the resistance trap itself, is likely due to the synergistic effects of a complex array of phytochemicals contained in the plant’s leaves.

Several of these phytochemicals are known to have antimalarial properties, and others may act both to enhance the absorption of artemisinin into the bloodstream and bolster its effectiveness against malaria.

In effect, the dried leaves constitute a robust natural combination therapy, one whose benefits surpass those of ACT and other combination drugs.

“We have done a lot of work to understand the biochemistry of these compounds, which include a number of flavonoids and terpenes, so we can better understand the role they play in the pharmacological activity of the dried leaves,” Dr Weathers said.

“The more we learn, the more excited we become about the potential for DLA to be the medication of choice for combating malaria worldwide. Artemisia annua is known to be efficacious against a range of other diseases, including other tropical maladies and certain cancers. So, in our lab, we are already at work investigating the effectiveness of DLA with other diseases.”

Another advantage of DLA over conventional malaria treatments is its low cost and the relative simplicity of its manufacture, Dr Weathers said. When compared to ACT, producing DLA tablets can be accomplished with simpler equipment and a modest amount of training.

Growing Artemisia annua and producing and testing the tablets, Dr Weathers noted, are ideal local business ventures that can provide jobs in impoverished areas and greatly expand access to antimalarial therapy.

In fact, she has already established a supply chain in Africa that includes growing and harvesting high-producing cultivars in East Africa, along with Good Manufacturing Practice processing operations in Uganda where the leaves are dried, pulverized, and homogenized; the powder is compacted into tablets; and the tablets are tested to verify their dosage.

This supply chain helped produce the tablets used to treat the 18 patients in the Democratic Republic of Congo.

Polytechnic Institute

Researchers have reported that tablets made from dried leaves of the Artemisia annua plant were able to cure malaria in 18 critically ill patients in a clinic in Africa.

When standard malaria medications failed to help the patients, the attending physician at the clinic acted under the compassionate use doctrine and prescribed the unapproved therapy, known as dried-leaf Artemisia (DLA).

Within 5 days, all 18 patients had fully recovered, with lab tests showing no parasites in their blood.

Details on this small trial were published in Phytomedicine.

The trial included 18 patients in the North Kivu province of the Democratic Republic of Congo who showed symptoms of malaria and were originally treated with artemisinin-based combination therapy (ACT).

The patients, who ranged in age from 14 months to 60 years, did not respond to ACT and lapsed into severe malaria.

Seven of the patients had anemia, 6 had convulsions, and 4 had vomiting and diarrhea. One patient, a 5-year-old child, became comatose.

All of the patients were then treated with intravenous artesunate, but they showed no improvement.

As a last resort, doctors turned to DLA. After 5 days of treatment with DLA tablets, all 18 patients fully recovered. Tests showed they had no parasites remaining in their blood.

The researchers said the DLA tablets were well-tolerated, as there were no side effects observed.

“These 18 patients were dying,” said study author Pamela Weathers, PhD, of Worcester Polytechnic Institute in Massachusetts.

“So to see 100% recover, even the child who had lapsed into a coma, was just amazing. It’s a small study, but the results are powerful.”

Dr Weathers noted that more than 100 other drug-resistant patients have been successfully treated with DLA tablets.

She said the superior performance of DLA in comparison to ACT, as well as DLA’s ability to kill drug-resistant parasites and avoid the resistance trap itself, is likely due to the synergistic effects of a complex array of phytochemicals contained in the plant’s leaves.

Several of these phytochemicals are known to have antimalarial properties, and others may act both to enhance the absorption of artemisinin into the bloodstream and bolster its effectiveness against malaria.

In effect, the dried leaves constitute a robust natural combination therapy, one whose benefits surpass those of ACT and other combination drugs.

“We have done a lot of work to understand the biochemistry of these compounds, which include a number of flavonoids and terpenes, so we can better understand the role they play in the pharmacological activity of the dried leaves,” Dr Weathers said.

“The more we learn, the more excited we become about the potential for DLA to be the medication of choice for combating malaria worldwide. Artemisia annua is known to be efficacious against a range of other diseases, including other tropical maladies and certain cancers. So, in our lab, we are already at work investigating the effectiveness of DLA with other diseases.”

Another advantage of DLA over conventional malaria treatments is its low cost and the relative simplicity of its manufacture, Dr Weathers said. When compared to ACT, producing DLA tablets can be accomplished with simpler equipment and a modest amount of training.

Growing Artemisia annua and producing and testing the tablets, Dr Weathers noted, are ideal local business ventures that can provide jobs in impoverished areas and greatly expand access to antimalarial therapy.

In fact, she has already established a supply chain in Africa that includes growing and harvesting high-producing cultivars in East Africa, along with Good Manufacturing Practice processing operations in Uganda where the leaves are dried, pulverized, and homogenized; the powder is compacted into tablets; and the tablets are tested to verify their dosage.

This supply chain helped produce the tablets used to treat the 18 patients in the Democratic Republic of Congo.

Polytechnic Institute

Researchers have reported that tablets made from dried leaves of the Artemisia annua plant were able to cure malaria in 18 critically ill patients in a clinic in Africa.

When standard malaria medications failed to help the patients, the attending physician at the clinic acted under the compassionate use doctrine and prescribed the unapproved therapy, known as dried-leaf Artemisia (DLA).

Within 5 days, all 18 patients had fully recovered, with lab tests showing no parasites in their blood.

Details on this small trial were published in Phytomedicine.

The trial included 18 patients in the North Kivu province of the Democratic Republic of Congo who showed symptoms of malaria and were originally treated with artemisinin-based combination therapy (ACT).

The patients, who ranged in age from 14 months to 60 years, did not respond to ACT and lapsed into severe malaria.

Seven of the patients had anemia, 6 had convulsions, and 4 had vomiting and diarrhea. One patient, a 5-year-old child, became comatose.

All of the patients were then treated with intravenous artesunate, but they showed no improvement.

As a last resort, doctors turned to DLA. After 5 days of treatment with DLA tablets, all 18 patients fully recovered. Tests showed they had no parasites remaining in their blood.

The researchers said the DLA tablets were well-tolerated, as there were no side effects observed.

“These 18 patients were dying,” said study author Pamela Weathers, PhD, of Worcester Polytechnic Institute in Massachusetts.

“So to see 100% recover, even the child who had lapsed into a coma, was just amazing. It’s a small study, but the results are powerful.”

Dr Weathers noted that more than 100 other drug-resistant patients have been successfully treated with DLA tablets.

She said the superior performance of DLA in comparison to ACT, as well as DLA’s ability to kill drug-resistant parasites and avoid the resistance trap itself, is likely due to the synergistic effects of a complex array of phytochemicals contained in the plant’s leaves.

Several of these phytochemicals are known to have antimalarial properties, and others may act both to enhance the absorption of artemisinin into the bloodstream and bolster its effectiveness against malaria.

In effect, the dried leaves constitute a robust natural combination therapy, one whose benefits surpass those of ACT and other combination drugs.

“We have done a lot of work to understand the biochemistry of these compounds, which include a number of flavonoids and terpenes, so we can better understand the role they play in the pharmacological activity of the dried leaves,” Dr Weathers said.

“The more we learn, the more excited we become about the potential for DLA to be the medication of choice for combating malaria worldwide. Artemisia annua is known to be efficacious against a range of other diseases, including other tropical maladies and certain cancers. So, in our lab, we are already at work investigating the effectiveness of DLA with other diseases.”

Another advantage of DLA over conventional malaria treatments is its low cost and the relative simplicity of its manufacture, Dr Weathers said. When compared to ACT, producing DLA tablets can be accomplished with simpler equipment and a modest amount of training.

Growing Artemisia annua and producing and testing the tablets, Dr Weathers noted, are ideal local business ventures that can provide jobs in impoverished areas and greatly expand access to antimalarial therapy.

In fact, she has already established a supply chain in Africa that includes growing and harvesting high-producing cultivars in East Africa, along with Good Manufacturing Practice processing operations in Uganda where the leaves are dried, pulverized, and homogenized; the powder is compacted into tablets; and the tablets are tested to verify their dosage.

This supply chain helped produce the tablets used to treat the 18 patients in the Democratic Republic of Congo.

The family physician (FP) recognized the multiple vesicles on the patient’s hands as pompholyx, also known as dyshidrotic eczema. The term “pompholyx” means bubble, while the term “dyshidrotic” means "difficult sweating," as problems with sweating were once believed to be the cause of this condition. Some dermatologists prefer the name “vesicular hand dermatitis.” Regardless of the terminology, this can be a mild condition that is a minor nuisance or a severe chronic condition that impairs the patient's quality of life.

The FP prescribed 0.1% triamcinolone cream to be applied twice daily and gave the patient a referral to a dermatologist. While waiting for the dermatology appointment, the patient was not improving, so she went to an emergency room, where she received a prescription for oral prednisone.

When she arrived at the dermatology office, she stated that neither the topical cream nor the oral prednisone helped to improve the rash on her hands. The dermatologist performed patch testing and discovered that she had a contact allergy to topical steroids. He withdrew the steroids and started her on oral cyclosporine, which cleared the rash.

One major lesson from this case is that patients can actually be allergic to topical steroids. Referral to Dermatology was appropriate as the complexity of this case was beyond the scope of family medicine.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The family physician (FP) recognized the multiple vesicles on the patient’s hands as pompholyx, also known as dyshidrotic eczema. The term “pompholyx” means bubble, while the term “dyshidrotic” means "difficult sweating," as problems with sweating were once believed to be the cause of this condition. Some dermatologists prefer the name “vesicular hand dermatitis.” Regardless of the terminology, this can be a mild condition that is a minor nuisance or a severe chronic condition that impairs the patient's quality of life.

The FP prescribed 0.1% triamcinolone cream to be applied twice daily and gave the patient a referral to a dermatologist. While waiting for the dermatology appointment, the patient was not improving, so she went to an emergency room, where she received a prescription for oral prednisone.

When she arrived at the dermatology office, she stated that neither the topical cream nor the oral prednisone helped to improve the rash on her hands. The dermatologist performed patch testing and discovered that she had a contact allergy to topical steroids. He withdrew the steroids and started her on oral cyclosporine, which cleared the rash.

One major lesson from this case is that patients can actually be allergic to topical steroids. Referral to Dermatology was appropriate as the complexity of this case was beyond the scope of family medicine.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The family physician (FP) recognized the multiple vesicles on the patient’s hands as pompholyx, also known as dyshidrotic eczema. The term “pompholyx” means bubble, while the term “dyshidrotic” means "difficult sweating," as problems with sweating were once believed to be the cause of this condition. Some dermatologists prefer the name “vesicular hand dermatitis.” Regardless of the terminology, this can be a mild condition that is a minor nuisance or a severe chronic condition that impairs the patient's quality of life.

The FP prescribed 0.1% triamcinolone cream to be applied twice daily and gave the patient a referral to a dermatologist. While waiting for the dermatology appointment, the patient was not improving, so she went to an emergency room, where she received a prescription for oral prednisone.

When she arrived at the dermatology office, she stated that neither the topical cream nor the oral prednisone helped to improve the rash on her hands. The dermatologist performed patch testing and discovered that she had a contact allergy to topical steroids. He withdrew the steroids and started her on oral cyclosporine, which cleared the rash.

One major lesson from this case is that patients can actually be allergic to topical steroids. Referral to Dermatology was appropriate as the complexity of this case was beyond the scope of family medicine.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.

“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.

The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.

Sara Freeman/Frontline Medical News

[email protected]

BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.

“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.

The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.

Sara Freeman/Frontline Medical News

[email protected]

BIRMINGHAM, ENGLAND – Naproxen may be considered the first-choice treatment for patients with acute gout in primary care, based on the results of the CONTACT (Colchicine or Naproxen Treatment for Acute Gout) trial.

“Our findings suggest that both naproxen and low-dose colchicine are effective treatments for acute gout,” Edward Roddy, MD, said at the British Society for Rheumatology annual conference.

The trial results showed, however, that there might be “a small, early treatment difference” favoring naproxen, and that the nonsteroidal anti-inflammatory drug “appeared to be associated with fewer side effects and less use of rescue analgesia for gout than low-dose colchicine,” said Dr. Roddy, a rheumatologist at Keele University, Staffordshire, England.

Sara Freeman/Frontline Medical News

[email protected]

Adjuvant cisplatin-based chemotherapy is recommended for routine use in non–small cell lung cancer patients with stage IIA, IIB, or IIIA disease who have undergone complete surgical resections, according to updated guidelines from the American Society of Clinical Oncology.

In patients with stage IA disease, the guidelines recommend against cisplatin-based chemotherapy. The new guidelines are based on a systematic review current to January 2016 and an American Society for Radiation Oncology guideline and systematic review, which ASCO had already endorsed, which formed the basis for recommendations on adjuvant radiation therapy, Mark G. Kris, MD, and panel authors said (J Clin Oncol. 2017 April 26. doi: 10.1200/JCO.2017.72.4401).

The guidelines, available online, also recommend against routine cisplatin-based chemotherapy in patients with stage IB disease, but they suggest an evaluation of these patients to explore the pros and cons of adjuvant chemotherapy.

With respect to radiation, the authors recommend against it for patients with resected stage I or stage II disease, and they recommend against it for routine use in patients with stage IIIA. However, in patients with IIIA N2 disease, patients should be evaluated postoperatively, in consultation with a medical oncologist, for the potential risks and benefits of adjuvant radiation.

The authors also provide some recommendations for communicating with patients regarding treatment decisions. There are few studies examining this question, so the recommendations are based on low-quality evidence.

Non–small cell lung cancer patients may have complex social, psychological, and medical issues, and discussions should be carried out with this in mind. Pain, impaired breathing, and fatigue are common after surgery, and smoking cessation can lead to short-term stress as a result of nicotine withdrawal. Older patients may have a range of comorbidities.

Studies show that patients are most satisfied if they feel that physicians allow them to share in the decision making, and if they are given sufficient time to choose. To that end, the authors recommend a session dedicated to discussion of adjuvant therapy.

Communicating risk of death is challenging for many reasons. Patients should be asked how they would like to hear about their risks: some prefer general terms, while others may opt for numbers, charts, or graphs. The guidelines include a risk chart that can help patients understand the potential benefits and risks of chemotherapy.

The study authors report financial relationships with numerous pharmaceutical companies.

[email protected]

Adjuvant cisplatin-based chemotherapy is recommended for routine use in non–small cell lung cancer patients with stage IIA, IIB, or IIIA disease who have undergone complete surgical resections, according to updated guidelines from the American Society of Clinical Oncology.

In patients with stage IA disease, the guidelines recommend against cisplatin-based chemotherapy. The new guidelines are based on a systematic review current to January 2016 and an American Society for Radiation Oncology guideline and systematic review, which ASCO had already endorsed, which formed the basis for recommendations on adjuvant radiation therapy, Mark G. Kris, MD, and panel authors said (J Clin Oncol. 2017 April 26. doi: 10.1200/JCO.2017.72.4401).

The guidelines, available online, also recommend against routine cisplatin-based chemotherapy in patients with stage IB disease, but they suggest an evaluation of these patients to explore the pros and cons of adjuvant chemotherapy.

With respect to radiation, the authors recommend against it for patients with resected stage I or stage II disease, and they recommend against it for routine use in patients with stage IIIA. However, in patients with IIIA N2 disease, patients should be evaluated postoperatively, in consultation with a medical oncologist, for the potential risks and benefits of adjuvant radiation.

The authors also provide some recommendations for communicating with patients regarding treatment decisions. There are few studies examining this question, so the recommendations are based on low-quality evidence.

Non–small cell lung cancer patients may have complex social, psychological, and medical issues, and discussions should be carried out with this in mind. Pain, impaired breathing, and fatigue are common after surgery, and smoking cessation can lead to short-term stress as a result of nicotine withdrawal. Older patients may have a range of comorbidities.

Studies show that patients are most satisfied if they feel that physicians allow them to share in the decision making, and if they are given sufficient time to choose. To that end, the authors recommend a session dedicated to discussion of adjuvant therapy.

Communicating risk of death is challenging for many reasons. Patients should be asked how they would like to hear about their risks: some prefer general terms, while others may opt for numbers, charts, or graphs. The guidelines include a risk chart that can help patients understand the potential benefits and risks of chemotherapy.

The study authors report financial relationships with numerous pharmaceutical companies.

[email protected]

Adjuvant cisplatin-based chemotherapy is recommended for routine use in non–small cell lung cancer patients with stage IIA, IIB, or IIIA disease who have undergone complete surgical resections, according to updated guidelines from the American Society of Clinical Oncology.

In patients with stage IA disease, the guidelines recommend against cisplatin-based chemotherapy. The new guidelines are based on a systematic review current to January 2016 and an American Society for Radiation Oncology guideline and systematic review, which ASCO had already endorsed, which formed the basis for recommendations on adjuvant radiation therapy, Mark G. Kris, MD, and panel authors said (J Clin Oncol. 2017 April 26. doi: 10.1200/JCO.2017.72.4401).

The guidelines, available online, also recommend against routine cisplatin-based chemotherapy in patients with stage IB disease, but they suggest an evaluation of these patients to explore the pros and cons of adjuvant chemotherapy.

With respect to radiation, the authors recommend against it for patients with resected stage I or stage II disease, and they recommend against it for routine use in patients with stage IIIA. However, in patients with IIIA N2 disease, patients should be evaluated postoperatively, in consultation with a medical oncologist, for the potential risks and benefits of adjuvant radiation.

The authors also provide some recommendations for communicating with patients regarding treatment decisions. There are few studies examining this question, so the recommendations are based on low-quality evidence.

Non–small cell lung cancer patients may have complex social, psychological, and medical issues, and discussions should be carried out with this in mind. Pain, impaired breathing, and fatigue are common after surgery, and smoking cessation can lead to short-term stress as a result of nicotine withdrawal. Older patients may have a range of comorbidities.

Studies show that patients are most satisfied if they feel that physicians allow them to share in the decision making, and if they are given sufficient time to choose. To that end, the authors recommend a session dedicated to discussion of adjuvant therapy.

Communicating risk of death is challenging for many reasons. Patients should be asked how they would like to hear about their risks: some prefer general terms, while others may opt for numbers, charts, or graphs. The guidelines include a risk chart that can help patients understand the potential benefits and risks of chemotherapy.

The study authors report financial relationships with numerous pharmaceutical companies.

[email protected]

A variant in the TNFSF13B gene has been linked to susceptibility to both multiple sclerosis and systemic lupus erythematosus, according to a report published online April 26 in the New England Journal of Medicine.

This gene encodes the cytokine B-cell activating factor (BAFF), which is essential for B-cell activation, differentiation, and survival. BAFF is targeted by agents such as belimumab that are used in the treatment of autoimmune disorders, and is primarily produced by monocytes and neutrophils, said Maristella Steri, PhD, of Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato (Italy), and her associates.

The researchers have named this TNFSF13B variation “BAFF-var.”

Previous genome-wide association studies have identified more than 110 independent signals for MS and 43 for SLE but have not yet delineated the effector mechanisms for most of these associations. To explore these mechanisms in greater detail, Dr. Steri and her associates studied the population in Sardinia, Italy, which has the highest prevalences of MS and SLE in the world.

ktsimage/Thinkstock

[email protected]

A variant in the TNFSF13B gene has been linked to susceptibility to both multiple sclerosis and systemic lupus erythematosus, according to a report published online April 26 in the New England Journal of Medicine.

This gene encodes the cytokine B-cell activating factor (BAFF), which is essential for B-cell activation, differentiation, and survival. BAFF is targeted by agents such as belimumab that are used in the treatment of autoimmune disorders, and is primarily produced by monocytes and neutrophils, said Maristella Steri, PhD, of Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato (Italy), and her associates.

The researchers have named this TNFSF13B variation “BAFF-var.”

Previous genome-wide association studies have identified more than 110 independent signals for MS and 43 for SLE but have not yet delineated the effector mechanisms for most of these associations. To explore these mechanisms in greater detail, Dr. Steri and her associates studied the population in Sardinia, Italy, which has the highest prevalences of MS and SLE in the world.

ktsimage/Thinkstock

[email protected]

A variant in the TNFSF13B gene has been linked to susceptibility to both multiple sclerosis and systemic lupus erythematosus, according to a report published online April 26 in the New England Journal of Medicine.

This gene encodes the cytokine B-cell activating factor (BAFF), which is essential for B-cell activation, differentiation, and survival. BAFF is targeted by agents such as belimumab that are used in the treatment of autoimmune disorders, and is primarily produced by monocytes and neutrophils, said Maristella Steri, PhD, of Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato (Italy), and her associates.

The researchers have named this TNFSF13B variation “BAFF-var.”

Previous genome-wide association studies have identified more than 110 independent signals for MS and 43 for SLE but have not yet delineated the effector mechanisms for most of these associations. To explore these mechanisms in greater detail, Dr. Steri and her associates studied the population in Sardinia, Italy, which has the highest prevalences of MS and SLE in the world.

ktsimage/Thinkstock

[email protected]

ORLANDO – Fertility preservation techniques pioneered in young cancer patients may someday allow some women with Turner syndrome to give birth to their own children, without relying on donated eggs.

Spontaneous conception and live birth are exceedingly rare among women with the genetic disorder. Until very recently, adoption was the only practical way for most to grow a family. In the last decade, however, fertility specialists in Europe and the United States have had good success with in vitro fertilization using donated eggs. Now, those clinicians are aiming for a higher goal: babies born from a patient’s own eggs, cryopreserved either individually or within whole ovarian tissue.

These are not pipe dreams, according to experts interviewed for this story. Autologous oocyte freezing is well established in healthy women and is now coming of age in cancer patients, with recent reports of live births. Ovarian tissue freezing and reimplantation is a much newer technique, also pioneered in cancer patients. To date, more than 70 live births have occurred from ovarian cortical tissue conservation and later transplantation in adults. Last December brought the first report of a live birth to a childhood cancer survivor who had prepubertal ovarian tissue frozen before chemotherapy. And a 2015 report detailed the case of a girl with primary ovarian failure secondary to sickle cell anemia treatment. At 25, she gave birth to a healthy child conceived from ovarian tissue removed when she was 14 years old.

Not all clinicians so enthusiastically embrace this future, however. A new set of consensus guidelines for the management of girls and women with Turner syndrome is in the works and will recommend a more conservative clinical approach, according to Nelly Mauras, MD, chief of endocrinology, diabetes, and metabolism at the Nemours Children’s Health System in Jacksonville, Fla.

A group of academic and patient advocacy stakeholders is cooperatively honing the document based on a meeting last summer in Cincinnati. These groups include the European Society of Endocrinology, the Endocrine Society, the U.S. Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, Cardiology, and Reproductive Endocrinology, as well as Turner syndrome patient advocacy groups.

Dr. Mauras said the guideline will be “less discouraging” than the existing one issued in 2012 by the American Society of Reproductive Medicine. In its 2012 guidelines, the society identified Turner syndrome as a relative contraindication to pregnancy and an absolute contraindication in those with documented cardiac anomalies. However, greater experience has since been accrued in reproductive techniques of oocyte donation in Turner, with better outcomes.

The upcoming guidelines, however, will still recommend strongly against ovarian stimulation for fertility preservation for girls younger than 12, Dr. Mauras said, and will not recommend ovarian tissue conservation. “We just do not have the safety data and pregnancy outcomes that we need to give strong recommendations for these treatments,” she said. “These are still considered experimental treatments for girls with Turner syndrome.”

Turner syndrome, caused by a deletion of one X chromosome, throws a unique curve into the game – very early ovarian failure. Those with a complete deletion (45,X) begin losing their primordial ovarian follicles even before birth. Most will never experience spontaneous puberty; even if they do, their egg reserve is virtually gone soon after. Ovarian reserve may not be completely lost in girls with mosaicism, however, who have the X deletion in only a portion of their cells (46,XX/45,X). Some will enter puberty, and about 5% may even conceive spontaneously in younger years. But of the majority of Turner girls eventually experience complete ovarian failure.

This means that fertility preservation can’t be a wait-and-see issue, according to Kutluk Oktay, MD, PhD, a fertility specialist on the leading edge of this issue in the United States.

“We have to be proactive,” said Dr. Oktay, professor of obstetrics and gynecology at New York Medical College, Valhalla. “If we wait until girls are 12 or 13 to address this, a majority will have totally depleted their ovarian reserve by then. They will have no option other than an egg donor or adoption. We are suggesting that they should be screened as soon as they are diagnosed, and if they and their parents wish it, something should be done before it’s too late.”

Dr. Oktay is also the founder of fertilitypreservation.org, which specializes in advanced fertility treatments for cancer patients. He is one of a handful of physicians in the United States who advocate early oocyte harvesting in peripubertal girls and ovarian tissue harvesting in prepubertal girls with Turner syndrome. Last year, in conjunction with the Turner Syndrome Foundation, he and his colleagues published a set of guidelines for preserving fertility in these patients.

The paper recommends fertility assessment pathways for pre- and postpubertal girls. For both groups, Dr. Oktay employs serial assessments of ovarian reserve by monitoring several hormones, including follicle-stimulating hormone, luteinizing hormone, and antimüllerian hormone (AMH). Produced by primordial follicles, AMH declines as egg reserve declines over a lifetime, and is considered an accurate marker of ovarian reserve. When a girl experiences two consecutive AMH declines, egg depletion is probably accelerating. “This is the time to consider fertility preservation,” he said.

If a girl is peri- or postpubertal, the choice would probably be ovarian stimulation with the goal of retrieving mature oocytes. For prepubertal girls, the best choice is probably ovarian tissue cryopreservation. But because the egg reserve may already be spotty inside the ovary, he recommended freezing it en bloc, rather than preserving just cortical sections.

Because these techniques are only beginning to be used in young Turner patients, neither has been tested yet to see if it would result in a pregnancy. However, Dr. Oktay said, more than 80 babies have been born to women with other disorders who had ovaries frozen as adults. And European women with Turner syndrome have been successfully bearing children with donated oocytes for years.

“I don’t differentiate Europe from the U.S.,” he said. “We have no reason to believe Turner syndrome girls would be any different here than they are there.”

Pregnancy rates by egg donation in Turner syndrome patients are about half that typically seen in an otherwise healthy infertile woman, according to numerous sources; with a take-home baby rate of about 18%. There are numerous reasons for this. The miscarriage rate in Turner patients is about 44%. Women with Turner tend to have smaller uteri, with thinner endometrium, mostly because of the lack of estrogen.

But with careful management, those who do conceive can safely deliver a healthy baby, said Outi Hovatta, MD, a Finnish fertility specialist who has done extensive work in the area. “In Europe, we have been doing this quite liberally for years, and haven’t had a bad experience,” she said in an interview.

A 2013 review summarized both the success and the risks of these pregnancies. It examined obstetric and neonatal outcomes among 106 women with Turner syndrome who gave birth via egg donation from 1992 to 2011 in Sweden, Finland, and Denmark.

Most (70%) had a single embryo transferred, as virtually all guidelines recommend. Women with Turner are prone to cardiac and aortic defects that can worsen under the strain of pregnancy, or even present for the first time during gestation. Aortic dissection is a real threat; up to a third of patients with Turner experience it during adulthood, and it’s a major cause of death among them. In the Nordic series, 10 women (9%) had a known cardiac anomaly.

The multiple birth rate was 7%. More than a third (35%) developed a hypertensive disorder, including preeclampsia (20%). Four women had potentially life-threatening complications, including one with aortic dissection, one who developed mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and one who underwent a postpartum hysterectomy because of severe hemorrhaging.

The infants, nevertheless, did well. The preterm birth rate was 8%, with 9% of the singleton infants having a low birth weight. About 4% had a major birth defect. Of the 131 born, three died (2.3%), including a set of extremely preterm twins.

Close follow-up and cross-specialty cooperation are what make these positive outcomes possible, said Dr. Hovatta, who is now a professor emeritus at the Karolinska Institute, Sweden.

“We do everything we can to exclude things that could cause bad outcomes.” That includes extremely rigorous cardiac testing before pregnancy and continuous monitoring during it. “If a woman has any sign of cardiac anomaly, she is advised not to become pregnant. If she shows any signs of aortic dilation, we follow her extremely carefully with experienced cardiologists.”

Like Dr. Oktay, Dr. Hovatta and her European colleagues make fertility preservation an early topic of conversation. Unlike in the United States, where many girls aren’t diagnosed with the disorder until they fail to enter puberty, almost all Turner girls in Europe are identified very early in childhood. They receive early growth hormone treatment, and there is frequent consultation with interdisciplinary specialists. Fertility is spoken of early and often.

Early oocyte retrieval is common, Dr. Hovatta said. “Yes, it’s possible to wait until puberty, but for so many girls, most of the eggs have disappeared by then, so we typically don’t wait. We start looking at that option around 11 years, which is the same time we think about cryopreserving ovarian tissue.”

However, she added, as in the United States, the outcomes of these procedures are still unknown. But the existing data in other populations, the ability to carefully shepherd women through a successful pregnancy, and the willingness of families to provide the option all support further exploring them. Dr. Hovatta was at the Cincinnati gathering last summer and said she did not agree with the conservative tone she heard. Dr. Oktay also does not agree.

“This evidence we have so far is good evidence,” he said. “Look, where we are right now with Turner girls is where we were 15 years ago with cancer patients. People thought, ‘They have cancer. They should just be worrying about surviving cancer, not about their fertility.’ Now fertility counseling is a very important part of cancer care. We have all these tools available to us for cancer patients who don’t want to lose their fertility. This accumulated experience that has already been applied in other medical conditions … why not use that for Turner syndrome? This is my point: With all the data out there about the potential benefits and the ways to manage the risks, we shouldn’t have to tell girls, ‘Well, you have to become menopausal, and maybe you can adopt someday.’ That doesn’t sit well with parents any more. We want these girls to thrive. Not just to survive, but to have as close to a normal quality of life as possible.”
 

[email protected]

ORLANDO – Fertility preservation techniques pioneered in young cancer patients may someday allow some women with Turner syndrome to give birth to their own children, without relying on donated eggs.

Spontaneous conception and live birth are exceedingly rare among women with the genetic disorder. Until very recently, adoption was the only practical way for most to grow a family. In the last decade, however, fertility specialists in Europe and the United States have had good success with in vitro fertilization using donated eggs. Now, those clinicians are aiming for a higher goal: babies born from a patient’s own eggs, cryopreserved either individually or within whole ovarian tissue.

These are not pipe dreams, according to experts interviewed for this story. Autologous oocyte freezing is well established in healthy women and is now coming of age in cancer patients, with recent reports of live births. Ovarian tissue freezing and reimplantation is a much newer technique, also pioneered in cancer patients. To date, more than 70 live births have occurred from ovarian cortical tissue conservation and later transplantation in adults. Last December brought the first report of a live birth to a childhood cancer survivor who had prepubertal ovarian tissue frozen before chemotherapy. And a 2015 report detailed the case of a girl with primary ovarian failure secondary to sickle cell anemia treatment. At 25, she gave birth to a healthy child conceived from ovarian tissue removed when she was 14 years old.

Not all clinicians so enthusiastically embrace this future, however. A new set of consensus guidelines for the management of girls and women with Turner syndrome is in the works and will recommend a more conservative clinical approach, according to Nelly Mauras, MD, chief of endocrinology, diabetes, and metabolism at the Nemours Children’s Health System in Jacksonville, Fla.

A group of academic and patient advocacy stakeholders is cooperatively honing the document based on a meeting last summer in Cincinnati. These groups include the European Society of Endocrinology, the Endocrine Society, the U.S. Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, Cardiology, and Reproductive Endocrinology, as well as Turner syndrome patient advocacy groups.

Dr. Mauras said the guideline will be “less discouraging” than the existing one issued in 2012 by the American Society of Reproductive Medicine. In its 2012 guidelines, the society identified Turner syndrome as a relative contraindication to pregnancy and an absolute contraindication in those with documented cardiac anomalies. However, greater experience has since been accrued in reproductive techniques of oocyte donation in Turner, with better outcomes.

The upcoming guidelines, however, will still recommend strongly against ovarian stimulation for fertility preservation for girls younger than 12, Dr. Mauras said, and will not recommend ovarian tissue conservation. “We just do not have the safety data and pregnancy outcomes that we need to give strong recommendations for these treatments,” she said. “These are still considered experimental treatments for girls with Turner syndrome.”

Turner syndrome, caused by a deletion of one X chromosome, throws a unique curve into the game – very early ovarian failure. Those with a complete deletion (45,X) begin losing their primordial ovarian follicles even before birth. Most will never experience spontaneous puberty; even if they do, their egg reserve is virtually gone soon after. Ovarian reserve may not be completely lost in girls with mosaicism, however, who have the X deletion in only a portion of their cells (46,XX/45,X). Some will enter puberty, and about 5% may even conceive spontaneously in younger years. But of the majority of Turner girls eventually experience complete ovarian failure.

This means that fertility preservation can’t be a wait-and-see issue, according to Kutluk Oktay, MD, PhD, a fertility specialist on the leading edge of this issue in the United States.

“We have to be proactive,” said Dr. Oktay, professor of obstetrics and gynecology at New York Medical College, Valhalla. “If we wait until girls are 12 or 13 to address this, a majority will have totally depleted their ovarian reserve by then. They will have no option other than an egg donor or adoption. We are suggesting that they should be screened as soon as they are diagnosed, and if they and their parents wish it, something should be done before it’s too late.”

Dr. Oktay is also the founder of fertilitypreservation.org, which specializes in advanced fertility treatments for cancer patients. He is one of a handful of physicians in the United States who advocate early oocyte harvesting in peripubertal girls and ovarian tissue harvesting in prepubertal girls with Turner syndrome. Last year, in conjunction with the Turner Syndrome Foundation, he and his colleagues published a set of guidelines for preserving fertility in these patients.

The paper recommends fertility assessment pathways for pre- and postpubertal girls. For both groups, Dr. Oktay employs serial assessments of ovarian reserve by monitoring several hormones, including follicle-stimulating hormone, luteinizing hormone, and antimüllerian hormone (AMH). Produced by primordial follicles, AMH declines as egg reserve declines over a lifetime, and is considered an accurate marker of ovarian reserve. When a girl experiences two consecutive AMH declines, egg depletion is probably accelerating. “This is the time to consider fertility preservation,” he said.

If a girl is peri- or postpubertal, the choice would probably be ovarian stimulation with the goal of retrieving mature oocytes. For prepubertal girls, the best choice is probably ovarian tissue cryopreservation. But because the egg reserve may already be spotty inside the ovary, he recommended freezing it en bloc, rather than preserving just cortical sections.

Because these techniques are only beginning to be used in young Turner patients, neither has been tested yet to see if it would result in a pregnancy. However, Dr. Oktay said, more than 80 babies have been born to women with other disorders who had ovaries frozen as adults. And European women with Turner syndrome have been successfully bearing children with donated oocytes for years.

“I don’t differentiate Europe from the U.S.,” he said. “We have no reason to believe Turner syndrome girls would be any different here than they are there.”

Pregnancy rates by egg donation in Turner syndrome patients are about half that typically seen in an otherwise healthy infertile woman, according to numerous sources; with a take-home baby rate of about 18%. There are numerous reasons for this. The miscarriage rate in Turner patients is about 44%. Women with Turner tend to have smaller uteri, with thinner endometrium, mostly because of the lack of estrogen.

But with careful management, those who do conceive can safely deliver a healthy baby, said Outi Hovatta, MD, a Finnish fertility specialist who has done extensive work in the area. “In Europe, we have been doing this quite liberally for years, and haven’t had a bad experience,” she said in an interview.

A 2013 review summarized both the success and the risks of these pregnancies. It examined obstetric and neonatal outcomes among 106 women with Turner syndrome who gave birth via egg donation from 1992 to 2011 in Sweden, Finland, and Denmark.

Most (70%) had a single embryo transferred, as virtually all guidelines recommend. Women with Turner are prone to cardiac and aortic defects that can worsen under the strain of pregnancy, or even present for the first time during gestation. Aortic dissection is a real threat; up to a third of patients with Turner experience it during adulthood, and it’s a major cause of death among them. In the Nordic series, 10 women (9%) had a known cardiac anomaly.

The multiple birth rate was 7%. More than a third (35%) developed a hypertensive disorder, including preeclampsia (20%). Four women had potentially life-threatening complications, including one with aortic dissection, one who developed mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and one who underwent a postpartum hysterectomy because of severe hemorrhaging.

The infants, nevertheless, did well. The preterm birth rate was 8%, with 9% of the singleton infants having a low birth weight. About 4% had a major birth defect. Of the 131 born, three died (2.3%), including a set of extremely preterm twins.

Close follow-up and cross-specialty cooperation are what make these positive outcomes possible, said Dr. Hovatta, who is now a professor emeritus at the Karolinska Institute, Sweden.

“We do everything we can to exclude things that could cause bad outcomes.” That includes extremely rigorous cardiac testing before pregnancy and continuous monitoring during it. “If a woman has any sign of cardiac anomaly, she is advised not to become pregnant. If she shows any signs of aortic dilation, we follow her extremely carefully with experienced cardiologists.”

Like Dr. Oktay, Dr. Hovatta and her European colleagues make fertility preservation an early topic of conversation. Unlike in the United States, where many girls aren’t diagnosed with the disorder until they fail to enter puberty, almost all Turner girls in Europe are identified very early in childhood. They receive early growth hormone treatment, and there is frequent consultation with interdisciplinary specialists. Fertility is spoken of early and often.

Early oocyte retrieval is common, Dr. Hovatta said. “Yes, it’s possible to wait until puberty, but for so many girls, most of the eggs have disappeared by then, so we typically don’t wait. We start looking at that option around 11 years, which is the same time we think about cryopreserving ovarian tissue.”

However, she added, as in the United States, the outcomes of these procedures are still unknown. But the existing data in other populations, the ability to carefully shepherd women through a successful pregnancy, and the willingness of families to provide the option all support further exploring them. Dr. Hovatta was at the Cincinnati gathering last summer and said she did not agree with the conservative tone she heard. Dr. Oktay also does not agree.

“This evidence we have so far is good evidence,” he said. “Look, where we are right now with Turner girls is where we were 15 years ago with cancer patients. People thought, ‘They have cancer. They should just be worrying about surviving cancer, not about their fertility.’ Now fertility counseling is a very important part of cancer care. We have all these tools available to us for cancer patients who don’t want to lose their fertility. This accumulated experience that has already been applied in other medical conditions … why not use that for Turner syndrome? This is my point: With all the data out there about the potential benefits and the ways to manage the risks, we shouldn’t have to tell girls, ‘Well, you have to become menopausal, and maybe you can adopt someday.’ That doesn’t sit well with parents any more. We want these girls to thrive. Not just to survive, but to have as close to a normal quality of life as possible.”
 

[email protected]

ORLANDO – Fertility preservation techniques pioneered in young cancer patients may someday allow some women with Turner syndrome to give birth to their own children, without relying on donated eggs.

Spontaneous conception and live birth are exceedingly rare among women with the genetic disorder. Until very recently, adoption was the only practical way for most to grow a family. In the last decade, however, fertility specialists in Europe and the United States have had good success with in vitro fertilization using donated eggs. Now, those clinicians are aiming for a higher goal: babies born from a patient’s own eggs, cryopreserved either individually or within whole ovarian tissue.

These are not pipe dreams, according to experts interviewed for this story. Autologous oocyte freezing is well established in healthy women and is now coming of age in cancer patients, with recent reports of live births. Ovarian tissue freezing and reimplantation is a much newer technique, also pioneered in cancer patients. To date, more than 70 live births have occurred from ovarian cortical tissue conservation and later transplantation in adults. Last December brought the first report of a live birth to a childhood cancer survivor who had prepubertal ovarian tissue frozen before chemotherapy. And a 2015 report detailed the case of a girl with primary ovarian failure secondary to sickle cell anemia treatment. At 25, she gave birth to a healthy child conceived from ovarian tissue removed when she was 14 years old.

Not all clinicians so enthusiastically embrace this future, however. A new set of consensus guidelines for the management of girls and women with Turner syndrome is in the works and will recommend a more conservative clinical approach, according to Nelly Mauras, MD, chief of endocrinology, diabetes, and metabolism at the Nemours Children’s Health System in Jacksonville, Fla.

A group of academic and patient advocacy stakeholders is cooperatively honing the document based on a meeting last summer in Cincinnati. These groups include the European Society of Endocrinology, the Endocrine Society, the U.S. Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, Cardiology, and Reproductive Endocrinology, as well as Turner syndrome patient advocacy groups.

Dr. Mauras said the guideline will be “less discouraging” than the existing one issued in 2012 by the American Society of Reproductive Medicine. In its 2012 guidelines, the society identified Turner syndrome as a relative contraindication to pregnancy and an absolute contraindication in those with documented cardiac anomalies. However, greater experience has since been accrued in reproductive techniques of oocyte donation in Turner, with better outcomes.

The upcoming guidelines, however, will still recommend strongly against ovarian stimulation for fertility preservation for girls younger than 12, Dr. Mauras said, and will not recommend ovarian tissue conservation. “We just do not have the safety data and pregnancy outcomes that we need to give strong recommendations for these treatments,” she said. “These are still considered experimental treatments for girls with Turner syndrome.”

Turner syndrome, caused by a deletion of one X chromosome, throws a unique curve into the game – very early ovarian failure. Those with a complete deletion (45,X) begin losing their primordial ovarian follicles even before birth. Most will never experience spontaneous puberty; even if they do, their egg reserve is virtually gone soon after. Ovarian reserve may not be completely lost in girls with mosaicism, however, who have the X deletion in only a portion of their cells (46,XX/45,X). Some will enter puberty, and about 5% may even conceive spontaneously in younger years. But of the majority of Turner girls eventually experience complete ovarian failure.

This means that fertility preservation can’t be a wait-and-see issue, according to Kutluk Oktay, MD, PhD, a fertility specialist on the leading edge of this issue in the United States.

“We have to be proactive,” said Dr. Oktay, professor of obstetrics and gynecology at New York Medical College, Valhalla. “If we wait until girls are 12 or 13 to address this, a majority will have totally depleted their ovarian reserve by then. They will have no option other than an egg donor or adoption. We are suggesting that they should be screened as soon as they are diagnosed, and if they and their parents wish it, something should be done before it’s too late.”

Dr. Oktay is also the founder of fertilitypreservation.org, which specializes in advanced fertility treatments for cancer patients. He is one of a handful of physicians in the United States who advocate early oocyte harvesting in peripubertal girls and ovarian tissue harvesting in prepubertal girls with Turner syndrome. Last year, in conjunction with the Turner Syndrome Foundation, he and his colleagues published a set of guidelines for preserving fertility in these patients.

The paper recommends fertility assessment pathways for pre- and postpubertal girls. For both groups, Dr. Oktay employs serial assessments of ovarian reserve by monitoring several hormones, including follicle-stimulating hormone, luteinizing hormone, and antimüllerian hormone (AMH). Produced by primordial follicles, AMH declines as egg reserve declines over a lifetime, and is considered an accurate marker of ovarian reserve. When a girl experiences two consecutive AMH declines, egg depletion is probably accelerating. “This is the time to consider fertility preservation,” he said.

If a girl is peri- or postpubertal, the choice would probably be ovarian stimulation with the goal of retrieving mature oocytes. For prepubertal girls, the best choice is probably ovarian tissue cryopreservation. But because the egg reserve may already be spotty inside the ovary, he recommended freezing it en bloc, rather than preserving just cortical sections.

Because these techniques are only beginning to be used in young Turner patients, neither has been tested yet to see if it would result in a pregnancy. However, Dr. Oktay said, more than 80 babies have been born to women with other disorders who had ovaries frozen as adults. And European women with Turner syndrome have been successfully bearing children with donated oocytes for years.

“I don’t differentiate Europe from the U.S.,” he said. “We have no reason to believe Turner syndrome girls would be any different here than they are there.”

Pregnancy rates by egg donation in Turner syndrome patients are about half that typically seen in an otherwise healthy infertile woman, according to numerous sources; with a take-home baby rate of about 18%. There are numerous reasons for this. The miscarriage rate in Turner patients is about 44%. Women with Turner tend to have smaller uteri, with thinner endometrium, mostly because of the lack of estrogen.

But with careful management, those who do conceive can safely deliver a healthy baby, said Outi Hovatta, MD, a Finnish fertility specialist who has done extensive work in the area. “In Europe, we have been doing this quite liberally for years, and haven’t had a bad experience,” she said in an interview.

A 2013 review summarized both the success and the risks of these pregnancies. It examined obstetric and neonatal outcomes among 106 women with Turner syndrome who gave birth via egg donation from 1992 to 2011 in Sweden, Finland, and Denmark.

Most (70%) had a single embryo transferred, as virtually all guidelines recommend. Women with Turner are prone to cardiac and aortic defects that can worsen under the strain of pregnancy, or even present for the first time during gestation. Aortic dissection is a real threat; up to a third of patients with Turner experience it during adulthood, and it’s a major cause of death among them. In the Nordic series, 10 women (9%) had a known cardiac anomaly.

The multiple birth rate was 7%. More than a third (35%) developed a hypertensive disorder, including preeclampsia (20%). Four women had potentially life-threatening complications, including one with aortic dissection, one who developed mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and one who underwent a postpartum hysterectomy because of severe hemorrhaging.

The infants, nevertheless, did well. The preterm birth rate was 8%, with 9% of the singleton infants having a low birth weight. About 4% had a major birth defect. Of the 131 born, three died (2.3%), including a set of extremely preterm twins.

Close follow-up and cross-specialty cooperation are what make these positive outcomes possible, said Dr. Hovatta, who is now a professor emeritus at the Karolinska Institute, Sweden.

“We do everything we can to exclude things that could cause bad outcomes.” That includes extremely rigorous cardiac testing before pregnancy and continuous monitoring during it. “If a woman has any sign of cardiac anomaly, she is advised not to become pregnant. If she shows any signs of aortic dilation, we follow her extremely carefully with experienced cardiologists.”

Like Dr. Oktay, Dr. Hovatta and her European colleagues make fertility preservation an early topic of conversation. Unlike in the United States, where many girls aren’t diagnosed with the disorder until they fail to enter puberty, almost all Turner girls in Europe are identified very early in childhood. They receive early growth hormone treatment, and there is frequent consultation with interdisciplinary specialists. Fertility is spoken of early and often.

Early oocyte retrieval is common, Dr. Hovatta said. “Yes, it’s possible to wait until puberty, but for so many girls, most of the eggs have disappeared by then, so we typically don’t wait. We start looking at that option around 11 years, which is the same time we think about cryopreserving ovarian tissue.”

However, she added, as in the United States, the outcomes of these procedures are still unknown. But the existing data in other populations, the ability to carefully shepherd women through a successful pregnancy, and the willingness of families to provide the option all support further exploring them. Dr. Hovatta was at the Cincinnati gathering last summer and said she did not agree with the conservative tone she heard. Dr. Oktay also does not agree.

“This evidence we have so far is good evidence,” he said. “Look, where we are right now with Turner girls is where we were 15 years ago with cancer patients. People thought, ‘They have cancer. They should just be worrying about surviving cancer, not about their fertility.’ Now fertility counseling is a very important part of cancer care. We have all these tools available to us for cancer patients who don’t want to lose their fertility. This accumulated experience that has already been applied in other medical conditions … why not use that for Turner syndrome? This is my point: With all the data out there about the potential benefits and the ways to manage the risks, we shouldn’t have to tell girls, ‘Well, you have to become menopausal, and maybe you can adopt someday.’ That doesn’t sit well with parents any more. We want these girls to thrive. Not just to survive, but to have as close to a normal quality of life as possible.”
 

[email protected]

The importance of establishing a bond with a patient early in treatment is instilled in psychiatry trainees during their first year of residency. It is well-known that a strong therapeutic connection is correlated with successful treatment and favorable outcomes.¹ But what if social and cultural factors that could provide an almost immediate familiarity threatened the therapeutic alliance?

We present a case in which sharing my cultural background with a patient was detrimental to the therapeutic relationship and forced me to look beyond superficial similarities to forge a meaningful connection.

A shared language, a shared connection?

When I, a psychiatry intern who emigrated from Honduras 11 years ago, met Ms. M, a middle-age, Spanish-speaking Honduran immigrant with schizoaffective disorder, I was curious to hear the story of how her immigration intermingled with her mental illness. As a budding psychiatrist, I was certain our common culture would intensify our interactions. It did, although in ways I did not expect.

Despite my enthusiasm and best intentions, our first meeting was less than ideal. Ms. M believed she not only was God’s wife and my attending physician’s wife, but that I was her rival for my attending’s affections. “I heard you are from Honduras. I am from Honduras, too. What part are you from?” I asked her. She became angry. “I am not from there. I am from Israel,” she said. For many days, we had the same hostile and disappointing conversations, during which I would try to tease out the basis for her delusions and understand our lack of connection. I felt hurt and puzzled. If I could not connect with someone with whom I shared a common background, then to whom could I connect with? I had to re-evaluate my approach. Should I alter my attire to seem less feminine? Should I tell her I am happily married? Should I not speak Spanish? Would these changes make our interactions feel less threatening to her?

“You are focused too much on you and not enough on her,” my attending retorted. I came to realize that, in my crusade to have Ms. M perceive me a certain way, I had lost sight of who she was and what lay at the core of her delusions. I stepped back and considered Ms. M: a patient, yes, but also a woman who was unable to communicate freely with others because she did not speak English. Because of her perpetual paranoia and psychosis, she was emotionally isolated, lacked necessary social support from her family, and had no sense of community. However, in her delusions she was a prophet, a herald for God’s news, with a vital role in His plans. In her mind, she was a mother and had the support of a life-long partner.

As I considered her struggles, I thought about myself. When I first came to the United States, it was difficult to develop relationships with my peers because I worried about my accent and idioms. In Honduras, my friends and family knew me as a gregarious, quick-witted individual. In acculturating to my new home, I became reclusive and insecure. It took years to regain a semblance of identity.

In my attending’s office, I found that it was not our shared heritage that was the path to engaging Ms. M, but rather our shared isolation, which I had not been validating. This helped me reframe the way I viewed the therapeutic relationship and changed the focus of my attempts to engage her. I stopped taking her rejection personally and focused on providing her support and solace. By tapping into her isolation, she opened up and eventually agreed to medication changes, which slowly reduced—but did not eliminate—her delusions, hallucinations, and hostility toward others. Because of her intractable psychotic symptoms, she required a long-term structured care setting and was transferred to the state hospital.

Culture is only ‘skin deep’

I assumed our shared background would have effortlessly led to a trustworthy relationship, but her resistance challenged that notion. My own desires to have a deep connection with a fellow immigrant contributed to my internalization of her rejection. Our physical and cultural similarities acted as a hindrance because she subconsciously projected her idealized image of a woman onto me. Nevertheless, she helped me recognize the importance of unexamined projective identification and countertransference, evidenced by wanting to change my appearance and behavior and my increased willingness for self-disclosure.

As I start my second year of residency and reflect on my experiences as an intern, Ms. M always comes to mind. She taught me that culture may be only “skin deep” and similarities between therapist and patient do not guarantee a successful bond. Searching for deeper, fundamental connections and validating these bonds can open the doors to connecting with those from all walks of life, from whichever road they come.

The importance of establishing a bond with a patient early in treatment is instilled in psychiatry trainees during their first year of residency. It is well-known that a strong therapeutic connection is correlated with successful treatment and favorable outcomes.¹ But what if social and cultural factors that could provide an almost immediate familiarity threatened the therapeutic alliance?

We present a case in which sharing my cultural background with a patient was detrimental to the therapeutic relationship and forced me to look beyond superficial similarities to forge a meaningful connection.

A shared language, a shared connection?

When I, a psychiatry intern who emigrated from Honduras 11 years ago, met Ms. M, a middle-age, Spanish-speaking Honduran immigrant with schizoaffective disorder, I was curious to hear the story of how her immigration intermingled with her mental illness. As a budding psychiatrist, I was certain our common culture would intensify our interactions. It did, although in ways I did not expect.

Despite my enthusiasm and best intentions, our first meeting was less than ideal. Ms. M believed she not only was God’s wife and my attending physician’s wife, but that I was her rival for my attending’s affections. “I heard you are from Honduras. I am from Honduras, too. What part are you from?” I asked her. She became angry. “I am not from there. I am from Israel,” she said. For many days, we had the same hostile and disappointing conversations, during which I would try to tease out the basis for her delusions and understand our lack of connection. I felt hurt and puzzled. If I could not connect with someone with whom I shared a common background, then to whom could I connect with? I had to re-evaluate my approach. Should I alter my attire to seem less feminine? Should I tell her I am happily married? Should I not speak Spanish? Would these changes make our interactions feel less threatening to her?

“You are focused too much on you and not enough on her,” my attending retorted. I came to realize that, in my crusade to have Ms. M perceive me a certain way, I had lost sight of who she was and what lay at the core of her delusions. I stepped back and considered Ms. M: a patient, yes, but also a woman who was unable to communicate freely with others because she did not speak English. Because of her perpetual paranoia and psychosis, she was emotionally isolated, lacked necessary social support from her family, and had no sense of community. However, in her delusions she was a prophet, a herald for God’s news, with a vital role in His plans. In her mind, she was a mother and had the support of a life-long partner.

As I considered her struggles, I thought about myself. When I first came to the United States, it was difficult to develop relationships with my peers because I worried about my accent and idioms. In Honduras, my friends and family knew me as a gregarious, quick-witted individual. In acculturating to my new home, I became reclusive and insecure. It took years to regain a semblance of identity.

In my attending’s office, I found that it was not our shared heritage that was the path to engaging Ms. M, but rather our shared isolation, which I had not been validating. This helped me reframe the way I viewed the therapeutic relationship and changed the focus of my attempts to engage her. I stopped taking her rejection personally and focused on providing her support and solace. By tapping into her isolation, she opened up and eventually agreed to medication changes, which slowly reduced—but did not eliminate—her delusions, hallucinations, and hostility toward others. Because of her intractable psychotic symptoms, she required a long-term structured care setting and was transferred to the state hospital.

Culture is only ‘skin deep’

I assumed our shared background would have effortlessly led to a trustworthy relationship, but her resistance challenged that notion. My own desires to have a deep connection with a fellow immigrant contributed to my internalization of her rejection. Our physical and cultural similarities acted as a hindrance because she subconsciously projected her idealized image of a woman onto me. Nevertheless, she helped me recognize the importance of unexamined projective identification and countertransference, evidenced by wanting to change my appearance and behavior and my increased willingness for self-disclosure.

As I start my second year of residency and reflect on my experiences as an intern, Ms. M always comes to mind. She taught me that culture may be only “skin deep” and similarities between therapist and patient do not guarantee a successful bond. Searching for deeper, fundamental connections and validating these bonds can open the doors to connecting with those from all walks of life, from whichever road they come.

The importance of establishing a bond with a patient early in treatment is instilled in psychiatry trainees during their first year of residency. It is well-known that a strong therapeutic connection is correlated with successful treatment and favorable outcomes.¹ But what if social and cultural factors that could provide an almost immediate familiarity threatened the therapeutic alliance?

We present a case in which sharing my cultural background with a patient was detrimental to the therapeutic relationship and forced me to look beyond superficial similarities to forge a meaningful connection.

A shared language, a shared connection?

When I, a psychiatry intern who emigrated from Honduras 11 years ago, met Ms. M, a middle-age, Spanish-speaking Honduran immigrant with schizoaffective disorder, I was curious to hear the story of how her immigration intermingled with her mental illness. As a budding psychiatrist, I was certain our common culture would intensify our interactions. It did, although in ways I did not expect.

Despite my enthusiasm and best intentions, our first meeting was less than ideal. Ms. M believed she not only was God’s wife and my attending physician’s wife, but that I was her rival for my attending’s affections. “I heard you are from Honduras. I am from Honduras, too. What part are you from?” I asked her. She became angry. “I am not from there. I am from Israel,” she said. For many days, we had the same hostile and disappointing conversations, during which I would try to tease out the basis for her delusions and understand our lack of connection. I felt hurt and puzzled. If I could not connect with someone with whom I shared a common background, then to whom could I connect with? I had to re-evaluate my approach. Should I alter my attire to seem less feminine? Should I tell her I am happily married? Should I not speak Spanish? Would these changes make our interactions feel less threatening to her?

“You are focused too much on you and not enough on her,” my attending retorted. I came to realize that, in my crusade to have Ms. M perceive me a certain way, I had lost sight of who she was and what lay at the core of her delusions. I stepped back and considered Ms. M: a patient, yes, but also a woman who was unable to communicate freely with others because she did not speak English. Because of her perpetual paranoia and psychosis, she was emotionally isolated, lacked necessary social support from her family, and had no sense of community. However, in her delusions she was a prophet, a herald for God’s news, with a vital role in His plans. In her mind, she was a mother and had the support of a life-long partner.

As I considered her struggles, I thought about myself. When I first came to the United States, it was difficult to develop relationships with my peers because I worried about my accent and idioms. In Honduras, my friends and family knew me as a gregarious, quick-witted individual. In acculturating to my new home, I became reclusive and insecure. It took years to regain a semblance of identity.

In my attending’s office, I found that it was not our shared heritage that was the path to engaging Ms. M, but rather our shared isolation, which I had not been validating. This helped me reframe the way I viewed the therapeutic relationship and changed the focus of my attempts to engage her. I stopped taking her rejection personally and focused on providing her support and solace. By tapping into her isolation, she opened up and eventually agreed to medication changes, which slowly reduced—but did not eliminate—her delusions, hallucinations, and hostility toward others. Because of her intractable psychotic symptoms, she required a long-term structured care setting and was transferred to the state hospital.

Culture is only ‘skin deep’

I assumed our shared background would have effortlessly led to a trustworthy relationship, but her resistance challenged that notion. My own desires to have a deep connection with a fellow immigrant contributed to my internalization of her rejection. Our physical and cultural similarities acted as a hindrance because she subconsciously projected her idealized image of a woman onto me. Nevertheless, she helped me recognize the importance of unexamined projective identification and countertransference, evidenced by wanting to change my appearance and behavior and my increased willingness for self-disclosure.

As I start my second year of residency and reflect on my experiences as an intern, Ms. M always comes to mind. She taught me that culture may be only “skin deep” and similarities between therapist and patient do not guarantee a successful bond. Searching for deeper, fundamental connections and validating these bonds can open the doors to connecting with those from all walks of life, from whichever road they come.