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Lab results may help predict complications in ALL treatment
(ALL) who were treated with four-drug induction therapy.
Kasper Warrick, MD, and his colleagues at Indiana University in Indianapolis reported findings from a retrospective study of 73 ALL patients at their hospital. They performed chart reviews comparing a cohort of 42 patients who were discharged on day 4 of their induction treatment with 31 similar patients who had a longer hospital stay or admission to the intensive care unit. The report was published in Leukemia Research.
Univariate analysis found that patients with a longer length of stay were more likely to have a fever, pretransfusion hemoglobin of less than 8 g/dL, lower serum bicarbonate values, abnormal serum calcium, and abnormal serum phosphate. Multivariate stepwise logistic regression found that low serum bicarbonate and a lower platelet count on day 4 of admission was predictive of a prolonged hospital stay. About a third of patients from each group had an unplanned readmission within 30 days.
The researchers concluded that early discharge is safe in only a subgroup of high-risk ALL patients undergoing induction chemotherapy. “Treating physicians could opt for a discharge only after normalization of electrolyte abnormalities and renal functions, and when no transfusion support is needed (stable hematocrit and platelet count),” they wrote. Even in those cases, they recommended “aggressive and close outpatient follow” since patients are vulnerable to complications and readmissions.
SOURCE: Warrick K et al. Leuk Res. 2018 Jun 30:71:36-42.
(ALL) who were treated with four-drug induction therapy.
Kasper Warrick, MD, and his colleagues at Indiana University in Indianapolis reported findings from a retrospective study of 73 ALL patients at their hospital. They performed chart reviews comparing a cohort of 42 patients who were discharged on day 4 of their induction treatment with 31 similar patients who had a longer hospital stay or admission to the intensive care unit. The report was published in Leukemia Research.
Univariate analysis found that patients with a longer length of stay were more likely to have a fever, pretransfusion hemoglobin of less than 8 g/dL, lower serum bicarbonate values, abnormal serum calcium, and abnormal serum phosphate. Multivariate stepwise logistic regression found that low serum bicarbonate and a lower platelet count on day 4 of admission was predictive of a prolonged hospital stay. About a third of patients from each group had an unplanned readmission within 30 days.
The researchers concluded that early discharge is safe in only a subgroup of high-risk ALL patients undergoing induction chemotherapy. “Treating physicians could opt for a discharge only after normalization of electrolyte abnormalities and renal functions, and when no transfusion support is needed (stable hematocrit and platelet count),” they wrote. Even in those cases, they recommended “aggressive and close outpatient follow” since patients are vulnerable to complications and readmissions.
SOURCE: Warrick K et al. Leuk Res. 2018 Jun 30:71:36-42.
(ALL) who were treated with four-drug induction therapy.
Kasper Warrick, MD, and his colleagues at Indiana University in Indianapolis reported findings from a retrospective study of 73 ALL patients at their hospital. They performed chart reviews comparing a cohort of 42 patients who were discharged on day 4 of their induction treatment with 31 similar patients who had a longer hospital stay or admission to the intensive care unit. The report was published in Leukemia Research.
Univariate analysis found that patients with a longer length of stay were more likely to have a fever, pretransfusion hemoglobin of less than 8 g/dL, lower serum bicarbonate values, abnormal serum calcium, and abnormal serum phosphate. Multivariate stepwise logistic regression found that low serum bicarbonate and a lower platelet count on day 4 of admission was predictive of a prolonged hospital stay. About a third of patients from each group had an unplanned readmission within 30 days.
The researchers concluded that early discharge is safe in only a subgroup of high-risk ALL patients undergoing induction chemotherapy. “Treating physicians could opt for a discharge only after normalization of electrolyte abnormalities and renal functions, and when no transfusion support is needed (stable hematocrit and platelet count),” they wrote. Even in those cases, they recommended “aggressive and close outpatient follow” since patients are vulnerable to complications and readmissions.
SOURCE: Warrick K et al. Leuk Res. 2018 Jun 30:71:36-42.
FROM LEUKEMIA RESEARCH
Better ICU staff communication with family may improve end-of-life choices
A nurse-led support intervention for the families of critically ill patients did little to ease families’ psychological symptoms, but it did improve their perception of staff communication and family-centered care in the intensive care unit.
The length of ICU stay was also significantly shorter and the in-unit death rate higher among patients whose families received the intervention – a finding that suggests difficult end-of-life choices may have been eased, reported Douglas B. White, MD, and his colleagues (N Engl J Med. 2018;378:2365-75).
“The intervention resulted in significant improvements in markers of the quality of decision making, including the patient- and family-centeredness of care and the quality of clinician-family communication. Taken together, these findings suggest that the intervention allowed surrogates to transition a patient’s treatment to comfort-focused care when doing so aligned with the patient’s values,” wrote Dr. White of the University of Pittsburgh. “A previous study that was conducted in the context of advanced illness suggested that treatment that accords with the patient’s preferences may lead to shorter survival among those who prioritize comfort over longevity.”
The trial randomized 1,420 patients and their family surrogates in five ICUs to usual care, or to the multicomponent family-support intervention. The primary outcome was change in the surrogates’ scores on the Hospital Anxiety Depression Scale (HADS) at 6 months. The secondary outcomes were changes in Impact of Event Scale (IES; a measure of posttraumatic stress) the Quality of Communication (QOC) scale, quality of clinician-family communication measured by the Patient Perception of Patient Centeredness (PPPC) scale and the mean length of ICU stay.
The intervention was delivered by nurses who received special training on communication and other skills needed to support the families of critically ill patients. Nurses met with families every day and arranged regular meetings with ICU clinicians. A quality improvement specialist incorporated the family support into daily work flow.
In a fully adjusted model, there was no significant between-group difference in the 6-month HADS scores (11.7 vs. 12 points). Likewise, there was no significant difference between the groups in the mean IES score at 6 months.
Family members in the active group did rate the quality of clinician-family communication as significantly better, and they also gave significantly higher ratings to the quality of patient- and family-centered care during the ICU stay.
The shorter length of stay was reflected in the time to death among patients who died during the stay (4.4 days in the intervention group vs. 6.8 days in the control group), although there was no significant difference in length of stay among patients who survived to discharge. Significantly more patients in the intervention group died in the ICU as well (36% vs. 28.5%); however, there was no significant difference in 6-month mortality (60.4% vs. 55.4%).
The study was supported by an Innovation Award from the University of Pittsburgh Medical Center Health System and by the Greenwell Foundation. Dr. White reported having no financial disclosures
Although the results by White and colleagues “cannot be interpreted as clinically directive,” the study offers a glimpse of the path forward in improving the experience of families with critically ill loved ones, Daniela Lamas, MD, wrote in an accompanying editorial (N Engl J Med. 2018; 378:2431-2).
The study didn’t meet its primary endpoint of reducing surrogates’ psychological symptoms at 6 months, but it did lead to an improved ICU experience, with better clinician communication. There was another finding that deserves a close look: In the intervention group, ICU length of stay was shorter and in-hospital mortality greater, although mortality among those who survived to discharge was similar at 6 months.
These findings suggest that the intervention did not lead to the premature death of patients who would have otherwise done well, but rather was associated with a shorter dying process for those who faced a dismal prognosis, according to Dr. Lamas.
“As we increasingly look beyond mortality as the primary outcome that matters, seeking to maximize quality of life and minimize suffering, this work represents an ‘end of the beginning’ by suggesting the next steps in moving closer to achieving these goals.”
Dr. Lamas is a pulmonary and critical care doctor at Brigham & Women’s Hospital and on the faculty at Harvard Medical School, Boston.
Although the results by White and colleagues “cannot be interpreted as clinically directive,” the study offers a glimpse of the path forward in improving the experience of families with critically ill loved ones, Daniela Lamas, MD, wrote in an accompanying editorial (N Engl J Med. 2018; 378:2431-2).
The study didn’t meet its primary endpoint of reducing surrogates’ psychological symptoms at 6 months, but it did lead to an improved ICU experience, with better clinician communication. There was another finding that deserves a close look: In the intervention group, ICU length of stay was shorter and in-hospital mortality greater, although mortality among those who survived to discharge was similar at 6 months.
These findings suggest that the intervention did not lead to the premature death of patients who would have otherwise done well, but rather was associated with a shorter dying process for those who faced a dismal prognosis, according to Dr. Lamas.
“As we increasingly look beyond mortality as the primary outcome that matters, seeking to maximize quality of life and minimize suffering, this work represents an ‘end of the beginning’ by suggesting the next steps in moving closer to achieving these goals.”
Dr. Lamas is a pulmonary and critical care doctor at Brigham & Women’s Hospital and on the faculty at Harvard Medical School, Boston.
Although the results by White and colleagues “cannot be interpreted as clinically directive,” the study offers a glimpse of the path forward in improving the experience of families with critically ill loved ones, Daniela Lamas, MD, wrote in an accompanying editorial (N Engl J Med. 2018; 378:2431-2).
The study didn’t meet its primary endpoint of reducing surrogates’ psychological symptoms at 6 months, but it did lead to an improved ICU experience, with better clinician communication. There was another finding that deserves a close look: In the intervention group, ICU length of stay was shorter and in-hospital mortality greater, although mortality among those who survived to discharge was similar at 6 months.
These findings suggest that the intervention did not lead to the premature death of patients who would have otherwise done well, but rather was associated with a shorter dying process for those who faced a dismal prognosis, according to Dr. Lamas.
“As we increasingly look beyond mortality as the primary outcome that matters, seeking to maximize quality of life and minimize suffering, this work represents an ‘end of the beginning’ by suggesting the next steps in moving closer to achieving these goals.”
Dr. Lamas is a pulmonary and critical care doctor at Brigham & Women’s Hospital and on the faculty at Harvard Medical School, Boston.
A nurse-led support intervention for the families of critically ill patients did little to ease families’ psychological symptoms, but it did improve their perception of staff communication and family-centered care in the intensive care unit.
The length of ICU stay was also significantly shorter and the in-unit death rate higher among patients whose families received the intervention – a finding that suggests difficult end-of-life choices may have been eased, reported Douglas B. White, MD, and his colleagues (N Engl J Med. 2018;378:2365-75).
“The intervention resulted in significant improvements in markers of the quality of decision making, including the patient- and family-centeredness of care and the quality of clinician-family communication. Taken together, these findings suggest that the intervention allowed surrogates to transition a patient’s treatment to comfort-focused care when doing so aligned with the patient’s values,” wrote Dr. White of the University of Pittsburgh. “A previous study that was conducted in the context of advanced illness suggested that treatment that accords with the patient’s preferences may lead to shorter survival among those who prioritize comfort over longevity.”
The trial randomized 1,420 patients and their family surrogates in five ICUs to usual care, or to the multicomponent family-support intervention. The primary outcome was change in the surrogates’ scores on the Hospital Anxiety Depression Scale (HADS) at 6 months. The secondary outcomes were changes in Impact of Event Scale (IES; a measure of posttraumatic stress) the Quality of Communication (QOC) scale, quality of clinician-family communication measured by the Patient Perception of Patient Centeredness (PPPC) scale and the mean length of ICU stay.
The intervention was delivered by nurses who received special training on communication and other skills needed to support the families of critically ill patients. Nurses met with families every day and arranged regular meetings with ICU clinicians. A quality improvement specialist incorporated the family support into daily work flow.
In a fully adjusted model, there was no significant between-group difference in the 6-month HADS scores (11.7 vs. 12 points). Likewise, there was no significant difference between the groups in the mean IES score at 6 months.
Family members in the active group did rate the quality of clinician-family communication as significantly better, and they also gave significantly higher ratings to the quality of patient- and family-centered care during the ICU stay.
The shorter length of stay was reflected in the time to death among patients who died during the stay (4.4 days in the intervention group vs. 6.8 days in the control group), although there was no significant difference in length of stay among patients who survived to discharge. Significantly more patients in the intervention group died in the ICU as well (36% vs. 28.5%); however, there was no significant difference in 6-month mortality (60.4% vs. 55.4%).
The study was supported by an Innovation Award from the University of Pittsburgh Medical Center Health System and by the Greenwell Foundation. Dr. White reported having no financial disclosures
A nurse-led support intervention for the families of critically ill patients did little to ease families’ psychological symptoms, but it did improve their perception of staff communication and family-centered care in the intensive care unit.
The length of ICU stay was also significantly shorter and the in-unit death rate higher among patients whose families received the intervention – a finding that suggests difficult end-of-life choices may have been eased, reported Douglas B. White, MD, and his colleagues (N Engl J Med. 2018;378:2365-75).
“The intervention resulted in significant improvements in markers of the quality of decision making, including the patient- and family-centeredness of care and the quality of clinician-family communication. Taken together, these findings suggest that the intervention allowed surrogates to transition a patient’s treatment to comfort-focused care when doing so aligned with the patient’s values,” wrote Dr. White of the University of Pittsburgh. “A previous study that was conducted in the context of advanced illness suggested that treatment that accords with the patient’s preferences may lead to shorter survival among those who prioritize comfort over longevity.”
The trial randomized 1,420 patients and their family surrogates in five ICUs to usual care, or to the multicomponent family-support intervention. The primary outcome was change in the surrogates’ scores on the Hospital Anxiety Depression Scale (HADS) at 6 months. The secondary outcomes were changes in Impact of Event Scale (IES; a measure of posttraumatic stress) the Quality of Communication (QOC) scale, quality of clinician-family communication measured by the Patient Perception of Patient Centeredness (PPPC) scale and the mean length of ICU stay.
The intervention was delivered by nurses who received special training on communication and other skills needed to support the families of critically ill patients. Nurses met with families every day and arranged regular meetings with ICU clinicians. A quality improvement specialist incorporated the family support into daily work flow.
In a fully adjusted model, there was no significant between-group difference in the 6-month HADS scores (11.7 vs. 12 points). Likewise, there was no significant difference between the groups in the mean IES score at 6 months.
Family members in the active group did rate the quality of clinician-family communication as significantly better, and they also gave significantly higher ratings to the quality of patient- and family-centered care during the ICU stay.
The shorter length of stay was reflected in the time to death among patients who died during the stay (4.4 days in the intervention group vs. 6.8 days in the control group), although there was no significant difference in length of stay among patients who survived to discharge. Significantly more patients in the intervention group died in the ICU as well (36% vs. 28.5%); however, there was no significant difference in 6-month mortality (60.4% vs. 55.4%).
The study was supported by an Innovation Award from the University of Pittsburgh Medical Center Health System and by the Greenwell Foundation. Dr. White reported having no financial disclosures
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: A family communication intervention didn’t improve 6-month psychological symptoms among those with loved ones in intensive care units.
Major finding: There was no significant difference on the Hospital Anxiety and Depression Scale at 6 months (11.7 vs. 12 points).
Study details: The study randomized 1,420 ICU patients and surrogates to the intervention or to usual care.
Disclosures: The study was supported by an Innovation Award from the University of Pittsburgh Medical Center Health System and by the Greenwell Foundation. Dr. White had no financial disclosures.
Source: White et al. N Engl J Med. 2018;378:2365-75.
Intranasal naloxone promising for type 1 hypoglycemia
ORLANDO –
“This has been a clinical problem for a very long time, and we see it all the time. A patient comes into my clinic, the nurses check their blood sugar, it’s 50 mg/dL, and they’re just sitting there without any symptoms,” said lead investigator Sandra Aleksic, MD, of the Albert Einstein College of Medicine, New York.
As blood glucose in the brain drops, people get confused, and their behavioral defenses are compromised. They might crash if they’re driving. “If you have HAAF, it makes you prone to more hypoglycemia, which blunts your response even more. It’s a vicious cycle,” she said at the annual scientific sessions of the American Diabetes Association.
Endogenous opioids are at least partly to blame. Hypoglycemia induces release of beta-endorphin, which in turn inhibits production of epinephrine. Einstein investigators have shown in previous small studies with healthy subjects that morphine blunts the response to induced hypoglycemia, and intravenous naloxone – an opioid blocker – prevents HAAF (Diabetes. 2017 Nov;66[11]:2764-73).
Intravenous naloxone, however, isn’t practical for outpatients, so the team wanted to see whether intranasal naloxone also prevented HAAF. The results “are very promising, but this is preliminary.” If it pans out, though, patients may one day carry intranasal naloxone along with their glucose pills and glucagon to treat hypoglycemia. “Any time they are getting low, they would take the spray,” Dr. Aleksic said.
The team used hypoglycemic, hyperinsulinemic clamps to drop blood glucose levels in seven healthy subjects down to 54 mg/dL for 2 hours twice in one day and gave them hourly sprays of either intranasal saline or 4 mg of intranasal naloxone; hypoglycemia was induced again for 2 hours the following day. The 2-day experiment was repeated 5 weeks later.
Overall, there was no difference in peak epinephrine levels between the first hypoglycemic episode on day 1 and the third episode on day 2 in subjects randomized to naloxone (942 pg/mL plus or minus 190 versus 857 pg/mL plus or minus 134; P = .4). The third episode, meanwhile, placed placebo subjects into HAAF (first hypoglycemic episode 1,375 pg/mL plus or minus 182 versus 858 pg/mL plus or minus 235; P = .004). There was also a trend toward higher hepatic glucose production in the naloxone group.
“These findings suggest that HAAF can be prevented by acute blockade of opioid receptors during hypoglycemia. ... Acute self-administration of intranasal naloxone could be an effective and feasible real-world approach to ameliorate HAAF in type 1 diabetes,” the investigators concluded. A trial in patients with T1DM is being considered.
Dr. Aleksic estimated that patients with T1DM drop blood glucose below 54 mg/dL maybe three or four times a month, on average, depending on how well they manage the condition. For now, it’s unknown how long protection from naloxone would last.
The study subjects were men, 43 years old, on average, with a mean body mass index of 26 kg/m2.
The investigators didn’t have any disclosures, and there was no industry funding for the work.
SOURCE: Aleksic S et al. ADA 2018, Abstract 10-LB.
ORLANDO –
“This has been a clinical problem for a very long time, and we see it all the time. A patient comes into my clinic, the nurses check their blood sugar, it’s 50 mg/dL, and they’re just sitting there without any symptoms,” said lead investigator Sandra Aleksic, MD, of the Albert Einstein College of Medicine, New York.
As blood glucose in the brain drops, people get confused, and their behavioral defenses are compromised. They might crash if they’re driving. “If you have HAAF, it makes you prone to more hypoglycemia, which blunts your response even more. It’s a vicious cycle,” she said at the annual scientific sessions of the American Diabetes Association.
Endogenous opioids are at least partly to blame. Hypoglycemia induces release of beta-endorphin, which in turn inhibits production of epinephrine. Einstein investigators have shown in previous small studies with healthy subjects that morphine blunts the response to induced hypoglycemia, and intravenous naloxone – an opioid blocker – prevents HAAF (Diabetes. 2017 Nov;66[11]:2764-73).
Intravenous naloxone, however, isn’t practical for outpatients, so the team wanted to see whether intranasal naloxone also prevented HAAF. The results “are very promising, but this is preliminary.” If it pans out, though, patients may one day carry intranasal naloxone along with their glucose pills and glucagon to treat hypoglycemia. “Any time they are getting low, they would take the spray,” Dr. Aleksic said.
The team used hypoglycemic, hyperinsulinemic clamps to drop blood glucose levels in seven healthy subjects down to 54 mg/dL for 2 hours twice in one day and gave them hourly sprays of either intranasal saline or 4 mg of intranasal naloxone; hypoglycemia was induced again for 2 hours the following day. The 2-day experiment was repeated 5 weeks later.
Overall, there was no difference in peak epinephrine levels between the first hypoglycemic episode on day 1 and the third episode on day 2 in subjects randomized to naloxone (942 pg/mL plus or minus 190 versus 857 pg/mL plus or minus 134; P = .4). The third episode, meanwhile, placed placebo subjects into HAAF (first hypoglycemic episode 1,375 pg/mL plus or minus 182 versus 858 pg/mL plus or minus 235; P = .004). There was also a trend toward higher hepatic glucose production in the naloxone group.
“These findings suggest that HAAF can be prevented by acute blockade of opioid receptors during hypoglycemia. ... Acute self-administration of intranasal naloxone could be an effective and feasible real-world approach to ameliorate HAAF in type 1 diabetes,” the investigators concluded. A trial in patients with T1DM is being considered.
Dr. Aleksic estimated that patients with T1DM drop blood glucose below 54 mg/dL maybe three or four times a month, on average, depending on how well they manage the condition. For now, it’s unknown how long protection from naloxone would last.
The study subjects were men, 43 years old, on average, with a mean body mass index of 26 kg/m2.
The investigators didn’t have any disclosures, and there was no industry funding for the work.
SOURCE: Aleksic S et al. ADA 2018, Abstract 10-LB.
ORLANDO –
“This has been a clinical problem for a very long time, and we see it all the time. A patient comes into my clinic, the nurses check their blood sugar, it’s 50 mg/dL, and they’re just sitting there without any symptoms,” said lead investigator Sandra Aleksic, MD, of the Albert Einstein College of Medicine, New York.
As blood glucose in the brain drops, people get confused, and their behavioral defenses are compromised. They might crash if they’re driving. “If you have HAAF, it makes you prone to more hypoglycemia, which blunts your response even more. It’s a vicious cycle,” she said at the annual scientific sessions of the American Diabetes Association.
Endogenous opioids are at least partly to blame. Hypoglycemia induces release of beta-endorphin, which in turn inhibits production of epinephrine. Einstein investigators have shown in previous small studies with healthy subjects that morphine blunts the response to induced hypoglycemia, and intravenous naloxone – an opioid blocker – prevents HAAF (Diabetes. 2017 Nov;66[11]:2764-73).
Intravenous naloxone, however, isn’t practical for outpatients, so the team wanted to see whether intranasal naloxone also prevented HAAF. The results “are very promising, but this is preliminary.” If it pans out, though, patients may one day carry intranasal naloxone along with their glucose pills and glucagon to treat hypoglycemia. “Any time they are getting low, they would take the spray,” Dr. Aleksic said.
The team used hypoglycemic, hyperinsulinemic clamps to drop blood glucose levels in seven healthy subjects down to 54 mg/dL for 2 hours twice in one day and gave them hourly sprays of either intranasal saline or 4 mg of intranasal naloxone; hypoglycemia was induced again for 2 hours the following day. The 2-day experiment was repeated 5 weeks later.
Overall, there was no difference in peak epinephrine levels between the first hypoglycemic episode on day 1 and the third episode on day 2 in subjects randomized to naloxone (942 pg/mL plus or minus 190 versus 857 pg/mL plus or minus 134; P = .4). The third episode, meanwhile, placed placebo subjects into HAAF (first hypoglycemic episode 1,375 pg/mL plus or minus 182 versus 858 pg/mL plus or minus 235; P = .004). There was also a trend toward higher hepatic glucose production in the naloxone group.
“These findings suggest that HAAF can be prevented by acute blockade of opioid receptors during hypoglycemia. ... Acute self-administration of intranasal naloxone could be an effective and feasible real-world approach to ameliorate HAAF in type 1 diabetes,” the investigators concluded. A trial in patients with T1DM is being considered.
Dr. Aleksic estimated that patients with T1DM drop blood glucose below 54 mg/dL maybe three or four times a month, on average, depending on how well they manage the condition. For now, it’s unknown how long protection from naloxone would last.
The study subjects were men, 43 years old, on average, with a mean body mass index of 26 kg/m2.
The investigators didn’t have any disclosures, and there was no industry funding for the work.
SOURCE: Aleksic S et al. ADA 2018, Abstract 10-LB.
REPORTING FROM ADA 2018
Key clinical point: Intranasal naloxone might be just the ticket to prevent hypoglycemia-associated autonomic failure in type 1 diabetes mellitus.
Major finding: Overall, there was no difference in peak epinephrine levels between the first day 1 hypoglycemic episode and the third episode on day 2 in subjects randomized to naloxone (942 plus or minus 190 pg/mL versus 857 plus or minus 134 pg/mL; P = 0.4).
Study details: Randomized trial with seven healthy volunteers
Disclosures: There was no industry funding for the work, and the investigators didn’t have any disclosures.
Source: Aleksic S et al. ADA 2018, Abstract 10-LB
Transgender Care in the Primary Care Setting: A Review of Guidelines and Literature
Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant difficulties in obtaining high-quality,compassionate medical care, much of which has been attributed to inadequate provider knowledge. In this article, the authors present a transgender patient seen in primary care and discuss the knowledge gleaned to inform future care of this patient as well as the care of other similar patients.
The following case discussion and review of the literature also seeks to improve the practice of other primary care providers (PCPs) who are inexperienced in this arena. This article aims to review the basics to permit PCPs to venture into transgender care, including a review of basic terminology; a few interactive tips; and basics in medical and hormonal treatment, follow-up, contraindications, and risk. More details can be obtained through electronic consultation (Transgender eConsult) in the VA.
Case Presentation
A 35-year-old patient who was assigned male sex at birth presented to the primary care clinic to discuss her desire to undergo male-to-female (MTF) transition. The patient stated that she had started taking female estrogen hormones 9 years previously purchased from craigslist without a prescription. She tried oral contraceptives as well as oral and injectable estradiol. While the patient was taking injectable estradiol she had breast growth, decreased anxiety, weight gain, and a feeling of peacefulness. The patient also reported that she had received several laser treatments for whole body hair removal, beginning 8 to 10 years before and more regularly in the past 2 to 3 years. She asked whether transition-related care could be provided, because she could no longer afford the hormones.
The patient wanted to transition because she felt that “Women are beautiful, the way they carry themselves, wear their hair, their nails, I want to be like that.” She also mentioned that when she watched TV, she envisioned herself as a woman. She reported that she enjoyed wearing her mother’s clothing since age 10, which made her feel more like herself. The patient noted that she had desired to remove her body hair since childhood but could not afford to do it until recently. She bought female clothing, shoes and makeup, and did her nails from a young age. The patient also reported that she did not “know what transgender was” until a decade ago.
The patient struggled with her identity growing up; however, she tried not to think about it or talk about it with anyone. She related that she was ashamed of her thoughts and that only recently had made peace with being transgender. Thus, she pursued talking to her medical provider about transitioning. The patient reported that she felt more energetic when taking female hormones and was better able to discuss the issue. Specifically, she noted that if she were not on estrogen now she would not be able to talk about transitioning.
The patient related that she has done extensive research about transitioning, including reading online about other transgender people. She noted that she was aware of “possible backlash with society,” but ultimately, she had decided that transitioning was the right decision for her.
She expressed a desire to have an orchiectomy and continue hormonal therapy to permit her “to have a more feminine face, soft skin, hairless body, big breasts, more fat around the hips, and a high-pitched voice.” She additionally related a desire to be in a stable relationship and be her true self. She also stated that she had not identified herself as a female to anyone yet but would like to soon. The patient reported a history of depression, especially during her military service when she wanted to be a woman but did not feel she understood what was going on or how to manage her feelings. She said that for the past 2 months she felt much happier since beginning to take estradiol 4 mg orally daily, which she had found online. She also tried to purchase anti-androgen medication but could not afford it. In addition, she said that she would like to eventually proceed with gender affirmation surgery.
She was currently having sex with men, primarily via anal receptive intercourse. She had no history of sexually transmitted infections but reported that she did not use condoms regularly. She had no history of physical or sexual abuse. The patient was offered referral to the HIV clinic to receive HIV preexposure prophylaxis therapy (emtricitabine + tenofovir), which she declined, but she was counseled on safe sex practice.
The patient was referred to psychiatry both for supportive mental health care and to clarify that her concomitant mental health issues would not preclude the prescription of gender-affirming hormone treatment. Based on the psychiatric evaluation, the patient was felt to be appropriate for treatment with feminizing hormone therapy. The psychiatric assessment also noted that although the patient had a history of psychosis, she was not exhibiting psychotic symptoms currently, and this would not be a contraindication to treatment.
After discussion of the risks and benefits of cross-sex hormone therapy, the patient was started on estradiol 4 mg orally daily, as well as spironolactone 50 mg daily. She was then switched to estradiol 10 mg intramuscular every 2 weeks with the aim of using a less thrombogenic route of administration.
Treatment Outcomes
The patient remains under care. She has had follow-up visits every 3 months to ensure appropriate signs of feminization and monitoring of adverse effects (AEs). The patient’s testosterone and estradiol levels are being checked every 3 months to ensure total testosterone is 1,2
After 12 months on therapy with estradiol and spironolactone, the patient notes that her mood has improved, she feels more energetic, she has gained some weight, and her skin is softer. Her voice pitch, with the help of speech therapy, is gradually changing to what she perceives as more feminine. Hormone levels and electrolytes are all in an acceptable range, and blood sugar and blood pressure (BP) are within normal range. The patient will be offered age-appropriate cancer screening at the appropriate time.
Discussion
The treatment of gender-nonconforming individuals has come a long way since Lili Elbe, the transgender artist depicted in The Danish Girl, underwent gender-affirmation surgery in the early 20th century. Lili and people like her paved the way for other transgender individuals by doggedly pursuing gender-affirming medical treatment although they faced rejection by society and forged a difficult path. In recent years, an increasing number of transgender individuals have begun to seek mainstream medical care; however, PCPs often lack the knowledge and training to properly interact with and care for transgender patients.3,4
Terminology
Although someone’s sex is typically assigned at birth based on the external appearance of their genitalia, gender identity refers to a person’s internal sense of self and how they fit in to the world. People often use these 2 terms interchangeably in everyday language, but these terms are different.1,2
Transgender refers to a person whose gender identity differs from the sex that was assigned at birth. A transgender man or transman, or female-to-male (FTM) transgender person, is an individual who is assigned female sex at birth but identifies as a male. A transgender woman, or transwoman or a male-to-female (MTF) transgender person, is an individual who is assigned male sex at birth but identifies as female. A nontransgender person may be referred to as cisgender.
Transsexual is a medical term and refers to a transgender individual who sought medical intervention to transition to their identified gender. 
Sexual orientation describes sexual attraction only and is not related to gender identity. The sexual orientation of a transgender person is determined by emotional and/or physical attraction and not gender identity.
Gender dysphoria refers to the distress experienced by an individual when one’s gender identity and sex are not completely congruent.
Improving Patient Interaction
Transgender patients might avoid seeking care due to previous negative experiences or a fear of being judged. It is very important to create a safe environment where the patients feel comfortable. Meeting patients “where they are” without judgment will enhance the patient-physician relationship. It is necessary to train all clinic staff about the importance of transgender health issues. All staff should address the patient with the name, pronouns, and gender identity that the patient prefers. For patients with a gender identity that is not strictly male or female (nonbinary patients), gender-neutral pronouns, such as they/them/their, may be chosen. It is helpful to be direct in asking: What is your preferred name? When I speak about you to other providers, what pronouns do you prefer I use, he, she, they? This information can then be documented in the electronic health record (EHR) so that all staff know from visit to visit. Thank the patient for the clarification.
The physical examination can be uncomfortable for both the patient and the physician. Experience and familiarity with the current recommendations can help. The physical examination should be relevant to the anatomy that is present, regardless of the gender presentation. An anatomic survey of the organs currently present in an individual can be useful.1 The physician should be sensitive in examining and obtaining information from the patient, focusing on only those issues relevant to the presenting concern. Chest and genital examinations may be particularly distressing for patients. If a chest or genital examination is indicated, the provider and patient should have a discussion explaining the importance of the examination and how the patient’s comfort can be optimized.
Medical Treatment
Gender-affirmation treatment should be multidisciplinary and include some or all of the following: diagnostic assessment, psychotherapy or counseling, real-life experience (RLE), hormone therapy, and surgical therapy..1,2,5 The World Professional Association for Transgender Health (WPATH) has established internationally accepted Standards of Care (SOC) for the treatment of gender dysphoria that provide detailed expert opinion reviewing the background and guidance for care of transgender individuals. Most commonly, the diagnosis of gender dysphoria is made by a mental health professional (MHP) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria for gender dysphoria.1,2 The involvement of a MHP can be crucial in assessing potential psychological and social risk factors for unfavorable outcomes of medical interventions. In case of severe psychopathology, which can interfere with diagnosis and treatment, the psychopathology should be addressed first.1,2 The MHP also can confirm that the patient has the capacity to make an informed decision.
The 2017 Endocrine Society guidelines for the treatment of gender-dysphoric/gender-incongruent persons emphasize the utility of evaluation of these patients by an expert MHP before starting the treatment.2 However, the guidelines from WPATH and the Center for Transgender Excellence at University of California, San Francisco (UCSF) have stipulated that any provider who feels comfortable assessing the informed decision-making process with a patient can make this determination.
The WPATH SOC states that RLE is essential to transition to the gender role that is congruent with the patient’s gender identity. The RLE is defined as the act of fully adopting a new or evolving gender role or gender presentation in everyday life. In the RLE, the person should fully experience life in the desired gender role before irreversible physical treatment is undertaken. Newer guidelines note that it may be too challenging to adopt the desired gender role without the benefit of feminizing or masculinizing treatment, and therefore, the treatment can be offered at the same time as adopting the new gender role.1
Medical treatment involves administration of masculinizing or feminizing hormone therapy. There are 2 major goals of this hormonal therapy. 
For many transgender adults, genital reconstruction surgery and/or gonadectomy is a necessary step toward achieving their goal. 
Pretreatment screening and appropriate medical monitoring is recommended for both FTM and MTF transgender patients during the endocrine transition and periodically thereafter.2 The physician should monitor the patient’s weight, BP, directed physical examinations, routine health questions focused on risk factors and medications, complete blood count, renal and liver functions, lipid and blood sugar.2 
Physical Changes With Hormone Therapy
Transgender men. Physical changes that are expected to occur during the first 1 to 6 months of testosterone therapy include cessation of menses, increased sexual desire, increased facial and body hair, increased oiliness of skin, increased muscle, and redistribution of fat mass. Changes that occur within the first year of testosterone therapy include deepening of the voice, clitoromegaly, and male pattern hair loss (in some cases). Deepening of the voice, and clitoromegaly are not reversible with discontinuation of hormonal therapy.2
Transgender women. Physical changes that may occur in transgender females in the first 3 to 12 months of estrogen and anti-androgen therapy include decreased sexual desire, decreased spontaneous erections, decreased facial and body hair (usually mild), decreased oiliness of skin, increased breast tissue growth, and redistribution of fat mass. Breast development is generally maximal at 2 years after initiating estrogen, and it is irreversible.2 Effect on fertility may be permanent. Medical therapy has little effect on voice, and most transwomen will require speech therapy to achieve desired pitch.
Routine Health Maintenance
Breast Cancer Screening
Although there are limited data, it is thought that gender-affirming hormone therapy has similar risks as sex hormone replacement therapy in nontransgender males and females. Most AEs arise from use of supraphysiologic doses or inadequate doses.2 Therefore, regular clinical and laboratory monitoring is essential to cross-sex hormone therapy. Treatment with exogenous estrogen and anti-androgens result in transgender women developing breast tissue with ducts, lobules, and acini that is histologically identical to breast tissue in nontransgender females.6
Breast cancer is a concern in transgender women due to prolonged exposure to estrogen. However, the relationship between breast cancer and cross-sex hormone therapy is controversial.
Many factors contribute to breast cancer risk in patients of all genders. Studies of premenopausal and menopausal women taking exogenous estrogen alone have not shown an increase in breast cancer risk. However, the combination of estrogen and progesterone has shown an association with a significant increase in the incidence of breast cancer in postmenopausal women.2,7-10
A study of 5,136 veterans showed a statistically insignificant increased incidence of breast cancer in transgender women compared with data collected from the Surveillance, Epidemiology, and End Results database, although the sample size and duration of the observation were limiting factors.8 A European cohort study found decreased incidence of breast cancer in both MTF and FTM transgender patients, but these patients were an overall younger cohort with decreased risk in general. A cohort of 2,236 MTF individuals in the Netherlands in 1997 showed no increase in all-cause mortality related to hormone therapy at 30-year follow-up. Patients were exposed to exogenous estrogen from 2 months to 41 years.9 A follow-up of this study published in 2013, which included 2,307 MTF individuals taking estrogen for 5 years to > 30 years, revealed only 2 cases of breast cancer, which was the same incidence rate (4.1 per 100,000 person-years) as that of nontransgender women.10
In general, the incidence of breast cancer is rare in nontransgender men, and therefore there have not been a lot of clinical studies to assess risk factors and detection methods. The following risk factors can increase the risk of breast cancer in nontransgender patients: known presence of BRCA mutation, estrogen exposure/androgen insufficiency, Klinefelter syndrome, liver cirrhosis, and obesity.11
Guidelines from the Endocrine Society, WPATH, and UCSF suggest that MTF transgender individuals who have a known increased risk for breast cancer should follow screening guidelines recommended for nontransgender women if they are aged > 50 years and have had more than 5 years of hormone use.2 For FTM patients who have not had chest surgery, screening guidelines should follow those for nontransgender women. For those patients who have had chest reconstruction, small residual amounts of breast tissue may remain. Screening guidelines for these patients do not exist. For these patients, mammography can be technically difficult. Clinical chest wall examination, magnetic resonance imaging (MRI), and/or ultrasound may be helpful modalities. An individual risk vs benefit discussion with the patient is recommended.
Prostate Cancer Screening
Although the prostate gland will undergo atrophy with extended treatment with feminizing hormone therapy, there are case reports of prostate cancer in transgender women.12,13 Usually these patients have started hormone treatment after age 50 years. Therefore, prostate cancer screening is recommended in transgender women as per general guidelines. Because the prostate-specific antigen (PSA) level is expected to be reduced, a PSA > 1.0 should be considered abnormal.1
Cervical Cancer Screening
When a transgender man has a pap smear, it is essential to make it clear to the laboratory that the sample is a cervical pap smear (especially if the gender is marked as male) to avoid the sample being run incorrectly as an anal pap. Also, it is essential to indicate on the pap smear request form that the patient is on testosterone therapy and amenorrhea is present, because the lack of the female hormone can cause atrophy of cervix. This population has a high rate of inadequate specimens. Pretreatment with 1 to 2 weeks of vaginal estrogen can improve the success rate of inadequate specimens. Transgender women who have undergone vaginoplasty do not have a cervix, therefore, cervical cancer screening is not recommended. The anatomy of the neovagina has a more posterior orientation, and an anoscope is a more appropriate tool to examine the neovagina when necessary.
Hematology Health
Transgender women on cross-sex hormone therapy with estrogens may be at increased risk for a venous thromboembolism (VTE). In 2 European studies, patients treated with oral ethinyl estradiol as well as the anti-androgen cyproterone acetate were found to have up to 20 times increased risk of VTE. However, in later studies, oral ethinyl estradiol was changed to either oral conjugated estrogens or transdermal/intramuscular estradiol, and these studies did not show a significant increase in VTE risk.14-16 Tobacco use in combination with estrogen therapy is associated with an increased risk of deep vein thrombosis (DVT).1 All transgender women who smoke should be counseled on tobacco risks and cessation options at every visit.1 The transgender individuals who are not willing to quit smoking may be offered transdermal estrogen, which has lower risk of DVT.14-16
Sexual Health
Clinicians should assess the risks for sexually transmitted infection (STIs) or HIV for transgender patients based on current anatomy and sexual behaviors. Presentations of STIs can be atypical due to varied sexual practices and gender-affirming surgeries. Thus, providers must remain vigilant for symptoms consistent with common STIs and screen for asymptomatic STIs on the basis of behavior history and sexual practices.17 Preexposure prophylaxis for HIV should be considered when appropriate. Serologic screening recommendations for transgender people (eg, HIV, hepatitis B and C, syphilis) do not differ in recommendations from those for nontransgender people.
Cardiovascular Health
The effect of cross-hormone treatment on cardiovascular (CV) health is still unknown. There are no randomized controlled trials that have investigated the relationship between cross-hormone treatment and CV health. Evidence from several studies suggests that CV risk is unchanged among transgender men using testosterone compared with that of nontransgender women.18,19 There is conflicting evidence for transgender women with respect to CV risk and cross-sex hormone treatment.1,18,19 The current American College of Cardiology/American Heart Association guideline advises using the ASCVD risk calculator to determine the need for aspirin and statin treatment based on race, age, gender, and risk factors. There is no guideline on whether to use natal sex or affirmed gender while using the ASCVD calculator. It is reasonable to use the calculator based on natal sex if the cross-hormone treatment has started later in life, but if the cross-sex hormone treatment started at a young age, then one should consider using the affirmed gender to calculate the risk.
As with all patients, life style modifications, including smoking cessation, weight loss, physical activity, and management of BP and blood sugar, are important for CV health. For transgender women with CV risk factors or known CV disease, transdermal route of estrogen is preferred due to lower rates of VTE.18,19
Conclusion
In recent years, an increased number of transgender individuals are seeking mainstream medical care. However, PCPs often lack the knowledge and training to properly interact with and care for transgender patients. It is critical that clinicians understand the difference between sex, gender, and sexuality. For patients who desire transgender care, providers must be able to comfortably ask the patient about their preferred name and prior care, know the basics in cross-sex hormone therapy, including appropriate follow-up of hormonal levels as well as laboratory tests that delineate risk, and know possible complications and AEs. The VA offers significant resources, including electronic transgender care consultation for cases where the provider does not have adequate expertise in the care of these patients.
Both medical schools and residency training programs are starting to incorporate curricula regarding LGBT care. For those who have already completed training, this article serves as a brief guide to terminology, interactive tips, and management of this growing and underserved group of individuals.
1. Deutsch MB. Guidelines for the primary and gender-affirming care of transgender and gender nonbinary people. http://transhealth.ucsf.edu/protocols. Updated June 17, 2016. Accessed June 13, 2018.
2. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoria/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869-3903.
3. Buchholz L. Transgender care moves into the mainstream. JAMA. 2015;314(17):1785-1787.
4. Sobralske M. Primary care needs of patients who have undergone gender reassignment. J Am Acad Nurse Pract. 2005;17(4):133-138.
5. Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877-884.
6. Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW. Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men. Am J Surg Pathol. 2000;24(1):74-80.
7. Braun H, Nash R, Tangpricha V, Brockman J, Ward K, Goodman M. Cancer in transgender people: evidence and methodological consideration. Epidemiol Rev. 2017;39(1):93-107.
8. Brown GR, Jones KT. Incidence of breast cancer in a cohort of 5,135 transgender veterans. Breast Cancer Res Treat. 2015;149(1):191-198.
9. Van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf). 1997;47(3):337-342.
10. Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ. Breast cancer development in transsexual subjects receiving cross-sex hormone treatment. J Sex Med. 2013;10(12):3129-3134.
11. Johansen Taber KA, Morisy LR, Osbahr AJ III, Dickinson BD. Male breast cancer: risk factors, diagnosis and management (review). Oncol Rep. 2010;24(5):1115-1120.
12. Miksad RA, Bubley G, Church P, et al. Prostate cancer in a transgender woman, 41 years after initiation of feminization. JAMA. 2006;296(19):2316-2317.
13. Turo R, Jallad S, Prescott S, Cross WR. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy. Can Urol Assoc J. 2013;7(7-8):E544-E546.
14. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 556: postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet Gynecol. 2013;121(4):887-890.
15. Asscheman H, Gooren LJ, Eklund PL. Mortality and morbidity in transsexual patients with cross-gender treatment. Metabolism. 1989;38(9):869-873.
16. Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-642.
17. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137.
18. Gooren LJ, Wierckx K, Giltay EJ. Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. Eur J Endocrinol. 2014;170(6):809-819.
19. Streed CG Jr, Harfouch O, Marvel F, Blumenthal RS, Martin SS, Mukherjee M. Cardiovascular disease among transgender adults receiving hormone therapy: a narrative review. Ann Int Med. 2017;167(4):256-267.
Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant difficulties in obtaining high-quality,compassionate medical care, much of which has been attributed to inadequate provider knowledge. In this article, the authors present a transgender patient seen in primary care and discuss the knowledge gleaned to inform future care of this patient as well as the care of other similar patients.
The following case discussion and review of the literature also seeks to improve the practice of other primary care providers (PCPs) who are inexperienced in this arena. This article aims to review the basics to permit PCPs to venture into transgender care, including a review of basic terminology; a few interactive tips; and basics in medical and hormonal treatment, follow-up, contraindications, and risk. More details can be obtained through electronic consultation (Transgender eConsult) in the VA.
Case Presentation
A 35-year-old patient who was assigned male sex at birth presented to the primary care clinic to discuss her desire to undergo male-to-female (MTF) transition. The patient stated that she had started taking female estrogen hormones 9 years previously purchased from craigslist without a prescription. She tried oral contraceptives as well as oral and injectable estradiol. While the patient was taking injectable estradiol she had breast growth, decreased anxiety, weight gain, and a feeling of peacefulness. The patient also reported that she had received several laser treatments for whole body hair removal, beginning 8 to 10 years before and more regularly in the past 2 to 3 years. She asked whether transition-related care could be provided, because she could no longer afford the hormones.
The patient wanted to transition because she felt that “Women are beautiful, the way they carry themselves, wear their hair, their nails, I want to be like that.” She also mentioned that when she watched TV, she envisioned herself as a woman. She reported that she enjoyed wearing her mother’s clothing since age 10, which made her feel more like herself. The patient noted that she had desired to remove her body hair since childhood but could not afford to do it until recently. She bought female clothing, shoes and makeup, and did her nails from a young age. The patient also reported that she did not “know what transgender was” until a decade ago.
The patient struggled with her identity growing up; however, she tried not to think about it or talk about it with anyone. She related that she was ashamed of her thoughts and that only recently had made peace with being transgender. Thus, she pursued talking to her medical provider about transitioning. The patient reported that she felt more energetic when taking female hormones and was better able to discuss the issue. Specifically, she noted that if she were not on estrogen now she would not be able to talk about transitioning.
The patient related that she has done extensive research about transitioning, including reading online about other transgender people. She noted that she was aware of “possible backlash with society,” but ultimately, she had decided that transitioning was the right decision for her.
She expressed a desire to have an orchiectomy and continue hormonal therapy to permit her “to have a more feminine face, soft skin, hairless body, big breasts, more fat around the hips, and a high-pitched voice.” She additionally related a desire to be in a stable relationship and be her true self. She also stated that she had not identified herself as a female to anyone yet but would like to soon. The patient reported a history of depression, especially during her military service when she wanted to be a woman but did not feel she understood what was going on or how to manage her feelings. She said that for the past 2 months she felt much happier since beginning to take estradiol 4 mg orally daily, which she had found online. She also tried to purchase anti-androgen medication but could not afford it. In addition, she said that she would like to eventually proceed with gender affirmation surgery.
She was currently having sex with men, primarily via anal receptive intercourse. She had no history of sexually transmitted infections but reported that she did not use condoms regularly. She had no history of physical or sexual abuse. The patient was offered referral to the HIV clinic to receive HIV preexposure prophylaxis therapy (emtricitabine + tenofovir), which she declined, but she was counseled on safe sex practice.
The patient was referred to psychiatry both for supportive mental health care and to clarify that her concomitant mental health issues would not preclude the prescription of gender-affirming hormone treatment. Based on the psychiatric evaluation, the patient was felt to be appropriate for treatment with feminizing hormone therapy. The psychiatric assessment also noted that although the patient had a history of psychosis, she was not exhibiting psychotic symptoms currently, and this would not be a contraindication to treatment.
After discussion of the risks and benefits of cross-sex hormone therapy, the patient was started on estradiol 4 mg orally daily, as well as spironolactone 50 mg daily. She was then switched to estradiol 10 mg intramuscular every 2 weeks with the aim of using a less thrombogenic route of administration.
Treatment Outcomes
The patient remains under care. She has had follow-up visits every 3 months to ensure appropriate signs of feminization and monitoring of adverse effects (AEs). The patient’s testosterone and estradiol levels are being checked every 3 months to ensure total testosterone is 1,2
After 12 months on therapy with estradiol and spironolactone, the patient notes that her mood has improved, she feels more energetic, she has gained some weight, and her skin is softer. Her voice pitch, with the help of speech therapy, is gradually changing to what she perceives as more feminine. Hormone levels and electrolytes are all in an acceptable range, and blood sugar and blood pressure (BP) are within normal range. The patient will be offered age-appropriate cancer screening at the appropriate time.
Discussion
The treatment of gender-nonconforming individuals has come a long way since Lili Elbe, the transgender artist depicted in The Danish Girl, underwent gender-affirmation surgery in the early 20th century. Lili and people like her paved the way for other transgender individuals by doggedly pursuing gender-affirming medical treatment although they faced rejection by society and forged a difficult path. In recent years, an increasing number of transgender individuals have begun to seek mainstream medical care; however, PCPs often lack the knowledge and training to properly interact with and care for transgender patients.3,4
Terminology
Although someone’s sex is typically assigned at birth based on the external appearance of their genitalia, gender identity refers to a person’s internal sense of self and how they fit in to the world. People often use these 2 terms interchangeably in everyday language, but these terms are different.1,2
Transgender refers to a person whose gender identity differs from the sex that was assigned at birth. A transgender man or transman, or female-to-male (FTM) transgender person, is an individual who is assigned female sex at birth but identifies as a male. A transgender woman, or transwoman or a male-to-female (MTF) transgender person, is an individual who is assigned male sex at birth but identifies as female. A nontransgender person may be referred to as cisgender.
Transsexual is a medical term and refers to a transgender individual who sought medical intervention to transition to their identified gender.
Sexual orientation describes sexual attraction only and is not related to gender identity. The sexual orientation of a transgender person is determined by emotional and/or physical attraction and not gender identity.
Gender dysphoria refers to the distress experienced by an individual when one’s gender identity and sex are not completely congruent.
Improving Patient Interaction
Transgender patients might avoid seeking care due to previous negative experiences or a fear of being judged. It is very important to create a safe environment where the patients feel comfortable. Meeting patients “where they are” without judgment will enhance the patient-physician relationship. It is necessary to train all clinic staff about the importance of transgender health issues. All staff should address the patient with the name, pronouns, and gender identity that the patient prefers. For patients with a gender identity that is not strictly male or female (nonbinary patients), gender-neutral pronouns, such as they/them/their, may be chosen. It is helpful to be direct in asking: What is your preferred name? When I speak about you to other providers, what pronouns do you prefer I use, he, she, they? This information can then be documented in the electronic health record (EHR) so that all staff know from visit to visit. Thank the patient for the clarification.
The physical examination can be uncomfortable for both the patient and the physician. Experience and familiarity with the current recommendations can help. The physical examination should be relevant to the anatomy that is present, regardless of the gender presentation. An anatomic survey of the organs currently present in an individual can be useful.1 The physician should be sensitive in examining and obtaining information from the patient, focusing on only those issues relevant to the presenting concern. Chest and genital examinations may be particularly distressing for patients. If a chest or genital examination is indicated, the provider and patient should have a discussion explaining the importance of the examination and how the patient’s comfort can be optimized.
Medical Treatment
Gender-affirmation treatment should be multidisciplinary and include some or all of the following: diagnostic assessment, psychotherapy or counseling, real-life experience (RLE), hormone therapy, and surgical therapy..1,2,5 The World Professional Association for Transgender Health (WPATH) has established internationally accepted Standards of Care (SOC) for the treatment of gender dysphoria that provide detailed expert opinion reviewing the background and guidance for care of transgender individuals. Most commonly, the diagnosis of gender dysphoria is made by a mental health professional (MHP) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria for gender dysphoria.1,2 The involvement of a MHP can be crucial in assessing potential psychological and social risk factors for unfavorable outcomes of medical interventions. In case of severe psychopathology, which can interfere with diagnosis and treatment, the psychopathology should be addressed first.1,2 The MHP also can confirm that the patient has the capacity to make an informed decision.
The 2017 Endocrine Society guidelines for the treatment of gender-dysphoric/gender-incongruent persons emphasize the utility of evaluation of these patients by an expert MHP before starting the treatment.2 However, the guidelines from WPATH and the Center for Transgender Excellence at University of California, San Francisco (UCSF) have stipulated that any provider who feels comfortable assessing the informed decision-making process with a patient can make this determination.
The WPATH SOC states that RLE is essential to transition to the gender role that is congruent with the patient’s gender identity. The RLE is defined as the act of fully adopting a new or evolving gender role or gender presentation in everyday life. In the RLE, the person should fully experience life in the desired gender role before irreversible physical treatment is undertaken. Newer guidelines note that it may be too challenging to adopt the desired gender role without the benefit of feminizing or masculinizing treatment, and therefore, the treatment can be offered at the same time as adopting the new gender role.1
Medical treatment involves administration of masculinizing or feminizing hormone therapy. There are 2 major goals of this hormonal therapy.
For many transgender adults, genital reconstruction surgery and/or gonadectomy is a necessary step toward achieving their goal.
Pretreatment screening and appropriate medical monitoring is recommended for both FTM and MTF transgender patients during the endocrine transition and periodically thereafter.2 The physician should monitor the patient’s weight, BP, directed physical examinations, routine health questions focused on risk factors and medications, complete blood count, renal and liver functions, lipid and blood sugar.2
Physical Changes With Hormone Therapy
Transgender men. Physical changes that are expected to occur during the first 1 to 6 months of testosterone therapy include cessation of menses, increased sexual desire, increased facial and body hair, increased oiliness of skin, increased muscle, and redistribution of fat mass. Changes that occur within the first year of testosterone therapy include deepening of the voice, clitoromegaly, and male pattern hair loss (in some cases). Deepening of the voice, and clitoromegaly are not reversible with discontinuation of hormonal therapy.2
Transgender women. Physical changes that may occur in transgender females in the first 3 to 12 months of estrogen and anti-androgen therapy include decreased sexual desire, decreased spontaneous erections, decreased facial and body hair (usually mild), decreased oiliness of skin, increased breast tissue growth, and redistribution of fat mass. Breast development is generally maximal at 2 years after initiating estrogen, and it is irreversible.2 Effect on fertility may be permanent. Medical therapy has little effect on voice, and most transwomen will require speech therapy to achieve desired pitch.
Routine Health Maintenance
Breast Cancer Screening
Although there are limited data, it is thought that gender-affirming hormone therapy has similar risks as sex hormone replacement therapy in nontransgender males and females. Most AEs arise from use of supraphysiologic doses or inadequate doses.2 Therefore, regular clinical and laboratory monitoring is essential to cross-sex hormone therapy. Treatment with exogenous estrogen and anti-androgens result in transgender women developing breast tissue with ducts, lobules, and acini that is histologically identical to breast tissue in nontransgender females.6
Breast cancer is a concern in transgender women due to prolonged exposure to estrogen. However, the relationship between breast cancer and cross-sex hormone therapy is controversial.
Many factors contribute to breast cancer risk in patients of all genders. Studies of premenopausal and menopausal women taking exogenous estrogen alone have not shown an increase in breast cancer risk. However, the combination of estrogen and progesterone has shown an association with a significant increase in the incidence of breast cancer in postmenopausal women.2,7-10
A study of 5,136 veterans showed a statistically insignificant increased incidence of breast cancer in transgender women compared with data collected from the Surveillance, Epidemiology, and End Results database, although the sample size and duration of the observation were limiting factors.8 A European cohort study found decreased incidence of breast cancer in both MTF and FTM transgender patients, but these patients were an overall younger cohort with decreased risk in general. A cohort of 2,236 MTF individuals in the Netherlands in 1997 showed no increase in all-cause mortality related to hormone therapy at 30-year follow-up. Patients were exposed to exogenous estrogen from 2 months to 41 years.9 A follow-up of this study published in 2013, which included 2,307 MTF individuals taking estrogen for 5 years to > 30 years, revealed only 2 cases of breast cancer, which was the same incidence rate (4.1 per 100,000 person-years) as that of nontransgender women.10
In general, the incidence of breast cancer is rare in nontransgender men, and therefore there have not been a lot of clinical studies to assess risk factors and detection methods. The following risk factors can increase the risk of breast cancer in nontransgender patients: known presence of BRCA mutation, estrogen exposure/androgen insufficiency, Klinefelter syndrome, liver cirrhosis, and obesity.11
Guidelines from the Endocrine Society, WPATH, and UCSF suggest that MTF transgender individuals who have a known increased risk for breast cancer should follow screening guidelines recommended for nontransgender women if they are aged > 50 years and have had more than 5 years of hormone use.2 For FTM patients who have not had chest surgery, screening guidelines should follow those for nontransgender women. For those patients who have had chest reconstruction, small residual amounts of breast tissue may remain. Screening guidelines for these patients do not exist. For these patients, mammography can be technically difficult. Clinical chest wall examination, magnetic resonance imaging (MRI), and/or ultrasound may be helpful modalities. An individual risk vs benefit discussion with the patient is recommended.
Prostate Cancer Screening
Although the prostate gland will undergo atrophy with extended treatment with feminizing hormone therapy, there are case reports of prostate cancer in transgender women.12,13 Usually these patients have started hormone treatment after age 50 years. Therefore, prostate cancer screening is recommended in transgender women as per general guidelines. Because the prostate-specific antigen (PSA) level is expected to be reduced, a PSA > 1.0 should be considered abnormal.1
Cervical Cancer Screening
When a transgender man has a pap smear, it is essential to make it clear to the laboratory that the sample is a cervical pap smear (especially if the gender is marked as male) to avoid the sample being run incorrectly as an anal pap. Also, it is essential to indicate on the pap smear request form that the patient is on testosterone therapy and amenorrhea is present, because the lack of the female hormone can cause atrophy of cervix. This population has a high rate of inadequate specimens. Pretreatment with 1 to 2 weeks of vaginal estrogen can improve the success rate of inadequate specimens. Transgender women who have undergone vaginoplasty do not have a cervix, therefore, cervical cancer screening is not recommended. The anatomy of the neovagina has a more posterior orientation, and an anoscope is a more appropriate tool to examine the neovagina when necessary.
Hematology Health
Transgender women on cross-sex hormone therapy with estrogens may be at increased risk for a venous thromboembolism (VTE). In 2 European studies, patients treated with oral ethinyl estradiol as well as the anti-androgen cyproterone acetate were found to have up to 20 times increased risk of VTE. However, in later studies, oral ethinyl estradiol was changed to either oral conjugated estrogens or transdermal/intramuscular estradiol, and these studies did not show a significant increase in VTE risk.14-16 Tobacco use in combination with estrogen therapy is associated with an increased risk of deep vein thrombosis (DVT).1 All transgender women who smoke should be counseled on tobacco risks and cessation options at every visit.1 The transgender individuals who are not willing to quit smoking may be offered transdermal estrogen, which has lower risk of DVT.14-16
Sexual Health
Clinicians should assess the risks for sexually transmitted infection (STIs) or HIV for transgender patients based on current anatomy and sexual behaviors. Presentations of STIs can be atypical due to varied sexual practices and gender-affirming surgeries. Thus, providers must remain vigilant for symptoms consistent with common STIs and screen for asymptomatic STIs on the basis of behavior history and sexual practices.17 Preexposure prophylaxis for HIV should be considered when appropriate. Serologic screening recommendations for transgender people (eg, HIV, hepatitis B and C, syphilis) do not differ in recommendations from those for nontransgender people.
Cardiovascular Health
The effect of cross-hormone treatment on cardiovascular (CV) health is still unknown. There are no randomized controlled trials that have investigated the relationship between cross-hormone treatment and CV health. Evidence from several studies suggests that CV risk is unchanged among transgender men using testosterone compared with that of nontransgender women.18,19 There is conflicting evidence for transgender women with respect to CV risk and cross-sex hormone treatment.1,18,19 The current American College of Cardiology/American Heart Association guideline advises using the ASCVD risk calculator to determine the need for aspirin and statin treatment based on race, age, gender, and risk factors. There is no guideline on whether to use natal sex or affirmed gender while using the ASCVD calculator. It is reasonable to use the calculator based on natal sex if the cross-hormone treatment has started later in life, but if the cross-sex hormone treatment started at a young age, then one should consider using the affirmed gender to calculate the risk.
As with all patients, life style modifications, including smoking cessation, weight loss, physical activity, and management of BP and blood sugar, are important for CV health. For transgender women with CV risk factors or known CV disease, transdermal route of estrogen is preferred due to lower rates of VTE.18,19
Conclusion
In recent years, an increased number of transgender individuals are seeking mainstream medical care. However, PCPs often lack the knowledge and training to properly interact with and care for transgender patients. It is critical that clinicians understand the difference between sex, gender, and sexuality. For patients who desire transgender care, providers must be able to comfortably ask the patient about their preferred name and prior care, know the basics in cross-sex hormone therapy, including appropriate follow-up of hormonal levels as well as laboratory tests that delineate risk, and know possible complications and AEs. The VA offers significant resources, including electronic transgender care consultation for cases where the provider does not have adequate expertise in the care of these patients.
Both medical schools and residency training programs are starting to incorporate curricula regarding LGBT care. For those who have already completed training, this article serves as a brief guide to terminology, interactive tips, and management of this growing and underserved group of individuals.
Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant difficulties in obtaining high-quality,compassionate medical care, much of which has been attributed to inadequate provider knowledge. In this article, the authors present a transgender patient seen in primary care and discuss the knowledge gleaned to inform future care of this patient as well as the care of other similar patients.
The following case discussion and review of the literature also seeks to improve the practice of other primary care providers (PCPs) who are inexperienced in this arena. This article aims to review the basics to permit PCPs to venture into transgender care, including a review of basic terminology; a few interactive tips; and basics in medical and hormonal treatment, follow-up, contraindications, and risk. More details can be obtained through electronic consultation (Transgender eConsult) in the VA.
Case Presentation
A 35-year-old patient who was assigned male sex at birth presented to the primary care clinic to discuss her desire to undergo male-to-female (MTF) transition. The patient stated that she had started taking female estrogen hormones 9 years previously purchased from craigslist without a prescription. She tried oral contraceptives as well as oral and injectable estradiol. While the patient was taking injectable estradiol she had breast growth, decreased anxiety, weight gain, and a feeling of peacefulness. The patient also reported that she had received several laser treatments for whole body hair removal, beginning 8 to 10 years before and more regularly in the past 2 to 3 years. She asked whether transition-related care could be provided, because she could no longer afford the hormones.
The patient wanted to transition because she felt that “Women are beautiful, the way they carry themselves, wear their hair, their nails, I want to be like that.” She also mentioned that when she watched TV, she envisioned herself as a woman. She reported that she enjoyed wearing her mother’s clothing since age 10, which made her feel more like herself. The patient noted that she had desired to remove her body hair since childhood but could not afford to do it until recently. She bought female clothing, shoes and makeup, and did her nails from a young age. The patient also reported that she did not “know what transgender was” until a decade ago.
The patient struggled with her identity growing up; however, she tried not to think about it or talk about it with anyone. She related that she was ashamed of her thoughts and that only recently had made peace with being transgender. Thus, she pursued talking to her medical provider about transitioning. The patient reported that she felt more energetic when taking female hormones and was better able to discuss the issue. Specifically, she noted that if she were not on estrogen now she would not be able to talk about transitioning.
The patient related that she has done extensive research about transitioning, including reading online about other transgender people. She noted that she was aware of “possible backlash with society,” but ultimately, she had decided that transitioning was the right decision for her.
She expressed a desire to have an orchiectomy and continue hormonal therapy to permit her “to have a more feminine face, soft skin, hairless body, big breasts, more fat around the hips, and a high-pitched voice.” She additionally related a desire to be in a stable relationship and be her true self. She also stated that she had not identified herself as a female to anyone yet but would like to soon. The patient reported a history of depression, especially during her military service when she wanted to be a woman but did not feel she understood what was going on or how to manage her feelings. She said that for the past 2 months she felt much happier since beginning to take estradiol 4 mg orally daily, which she had found online. She also tried to purchase anti-androgen medication but could not afford it. In addition, she said that she would like to eventually proceed with gender affirmation surgery.
She was currently having sex with men, primarily via anal receptive intercourse. She had no history of sexually transmitted infections but reported that she did not use condoms regularly. She had no history of physical or sexual abuse. The patient was offered referral to the HIV clinic to receive HIV preexposure prophylaxis therapy (emtricitabine + tenofovir), which she declined, but she was counseled on safe sex practice.
The patient was referred to psychiatry both for supportive mental health care and to clarify that her concomitant mental health issues would not preclude the prescription of gender-affirming hormone treatment. Based on the psychiatric evaluation, the patient was felt to be appropriate for treatment with feminizing hormone therapy. The psychiatric assessment also noted that although the patient had a history of psychosis, she was not exhibiting psychotic symptoms currently, and this would not be a contraindication to treatment.
After discussion of the risks and benefits of cross-sex hormone therapy, the patient was started on estradiol 4 mg orally daily, as well as spironolactone 50 mg daily. She was then switched to estradiol 10 mg intramuscular every 2 weeks with the aim of using a less thrombogenic route of administration.
Treatment Outcomes
The patient remains under care. She has had follow-up visits every 3 months to ensure appropriate signs of feminization and monitoring of adverse effects (AEs). The patient’s testosterone and estradiol levels are being checked every 3 months to ensure total testosterone is 1,2
After 12 months on therapy with estradiol and spironolactone, the patient notes that her mood has improved, she feels more energetic, she has gained some weight, and her skin is softer. Her voice pitch, with the help of speech therapy, is gradually changing to what she perceives as more feminine. Hormone levels and electrolytes are all in an acceptable range, and blood sugar and blood pressure (BP) are within normal range. The patient will be offered age-appropriate cancer screening at the appropriate time.
Discussion
The treatment of gender-nonconforming individuals has come a long way since Lili Elbe, the transgender artist depicted in The Danish Girl, underwent gender-affirmation surgery in the early 20th century. Lili and people like her paved the way for other transgender individuals by doggedly pursuing gender-affirming medical treatment although they faced rejection by society and forged a difficult path. In recent years, an increasing number of transgender individuals have begun to seek mainstream medical care; however, PCPs often lack the knowledge and training to properly interact with and care for transgender patients.3,4
Terminology
Although someone’s sex is typically assigned at birth based on the external appearance of their genitalia, gender identity refers to a person’s internal sense of self and how they fit in to the world. People often use these 2 terms interchangeably in everyday language, but these terms are different.1,2
Transgender refers to a person whose gender identity differs from the sex that was assigned at birth. A transgender man or transman, or female-to-male (FTM) transgender person, is an individual who is assigned female sex at birth but identifies as a male. A transgender woman, or transwoman or a male-to-female (MTF) transgender person, is an individual who is assigned male sex at birth but identifies as female. A nontransgender person may be referred to as cisgender.
Transsexual is a medical term and refers to a transgender individual who sought medical intervention to transition to their identified gender.
Sexual orientation describes sexual attraction only and is not related to gender identity. The sexual orientation of a transgender person is determined by emotional and/or physical attraction and not gender identity.
Gender dysphoria refers to the distress experienced by an individual when one’s gender identity and sex are not completely congruent.
Improving Patient Interaction
Transgender patients might avoid seeking care due to previous negative experiences or a fear of being judged. It is very important to create a safe environment where the patients feel comfortable. Meeting patients “where they are” without judgment will enhance the patient-physician relationship. It is necessary to train all clinic staff about the importance of transgender health issues. All staff should address the patient with the name, pronouns, and gender identity that the patient prefers. For patients with a gender identity that is not strictly male or female (nonbinary patients), gender-neutral pronouns, such as they/them/their, may be chosen. It is helpful to be direct in asking: What is your preferred name? When I speak about you to other providers, what pronouns do you prefer I use, he, she, they? This information can then be documented in the electronic health record (EHR) so that all staff know from visit to visit. Thank the patient for the clarification.
The physical examination can be uncomfortable for both the patient and the physician. Experience and familiarity with the current recommendations can help. The physical examination should be relevant to the anatomy that is present, regardless of the gender presentation. An anatomic survey of the organs currently present in an individual can be useful.1 The physician should be sensitive in examining and obtaining information from the patient, focusing on only those issues relevant to the presenting concern. Chest and genital examinations may be particularly distressing for patients. If a chest or genital examination is indicated, the provider and patient should have a discussion explaining the importance of the examination and how the patient’s comfort can be optimized.
Medical Treatment
Gender-affirmation treatment should be multidisciplinary and include some or all of the following: diagnostic assessment, psychotherapy or counseling, real-life experience (RLE), hormone therapy, and surgical therapy..1,2,5 The World Professional Association for Transgender Health (WPATH) has established internationally accepted Standards of Care (SOC) for the treatment of gender dysphoria that provide detailed expert opinion reviewing the background and guidance for care of transgender individuals. Most commonly, the diagnosis of gender dysphoria is made by a mental health professional (MHP) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria for gender dysphoria.1,2 The involvement of a MHP can be crucial in assessing potential psychological and social risk factors for unfavorable outcomes of medical interventions. In case of severe psychopathology, which can interfere with diagnosis and treatment, the psychopathology should be addressed first.1,2 The MHP also can confirm that the patient has the capacity to make an informed decision.
The 2017 Endocrine Society guidelines for the treatment of gender-dysphoric/gender-incongruent persons emphasize the utility of evaluation of these patients by an expert MHP before starting the treatment.2 However, the guidelines from WPATH and the Center for Transgender Excellence at University of California, San Francisco (UCSF) have stipulated that any provider who feels comfortable assessing the informed decision-making process with a patient can make this determination.
The WPATH SOC states that RLE is essential to transition to the gender role that is congruent with the patient’s gender identity. The RLE is defined as the act of fully adopting a new or evolving gender role or gender presentation in everyday life. In the RLE, the person should fully experience life in the desired gender role before irreversible physical treatment is undertaken. Newer guidelines note that it may be too challenging to adopt the desired gender role without the benefit of feminizing or masculinizing treatment, and therefore, the treatment can be offered at the same time as adopting the new gender role.1
Medical treatment involves administration of masculinizing or feminizing hormone therapy. There are 2 major goals of this hormonal therapy.
For many transgender adults, genital reconstruction surgery and/or gonadectomy is a necessary step toward achieving their goal.
Pretreatment screening and appropriate medical monitoring is recommended for both FTM and MTF transgender patients during the endocrine transition and periodically thereafter.2 The physician should monitor the patient’s weight, BP, directed physical examinations, routine health questions focused on risk factors and medications, complete blood count, renal and liver functions, lipid and blood sugar.2
Physical Changes With Hormone Therapy
Transgender men. Physical changes that are expected to occur during the first 1 to 6 months of testosterone therapy include cessation of menses, increased sexual desire, increased facial and body hair, increased oiliness of skin, increased muscle, and redistribution of fat mass. Changes that occur within the first year of testosterone therapy include deepening of the voice, clitoromegaly, and male pattern hair loss (in some cases). Deepening of the voice, and clitoromegaly are not reversible with discontinuation of hormonal therapy.2
Transgender women. Physical changes that may occur in transgender females in the first 3 to 12 months of estrogen and anti-androgen therapy include decreased sexual desire, decreased spontaneous erections, decreased facial and body hair (usually mild), decreased oiliness of skin, increased breast tissue growth, and redistribution of fat mass. Breast development is generally maximal at 2 years after initiating estrogen, and it is irreversible.2 Effect on fertility may be permanent. Medical therapy has little effect on voice, and most transwomen will require speech therapy to achieve desired pitch.
Routine Health Maintenance
Breast Cancer Screening
Although there are limited data, it is thought that gender-affirming hormone therapy has similar risks as sex hormone replacement therapy in nontransgender males and females. Most AEs arise from use of supraphysiologic doses or inadequate doses.2 Therefore, regular clinical and laboratory monitoring is essential to cross-sex hormone therapy. Treatment with exogenous estrogen and anti-androgens result in transgender women developing breast tissue with ducts, lobules, and acini that is histologically identical to breast tissue in nontransgender females.6
Breast cancer is a concern in transgender women due to prolonged exposure to estrogen. However, the relationship between breast cancer and cross-sex hormone therapy is controversial.
Many factors contribute to breast cancer risk in patients of all genders. Studies of premenopausal and menopausal women taking exogenous estrogen alone have not shown an increase in breast cancer risk. However, the combination of estrogen and progesterone has shown an association with a significant increase in the incidence of breast cancer in postmenopausal women.2,7-10
A study of 5,136 veterans showed a statistically insignificant increased incidence of breast cancer in transgender women compared with data collected from the Surveillance, Epidemiology, and End Results database, although the sample size and duration of the observation were limiting factors.8 A European cohort study found decreased incidence of breast cancer in both MTF and FTM transgender patients, but these patients were an overall younger cohort with decreased risk in general. A cohort of 2,236 MTF individuals in the Netherlands in 1997 showed no increase in all-cause mortality related to hormone therapy at 30-year follow-up. Patients were exposed to exogenous estrogen from 2 months to 41 years.9 A follow-up of this study published in 2013, which included 2,307 MTF individuals taking estrogen for 5 years to > 30 years, revealed only 2 cases of breast cancer, which was the same incidence rate (4.1 per 100,000 person-years) as that of nontransgender women.10
In general, the incidence of breast cancer is rare in nontransgender men, and therefore there have not been a lot of clinical studies to assess risk factors and detection methods. The following risk factors can increase the risk of breast cancer in nontransgender patients: known presence of BRCA mutation, estrogen exposure/androgen insufficiency, Klinefelter syndrome, liver cirrhosis, and obesity.11
Guidelines from the Endocrine Society, WPATH, and UCSF suggest that MTF transgender individuals who have a known increased risk for breast cancer should follow screening guidelines recommended for nontransgender women if they are aged > 50 years and have had more than 5 years of hormone use.2 For FTM patients who have not had chest surgery, screening guidelines should follow those for nontransgender women. For those patients who have had chest reconstruction, small residual amounts of breast tissue may remain. Screening guidelines for these patients do not exist. For these patients, mammography can be technically difficult. Clinical chest wall examination, magnetic resonance imaging (MRI), and/or ultrasound may be helpful modalities. An individual risk vs benefit discussion with the patient is recommended.
Prostate Cancer Screening
Although the prostate gland will undergo atrophy with extended treatment with feminizing hormone therapy, there are case reports of prostate cancer in transgender women.12,13 Usually these patients have started hormone treatment after age 50 years. Therefore, prostate cancer screening is recommended in transgender women as per general guidelines. Because the prostate-specific antigen (PSA) level is expected to be reduced, a PSA > 1.0 should be considered abnormal.1
Cervical Cancer Screening
When a transgender man has a pap smear, it is essential to make it clear to the laboratory that the sample is a cervical pap smear (especially if the gender is marked as male) to avoid the sample being run incorrectly as an anal pap. Also, it is essential to indicate on the pap smear request form that the patient is on testosterone therapy and amenorrhea is present, because the lack of the female hormone can cause atrophy of cervix. This population has a high rate of inadequate specimens. Pretreatment with 1 to 2 weeks of vaginal estrogen can improve the success rate of inadequate specimens. Transgender women who have undergone vaginoplasty do not have a cervix, therefore, cervical cancer screening is not recommended. The anatomy of the neovagina has a more posterior orientation, and an anoscope is a more appropriate tool to examine the neovagina when necessary.
Hematology Health
Transgender women on cross-sex hormone therapy with estrogens may be at increased risk for a venous thromboembolism (VTE). In 2 European studies, patients treated with oral ethinyl estradiol as well as the anti-androgen cyproterone acetate were found to have up to 20 times increased risk of VTE. However, in later studies, oral ethinyl estradiol was changed to either oral conjugated estrogens or transdermal/intramuscular estradiol, and these studies did not show a significant increase in VTE risk.14-16 Tobacco use in combination with estrogen therapy is associated with an increased risk of deep vein thrombosis (DVT).1 All transgender women who smoke should be counseled on tobacco risks and cessation options at every visit.1 The transgender individuals who are not willing to quit smoking may be offered transdermal estrogen, which has lower risk of DVT.14-16
Sexual Health
Clinicians should assess the risks for sexually transmitted infection (STIs) or HIV for transgender patients based on current anatomy and sexual behaviors. Presentations of STIs can be atypical due to varied sexual practices and gender-affirming surgeries. Thus, providers must remain vigilant for symptoms consistent with common STIs and screen for asymptomatic STIs on the basis of behavior history and sexual practices.17 Preexposure prophylaxis for HIV should be considered when appropriate. Serologic screening recommendations for transgender people (eg, HIV, hepatitis B and C, syphilis) do not differ in recommendations from those for nontransgender people.
Cardiovascular Health
The effect of cross-hormone treatment on cardiovascular (CV) health is still unknown. There are no randomized controlled trials that have investigated the relationship between cross-hormone treatment and CV health. Evidence from several studies suggests that CV risk is unchanged among transgender men using testosterone compared with that of nontransgender women.18,19 There is conflicting evidence for transgender women with respect to CV risk and cross-sex hormone treatment.1,18,19 The current American College of Cardiology/American Heart Association guideline advises using the ASCVD risk calculator to determine the need for aspirin and statin treatment based on race, age, gender, and risk factors. There is no guideline on whether to use natal sex or affirmed gender while using the ASCVD calculator. It is reasonable to use the calculator based on natal sex if the cross-hormone treatment has started later in life, but if the cross-sex hormone treatment started at a young age, then one should consider using the affirmed gender to calculate the risk.
As with all patients, life style modifications, including smoking cessation, weight loss, physical activity, and management of BP and blood sugar, are important for CV health. For transgender women with CV risk factors or known CV disease, transdermal route of estrogen is preferred due to lower rates of VTE.18,19
Conclusion
In recent years, an increased number of transgender individuals are seeking mainstream medical care. However, PCPs often lack the knowledge and training to properly interact with and care for transgender patients. It is critical that clinicians understand the difference between sex, gender, and sexuality. For patients who desire transgender care, providers must be able to comfortably ask the patient about their preferred name and prior care, know the basics in cross-sex hormone therapy, including appropriate follow-up of hormonal levels as well as laboratory tests that delineate risk, and know possible complications and AEs. The VA offers significant resources, including electronic transgender care consultation for cases where the provider does not have adequate expertise in the care of these patients.
Both medical schools and residency training programs are starting to incorporate curricula regarding LGBT care. For those who have already completed training, this article serves as a brief guide to terminology, interactive tips, and management of this growing and underserved group of individuals.
1. Deutsch MB. Guidelines for the primary and gender-affirming care of transgender and gender nonbinary people. http://transhealth.ucsf.edu/protocols. Updated June 17, 2016. Accessed June 13, 2018.
2. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoria/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869-3903.
3. Buchholz L. Transgender care moves into the mainstream. JAMA. 2015;314(17):1785-1787.
4. Sobralske M. Primary care needs of patients who have undergone gender reassignment. J Am Acad Nurse Pract. 2005;17(4):133-138.
5. Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877-884.
6. Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW. Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men. Am J Surg Pathol. 2000;24(1):74-80.
7. Braun H, Nash R, Tangpricha V, Brockman J, Ward K, Goodman M. Cancer in transgender people: evidence and methodological consideration. Epidemiol Rev. 2017;39(1):93-107.
8. Brown GR, Jones KT. Incidence of breast cancer in a cohort of 5,135 transgender veterans. Breast Cancer Res Treat. 2015;149(1):191-198.
9. Van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf). 1997;47(3):337-342.
10. Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ. Breast cancer development in transsexual subjects receiving cross-sex hormone treatment. J Sex Med. 2013;10(12):3129-3134.
11. Johansen Taber KA, Morisy LR, Osbahr AJ III, Dickinson BD. Male breast cancer: risk factors, diagnosis and management (review). Oncol Rep. 2010;24(5):1115-1120.
12. Miksad RA, Bubley G, Church P, et al. Prostate cancer in a transgender woman, 41 years after initiation of feminization. JAMA. 2006;296(19):2316-2317.
13. Turo R, Jallad S, Prescott S, Cross WR. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy. Can Urol Assoc J. 2013;7(7-8):E544-E546.
14. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 556: postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet Gynecol. 2013;121(4):887-890.
15. Asscheman H, Gooren LJ, Eklund PL. Mortality and morbidity in transsexual patients with cross-gender treatment. Metabolism. 1989;38(9):869-873.
16. Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-642.
17. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137.
18. Gooren LJ, Wierckx K, Giltay EJ. Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. Eur J Endocrinol. 2014;170(6):809-819.
19. Streed CG Jr, Harfouch O, Marvel F, Blumenthal RS, Martin SS, Mukherjee M. Cardiovascular disease among transgender adults receiving hormone therapy: a narrative review. Ann Int Med. 2017;167(4):256-267.
1. Deutsch MB. Guidelines for the primary and gender-affirming care of transgender and gender nonbinary people. http://transhealth.ucsf.edu/protocols. Updated June 17, 2016. Accessed June 13, 2018.
2. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoria/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869-3903.
3. Buchholz L. Transgender care moves into the mainstream. JAMA. 2015;314(17):1785-1787.
4. Sobralske M. Primary care needs of patients who have undergone gender reassignment. J Am Acad Nurse Pract. 2005;17(4):133-138.
5. Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877-884.
6. Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW. Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men. Am J Surg Pathol. 2000;24(1):74-80.
7. Braun H, Nash R, Tangpricha V, Brockman J, Ward K, Goodman M. Cancer in transgender people: evidence and methodological consideration. Epidemiol Rev. 2017;39(1):93-107.
8. Brown GR, Jones KT. Incidence of breast cancer in a cohort of 5,135 transgender veterans. Breast Cancer Res Treat. 2015;149(1):191-198.
9. Van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf). 1997;47(3):337-342.
10. Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ. Breast cancer development in transsexual subjects receiving cross-sex hormone treatment. J Sex Med. 2013;10(12):3129-3134.
11. Johansen Taber KA, Morisy LR, Osbahr AJ III, Dickinson BD. Male breast cancer: risk factors, diagnosis and management (review). Oncol Rep. 2010;24(5):1115-1120.
12. Miksad RA, Bubley G, Church P, et al. Prostate cancer in a transgender woman, 41 years after initiation of feminization. JAMA. 2006;296(19):2316-2317.
13. Turo R, Jallad S, Prescott S, Cross WR. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy. Can Urol Assoc J. 2013;7(7-8):E544-E546.
14. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 556: postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet Gynecol. 2013;121(4):887-890.
15. Asscheman H, Gooren LJ, Eklund PL. Mortality and morbidity in transsexual patients with cross-gender treatment. Metabolism. 1989;38(9):869-873.
16. Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-642.
17. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137.
18. Gooren LJ, Wierckx K, Giltay EJ. Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. Eur J Endocrinol. 2014;170(6):809-819.
19. Streed CG Jr, Harfouch O, Marvel F, Blumenthal RS, Martin SS, Mukherjee M. Cardiovascular disease among transgender adults receiving hormone therapy: a narrative review. Ann Int Med. 2017;167(4):256-267.
Explaining enasidenib resistance in AML
New research helps explain enasidenib resistance among patients with IDH2-mutant acute myeloid leukemia (AML).
Researchers found that leukemic cells stop responding to enasidenib when IDH2 clones develop additional mutations.
This may mean that enasidenib will have to be combined with other drugs to prevent AML relapse, the researchers said.
They reported their findings in Nature Medicine.
Previous research indicated that enasidenib prompts differentiation to induce responses in AML. In a phase 1/2 trial, enasidenib produced responses in about 40% of patients with relapsed/refractory, IDH2-mutated AML. However, most patients eventually relapsed.
“[T]he initial studies did not show which AML cells responded to enasidenib and started to differentiate again,” said Stéphane de Botton, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
“It was also unclear how the cells become resistant to therapy. We wanted to answer these questions.”
To do so, Dr de Botton and his colleagues analyzed sequential samples from 37 AML patients treated with enasidenib on the phase 1/2 trial. Thirty of these patients had initially responded to the drug.
“We used techniques to study genetic mutations on a cell-by-cell basis and reconstructed the ‘family tree’ of a patient’s AML,” said Lynn Quek, MD, of the University of Oxford in the UK.
“We then tracked changes in the family of AML cells as they responded to enasidenib and as patients lost response to the drug. This is the first time that anyone has done such a detailed study at a single-cell level.”
The researchers said they observed variable differentiation arrest in IDH2-mutant clones before enasidenib treatment.
Overall, treatment promoted hematopoietic differentiation from either terminal or ancestral mutant clones. However, enasidenib also promoted differentiation of nonmutant cells in a minority of patients.
When the researchers compared samples taken at diagnosis and relapse, they did not find second-site mutations in IDH2 at relapse.
The team said relapse was the result of clonal evolution or selection of terminal or ancestral clones, which suggests there are multiple pathways that could potentially be targeted to restore differentiation arrest.
“We have provided genetic proof that enasidenib was able to differentiate cancer cells so that some of their normal functions were restored, even though they still contained the IDH2 mutation,” said Virginie Penard-Lacronique, of Gustave Roussy.
“This is important because, unless we can track these clones, we don’t know whether the mature cells in a patient are coming from normal cells after all the cancer cells have been killed or from leukemic cells that are now able to mature. In this paper, we show that, in 4 out of 5 cases, the mature cells are coming from leukemic bone marrow cells that can be induced to differentiate by this new drug.”
The researchers said these results suggest enasidenib must be combined with other drugs to prevent AML relapse.
“Now that we have shown that [enasidenib] needs to be combined with other drugs to stop the cancer returning, we think that it’s important that the combination therapy should be given to AML patients early on in their disease,” Dr de Botton said. “International trials are now taking place comparing combinations of enasidenib and other drugs with the normal standard of care.”
New research helps explain enasidenib resistance among patients with IDH2-mutant acute myeloid leukemia (AML).
Researchers found that leukemic cells stop responding to enasidenib when IDH2 clones develop additional mutations.
This may mean that enasidenib will have to be combined with other drugs to prevent AML relapse, the researchers said.
They reported their findings in Nature Medicine.
Previous research indicated that enasidenib prompts differentiation to induce responses in AML. In a phase 1/2 trial, enasidenib produced responses in about 40% of patients with relapsed/refractory, IDH2-mutated AML. However, most patients eventually relapsed.
“[T]he initial studies did not show which AML cells responded to enasidenib and started to differentiate again,” said Stéphane de Botton, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
“It was also unclear how the cells become resistant to therapy. We wanted to answer these questions.”
To do so, Dr de Botton and his colleagues analyzed sequential samples from 37 AML patients treated with enasidenib on the phase 1/2 trial. Thirty of these patients had initially responded to the drug.
“We used techniques to study genetic mutations on a cell-by-cell basis and reconstructed the ‘family tree’ of a patient’s AML,” said Lynn Quek, MD, of the University of Oxford in the UK.
“We then tracked changes in the family of AML cells as they responded to enasidenib and as patients lost response to the drug. This is the first time that anyone has done such a detailed study at a single-cell level.”
The researchers said they observed variable differentiation arrest in IDH2-mutant clones before enasidenib treatment.
Overall, treatment promoted hematopoietic differentiation from either terminal or ancestral mutant clones. However, enasidenib also promoted differentiation of nonmutant cells in a minority of patients.
When the researchers compared samples taken at diagnosis and relapse, they did not find second-site mutations in IDH2 at relapse.
The team said relapse was the result of clonal evolution or selection of terminal or ancestral clones, which suggests there are multiple pathways that could potentially be targeted to restore differentiation arrest.
“We have provided genetic proof that enasidenib was able to differentiate cancer cells so that some of their normal functions were restored, even though they still contained the IDH2 mutation,” said Virginie Penard-Lacronique, of Gustave Roussy.
“This is important because, unless we can track these clones, we don’t know whether the mature cells in a patient are coming from normal cells after all the cancer cells have been killed or from leukemic cells that are now able to mature. In this paper, we show that, in 4 out of 5 cases, the mature cells are coming from leukemic bone marrow cells that can be induced to differentiate by this new drug.”
The researchers said these results suggest enasidenib must be combined with other drugs to prevent AML relapse.
“Now that we have shown that [enasidenib] needs to be combined with other drugs to stop the cancer returning, we think that it’s important that the combination therapy should be given to AML patients early on in their disease,” Dr de Botton said. “International trials are now taking place comparing combinations of enasidenib and other drugs with the normal standard of care.”
New research helps explain enasidenib resistance among patients with IDH2-mutant acute myeloid leukemia (AML).
Researchers found that leukemic cells stop responding to enasidenib when IDH2 clones develop additional mutations.
This may mean that enasidenib will have to be combined with other drugs to prevent AML relapse, the researchers said.
They reported their findings in Nature Medicine.
Previous research indicated that enasidenib prompts differentiation to induce responses in AML. In a phase 1/2 trial, enasidenib produced responses in about 40% of patients with relapsed/refractory, IDH2-mutated AML. However, most patients eventually relapsed.
“[T]he initial studies did not show which AML cells responded to enasidenib and started to differentiate again,” said Stéphane de Botton, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
“It was also unclear how the cells become resistant to therapy. We wanted to answer these questions.”
To do so, Dr de Botton and his colleagues analyzed sequential samples from 37 AML patients treated with enasidenib on the phase 1/2 trial. Thirty of these patients had initially responded to the drug.
“We used techniques to study genetic mutations on a cell-by-cell basis and reconstructed the ‘family tree’ of a patient’s AML,” said Lynn Quek, MD, of the University of Oxford in the UK.
“We then tracked changes in the family of AML cells as they responded to enasidenib and as patients lost response to the drug. This is the first time that anyone has done such a detailed study at a single-cell level.”
The researchers said they observed variable differentiation arrest in IDH2-mutant clones before enasidenib treatment.
Overall, treatment promoted hematopoietic differentiation from either terminal or ancestral mutant clones. However, enasidenib also promoted differentiation of nonmutant cells in a minority of patients.
When the researchers compared samples taken at diagnosis and relapse, they did not find second-site mutations in IDH2 at relapse.
The team said relapse was the result of clonal evolution or selection of terminal or ancestral clones, which suggests there are multiple pathways that could potentially be targeted to restore differentiation arrest.
“We have provided genetic proof that enasidenib was able to differentiate cancer cells so that some of their normal functions were restored, even though they still contained the IDH2 mutation,” said Virginie Penard-Lacronique, of Gustave Roussy.
“This is important because, unless we can track these clones, we don’t know whether the mature cells in a patient are coming from normal cells after all the cancer cells have been killed or from leukemic cells that are now able to mature. In this paper, we show that, in 4 out of 5 cases, the mature cells are coming from leukemic bone marrow cells that can be induced to differentiate by this new drug.”
The researchers said these results suggest enasidenib must be combined with other drugs to prevent AML relapse.
“Now that we have shown that [enasidenib] needs to be combined with other drugs to stop the cancer returning, we think that it’s important that the combination therapy should be given to AML patients early on in their disease,” Dr de Botton said. “International trials are now taking place comparing combinations of enasidenib and other drugs with the normal standard of care.”
Investigators question utility of SFLCA
Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.
The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.
“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.
“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.
Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.
The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).
In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.
This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.
The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.
The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.
“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.
However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.
*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.
Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.
The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.
“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.
“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.
Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.
The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).
In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.
This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.
The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.
The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.
“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.
However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.
*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.
Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.
The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.
“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.
“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.
Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.
The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).
In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.
This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.
The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.
The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.
“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.
However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.
*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.
Vaccine protects mice from malaria
An RNA replicon-based vaccine can fight malaria infection in mice, according to research published in Nature Communications.
The vaccine targets a protein, Plasmodium macrophage migration inhibitory factor (PMIF), which is produced by malaria parasites and suppresses memory T cells.
The vaccine provided improved control of existing malaria infection as well as protection from reinfection in mice.
This work was funded by National Institutes of Health grants and Novartis Vaccines, Inc.
The research began with a strain of Plasmodium berghei in which PMIF was genetically deleted. Investigators found that mice infected with this strain developed memory T cells and showed stronger anti-parasite immunity.
This led the researchers to test a vaccine targeting PMIF in 2 mouse models of malaria. One model was an early stage liver infection, and the other was a severe, late-stage blood infection.
The vaccine reduced parasitemia in both models and prolonged survival in mice with the late-stage blood infection.
The investigators then cured vaccinated mice of malaria (via treatment with chloroquine) and reinfected them.
Mice reinfected with late-stage malaria had no evidence of parasites in the blood or organs after reinfection.
The mice reinfected with liver-stage malaria had a 70% reduction in liver parasites (compared to control mice) upon reinfection, and they did not develop blood-stage infection.
“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against reinfection,” said study author Richard Bucala, MD, of Yale School of Medicine in New Haven, Connecticut.
“To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”
The researchers also transferred memory T cells from immunized mice to naïve mice that had never been exposed to malaria. The T-cell recipients were completely protected from malaria infection.
The investigators’ next step with this work is to develop a vaccine for humans who have never had malaria, primarily young children.
“The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T-cell response, clear the parasite, and be protected from future infection,” Dr Bucala said.
An RNA replicon-based vaccine can fight malaria infection in mice, according to research published in Nature Communications.
The vaccine targets a protein, Plasmodium macrophage migration inhibitory factor (PMIF), which is produced by malaria parasites and suppresses memory T cells.
The vaccine provided improved control of existing malaria infection as well as protection from reinfection in mice.
This work was funded by National Institutes of Health grants and Novartis Vaccines, Inc.
The research began with a strain of Plasmodium berghei in which PMIF was genetically deleted. Investigators found that mice infected with this strain developed memory T cells and showed stronger anti-parasite immunity.
This led the researchers to test a vaccine targeting PMIF in 2 mouse models of malaria. One model was an early stage liver infection, and the other was a severe, late-stage blood infection.
The vaccine reduced parasitemia in both models and prolonged survival in mice with the late-stage blood infection.
The investigators then cured vaccinated mice of malaria (via treatment with chloroquine) and reinfected them.
Mice reinfected with late-stage malaria had no evidence of parasites in the blood or organs after reinfection.
The mice reinfected with liver-stage malaria had a 70% reduction in liver parasites (compared to control mice) upon reinfection, and they did not develop blood-stage infection.
“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against reinfection,” said study author Richard Bucala, MD, of Yale School of Medicine in New Haven, Connecticut.
“To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”
The researchers also transferred memory T cells from immunized mice to naïve mice that had never been exposed to malaria. The T-cell recipients were completely protected from malaria infection.
The investigators’ next step with this work is to develop a vaccine for humans who have never had malaria, primarily young children.
“The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T-cell response, clear the parasite, and be protected from future infection,” Dr Bucala said.
An RNA replicon-based vaccine can fight malaria infection in mice, according to research published in Nature Communications.
The vaccine targets a protein, Plasmodium macrophage migration inhibitory factor (PMIF), which is produced by malaria parasites and suppresses memory T cells.
The vaccine provided improved control of existing malaria infection as well as protection from reinfection in mice.
This work was funded by National Institutes of Health grants and Novartis Vaccines, Inc.
The research began with a strain of Plasmodium berghei in which PMIF was genetically deleted. Investigators found that mice infected with this strain developed memory T cells and showed stronger anti-parasite immunity.
This led the researchers to test a vaccine targeting PMIF in 2 mouse models of malaria. One model was an early stage liver infection, and the other was a severe, late-stage blood infection.
The vaccine reduced parasitemia in both models and prolonged survival in mice with the late-stage blood infection.
The investigators then cured vaccinated mice of malaria (via treatment with chloroquine) and reinfected them.
Mice reinfected with late-stage malaria had no evidence of parasites in the blood or organs after reinfection.
The mice reinfected with liver-stage malaria had a 70% reduction in liver parasites (compared to control mice) upon reinfection, and they did not develop blood-stage infection.
“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against reinfection,” said study author Richard Bucala, MD, of Yale School of Medicine in New Haven, Connecticut.
“To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”
The researchers also transferred memory T cells from immunized mice to naïve mice that had never been exposed to malaria. The T-cell recipients were completely protected from malaria infection.
The investigators’ next step with this work is to develop a vaccine for humans who have never had malaria, primarily young children.
“The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T-cell response, clear the parasite, and be protected from future infection,” Dr Bucala said.
Let Low-risk Moms Eat During Labor?
A 23-year-old nulliparous woman at term with an uncomplicated pregnancy presents to labor and delivery. She reports regular contractions for the last several hours and is admitted in labor for an anticipated vaginal delivery. She has not had anything to eat or drink for the past three hours and says she’s hungry. What type of diet should you order for this patient? Should you place any restrictions in the order?
Since the first reports of Mendelson syndrome (aspiration during general anesthesia) in the early 1940s, many health care providers managing laboring women restrict their diets to clear liquids or less, with little evidence to support the decision.2 In a recent survey of Canadian hospitals, for example, 51% of laboring women who did not receive an epidural during the active phase of labor were placed on restricted diets of only clear fluids and/or ice chips; this number rose to 83% for women who did receive an epidural.3
Dietary restrictions continue to be enforced despite the fact that only about 5% of obstetric patients require general anesthesia.1 In a general-population study of 172,334 adults who underwent a total of 215,488 surgeries with general anesthesia, the risk for aspiration was 1:895 for emergency procedures and 1:3886 for elective procedures.4 Of the 66 patients who aspirated, 42 had no respiratory sequelae.
Similarly, Robinson et al noted that anesthesia-associated aspiration fatalities have been much lower in more recent studies than in historical ones—approximately 1 in 350,000 anesthesia events compared with 1 in 45,000 to 240,000—and are more commonly observed during intubation for emergency surgery.5
The current American College of Obstetricians and Gynecologists guidance is to restrict oral intake to clear liquids during labor for low-risk patients, with further restriction for those at increased risk for aspiration.6 The meta-analysis described here looked at the risks and benefits of a less-restrictive diet during labor.
STUDY SUMMARY
Not one case of aspiration
This meta-analysis of 10 RCTs, including 3,982 laboring women, analyzed the effect of food intake on labor and the risks and benefits associated with less-restrictive diets for low-risk women in labor.1 Women were included in the trials if they had singleton pregnancies with cephalic presentation at the time of delivery. The women had varying cervical dilation at the time of presentation. Seven of 10 studies involved women with a gestational age ≥ 37 weeks, two studies set the gestational age threshold at 36 weeks, and one study included women with a gestational age ≥ 30 weeks.
In the intervention groups, the authors studied varying degrees of diets and/or intakes, ranging from oral carbohydrate solutions to low-fat food to a completely unrestricted diet. One study accounted for 61% of the patients in this review and compared intake of low-fat foods to ice chips, water, or sips of water until delivery. The primary outcome of the meta-analysis was duration of labor.
Continue to: Results
Results. The authors of the meta-analysis found that the patients in the intervention groups, compared with the control groups, had a shorter mean duration of labor by 16 minutes. Apgar scores and the rates of Cesarean delivery, operative vaginal delivery, epidural analgesia, and admission to the neonatal ICU were similar in the intervention and control groups. Maternal vomiting was also similar: 37.6% in the intervention group and 36.5% in the control group (relative risk, 1.00). None of the 3,982 patients experienced aspiration pneumonia or pneumonitis.1
WHAT’S NEW
An outdated practice, per the data
For years, women’s diets have been restricted during labor without sufficient evidence to support the practice. In this systematic review and meta-analysis, Ciardulli and colleagues did not find a single case of aspiration pneumonitis—the outcome on which the rationale for restricting diets during labor is based. A 2013 Cochrane review by Singata et al also found no harm in less-restrictive diets for low-risk women in labor.7 Ciardulli et al concluded that dietary restrictions for women at low risk for complications/surgery during labor are not justified based on current data.
CAVEATS
Underpowered and missing information
This meta-analysis found no occurrences of aspiration pneumonia or pneumonitis; however, it was underpowered to identify these rare complications. This is partially due to the unusual need for general anesthesia in low-risk patients, as noted earlier. Data on the total number of women who underwent general anesthesia in the current review were limited, as not every study within the meta-analysis included this information.
CHALLENGES TO IMPLEMENTATION
Stemming the cultural tide
One challenge to implementation is changing the culture of practice regarding low-risk pregnant women in labor, as well as the opinions of other health care providers and hospital policies that oppose less-restrictive oral intake during labor.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[6]:379-380).
1. Ciardulli A, Saccone G, Anastasio H, Berghella V. Less-restrictive food intake during labor in low-risk singleton pregnancies: a systematic review and meta-analysis. Obstet Gynecol. 2017;129(3):473-480.
2. Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol. 1946;52:191-205.
3. Chackowicz A, Spence AR, Abenhaim HA. Restrictions on oral and parenteral intake for low-risk labouring women in hospitals across Canada: a cross-sectional study. J Obstet Gynaecol Can. 2016;38(11):1009-1014.
4. Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology. 1993;78(1):56-62.
5. Robinson M, Davidson A. Aspiration under anaesthesia: risk assessment and decision-making. Cont Educ Anaesth Crit Care Pain. 2014;14(4):171-175.
6. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 441. Oral intake during labor. Obstet Gynecol. 2009;114:714. Reaffirmed 2017.
7. Singata M, Tranmer J, Gyte GM. Restricting oral fluid and food intake during labour. Cochrane Database Syst Rev. 2013;(8):CD003930.
A 23-year-old nulliparous woman at term with an uncomplicated pregnancy presents to labor and delivery. She reports regular contractions for the last several hours and is admitted in labor for an anticipated vaginal delivery. She has not had anything to eat or drink for the past three hours and says she’s hungry. What type of diet should you order for this patient? Should you place any restrictions in the order?
Since the first reports of Mendelson syndrome (aspiration during general anesthesia) in the early 1940s, many health care providers managing laboring women restrict their diets to clear liquids or less, with little evidence to support the decision.2 In a recent survey of Canadian hospitals, for example, 51% of laboring women who did not receive an epidural during the active phase of labor were placed on restricted diets of only clear fluids and/or ice chips; this number rose to 83% for women who did receive an epidural.3
Dietary restrictions continue to be enforced despite the fact that only about 5% of obstetric patients require general anesthesia.1 In a general-population study of 172,334 adults who underwent a total of 215,488 surgeries with general anesthesia, the risk for aspiration was 1:895 for emergency procedures and 1:3886 for elective procedures.4 Of the 66 patients who aspirated, 42 had no respiratory sequelae.
Similarly, Robinson et al noted that anesthesia-associated aspiration fatalities have been much lower in more recent studies than in historical ones—approximately 1 in 350,000 anesthesia events compared with 1 in 45,000 to 240,000—and are more commonly observed during intubation for emergency surgery.5
The current American College of Obstetricians and Gynecologists guidance is to restrict oral intake to clear liquids during labor for low-risk patients, with further restriction for those at increased risk for aspiration.6 The meta-analysis described here looked at the risks and benefits of a less-restrictive diet during labor.
STUDY SUMMARY
Not one case of aspiration
This meta-analysis of 10 RCTs, including 3,982 laboring women, analyzed the effect of food intake on labor and the risks and benefits associated with less-restrictive diets for low-risk women in labor.1 Women were included in the trials if they had singleton pregnancies with cephalic presentation at the time of delivery. The women had varying cervical dilation at the time of presentation. Seven of 10 studies involved women with a gestational age ≥ 37 weeks, two studies set the gestational age threshold at 36 weeks, and one study included women with a gestational age ≥ 30 weeks.
In the intervention groups, the authors studied varying degrees of diets and/or intakes, ranging from oral carbohydrate solutions to low-fat food to a completely unrestricted diet. One study accounted for 61% of the patients in this review and compared intake of low-fat foods to ice chips, water, or sips of water until delivery. The primary outcome of the meta-analysis was duration of labor.
Continue to: Results
Results. The authors of the meta-analysis found that the patients in the intervention groups, compared with the control groups, had a shorter mean duration of labor by 16 minutes. Apgar scores and the rates of Cesarean delivery, operative vaginal delivery, epidural analgesia, and admission to the neonatal ICU were similar in the intervention and control groups. Maternal vomiting was also similar: 37.6% in the intervention group and 36.5% in the control group (relative risk, 1.00). None of the 3,982 patients experienced aspiration pneumonia or pneumonitis.1
WHAT’S NEW
An outdated practice, per the data
For years, women’s diets have been restricted during labor without sufficient evidence to support the practice. In this systematic review and meta-analysis, Ciardulli and colleagues did not find a single case of aspiration pneumonitis—the outcome on which the rationale for restricting diets during labor is based. A 2013 Cochrane review by Singata et al also found no harm in less-restrictive diets for low-risk women in labor.7 Ciardulli et al concluded that dietary restrictions for women at low risk for complications/surgery during labor are not justified based on current data.
CAVEATS
Underpowered and missing information
This meta-analysis found no occurrences of aspiration pneumonia or pneumonitis; however, it was underpowered to identify these rare complications. This is partially due to the unusual need for general anesthesia in low-risk patients, as noted earlier. Data on the total number of women who underwent general anesthesia in the current review were limited, as not every study within the meta-analysis included this information.
CHALLENGES TO IMPLEMENTATION
Stemming the cultural tide
One challenge to implementation is changing the culture of practice regarding low-risk pregnant women in labor, as well as the opinions of other health care providers and hospital policies that oppose less-restrictive oral intake during labor.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[6]:379-380).
A 23-year-old nulliparous woman at term with an uncomplicated pregnancy presents to labor and delivery. She reports regular contractions for the last several hours and is admitted in labor for an anticipated vaginal delivery. She has not had anything to eat or drink for the past three hours and says she’s hungry. What type of diet should you order for this patient? Should you place any restrictions in the order?
Since the first reports of Mendelson syndrome (aspiration during general anesthesia) in the early 1940s, many health care providers managing laboring women restrict their diets to clear liquids or less, with little evidence to support the decision.2 In a recent survey of Canadian hospitals, for example, 51% of laboring women who did not receive an epidural during the active phase of labor were placed on restricted diets of only clear fluids and/or ice chips; this number rose to 83% for women who did receive an epidural.3
Dietary restrictions continue to be enforced despite the fact that only about 5% of obstetric patients require general anesthesia.1 In a general-population study of 172,334 adults who underwent a total of 215,488 surgeries with general anesthesia, the risk for aspiration was 1:895 for emergency procedures and 1:3886 for elective procedures.4 Of the 66 patients who aspirated, 42 had no respiratory sequelae.
Similarly, Robinson et al noted that anesthesia-associated aspiration fatalities have been much lower in more recent studies than in historical ones—approximately 1 in 350,000 anesthesia events compared with 1 in 45,000 to 240,000—and are more commonly observed during intubation for emergency surgery.5
The current American College of Obstetricians and Gynecologists guidance is to restrict oral intake to clear liquids during labor for low-risk patients, with further restriction for those at increased risk for aspiration.6 The meta-analysis described here looked at the risks and benefits of a less-restrictive diet during labor.
STUDY SUMMARY
Not one case of aspiration
This meta-analysis of 10 RCTs, including 3,982 laboring women, analyzed the effect of food intake on labor and the risks and benefits associated with less-restrictive diets for low-risk women in labor.1 Women were included in the trials if they had singleton pregnancies with cephalic presentation at the time of delivery. The women had varying cervical dilation at the time of presentation. Seven of 10 studies involved women with a gestational age ≥ 37 weeks, two studies set the gestational age threshold at 36 weeks, and one study included women with a gestational age ≥ 30 weeks.
In the intervention groups, the authors studied varying degrees of diets and/or intakes, ranging from oral carbohydrate solutions to low-fat food to a completely unrestricted diet. One study accounted for 61% of the patients in this review and compared intake of low-fat foods to ice chips, water, or sips of water until delivery. The primary outcome of the meta-analysis was duration of labor.
Continue to: Results
Results. The authors of the meta-analysis found that the patients in the intervention groups, compared with the control groups, had a shorter mean duration of labor by 16 minutes. Apgar scores and the rates of Cesarean delivery, operative vaginal delivery, epidural analgesia, and admission to the neonatal ICU were similar in the intervention and control groups. Maternal vomiting was also similar: 37.6% in the intervention group and 36.5% in the control group (relative risk, 1.00). None of the 3,982 patients experienced aspiration pneumonia or pneumonitis.1
WHAT’S NEW
An outdated practice, per the data
For years, women’s diets have been restricted during labor without sufficient evidence to support the practice. In this systematic review and meta-analysis, Ciardulli and colleagues did not find a single case of aspiration pneumonitis—the outcome on which the rationale for restricting diets during labor is based. A 2013 Cochrane review by Singata et al also found no harm in less-restrictive diets for low-risk women in labor.7 Ciardulli et al concluded that dietary restrictions for women at low risk for complications/surgery during labor are not justified based on current data.
CAVEATS
Underpowered and missing information
This meta-analysis found no occurrences of aspiration pneumonia or pneumonitis; however, it was underpowered to identify these rare complications. This is partially due to the unusual need for general anesthesia in low-risk patients, as noted earlier. Data on the total number of women who underwent general anesthesia in the current review were limited, as not every study within the meta-analysis included this information.
CHALLENGES TO IMPLEMENTATION
Stemming the cultural tide
One challenge to implementation is changing the culture of practice regarding low-risk pregnant women in labor, as well as the opinions of other health care providers and hospital policies that oppose less-restrictive oral intake during labor.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[6]:379-380).
1. Ciardulli A, Saccone G, Anastasio H, Berghella V. Less-restrictive food intake during labor in low-risk singleton pregnancies: a systematic review and meta-analysis. Obstet Gynecol. 2017;129(3):473-480.
2. Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol. 1946;52:191-205.
3. Chackowicz A, Spence AR, Abenhaim HA. Restrictions on oral and parenteral intake for low-risk labouring women in hospitals across Canada: a cross-sectional study. J Obstet Gynaecol Can. 2016;38(11):1009-1014.
4. Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology. 1993;78(1):56-62.
5. Robinson M, Davidson A. Aspiration under anaesthesia: risk assessment and decision-making. Cont Educ Anaesth Crit Care Pain. 2014;14(4):171-175.
6. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 441. Oral intake during labor. Obstet Gynecol. 2009;114:714. Reaffirmed 2017.
7. Singata M, Tranmer J, Gyte GM. Restricting oral fluid and food intake during labour. Cochrane Database Syst Rev. 2013;(8):CD003930.
1. Ciardulli A, Saccone G, Anastasio H, Berghella V. Less-restrictive food intake during labor in low-risk singleton pregnancies: a systematic review and meta-analysis. Obstet Gynecol. 2017;129(3):473-480.
2. Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol. 1946;52:191-205.
3. Chackowicz A, Spence AR, Abenhaim HA. Restrictions on oral and parenteral intake for low-risk labouring women in hospitals across Canada: a cross-sectional study. J Obstet Gynaecol Can. 2016;38(11):1009-1014.
4. Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology. 1993;78(1):56-62.
5. Robinson M, Davidson A. Aspiration under anaesthesia: risk assessment and decision-making. Cont Educ Anaesth Crit Care Pain. 2014;14(4):171-175.
6. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 441. Oral intake during labor. Obstet Gynecol. 2009;114:714. Reaffirmed 2017.
7. Singata M, Tranmer J, Gyte GM. Restricting oral fluid and food intake during labour. Cochrane Database Syst Rev. 2013;(8):CD003930.
Make The Diagnosis - August 2018
respectively, of pityriasis lichenoides, an uncommon clonal T-cell disorder. The cause is unknown, although associations with infections have been reported. Pityriasis lichenoides more commonly affects children or young adults, usually before age 30 years. The disease can occur in all races.
In PLEVA, erythematous to brown papules and macules, in various stages of evolution, appear suddenly and in crops. The trunk and flexural areas are most often affected, but lesions may become widespread and may be pruritic or painful. Lesions may crust, ulcerate, or become necrotic and can heal with scarring. In general, patients don’t have constitutional symptoms. Lesions tend to resolve spontaneously over 1-3 years.
Rarely, PLEVA may develop into a more severe form called febrile ulceronecrotic Mucha-Habermann disease, a dermatologic emergency. Patients (more commonly, young males) may present with high fever, malaise, and lymphadenopathy. Lesions become very painful, ulcerated, and necrotic, and extensive necrosis may be present. Changes in mental status, breathing difficulties, anemia, arthritis, abdominal pain, and sepsis may occur. Patients require hospitalization. There is a 25% mortality rate.
PLC is at the other end of this disease spectrum, representing the chronic, more mild stage of the disorder. Lesions present as indolent, asymptomatic, scaly macules and erythematous papules, favoring the trunk and proximal extremities. Lesions tend to be fewer in number than seen in PLEVA. They resolve over several months and may result in hypopigmentation, but usually don’t cause scarring. Patients may have long periods of remission between outbreaks. T-cell gene rearrangement may demonstrate monoclonality. PLC is generally considered a benign disease, although there are patients who have developed cutaneous T-cell lymphoma. For this reason, patients should be followed carefully for signs of malignant transformation.
Both forms share a common histologic picture. In PLEVA, focal parakeratosis and crusting is present. A dense, wedge-shaped infiltrate can be seen with prominent lymphocytic exocystosis in the epidermis. Necrotic keratinocytes are often seen. There may be spongiosis and intraepidermal vesicles. Extravasation of erythrocytes often occurs in the epidermis. PLC is histologically similar but far more subtle. There is less crusting, less spongiosis, fewer vesicles, and fewer necrotic keratinocytes. Generally, atypia of lymphocytes is absent.
Mucha-Habermann requires treatment with systemic steroids. Methotrexate, cyclosporine, or dapsone may be used as steroid-sparing agents. Upon treatment, lesions may resolve or revert back to more typical lesions of PLEVA. Treatment for PLEVA and PLC includes oral tetracycline or erythromycin, antihistamines (if pruritus is present), topical steroids, topical tacrolimus or pimecrolimus, or phototherapy. Low-dose weekly methotrexate may be helpful.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
respectively, of pityriasis lichenoides, an uncommon clonal T-cell disorder. The cause is unknown, although associations with infections have been reported. Pityriasis lichenoides more commonly affects children or young adults, usually before age 30 years. The disease can occur in all races.
In PLEVA, erythematous to brown papules and macules, in various stages of evolution, appear suddenly and in crops. The trunk and flexural areas are most often affected, but lesions may become widespread and may be pruritic or painful. Lesions may crust, ulcerate, or become necrotic and can heal with scarring. In general, patients don’t have constitutional symptoms. Lesions tend to resolve spontaneously over 1-3 years.
Rarely, PLEVA may develop into a more severe form called febrile ulceronecrotic Mucha-Habermann disease, a dermatologic emergency. Patients (more commonly, young males) may present with high fever, malaise, and lymphadenopathy. Lesions become very painful, ulcerated, and necrotic, and extensive necrosis may be present. Changes in mental status, breathing difficulties, anemia, arthritis, abdominal pain, and sepsis may occur. Patients require hospitalization. There is a 25% mortality rate.
PLC is at the other end of this disease spectrum, representing the chronic, more mild stage of the disorder. Lesions present as indolent, asymptomatic, scaly macules and erythematous papules, favoring the trunk and proximal extremities. Lesions tend to be fewer in number than seen in PLEVA. They resolve over several months and may result in hypopigmentation, but usually don’t cause scarring. Patients may have long periods of remission between outbreaks. T-cell gene rearrangement may demonstrate monoclonality. PLC is generally considered a benign disease, although there are patients who have developed cutaneous T-cell lymphoma. For this reason, patients should be followed carefully for signs of malignant transformation.
Both forms share a common histologic picture. In PLEVA, focal parakeratosis and crusting is present. A dense, wedge-shaped infiltrate can be seen with prominent lymphocytic exocystosis in the epidermis. Necrotic keratinocytes are often seen. There may be spongiosis and intraepidermal vesicles. Extravasation of erythrocytes often occurs in the epidermis. PLC is histologically similar but far more subtle. There is less crusting, less spongiosis, fewer vesicles, and fewer necrotic keratinocytes. Generally, atypia of lymphocytes is absent.
Mucha-Habermann requires treatment with systemic steroids. Methotrexate, cyclosporine, or dapsone may be used as steroid-sparing agents. Upon treatment, lesions may resolve or revert back to more typical lesions of PLEVA. Treatment for PLEVA and PLC includes oral tetracycline or erythromycin, antihistamines (if pruritus is present), topical steroids, topical tacrolimus or pimecrolimus, or phototherapy. Low-dose weekly methotrexate may be helpful.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
respectively, of pityriasis lichenoides, an uncommon clonal T-cell disorder. The cause is unknown, although associations with infections have been reported. Pityriasis lichenoides more commonly affects children or young adults, usually before age 30 years. The disease can occur in all races.
In PLEVA, erythematous to brown papules and macules, in various stages of evolution, appear suddenly and in crops. The trunk and flexural areas are most often affected, but lesions may become widespread and may be pruritic or painful. Lesions may crust, ulcerate, or become necrotic and can heal with scarring. In general, patients don’t have constitutional symptoms. Lesions tend to resolve spontaneously over 1-3 years.
Rarely, PLEVA may develop into a more severe form called febrile ulceronecrotic Mucha-Habermann disease, a dermatologic emergency. Patients (more commonly, young males) may present with high fever, malaise, and lymphadenopathy. Lesions become very painful, ulcerated, and necrotic, and extensive necrosis may be present. Changes in mental status, breathing difficulties, anemia, arthritis, abdominal pain, and sepsis may occur. Patients require hospitalization. There is a 25% mortality rate.
PLC is at the other end of this disease spectrum, representing the chronic, more mild stage of the disorder. Lesions present as indolent, asymptomatic, scaly macules and erythematous papules, favoring the trunk and proximal extremities. Lesions tend to be fewer in number than seen in PLEVA. They resolve over several months and may result in hypopigmentation, but usually don’t cause scarring. Patients may have long periods of remission between outbreaks. T-cell gene rearrangement may demonstrate monoclonality. PLC is generally considered a benign disease, although there are patients who have developed cutaneous T-cell lymphoma. For this reason, patients should be followed carefully for signs of malignant transformation.
Both forms share a common histologic picture. In PLEVA, focal parakeratosis and crusting is present. A dense, wedge-shaped infiltrate can be seen with prominent lymphocytic exocystosis in the epidermis. Necrotic keratinocytes are often seen. There may be spongiosis and intraepidermal vesicles. Extravasation of erythrocytes often occurs in the epidermis. PLC is histologically similar but far more subtle. There is less crusting, less spongiosis, fewer vesicles, and fewer necrotic keratinocytes. Generally, atypia of lymphocytes is absent.
Mucha-Habermann requires treatment with systemic steroids. Methotrexate, cyclosporine, or dapsone may be used as steroid-sparing agents. Upon treatment, lesions may resolve or revert back to more typical lesions of PLEVA. Treatment for PLEVA and PLC includes oral tetracycline or erythromycin, antihistamines (if pruritus is present), topical steroids, topical tacrolimus or pimecrolimus, or phototherapy. Low-dose weekly methotrexate may be helpful.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
A 28-year-old white female with no significant past medical history presents with a 10-year history of asymptomatic erythematous papules and scaly patches that come and go. She has used topical steroids in the past.
Assessing adverse events tied to outpatient opioid use in children
Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.
Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.
In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.
Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).
Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.
The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.
“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.
The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.
The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.
“We know that opioids are associated with many untoward side effects and are potentially lethal. But we believe there is a reason why opioids have been used to treat pain since the Sumerians 5,000 years ago,” Elliot J. Krane, MD, Steven J. Weisman, MD, and Gary A. Walco, PhD, wrote in an accompanying editorial.
The editorialists noted that they are not blanket advocates of opioid prescriptions for children, but they do believe in the importance of pain management for conditions including postsurgical pain, burns, physical trauma, and medical illnesses. In many cases, opioids are the most effective treatment option.
In addition, data on opioid-related deaths in the United States have been shown inaccurate for various reasons including the coding of deaths as opioid related if opioids were present among a number of other drugs, even if the cause of death was another substance or an act such as suicide, the writers noted. Even the Centers for Disease Control and Prevention has admitted overestimating the prevalence of opioid-related deaths by as much as 100%. Consequently, the opioid epidemic portrayed in the media, “pales in comparison with other public health hazards and causes of deaths in America such as tobacco-related deaths, alcoholic hepatic disease, and even hospital-acquired infections,” Dr. Krane, Dr. Weisman, and Dr. Walco said.
“The data as presented cannot be considered causal for associating opioid prescribing with severe morbidity, more hospital emergency department visits, and even death,” the editorialists concluded. They emphasized the need for good judgment on the part of clinicians when prescribing opioids to children and advocated always making good use of nonopioid alternatives, but Dr. Krane, Dr. Weisman, and Dr. Walco added that the findings of this study should not deter doctors from prescribing an opioid when they think it is the most effective and appropriate option for moderately to severely painful conditions.
“Too often, consideration of the need to prevent and treat pain can be lost in the national discussion,” they said.
Dr. Krane is affiliated with Stanford University in Palo Alto, Calif., Dr. Weisman is affiliated with the Medical College of Milwaukee, Wisc., and Dr. Walco is affiliated with the University of Washington, Seattle. Dr. Krane disclosed consulting for Collegium Pharmaceuticals and honoraria for lecturing on pain and analgesia. Dr. Weisman disclosed consulting for Grünenthal Pharmaceuticals and Pfizer Pharmaceuticals and has conducted clinical trials for Grünenthal Pharmaceuticals, Cadence Pharmaceuticals, and The Medicines Company. Their editorial accompanying the article by Chung et al. appeared in Pediatrics (2018 Jul 16. doi: 10.1542/peds.2018-1623).
“We know that opioids are associated with many untoward side effects and are potentially lethal. But we believe there is a reason why opioids have been used to treat pain since the Sumerians 5,000 years ago,” Elliot J. Krane, MD, Steven J. Weisman, MD, and Gary A. Walco, PhD, wrote in an accompanying editorial.
The editorialists noted that they are not blanket advocates of opioid prescriptions for children, but they do believe in the importance of pain management for conditions including postsurgical pain, burns, physical trauma, and medical illnesses. In many cases, opioids are the most effective treatment option.
In addition, data on opioid-related deaths in the United States have been shown inaccurate for various reasons including the coding of deaths as opioid related if opioids were present among a number of other drugs, even if the cause of death was another substance or an act such as suicide, the writers noted. Even the Centers for Disease Control and Prevention has admitted overestimating the prevalence of opioid-related deaths by as much as 100%. Consequently, the opioid epidemic portrayed in the media, “pales in comparison with other public health hazards and causes of deaths in America such as tobacco-related deaths, alcoholic hepatic disease, and even hospital-acquired infections,” Dr. Krane, Dr. Weisman, and Dr. Walco said.
“The data as presented cannot be considered causal for associating opioid prescribing with severe morbidity, more hospital emergency department visits, and even death,” the editorialists concluded. They emphasized the need for good judgment on the part of clinicians when prescribing opioids to children and advocated always making good use of nonopioid alternatives, but Dr. Krane, Dr. Weisman, and Dr. Walco added that the findings of this study should not deter doctors from prescribing an opioid when they think it is the most effective and appropriate option for moderately to severely painful conditions.
“Too often, consideration of the need to prevent and treat pain can be lost in the national discussion,” they said.
Dr. Krane is affiliated with Stanford University in Palo Alto, Calif., Dr. Weisman is affiliated with the Medical College of Milwaukee, Wisc., and Dr. Walco is affiliated with the University of Washington, Seattle. Dr. Krane disclosed consulting for Collegium Pharmaceuticals and honoraria for lecturing on pain and analgesia. Dr. Weisman disclosed consulting for Grünenthal Pharmaceuticals and Pfizer Pharmaceuticals and has conducted clinical trials for Grünenthal Pharmaceuticals, Cadence Pharmaceuticals, and The Medicines Company. Their editorial accompanying the article by Chung et al. appeared in Pediatrics (2018 Jul 16. doi: 10.1542/peds.2018-1623).
“We know that opioids are associated with many untoward side effects and are potentially lethal. But we believe there is a reason why opioids have been used to treat pain since the Sumerians 5,000 years ago,” Elliot J. Krane, MD, Steven J. Weisman, MD, and Gary A. Walco, PhD, wrote in an accompanying editorial.
The editorialists noted that they are not blanket advocates of opioid prescriptions for children, but they do believe in the importance of pain management for conditions including postsurgical pain, burns, physical trauma, and medical illnesses. In many cases, opioids are the most effective treatment option.
In addition, data on opioid-related deaths in the United States have been shown inaccurate for various reasons including the coding of deaths as opioid related if opioids were present among a number of other drugs, even if the cause of death was another substance or an act such as suicide, the writers noted. Even the Centers for Disease Control and Prevention has admitted overestimating the prevalence of opioid-related deaths by as much as 100%. Consequently, the opioid epidemic portrayed in the media, “pales in comparison with other public health hazards and causes of deaths in America such as tobacco-related deaths, alcoholic hepatic disease, and even hospital-acquired infections,” Dr. Krane, Dr. Weisman, and Dr. Walco said.
“The data as presented cannot be considered causal for associating opioid prescribing with severe morbidity, more hospital emergency department visits, and even death,” the editorialists concluded. They emphasized the need for good judgment on the part of clinicians when prescribing opioids to children and advocated always making good use of nonopioid alternatives, but Dr. Krane, Dr. Weisman, and Dr. Walco added that the findings of this study should not deter doctors from prescribing an opioid when they think it is the most effective and appropriate option for moderately to severely painful conditions.
“Too often, consideration of the need to prevent and treat pain can be lost in the national discussion,” they said.
Dr. Krane is affiliated with Stanford University in Palo Alto, Calif., Dr. Weisman is affiliated with the Medical College of Milwaukee, Wisc., and Dr. Walco is affiliated with the University of Washington, Seattle. Dr. Krane disclosed consulting for Collegium Pharmaceuticals and honoraria for lecturing on pain and analgesia. Dr. Weisman disclosed consulting for Grünenthal Pharmaceuticals and Pfizer Pharmaceuticals and has conducted clinical trials for Grünenthal Pharmaceuticals, Cadence Pharmaceuticals, and The Medicines Company. Their editorial accompanying the article by Chung et al. appeared in Pediatrics (2018 Jul 16. doi: 10.1542/peds.2018-1623).
Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.
Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.
In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.
Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).
Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.
The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.
“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.
The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.
The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.
Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.
Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.
In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.
Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).
Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.
The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.
“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.
The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.
The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.
FROM PEDIATRICS
Key clinical point: One in every 2,611 opioid prescriptions in children and teens was followed by an ED visit, hospitalization, or death related to an adverse event associated with opioid use.
Major finding: A total of 437 cases of opioid-related adverse events were confirmed; most were associated with therapeutic medication use.
Study details: The data come from a retrospective cohort study of 401,972 children aged 2-17 years enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014.
Disclosures: The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development, and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.
Source: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156