VICTORIA, B.C. – Ultrasound risk criteria for adults are no match for the training, skill, and gut instinct of an experienced radiologist when evaluating pediatric thyroid nodules, results of a retrospective cohort study reported at the annual meeting of the American Thyroid Association suggest.

“In 2015, the ATA commissioned a pediatric task force that developed valuable guidelines specific to our pediatric patients. These guidelines recommend performing an FNA [fine-needle aspiration biopsy] in any nodule with a concerning clinical history or a concerning ultrasound feature,” commented first author Ana L. Creo, MD, a pediatric endocrinology fellow at the Mayo Clinic in Rochester, Minn.

Study details

The investigators studied pediatric patients (mean age, 15.5 years) with thyroid nodules who underwent initial ultrasound at the Mayo Clinic during 1996-2015, had at least a year of follow-up, and for whom histology or cytology results were available. Those with a known genetic tumor syndrome or a history of radiation exposure were excluded.

Two blinded radiologists assessed nodule ultrasound features using the Thyroid Imaging and Reporting Data System (TIRADS) (J Am Coll Radiol. 2015;12[12 Pt A]:1272-9) and then rendered their overall impression: malignant, indeterminate, or benign.

Next, an independent reviewer assigned each nodule an ATA adult risk category (Thyroid. 2016;26:1-133): high, intermediate, low, or very low suspicion.

Finally, both measures were compared against the reference standard of the nodule’s histology or cytology results.

Ultimately, 34% of the patients had malignant nodules, Dr. Creo reported. “This is likely quite a bit elevated from the true prevalence due to our intentional study design requiring follow-up, likely excluding some patients with benign nodules,” she commented.

Patients with benign and malignant nodules did not differ significantly on any of a variety of sociodemographic and clinical factors, such as family history and mode of detection.

For comparison of sensitivity, the investigators combined the ATA risk categories of high and intermediate suspicion and combined the overall radiologists’ impression of malignant and indeterminate. “We felt this best answered the practical clinical question of how many malignant nodules would be missed if FNA was not performed, assuming FNA would typically be performed if the ATA risk stratification was high or intermediate or if the radiologist’s overall impression was malignant or indeterminate,” Dr. Creo explained.

Results here showed that the ATA risk stratification and the radiologists’ overall impression had the same high sensitivity of 90%.

For comparison of specificity, the investigators compared the ATA risk category of high suspicion with the radiologists’ overall impression of malignant.

Results showed that the overall impression had specificity of 80%, whereas the risk category had a specificity of only about 52%. Findings were similar when analyses instead used ATA high suspicion and intermediate suspicion combined.

“The key ultrasound characteristics that drove the diagnosis included having a solid component, calcifications, irregular margins, and hypoechogenicity – all similar to those seen in pediatric studies and similar to those in adult studies as well,” Dr. Creo noted.

Compared with benign nodules, malignant nodules significantly more often had a greater than 75% solid component (84% vs. 64%; P = .01), contained calcifications (60% vs. 18%; P less than .0001), had irregular margins (70% vs. 46%; P = .0073), and were hypoechogenic (74% vs. 51%; P = .0073). Notably, size and presence of halo did not differ significantly.

“Our study adds to previous work in that it had a relatively large pediatric sample size, used strict inclusion criteria with at least a year of follow-up to increase the validity of the diagnosis, and had precise definitions of the ultrasound features,” concluded Dr. Creo, who disclosed that she had no relevant conflicts of interest.

At the same time, the study had limitations, such as its use of a referral population, likely loss to follow-up of some patients with benign nodules, and possible clustering effect. “Lastly, we had the benefit of extremely experienced pediatric radiologists, and their overall diagnostic accuracy may not universally apply across all radiologists,” she said.

VICTORIA, B.C. – Ultrasound risk criteria for adults are no match for the training, skill, and gut instinct of an experienced radiologist when evaluating pediatric thyroid nodules, results of a retrospective cohort study reported at the annual meeting of the American Thyroid Association suggest.

“In 2015, the ATA commissioned a pediatric task force that developed valuable guidelines specific to our pediatric patients. These guidelines recommend performing an FNA [fine-needle aspiration biopsy] in any nodule with a concerning clinical history or a concerning ultrasound feature,” commented first author Ana L. Creo, MD, a pediatric endocrinology fellow at the Mayo Clinic in Rochester, Minn.

Study details

The investigators studied pediatric patients (mean age, 15.5 years) with thyroid nodules who underwent initial ultrasound at the Mayo Clinic during 1996-2015, had at least a year of follow-up, and for whom histology or cytology results were available. Those with a known genetic tumor syndrome or a history of radiation exposure were excluded.

Two blinded radiologists assessed nodule ultrasound features using the Thyroid Imaging and Reporting Data System (TIRADS) (J Am Coll Radiol. 2015;12[12 Pt A]:1272-9) and then rendered their overall impression: malignant, indeterminate, or benign.

Next, an independent reviewer assigned each nodule an ATA adult risk category (Thyroid. 2016;26:1-133): high, intermediate, low, or very low suspicion.

Finally, both measures were compared against the reference standard of the nodule’s histology or cytology results.

Ultimately, 34% of the patients had malignant nodules, Dr. Creo reported. “This is likely quite a bit elevated from the true prevalence due to our intentional study design requiring follow-up, likely excluding some patients with benign nodules,” she commented.

Patients with benign and malignant nodules did not differ significantly on any of a variety of sociodemographic and clinical factors, such as family history and mode of detection.

For comparison of sensitivity, the investigators combined the ATA risk categories of high and intermediate suspicion and combined the overall radiologists’ impression of malignant and indeterminate. “We felt this best answered the practical clinical question of how many malignant nodules would be missed if FNA was not performed, assuming FNA would typically be performed if the ATA risk stratification was high or intermediate or if the radiologist’s overall impression was malignant or indeterminate,” Dr. Creo explained.

Results here showed that the ATA risk stratification and the radiologists’ overall impression had the same high sensitivity of 90%.

For comparison of specificity, the investigators compared the ATA risk category of high suspicion with the radiologists’ overall impression of malignant.

Results showed that the overall impression had specificity of 80%, whereas the risk category had a specificity of only about 52%. Findings were similar when analyses instead used ATA high suspicion and intermediate suspicion combined.

“The key ultrasound characteristics that drove the diagnosis included having a solid component, calcifications, irregular margins, and hypoechogenicity – all similar to those seen in pediatric studies and similar to those in adult studies as well,” Dr. Creo noted.

Compared with benign nodules, malignant nodules significantly more often had a greater than 75% solid component (84% vs. 64%; P = .01), contained calcifications (60% vs. 18%; P less than .0001), had irregular margins (70% vs. 46%; P = .0073), and were hypoechogenic (74% vs. 51%; P = .0073). Notably, size and presence of halo did not differ significantly.

“Our study adds to previous work in that it had a relatively large pediatric sample size, used strict inclusion criteria with at least a year of follow-up to increase the validity of the diagnosis, and had precise definitions of the ultrasound features,” concluded Dr. Creo, who disclosed that she had no relevant conflicts of interest.

At the same time, the study had limitations, such as its use of a referral population, likely loss to follow-up of some patients with benign nodules, and possible clustering effect. “Lastly, we had the benefit of extremely experienced pediatric radiologists, and their overall diagnostic accuracy may not universally apply across all radiologists,” she said.

VICTORIA, B.C. – Ultrasound risk criteria for adults are no match for the training, skill, and gut instinct of an experienced radiologist when evaluating pediatric thyroid nodules, results of a retrospective cohort study reported at the annual meeting of the American Thyroid Association suggest.

“In 2015, the ATA commissioned a pediatric task force that developed valuable guidelines specific to our pediatric patients. These guidelines recommend performing an FNA [fine-needle aspiration biopsy] in any nodule with a concerning clinical history or a concerning ultrasound feature,” commented first author Ana L. Creo, MD, a pediatric endocrinology fellow at the Mayo Clinic in Rochester, Minn.

Study details

The investigators studied pediatric patients (mean age, 15.5 years) with thyroid nodules who underwent initial ultrasound at the Mayo Clinic during 1996-2015, had at least a year of follow-up, and for whom histology or cytology results were available. Those with a known genetic tumor syndrome or a history of radiation exposure were excluded.

Two blinded radiologists assessed nodule ultrasound features using the Thyroid Imaging and Reporting Data System (TIRADS) (J Am Coll Radiol. 2015;12[12 Pt A]:1272-9) and then rendered their overall impression: malignant, indeterminate, or benign.

Next, an independent reviewer assigned each nodule an ATA adult risk category (Thyroid. 2016;26:1-133): high, intermediate, low, or very low suspicion.

Finally, both measures were compared against the reference standard of the nodule’s histology or cytology results.

Ultimately, 34% of the patients had malignant nodules, Dr. Creo reported. “This is likely quite a bit elevated from the true prevalence due to our intentional study design requiring follow-up, likely excluding some patients with benign nodules,” she commented.

Patients with benign and malignant nodules did not differ significantly on any of a variety of sociodemographic and clinical factors, such as family history and mode of detection.

For comparison of sensitivity, the investigators combined the ATA risk categories of high and intermediate suspicion and combined the overall radiologists’ impression of malignant and indeterminate. “We felt this best answered the practical clinical question of how many malignant nodules would be missed if FNA was not performed, assuming FNA would typically be performed if the ATA risk stratification was high or intermediate or if the radiologist’s overall impression was malignant or indeterminate,” Dr. Creo explained.

Results here showed that the ATA risk stratification and the radiologists’ overall impression had the same high sensitivity of 90%.

For comparison of specificity, the investigators compared the ATA risk category of high suspicion with the radiologists’ overall impression of malignant.

Results showed that the overall impression had specificity of 80%, whereas the risk category had a specificity of only about 52%. Findings were similar when analyses instead used ATA high suspicion and intermediate suspicion combined.

“The key ultrasound characteristics that drove the diagnosis included having a solid component, calcifications, irregular margins, and hypoechogenicity – all similar to those seen in pediatric studies and similar to those in adult studies as well,” Dr. Creo noted.

Compared with benign nodules, malignant nodules significantly more often had a greater than 75% solid component (84% vs. 64%; P = .01), contained calcifications (60% vs. 18%; P less than .0001), had irregular margins (70% vs. 46%; P = .0073), and were hypoechogenic (74% vs. 51%; P = .0073). Notably, size and presence of halo did not differ significantly.

“Our study adds to previous work in that it had a relatively large pediatric sample size, used strict inclusion criteria with at least a year of follow-up to increase the validity of the diagnosis, and had precise definitions of the ultrasound features,” concluded Dr. Creo, who disclosed that she had no relevant conflicts of interest.

At the same time, the study had limitations, such as its use of a referral population, likely loss to follow-up of some patients with benign nodules, and possible clustering effect. “Lastly, we had the benefit of extremely experienced pediatric radiologists, and their overall diagnostic accuracy may not universally apply across all radiologists,” she said.

SAN DIEGO – Among patients with systemic lupus erythematosus, a low level of vitamin D is associated with an increased risk of end-stage renal disease and total organ damage, results from a single-center cohort study showed.

“We had previously proved that vitamin D supplementation helped lupus activity,” lead study author Michelle Petri, MD, MPH, said in an interview in advance of the annual meeting of the American College of Rheumatology. “Now, we prove that it specifically helps renal activity as measured by the urine protein. By helping to reduce urine protein, it helps to prevent permanent renal damage and end-stage renal disease.”

[email protected]

SAN DIEGO – Among patients with systemic lupus erythematosus, a low level of vitamin D is associated with an increased risk of end-stage renal disease and total organ damage, results from a single-center cohort study showed.

“We had previously proved that vitamin D supplementation helped lupus activity,” lead study author Michelle Petri, MD, MPH, said in an interview in advance of the annual meeting of the American College of Rheumatology. “Now, we prove that it specifically helps renal activity as measured by the urine protein. By helping to reduce urine protein, it helps to prevent permanent renal damage and end-stage renal disease.”

[email protected]

SAN DIEGO – Among patients with systemic lupus erythematosus, a low level of vitamin D is associated with an increased risk of end-stage renal disease and total organ damage, results from a single-center cohort study showed.

“We had previously proved that vitamin D supplementation helped lupus activity,” lead study author Michelle Petri, MD, MPH, said in an interview in advance of the annual meeting of the American College of Rheumatology. “Now, we prove that it specifically helps renal activity as measured by the urine protein. By helping to reduce urine protein, it helps to prevent permanent renal damage and end-stage renal disease.”

[email protected]

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has approved vemurafenib for adults with Erdheim-Chester disease (ECD) with the BRAF V600 mutation.

The kinase inhibitor – marketed as Zelboraf – was approved on Nov. 6. It is the first approved treatment for ECD and is already on the market as a treatment for patients with unresectable or metastatic melanoma with BRAF V600E mutation.

The FDA expedited approval of the drug under the Priority Review and Breakthrough Therapy programs. The drug also received an orphan status designation, which makes the sponsor eligible for incentives such as tax credits for clinical testing.

The agency based its approval on results from 22 patients with BRAF-V600-mutation positive ECD. Half of the patients (11) experienced a partial reduction in tumor size and 1 patient experienced a complete response, according to the FDA. Initial results from the phase 2, open-label VE-BASKET study were published in 2015 (N Engl J Med. 2015 Aug 20;373[8]:726-36).

Common side effects of vemurafenib include arthralgias, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma. Severe side effects include development of new cancers, growth of tumors in patients with BRAF wild-type melanoma, anaphylaxis and DRESS syndrome, severe skin reactions, heart abnormalities, hepatotoxicity, photosensitivity, uveitis, radiation sensitization and radiation recall, and Dupuytren’s contracture and plantar fascial fibromatosis. The drug is also considered teratogenic and women should be advised to use contraception while taking it, according to the FDA.

The full prescribing information is available at zelboraf.com.

[email protected]

On Twitter @maryellenny

CHICAGO – Not only do you need to know the normal features of adolescent menstruation to identify what’s abnormal, but you also need to teach your patients what’s typical, according to S. Paige Hertweck, MD, chief of gynecology at Norton Children’s Hospital in Louisville, Ky.

“Remember to use the menstrual cycle as a vital sign,” Dr. Hertweck told attendees at the American Academy of Pediatrics annual meeting. “Even within the first year of menarche, most girls have a period at least every 90 days, so work up those who don’t.”

The median age of menarche is 12.4 years, typically beginning within 2-3 years of breast budding at Tanner Stage 4 breast development, she said. By 15 years of age, 98% of girls have begun menstruation.

Girls’ cycles typically last 21-45 days, an average of 32.2 days during their first year of menstruation, with flow for 7 days or less, requiring an average of 3-6 pads and/or tampons per day. Dr. Hertweck recommends you write down these features of normal menstruation so that your patients can tell you when their cycle is abnormal or menses doesn’t return.

“Cycle length is more variable for teens versus women 20-40 years old,” she said. However, “it’s not true that ‘anything goes’ for cycle length” in teens, she added. “Cycles that are consistently outside the range of 21-45 days are statistically uncommon.” Hence the need to evaluate causes of amenorrhea in girls whose cycles exceed 90 days.

Possible causes of amenorrhea include pregnancy, polycystic ovary syndrome, thyroid abnormalities, hyperprolactinemia, primary ovarian insufficiency, or hypogonadal amenorrhea, typically stimulated by the first instance of anorexia, Crohn’s disease, celiac disease, or a gluten intolerance.
 

Primary amenorrhea

Dr. Hertweck listed five benchmarks that indicate primary amenorrhea requiring evaluation. Those indicators include girls who have no menarche by age 15 years or within 3 years of breast budding, no breast development by age 13 years, or no menses by age 14 years with hirsutism or with a history of excessive exercise or of an eating disorder.

You can start by examining what normal menstruation relies on: an intact central nervous system with a functioning pituitary, an ovarian response, and a normal uterus, cervix, and vagina. You should check the patient’s follicle-stimulating hormone, thyroid-stimulating hormone, and prolactin levels to assess CNS functioning, and estradiol levels to assess ovarian response. A genital exam with a pelvic ultrasound can reveal any possible defects in the uterus, cervix, or vagina.

The presence of breasts without a uterus indicates normal estrogen production, so the missing uterus could be a congenital defect or result from androgen insensitivity, Dr. Hertweck explained. In those without breasts, gonadal dysgenesis or gonadal enzymatic deficiency may explain no estrogen production. If the patient has both breasts and a uterus, you should rule out pregnancy first and then track CNS changes via FSH, TSH, and prolactin levels.
 

Premature ovarian insufficiency

Approximately 1% of females experience premature ovarian insufficiency, which can be diagnosed as early as age 14 years and should be suspected in a patient with a uterus but without breasts who has low estradiol levels, CNS failure identified by a high FSH level, and gonadal failure.

Formal diagnosis requires two separate instances of FSH elevation, and chromosomal testing should be done to rule out gonadal dysgenesis. You also should test the serum anti-Müllerian hormone biomarker (readings above 8 are concerning) and look for two possible causes. The FMR1 (Fragile X) premutation carrier status could be a cause, or presence of 21-hydroxylase and/or adrenal antibodies indicate autoimmune polyglandular syndrome.

Catching premature ovarian insufficiency early enough may allow patients to preserve some fertility if they still have oocytes present. Aside from this, girls will need hormone replacement therapy to fulfill developmental emotional and physical needs, such as bone growth and overall health. Despite a history of treating teens with premature ovarian insufficiency like adults, you should follow the practice guidelines specific to adolescents by the American College of Obstetricians and Gynecologists committee opinion statement (Obstet Gynecol. 2014;123:193-7).
 

Menorrhagia: heavy menstrual bleeding

Even though average blood loss is estimated at 30 mL per period, that number means little in clinical practice because patients cannot measure the actual amount of menses. Better indicators of abnormally greater flow include flow lasting longer than 7 days, finding clots larger than a quarter, changing menstrual products every 1-2 hours, leaking onto clothing such that patients need to take extra clothes to school, and any heavy periods that occur with easy bruising or with a family history of bleeding disorders.

First-line treatment for heavy menstrual bleeding in teens is hormonal contraception, either combination oral contraceptive pills, the transdermal patch, or the intravaginal ring, which can be combined with other therapies.

An alternative for those under age 18 (per Food and Drug Administration labeling) is oral tranexamic acid, found in a crossover trial with an oral contraceptive pill to be just as effective at reducing average blood loss and improving quality of life, but with fewer side effects and better compliance. Before prescribing anything for heavy menstrual bleeding, however, you must consider possible causes and rule some out that require different management.

Aside from pregnancy, one potential cause of menorrhagia is infection such as chlamydia or gonorrhea, which should be considered even in those with a negative sexual history, Dr. Hertweck said. Other possible causes include an immature hypothalamic-pituitary-ovarian axis, polycystic ovary syndrome (even with low hemoglobin), malignancy with a hormone-producing tumor, hypothalamic dysfunction (often stimulated by eating disorders, obesity, rapid weight loss, or gluten intolerance), or coagulopathy.

“Teens with menorrhagia may need to be screened for a bleeding disorder,” Dr. Hertweck said. At a minimum, she recommends checking complete blood count, ferritin, and TSH. “The most common bleeding disorders associated with heavy menstrual bleeding include platelet function disorders and von Willebrand.”

Up to half of teen girls with menorrhagia who visit a hematologist or multidisciplinary clinic receive a diagnosis of a bleeding disorder, Dr. Hertweck said. And up to half of those with menorrhagia at menarche may have von Willebrand, as do one in six adolescents who go to the emergency department because of heavy menstrual bleeding.
 

Von Willebrand syndrome

Von Willebrand syndrome is a deficiency or dysfunction of von Willebrand factor (vWF), a protein with binding sites for platelets, collagen, and factor VIII that “serves as a bridge between platelets and injury sites in vessel walls” and “protects factor VIII from rapid proteolytic degradation,” Dr. Hertweck said. Von Willebrand syndrome is the most common inherited congenital bleeding disorder. Although acquired von Willebrand syndrome is rare, it has grown in incidence among those with complex cardiovascular, hematologic, or immunologic disorders.

“Correct diagnosis is complex and not always straightforward,” Dr. Hertweck said, but “a positive response to questions in four categories is highly sensitive.” They are as follows:

• Menses lasting at least 7 days and interfering with a person’s daily activities.

• “History of treatment for anemia.

• Family history of a diagnosed bleeding disorder.

• History of excessive bleeding after tooth extraction, delivery, miscarriage, or surgery.

Diagnostic assays include platelet concentration of vWF antigen, an activity test of vWF-platelet binding, and factor VIII activity. However, you often need to repeat diagnostic testing because vWF antigens vary according to race, blood type, age, acute phase response, and menstrual cycle timing, Dr. Hertweck said.

“Remember to draw von Willebrand testing only during the first 3 days of the menstrual cycle when estrogen levels are at the nadir,” she said.

Because estrogen increases vWF, treatment for von Willebrand syndrome should be progestin only, either oral pills, medroxyprogesterone acetate (MPA, or Depo-Provera injections), or an etonogestrel implant.

Dr. Hertweck presented several cases of abnormal menstruation and extreme conditions such as severe menorrhagia. Outside of von Willebrand in such patients, possible platelet disorders could include Glanzmann thrombasthenia (a platelet function disorder that is caused by an abnormality in the genes for glycoproteins IIb/IIIa) and platelet storage pool disorder, both of which should be diagnosed by a hematologist.

Dr. Hertweck reported having a research grant from Merck related to contraceptive implants in adolescents.

CHICAGO – Not only do you need to know the normal features of adolescent menstruation to identify what’s abnormal, but you also need to teach your patients what’s typical, according to S. Paige Hertweck, MD, chief of gynecology at Norton Children’s Hospital in Louisville, Ky.

“Remember to use the menstrual cycle as a vital sign,” Dr. Hertweck told attendees at the American Academy of Pediatrics annual meeting. “Even within the first year of menarche, most girls have a period at least every 90 days, so work up those who don’t.”

The median age of menarche is 12.4 years, typically beginning within 2-3 years of breast budding at Tanner Stage 4 breast development, she said. By 15 years of age, 98% of girls have begun menstruation.

Girls’ cycles typically last 21-45 days, an average of 32.2 days during their first year of menstruation, with flow for 7 days or less, requiring an average of 3-6 pads and/or tampons per day. Dr. Hertweck recommends you write down these features of normal menstruation so that your patients can tell you when their cycle is abnormal or menses doesn’t return.

“Cycle length is more variable for teens versus women 20-40 years old,” she said. However, “it’s not true that ‘anything goes’ for cycle length” in teens, she added. “Cycles that are consistently outside the range of 21-45 days are statistically uncommon.” Hence the need to evaluate causes of amenorrhea in girls whose cycles exceed 90 days.

Possible causes of amenorrhea include pregnancy, polycystic ovary syndrome, thyroid abnormalities, hyperprolactinemia, primary ovarian insufficiency, or hypogonadal amenorrhea, typically stimulated by the first instance of anorexia, Crohn’s disease, celiac disease, or a gluten intolerance.
 

Primary amenorrhea

Dr. Hertweck listed five benchmarks that indicate primary amenorrhea requiring evaluation. Those indicators include girls who have no menarche by age 15 years or within 3 years of breast budding, no breast development by age 13 years, or no menses by age 14 years with hirsutism or with a history of excessive exercise or of an eating disorder.

You can start by examining what normal menstruation relies on: an intact central nervous system with a functioning pituitary, an ovarian response, and a normal uterus, cervix, and vagina. You should check the patient’s follicle-stimulating hormone, thyroid-stimulating hormone, and prolactin levels to assess CNS functioning, and estradiol levels to assess ovarian response. A genital exam with a pelvic ultrasound can reveal any possible defects in the uterus, cervix, or vagina.

The presence of breasts without a uterus indicates normal estrogen production, so the missing uterus could be a congenital defect or result from androgen insensitivity, Dr. Hertweck explained. In those without breasts, gonadal dysgenesis or gonadal enzymatic deficiency may explain no estrogen production. If the patient has both breasts and a uterus, you should rule out pregnancy first and then track CNS changes via FSH, TSH, and prolactin levels.
 

Premature ovarian insufficiency

Approximately 1% of females experience premature ovarian insufficiency, which can be diagnosed as early as age 14 years and should be suspected in a patient with a uterus but without breasts who has low estradiol levels, CNS failure identified by a high FSH level, and gonadal failure.

Formal diagnosis requires two separate instances of FSH elevation, and chromosomal testing should be done to rule out gonadal dysgenesis. You also should test the serum anti-Müllerian hormone biomarker (readings above 8 are concerning) and look for two possible causes. The FMR1 (Fragile X) premutation carrier status could be a cause, or presence of 21-hydroxylase and/or adrenal antibodies indicate autoimmune polyglandular syndrome.

Catching premature ovarian insufficiency early enough may allow patients to preserve some fertility if they still have oocytes present. Aside from this, girls will need hormone replacement therapy to fulfill developmental emotional and physical needs, such as bone growth and overall health. Despite a history of treating teens with premature ovarian insufficiency like adults, you should follow the practice guidelines specific to adolescents by the American College of Obstetricians and Gynecologists committee opinion statement (Obstet Gynecol. 2014;123:193-7).
 

Menorrhagia: heavy menstrual bleeding

Even though average blood loss is estimated at 30 mL per period, that number means little in clinical practice because patients cannot measure the actual amount of menses. Better indicators of abnormally greater flow include flow lasting longer than 7 days, finding clots larger than a quarter, changing menstrual products every 1-2 hours, leaking onto clothing such that patients need to take extra clothes to school, and any heavy periods that occur with easy bruising or with a family history of bleeding disorders.

First-line treatment for heavy menstrual bleeding in teens is hormonal contraception, either combination oral contraceptive pills, the transdermal patch, or the intravaginal ring, which can be combined with other therapies.

An alternative for those under age 18 (per Food and Drug Administration labeling) is oral tranexamic acid, found in a crossover trial with an oral contraceptive pill to be just as effective at reducing average blood loss and improving quality of life, but with fewer side effects and better compliance. Before prescribing anything for heavy menstrual bleeding, however, you must consider possible causes and rule some out that require different management.

Aside from pregnancy, one potential cause of menorrhagia is infection such as chlamydia or gonorrhea, which should be considered even in those with a negative sexual history, Dr. Hertweck said. Other possible causes include an immature hypothalamic-pituitary-ovarian axis, polycystic ovary syndrome (even with low hemoglobin), malignancy with a hormone-producing tumor, hypothalamic dysfunction (often stimulated by eating disorders, obesity, rapid weight loss, or gluten intolerance), or coagulopathy.

“Teens with menorrhagia may need to be screened for a bleeding disorder,” Dr. Hertweck said. At a minimum, she recommends checking complete blood count, ferritin, and TSH. “The most common bleeding disorders associated with heavy menstrual bleeding include platelet function disorders and von Willebrand.”

Up to half of teen girls with menorrhagia who visit a hematologist or multidisciplinary clinic receive a diagnosis of a bleeding disorder, Dr. Hertweck said. And up to half of those with menorrhagia at menarche may have von Willebrand, as do one in six adolescents who go to the emergency department because of heavy menstrual bleeding.
 

Von Willebrand syndrome

Von Willebrand syndrome is a deficiency or dysfunction of von Willebrand factor (vWF), a protein with binding sites for platelets, collagen, and factor VIII that “serves as a bridge between platelets and injury sites in vessel walls” and “protects factor VIII from rapid proteolytic degradation,” Dr. Hertweck said. Von Willebrand syndrome is the most common inherited congenital bleeding disorder. Although acquired von Willebrand syndrome is rare, it has grown in incidence among those with complex cardiovascular, hematologic, or immunologic disorders.

“Correct diagnosis is complex and not always straightforward,” Dr. Hertweck said, but “a positive response to questions in four categories is highly sensitive.” They are as follows:

• Menses lasting at least 7 days and interfering with a person’s daily activities.

• “History of treatment for anemia.

• Family history of a diagnosed bleeding disorder.

• History of excessive bleeding after tooth extraction, delivery, miscarriage, or surgery.

Diagnostic assays include platelet concentration of vWF antigen, an activity test of vWF-platelet binding, and factor VIII activity. However, you often need to repeat diagnostic testing because vWF antigens vary according to race, blood type, age, acute phase response, and menstrual cycle timing, Dr. Hertweck said.

“Remember to draw von Willebrand testing only during the first 3 days of the menstrual cycle when estrogen levels are at the nadir,” she said.

Because estrogen increases vWF, treatment for von Willebrand syndrome should be progestin only, either oral pills, medroxyprogesterone acetate (MPA, or Depo-Provera injections), or an etonogestrel implant.

Dr. Hertweck presented several cases of abnormal menstruation and extreme conditions such as severe menorrhagia. Outside of von Willebrand in such patients, possible platelet disorders could include Glanzmann thrombasthenia (a platelet function disorder that is caused by an abnormality in the genes for glycoproteins IIb/IIIa) and platelet storage pool disorder, both of which should be diagnosed by a hematologist.

Dr. Hertweck reported having a research grant from Merck related to contraceptive implants in adolescents.

CHICAGO – Not only do you need to know the normal features of adolescent menstruation to identify what’s abnormal, but you also need to teach your patients what’s typical, according to S. Paige Hertweck, MD, chief of gynecology at Norton Children’s Hospital in Louisville, Ky.

“Remember to use the menstrual cycle as a vital sign,” Dr. Hertweck told attendees at the American Academy of Pediatrics annual meeting. “Even within the first year of menarche, most girls have a period at least every 90 days, so work up those who don’t.”

The median age of menarche is 12.4 years, typically beginning within 2-3 years of breast budding at Tanner Stage 4 breast development, she said. By 15 years of age, 98% of girls have begun menstruation.

Girls’ cycles typically last 21-45 days, an average of 32.2 days during their first year of menstruation, with flow for 7 days or less, requiring an average of 3-6 pads and/or tampons per day. Dr. Hertweck recommends you write down these features of normal menstruation so that your patients can tell you when their cycle is abnormal or menses doesn’t return.

“Cycle length is more variable for teens versus women 20-40 years old,” she said. However, “it’s not true that ‘anything goes’ for cycle length” in teens, she added. “Cycles that are consistently outside the range of 21-45 days are statistically uncommon.” Hence the need to evaluate causes of amenorrhea in girls whose cycles exceed 90 days.

Possible causes of amenorrhea include pregnancy, polycystic ovary syndrome, thyroid abnormalities, hyperprolactinemia, primary ovarian insufficiency, or hypogonadal amenorrhea, typically stimulated by the first instance of anorexia, Crohn’s disease, celiac disease, or a gluten intolerance.
 

Primary amenorrhea

Dr. Hertweck listed five benchmarks that indicate primary amenorrhea requiring evaluation. Those indicators include girls who have no menarche by age 15 years or within 3 years of breast budding, no breast development by age 13 years, or no menses by age 14 years with hirsutism or with a history of excessive exercise or of an eating disorder.

You can start by examining what normal menstruation relies on: an intact central nervous system with a functioning pituitary, an ovarian response, and a normal uterus, cervix, and vagina. You should check the patient’s follicle-stimulating hormone, thyroid-stimulating hormone, and prolactin levels to assess CNS functioning, and estradiol levels to assess ovarian response. A genital exam with a pelvic ultrasound can reveal any possible defects in the uterus, cervix, or vagina.

The presence of breasts without a uterus indicates normal estrogen production, so the missing uterus could be a congenital defect or result from androgen insensitivity, Dr. Hertweck explained. In those without breasts, gonadal dysgenesis or gonadal enzymatic deficiency may explain no estrogen production. If the patient has both breasts and a uterus, you should rule out pregnancy first and then track CNS changes via FSH, TSH, and prolactin levels.
 

Premature ovarian insufficiency

Approximately 1% of females experience premature ovarian insufficiency, which can be diagnosed as early as age 14 years and should be suspected in a patient with a uterus but without breasts who has low estradiol levels, CNS failure identified by a high FSH level, and gonadal failure.

Formal diagnosis requires two separate instances of FSH elevation, and chromosomal testing should be done to rule out gonadal dysgenesis. You also should test the serum anti-Müllerian hormone biomarker (readings above 8 are concerning) and look for two possible causes. The FMR1 (Fragile X) premutation carrier status could be a cause, or presence of 21-hydroxylase and/or adrenal antibodies indicate autoimmune polyglandular syndrome.

Catching premature ovarian insufficiency early enough may allow patients to preserve some fertility if they still have oocytes present. Aside from this, girls will need hormone replacement therapy to fulfill developmental emotional and physical needs, such as bone growth and overall health. Despite a history of treating teens with premature ovarian insufficiency like adults, you should follow the practice guidelines specific to adolescents by the American College of Obstetricians and Gynecologists committee opinion statement (Obstet Gynecol. 2014;123:193-7).
 

Menorrhagia: heavy menstrual bleeding

Even though average blood loss is estimated at 30 mL per period, that number means little in clinical practice because patients cannot measure the actual amount of menses. Better indicators of abnormally greater flow include flow lasting longer than 7 days, finding clots larger than a quarter, changing menstrual products every 1-2 hours, leaking onto clothing such that patients need to take extra clothes to school, and any heavy periods that occur with easy bruising or with a family history of bleeding disorders.

First-line treatment for heavy menstrual bleeding in teens is hormonal contraception, either combination oral contraceptive pills, the transdermal patch, or the intravaginal ring, which can be combined with other therapies.

An alternative for those under age 18 (per Food and Drug Administration labeling) is oral tranexamic acid, found in a crossover trial with an oral contraceptive pill to be just as effective at reducing average blood loss and improving quality of life, but with fewer side effects and better compliance. Before prescribing anything for heavy menstrual bleeding, however, you must consider possible causes and rule some out that require different management.

Aside from pregnancy, one potential cause of menorrhagia is infection such as chlamydia or gonorrhea, which should be considered even in those with a negative sexual history, Dr. Hertweck said. Other possible causes include an immature hypothalamic-pituitary-ovarian axis, polycystic ovary syndrome (even with low hemoglobin), malignancy with a hormone-producing tumor, hypothalamic dysfunction (often stimulated by eating disorders, obesity, rapid weight loss, or gluten intolerance), or coagulopathy.

“Teens with menorrhagia may need to be screened for a bleeding disorder,” Dr. Hertweck said. At a minimum, she recommends checking complete blood count, ferritin, and TSH. “The most common bleeding disorders associated with heavy menstrual bleeding include platelet function disorders and von Willebrand.”

Up to half of teen girls with menorrhagia who visit a hematologist or multidisciplinary clinic receive a diagnosis of a bleeding disorder, Dr. Hertweck said. And up to half of those with menorrhagia at menarche may have von Willebrand, as do one in six adolescents who go to the emergency department because of heavy menstrual bleeding.
 

Von Willebrand syndrome

Von Willebrand syndrome is a deficiency or dysfunction of von Willebrand factor (vWF), a protein with binding sites for platelets, collagen, and factor VIII that “serves as a bridge between platelets and injury sites in vessel walls” and “protects factor VIII from rapid proteolytic degradation,” Dr. Hertweck said. Von Willebrand syndrome is the most common inherited congenital bleeding disorder. Although acquired von Willebrand syndrome is rare, it has grown in incidence among those with complex cardiovascular, hematologic, or immunologic disorders.

“Correct diagnosis is complex and not always straightforward,” Dr. Hertweck said, but “a positive response to questions in four categories is highly sensitive.” They are as follows:

• Menses lasting at least 7 days and interfering with a person’s daily activities.

• “History of treatment for anemia.

• Family history of a diagnosed bleeding disorder.

• History of excessive bleeding after tooth extraction, delivery, miscarriage, or surgery.

Diagnostic assays include platelet concentration of vWF antigen, an activity test of vWF-platelet binding, and factor VIII activity. However, you often need to repeat diagnostic testing because vWF antigens vary according to race, blood type, age, acute phase response, and menstrual cycle timing, Dr. Hertweck said.

“Remember to draw von Willebrand testing only during the first 3 days of the menstrual cycle when estrogen levels are at the nadir,” she said.

Because estrogen increases vWF, treatment for von Willebrand syndrome should be progestin only, either oral pills, medroxyprogesterone acetate (MPA, or Depo-Provera injections), or an etonogestrel implant.

Dr. Hertweck presented several cases of abnormal menstruation and extreme conditions such as severe menorrhagia. Outside of von Willebrand in such patients, possible platelet disorders could include Glanzmann thrombasthenia (a platelet function disorder that is caused by an abnormality in the genes for glycoproteins IIb/IIIa) and platelet storage pool disorder, both of which should be diagnosed by a hematologist.

Dr. Hertweck reported having a research grant from Merck related to contraceptive implants in adolescents.

Take-Home Points

• PFA improved knee function and pain scores in patients with isolated patellofemoral arthritis.
• The majority (84.2%) of patients undergoing PFA were female.
• Regardless of age or gender, 72.2% of patients returned to their desired preoperative activity after PFA, and 52.8% returned at the same or higher level.
• The rate of conversion from PFA to TKA was 6.3%.
• PFA is an alternative to TKA in active patients with isolated patellofemoral arthritis.

Compared with total knee arthroplasty (TKA), single-compartment knee arthroplasty may provide better physiologic function, faster recovery, and higher rates of return to activities in patients with unicompartmental knee disease.^1-3 In 1955, McKeever⁴ introduced patellar arthroplasty for surgical management of isolated patellofemoral arthritis. In 1979, Lubinus⁵ improved on the technique and design by adding a femoral component. Since then, implants and techniques have been developed to effect better clinical outcomes. Patellofemoral arthroplasty (PFA) has many advantages over TKA in the treatment of patellofemoral arthritis. PFA is less invasive, requires shorter tourniquet times, has faster recovery, and spares the tibiofemoral compartment, leaving more native bone for potential conversion to TKA. Regarding activity and function, the resurfacing arthroplasty (vs TKA) allows maintenance of nearly normal knee kinematics.

Despite these advantages, the broader orthopedic surgery community has only cautiously accepted PFA. The procedure has high complication rates. Persistent instability, malalignment, wear, impingement, and tibiofemoral arthritis progression can occur after PFA.⁶ Although first-generation PFA prostheses often failed because of mechanical problems, loosening, maltracking, or instability,⁷ the most common indication for PFA revision has been, according to a recent large retrospective study,⁸ unexplained pain. More than 10 to 15 years after PFA, tibiofemoral arthritis may be the primary mechanism of failure.⁹ Nevertheless, compared with standard TKA for isolated patellofemoral arthritis, modern PFA does not have significantly different clinical outcomes, including complication and revision rates.⁶Numerous patient factors influence functional prognosis before and after knee arthroplasty, regardless of surgical technique and implant used. Age, comorbidities, athletic status, mental health, pain, functional limitations, excessive caution, “artificial joint”–related worries, and rehabilitation protocol all influence function.¹⁰ Return to activity and other quality-of-life indices are important aspects of postoperative patient satisfaction.

Methods

We conducted a retrospective cohort study to describe functional status after PFA for patellofemoral arthritis. We identified 48 consecutive PFAs (39 patients) performed by a team of 2 orthopedic surgeons (specialists in treating patellofemoral pathology) between 2009 and 2014.

Three validated patient-reported outcome measures (PROMs) were used to determine preoperative (baseline) and postoperative functional status: Kujala score, Lysholm score, and International Knee Documentation Committee (IKDC) score. The Kujala score is a measure of knee function specific to the patellofemoral joint; the Lysholm score focuses on activities related to the knee; and the IKDC score is a general measure of knee function. Charts were reviewed to extract patients’ clinical data, including preoperative outcome scores, medical history, physical examination data, intraoperative characteristics, and postoperative course. By telephone, patients answered questions about their postoperative clinical course and completed final follow-up questionnaires. They were also asked which sporting or fitness activity they had preferred before surgery and whether they were able to return to that activity after surgery.

Statistical analysis included the study population’s descriptive statistics. Means and SDs were reported for continuous variables, and frequencies and percentages were reported for categorical variables. Paired t tests were used to analyze changes in PROM scores. For comparison of differences between characteristics of patients who did and did not return to their previous activity level, independent-samples t tests were used for continuous variables. Chi-square tests or Fisher exact tests were used to compare discrete variables. Statistical significance was set at P ≤ .05. All analyses were performed with SPSS Version 22.0 (IBM).

Results

Discussion

Historically, the literature evaluating knee arthroplasty outcomes has focused on implant survivorship, pain relief, and patient satisfaction. Since the advent of partial knee arthroplasty options, more attention has been given to functional outcomes and return to activities after single-compartment knee resurfacing. TKA remains the gold standard by which newer, less invasive surgical options are measured. In a large prospective study, 97% of patients (age, >55 years) who had TKA for patellofemoral arthritis reported good or excellent clinical results, the majority being excellent.¹¹ Post-TKA functional status and activity levels may not be rated as highly. After TKA, many patients switch to lower impact sports or reduce or stop their participation in sports.¹² A small study of competitive adult tennis players found high levels of post-TKA satisfaction, ability to resume playing tennis, pain relief, and increased or continued enjoyment in playing.¹³ In a study of 355 patients (417 knees) who had underwent TKA, improvement in Knee Society function score showed a moderate correlation to an increase in weighted activity score (R = 0.362).¹⁴

Unicondylar knee arthroplasty (UKA) is becoming a popular treatment option for single-compartment tibiofemoral arthritis. A systematic review of 18 original studies of patients with knee osteoarthritis found that overall return to sports varied from 36% to 89% after TKA and from 75% to 100% after UKA.¹⁵ In another study, return-to-sports rates were similar for UKA (87%) and TKA (83%); the only significant difference was UKA patients returned quicker.¹⁶ The authors of a large meta-analysis conceded that significant heterogeneity of data prevented them from drawing definitive conclusions, but UKA patients seemed to return to low- and high-impact sports 2 weeks faster than their TKA counterparts.¹⁰ Overall, UKA and TKA patients (age, 51-71 years) had comparable return-to-sports rates at an average of 4 years after surgery.¹⁰ A smaller study corroborated faster return to sports for UKA over TKA patients and also found that, compared with TKA patients, UKA patients participated in sports more regularly and over a longer period.¹⁷ On the other hand, Walton and colleagues¹⁸ found similar return-to-sports rates but higher frequency of and satisfaction with sports participation in UKA over TKA patients.

A large retrospective study found no differences in rates of return to sports after TKA, UKA, patellar resurfacing, hip resurfacing, and total hip arthroplasty.¹⁹ Pain was the most common barrier to return. UKA patients who returned to sports tended to be younger than those who did not.²⁰ Naal and colleagues³ found that 95% of UKA patients returned to their activities—hiking, walking, cycling, and swimming being most common. Although 90.3% of patients said surgery maintained or improved their ability to participate in sports, participation in high-impact sports (eg, running) decreased after surgery.

Outcomes of PFA vary because of evolving patient selection, implant design, surgical technique, and return-to-activity expectations.^21,22 Most PFA outcome studies focus on implant survivorship, complication rates, and postoperative knee scores.^23-28 PFA studies focused on return to activities are limited. Kooijman and colleagues⁷ and Mertl and colleagues²⁹ reported good or excellent clinical results of PFA in 86% and 82% of patients, respectively. Neither study included a comprehensive analysis of postoperative functional status. Similarly, De Cloedt and colleagues³⁰ reported good PFA outcomes in 43% of patients with degenerative joint disease and in 83% of patients with instability. Specific activity status was not described. Dahm and colleagues³¹ and Farr and colleagues³² suggested postoperative pain resolution motivates some PFA patients not only to resume preoperative activities but to start participating in new, higher level activities after pain has subsided. However, the studies did not examine the characteristics of patients who returned to baseline activities and did not examine return-to-sports rates.

Study Strengths and Limitations

Our study focused on the PFA patient population of a surgical team of 2 fellowship-trained orthopedic surgeons (specialists in treating patellofemoral pathology). Although generalization of our findings to other surgeons and different implants may be limited, the study design standardized treatment in a way that makes these findings more reliable. The 100% follow-up strengthens these findings as well. Last, though the patient population was relatively small, it was consistent with or larger than the PFA patient groups studied previously.

Conclusion

In this study, PROM and pain scores were significantly improved after PFA. That almost 75% of patients returned to their preferred activities and >50% of patients returned at the same or a higher activity level provides useful information for preoperative discussions with patients who want to remain active after PFA. Prospective studies are needed to evaluate the longevity and durability of PFA, particularly in active patients.

Take-Home Points

• PFA improved knee function and pain scores in patients with isolated patellofemoral arthritis.
• The majority (84.2%) of patients undergoing PFA were female.
• Regardless of age or gender, 72.2% of patients returned to their desired preoperative activity after PFA, and 52.8% returned at the same or higher level.
• The rate of conversion from PFA to TKA was 6.3%.
• PFA is an alternative to TKA in active patients with isolated patellofemoral arthritis.

Compared with total knee arthroplasty (TKA), single-compartment knee arthroplasty may provide better physiologic function, faster recovery, and higher rates of return to activities in patients with unicompartmental knee disease.^1-3 In 1955, McKeever⁴ introduced patellar arthroplasty for surgical management of isolated patellofemoral arthritis. In 1979, Lubinus⁵ improved on the technique and design by adding a femoral component. Since then, implants and techniques have been developed to effect better clinical outcomes. Patellofemoral arthroplasty (PFA) has many advantages over TKA in the treatment of patellofemoral arthritis. PFA is less invasive, requires shorter tourniquet times, has faster recovery, and spares the tibiofemoral compartment, leaving more native bone for potential conversion to TKA. Regarding activity and function, the resurfacing arthroplasty (vs TKA) allows maintenance of nearly normal knee kinematics.

Despite these advantages, the broader orthopedic surgery community has only cautiously accepted PFA. The procedure has high complication rates. Persistent instability, malalignment, wear, impingement, and tibiofemoral arthritis progression can occur after PFA.⁶ Although first-generation PFA prostheses often failed because of mechanical problems, loosening, maltracking, or instability,⁷ the most common indication for PFA revision has been, according to a recent large retrospective study,⁸ unexplained pain. More than 10 to 15 years after PFA, tibiofemoral arthritis may be the primary mechanism of failure.⁹ Nevertheless, compared with standard TKA for isolated patellofemoral arthritis, modern PFA does not have significantly different clinical outcomes, including complication and revision rates.⁶Numerous patient factors influence functional prognosis before and after knee arthroplasty, regardless of surgical technique and implant used. Age, comorbidities, athletic status, mental health, pain, functional limitations, excessive caution, “artificial joint”–related worries, and rehabilitation protocol all influence function.¹⁰ Return to activity and other quality-of-life indices are important aspects of postoperative patient satisfaction.

Methods

We conducted a retrospective cohort study to describe functional status after PFA for patellofemoral arthritis. We identified 48 consecutive PFAs (39 patients) performed by a team of 2 orthopedic surgeons (specialists in treating patellofemoral pathology) between 2009 and 2014.

Three validated patient-reported outcome measures (PROMs) were used to determine preoperative (baseline) and postoperative functional status: Kujala score, Lysholm score, and International Knee Documentation Committee (IKDC) score. The Kujala score is a measure of knee function specific to the patellofemoral joint; the Lysholm score focuses on activities related to the knee; and the IKDC score is a general measure of knee function. Charts were reviewed to extract patients’ clinical data, including preoperative outcome scores, medical history, physical examination data, intraoperative characteristics, and postoperative course. By telephone, patients answered questions about their postoperative clinical course and completed final follow-up questionnaires. They were also asked which sporting or fitness activity they had preferred before surgery and whether they were able to return to that activity after surgery.

Statistical analysis included the study population’s descriptive statistics. Means and SDs were reported for continuous variables, and frequencies and percentages were reported for categorical variables. Paired t tests were used to analyze changes in PROM scores. For comparison of differences between characteristics of patients who did and did not return to their previous activity level, independent-samples t tests were used for continuous variables. Chi-square tests or Fisher exact tests were used to compare discrete variables. Statistical significance was set at P ≤ .05. All analyses were performed with SPSS Version 22.0 (IBM).

Results

Discussion

Historically, the literature evaluating knee arthroplasty outcomes has focused on implant survivorship, pain relief, and patient satisfaction. Since the advent of partial knee arthroplasty options, more attention has been given to functional outcomes and return to activities after single-compartment knee resurfacing. TKA remains the gold standard by which newer, less invasive surgical options are measured. In a large prospective study, 97% of patients (age, >55 years) who had TKA for patellofemoral arthritis reported good or excellent clinical results, the majority being excellent.¹¹ Post-TKA functional status and activity levels may not be rated as highly. After TKA, many patients switch to lower impact sports or reduce or stop their participation in sports.¹² A small study of competitive adult tennis players found high levels of post-TKA satisfaction, ability to resume playing tennis, pain relief, and increased or continued enjoyment in playing.¹³ In a study of 355 patients (417 knees) who had underwent TKA, improvement in Knee Society function score showed a moderate correlation to an increase in weighted activity score (R = 0.362).¹⁴

Unicondylar knee arthroplasty (UKA) is becoming a popular treatment option for single-compartment tibiofemoral arthritis. A systematic review of 18 original studies of patients with knee osteoarthritis found that overall return to sports varied from 36% to 89% after TKA and from 75% to 100% after UKA.¹⁵ In another study, return-to-sports rates were similar for UKA (87%) and TKA (83%); the only significant difference was UKA patients returned quicker.¹⁶ The authors of a large meta-analysis conceded that significant heterogeneity of data prevented them from drawing definitive conclusions, but UKA patients seemed to return to low- and high-impact sports 2 weeks faster than their TKA counterparts.¹⁰ Overall, UKA and TKA patients (age, 51-71 years) had comparable return-to-sports rates at an average of 4 years after surgery.¹⁰ A smaller study corroborated faster return to sports for UKA over TKA patients and also found that, compared with TKA patients, UKA patients participated in sports more regularly and over a longer period.¹⁷ On the other hand, Walton and colleagues¹⁸ found similar return-to-sports rates but higher frequency of and satisfaction with sports participation in UKA over TKA patients.

A large retrospective study found no differences in rates of return to sports after TKA, UKA, patellar resurfacing, hip resurfacing, and total hip arthroplasty.¹⁹ Pain was the most common barrier to return. UKA patients who returned to sports tended to be younger than those who did not.²⁰ Naal and colleagues³ found that 95% of UKA patients returned to their activities—hiking, walking, cycling, and swimming being most common. Although 90.3% of patients said surgery maintained or improved their ability to participate in sports, participation in high-impact sports (eg, running) decreased after surgery.

Outcomes of PFA vary because of evolving patient selection, implant design, surgical technique, and return-to-activity expectations.^21,22 Most PFA outcome studies focus on implant survivorship, complication rates, and postoperative knee scores.^23-28 PFA studies focused on return to activities are limited. Kooijman and colleagues⁷ and Mertl and colleagues²⁹ reported good or excellent clinical results of PFA in 86% and 82% of patients, respectively. Neither study included a comprehensive analysis of postoperative functional status. Similarly, De Cloedt and colleagues³⁰ reported good PFA outcomes in 43% of patients with degenerative joint disease and in 83% of patients with instability. Specific activity status was not described. Dahm and colleagues³¹ and Farr and colleagues³² suggested postoperative pain resolution motivates some PFA patients not only to resume preoperative activities but to start participating in new, higher level activities after pain has subsided. However, the studies did not examine the characteristics of patients who returned to baseline activities and did not examine return-to-sports rates.

Study Strengths and Limitations

Our study focused on the PFA patient population of a surgical team of 2 fellowship-trained orthopedic surgeons (specialists in treating patellofemoral pathology). Although generalization of our findings to other surgeons and different implants may be limited, the study design standardized treatment in a way that makes these findings more reliable. The 100% follow-up strengthens these findings as well. Last, though the patient population was relatively small, it was consistent with or larger than the PFA patient groups studied previously.

Conclusion

In this study, PROM and pain scores were significantly improved after PFA. That almost 75% of patients returned to their preferred activities and >50% of patients returned at the same or a higher activity level provides useful information for preoperative discussions with patients who want to remain active after PFA. Prospective studies are needed to evaluate the longevity and durability of PFA, particularly in active patients.

Take-Home Points

• PFA improved knee function and pain scores in patients with isolated patellofemoral arthritis.
• The majority (84.2%) of patients undergoing PFA were female.
• Regardless of age or gender, 72.2% of patients returned to their desired preoperative activity after PFA, and 52.8% returned at the same or higher level.
• The rate of conversion from PFA to TKA was 6.3%.
• PFA is an alternative to TKA in active patients with isolated patellofemoral arthritis.

Compared with total knee arthroplasty (TKA), single-compartment knee arthroplasty may provide better physiologic function, faster recovery, and higher rates of return to activities in patients with unicompartmental knee disease.^1-3 In 1955, McKeever⁴ introduced patellar arthroplasty for surgical management of isolated patellofemoral arthritis. In 1979, Lubinus⁵ improved on the technique and design by adding a femoral component. Since then, implants and techniques have been developed to effect better clinical outcomes. Patellofemoral arthroplasty (PFA) has many advantages over TKA in the treatment of patellofemoral arthritis. PFA is less invasive, requires shorter tourniquet times, has faster recovery, and spares the tibiofemoral compartment, leaving more native bone for potential conversion to TKA. Regarding activity and function, the resurfacing arthroplasty (vs TKA) allows maintenance of nearly normal knee kinematics.

Despite these advantages, the broader orthopedic surgery community has only cautiously accepted PFA. The procedure has high complication rates. Persistent instability, malalignment, wear, impingement, and tibiofemoral arthritis progression can occur after PFA.⁶ Although first-generation PFA prostheses often failed because of mechanical problems, loosening, maltracking, or instability,⁷ the most common indication for PFA revision has been, according to a recent large retrospective study,⁸ unexplained pain. More than 10 to 15 years after PFA, tibiofemoral arthritis may be the primary mechanism of failure.⁹ Nevertheless, compared with standard TKA for isolated patellofemoral arthritis, modern PFA does not have significantly different clinical outcomes, including complication and revision rates.⁶Numerous patient factors influence functional prognosis before and after knee arthroplasty, regardless of surgical technique and implant used. Age, comorbidities, athletic status, mental health, pain, functional limitations, excessive caution, “artificial joint”–related worries, and rehabilitation protocol all influence function.¹⁰ Return to activity and other quality-of-life indices are important aspects of postoperative patient satisfaction.

Methods

We conducted a retrospective cohort study to describe functional status after PFA for patellofemoral arthritis. We identified 48 consecutive PFAs (39 patients) performed by a team of 2 orthopedic surgeons (specialists in treating patellofemoral pathology) between 2009 and 2014.

Three validated patient-reported outcome measures (PROMs) were used to determine preoperative (baseline) and postoperative functional status: Kujala score, Lysholm score, and International Knee Documentation Committee (IKDC) score. The Kujala score is a measure of knee function specific to the patellofemoral joint; the Lysholm score focuses on activities related to the knee; and the IKDC score is a general measure of knee function. Charts were reviewed to extract patients’ clinical data, including preoperative outcome scores, medical history, physical examination data, intraoperative characteristics, and postoperative course. By telephone, patients answered questions about their postoperative clinical course and completed final follow-up questionnaires. They were also asked which sporting or fitness activity they had preferred before surgery and whether they were able to return to that activity after surgery.

Statistical analysis included the study population’s descriptive statistics. Means and SDs were reported for continuous variables, and frequencies and percentages were reported for categorical variables. Paired t tests were used to analyze changes in PROM scores. For comparison of differences between characteristics of patients who did and did not return to their previous activity level, independent-samples t tests were used for continuous variables. Chi-square tests or Fisher exact tests were used to compare discrete variables. Statistical significance was set at P ≤ .05. All analyses were performed with SPSS Version 22.0 (IBM).

Results

Discussion

Historically, the literature evaluating knee arthroplasty outcomes has focused on implant survivorship, pain relief, and patient satisfaction. Since the advent of partial knee arthroplasty options, more attention has been given to functional outcomes and return to activities after single-compartment knee resurfacing. TKA remains the gold standard by which newer, less invasive surgical options are measured. In a large prospective study, 97% of patients (age, >55 years) who had TKA for patellofemoral arthritis reported good or excellent clinical results, the majority being excellent.¹¹ Post-TKA functional status and activity levels may not be rated as highly. After TKA, many patients switch to lower impact sports or reduce or stop their participation in sports.¹² A small study of competitive adult tennis players found high levels of post-TKA satisfaction, ability to resume playing tennis, pain relief, and increased or continued enjoyment in playing.¹³ In a study of 355 patients (417 knees) who had underwent TKA, improvement in Knee Society function score showed a moderate correlation to an increase in weighted activity score (R = 0.362).¹⁴

Unicondylar knee arthroplasty (UKA) is becoming a popular treatment option for single-compartment tibiofemoral arthritis. A systematic review of 18 original studies of patients with knee osteoarthritis found that overall return to sports varied from 36% to 89% after TKA and from 75% to 100% after UKA.¹⁵ In another study, return-to-sports rates were similar for UKA (87%) and TKA (83%); the only significant difference was UKA patients returned quicker.¹⁶ The authors of a large meta-analysis conceded that significant heterogeneity of data prevented them from drawing definitive conclusions, but UKA patients seemed to return to low- and high-impact sports 2 weeks faster than their TKA counterparts.¹⁰ Overall, UKA and TKA patients (age, 51-71 years) had comparable return-to-sports rates at an average of 4 years after surgery.¹⁰ A smaller study corroborated faster return to sports for UKA over TKA patients and also found that, compared with TKA patients, UKA patients participated in sports more regularly and over a longer period.¹⁷ On the other hand, Walton and colleagues¹⁸ found similar return-to-sports rates but higher frequency of and satisfaction with sports participation in UKA over TKA patients.

A large retrospective study found no differences in rates of return to sports after TKA, UKA, patellar resurfacing, hip resurfacing, and total hip arthroplasty.¹⁹ Pain was the most common barrier to return. UKA patients who returned to sports tended to be younger than those who did not.²⁰ Naal and colleagues³ found that 95% of UKA patients returned to their activities—hiking, walking, cycling, and swimming being most common. Although 90.3% of patients said surgery maintained or improved their ability to participate in sports, participation in high-impact sports (eg, running) decreased after surgery.

Outcomes of PFA vary because of evolving patient selection, implant design, surgical technique, and return-to-activity expectations.^21,22 Most PFA outcome studies focus on implant survivorship, complication rates, and postoperative knee scores.^23-28 PFA studies focused on return to activities are limited. Kooijman and colleagues⁷ and Mertl and colleagues²⁹ reported good or excellent clinical results of PFA in 86% and 82% of patients, respectively. Neither study included a comprehensive analysis of postoperative functional status. Similarly, De Cloedt and colleagues³⁰ reported good PFA outcomes in 43% of patients with degenerative joint disease and in 83% of patients with instability. Specific activity status was not described. Dahm and colleagues³¹ and Farr and colleagues³² suggested postoperative pain resolution motivates some PFA patients not only to resume preoperative activities but to start participating in new, higher level activities after pain has subsided. However, the studies did not examine the characteristics of patients who returned to baseline activities and did not examine return-to-sports rates.

Study Strengths and Limitations

Our study focused on the PFA patient population of a surgical team of 2 fellowship-trained orthopedic surgeons (specialists in treating patellofemoral pathology). Although generalization of our findings to other surgeons and different implants may be limited, the study design standardized treatment in a way that makes these findings more reliable. The 100% follow-up strengthens these findings as well. Last, though the patient population was relatively small, it was consistent with or larger than the PFA patient groups studied previously.

Conclusion

In this study, PROM and pain scores were significantly improved after PFA. That almost 75% of patients returned to their preferred activities and >50% of patients returned at the same or a higher activity level provides useful information for preoperative discussions with patients who want to remain active after PFA. Prospective studies are needed to evaluate the longevity and durability of PFA, particularly in active patients.

Genotype-guided warfarin dosing reduced anticoagulation-related adverse events by almost 4% compared with a clinically based warfarin-dosing regimen in a randomized trial of 1,650 elderly patients undergoing hip or knee arthroplasty.

The difference in the composite endpoint (major bleeding within 30 days, international normalized ratio [INR] of 4 or greater within 30 days, venous thromboembolism within 60 days, or death within 30 days) in the Genetic Informatics Trial of Warfarin to Prevent Deep Vein Thrombosis (GIFT) trial was mainly driven by a significant difference in episodes of elevated INR, reported Brian F. Gage, MD, and his colleagues (JAMA 2017;318[12]:1115-1124. doi: 10.1001/jama.2017.11469).

A total of 1,597 patients completed the trial. Of 808 patients in the genotype-guided group, 10.8% met one of the endpoints. Of 789 in the clinically guided warfarin dosing group, 14.7% met at least 1 of the endpoints. There were no deaths in the study.

“Widespread use of genotype-guided dosing will depend on reimbursement, regulations, and logistics. Although several commercial platforms for warfarin-related genes have been approved by the Food and Drug Administration and the European Medicines Agency, routine genotyping is not yet recommended,” wrote Dr. Gage of Washington University, St. Louis, and his coauthors.

The Centers for Medicare and Medicaid Services used its Coverage with Evidence Development program to fund genotyping in this trial and will review the results to determine future coverage, the researchers added.

In GIFT, patients were randomized to an 11-day regimen of warfarin guided either by a clinical algorithm or by their individual genotype. The team tested for four polymorphisms known to affect warfarin metabolism: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. The treatment goal was an INR of 1.8-2. After 11 days, physicians could administer warfarin according to their own judgment.

The absolute difference of 3.9% in the composite endpoint was largely driven by a 2.8% absolute difference in the rate of an INR of 4 or greater. The rate difference between the two groups was 0.8% for major bleeding, and 0.7% for VTE.

About 41% of the cohort was considered to be at high risk of bleeding complications, and this group accrued the highest benefit from genotype-based dosing. Among them, the composite endpoint was 11.5% compared with 15.2% in the clinical algorithm group – an absolute difference of 3.76%.

The benefit was consistent among black patients, and those with CYP2C9.

By day 90, one VTE had occurred in each group. An intracranial hemorrhage occurred in one patient in the clinically guided group, 2 months after stopping warfarin.

The clinical benefit of genotype-based dosing influenced 90-day outcomes as well, with the composite endpoint occurring in 11% of the genotype group and 15% of the clinically guided group (absolute difference 3.9%).

Among the 1,588 patients who had their percentage of time in the therapeutic range (PTTR) calculated, genotyping improved PTTR time by 3.4% overall. The effect was especially strong from days 4 to 14, when it improved PTTR by 5.7% relative to clinical guidance.

Three other studies have examined the effect of a genotype-based warfarin dosing regimen, Dr. Gage and his coauthors noted: Two found no benefit, and a third found that such guidance improved INR control. GIFT has several advantages over those trials, which the authors said lend credence to its results.

“Compared with previous studies, this trial was larger, used genotype-guided dosing for a longer duration, and incorporated more genes into the dosing algorithm …The longer period of genotype-guided dosing likely prevented cases of supratherapeutic INR that were common in these trials,” they wrote.

Dr. Gage reported no financial disclosures, but several coauthors reported ties with pharmaceutical and imaging companies.

[email protected]

Genotype-guided warfarin dosing reduced anticoagulation-related adverse events by almost 4% compared with a clinically based warfarin-dosing regimen in a randomized trial of 1,650 elderly patients undergoing hip or knee arthroplasty.

The difference in the composite endpoint (major bleeding within 30 days, international normalized ratio [INR] of 4 or greater within 30 days, venous thromboembolism within 60 days, or death within 30 days) in the Genetic Informatics Trial of Warfarin to Prevent Deep Vein Thrombosis (GIFT) trial was mainly driven by a significant difference in episodes of elevated INR, reported Brian F. Gage, MD, and his colleagues (JAMA 2017;318[12]:1115-1124. doi: 10.1001/jama.2017.11469).

A total of 1,597 patients completed the trial. Of 808 patients in the genotype-guided group, 10.8% met one of the endpoints. Of 789 in the clinically guided warfarin dosing group, 14.7% met at least 1 of the endpoints. There were no deaths in the study.

“Widespread use of genotype-guided dosing will depend on reimbursement, regulations, and logistics. Although several commercial platforms for warfarin-related genes have been approved by the Food and Drug Administration and the European Medicines Agency, routine genotyping is not yet recommended,” wrote Dr. Gage of Washington University, St. Louis, and his coauthors.

The Centers for Medicare and Medicaid Services used its Coverage with Evidence Development program to fund genotyping in this trial and will review the results to determine future coverage, the researchers added.

In GIFT, patients were randomized to an 11-day regimen of warfarin guided either by a clinical algorithm or by their individual genotype. The team tested for four polymorphisms known to affect warfarin metabolism: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. The treatment goal was an INR of 1.8-2. After 11 days, physicians could administer warfarin according to their own judgment.

The absolute difference of 3.9% in the composite endpoint was largely driven by a 2.8% absolute difference in the rate of an INR of 4 or greater. The rate difference between the two groups was 0.8% for major bleeding, and 0.7% for VTE.

About 41% of the cohort was considered to be at high risk of bleeding complications, and this group accrued the highest benefit from genotype-based dosing. Among them, the composite endpoint was 11.5% compared with 15.2% in the clinical algorithm group – an absolute difference of 3.76%.

The benefit was consistent among black patients, and those with CYP2C9.

By day 90, one VTE had occurred in each group. An intracranial hemorrhage occurred in one patient in the clinically guided group, 2 months after stopping warfarin.

The clinical benefit of genotype-based dosing influenced 90-day outcomes as well, with the composite endpoint occurring in 11% of the genotype group and 15% of the clinically guided group (absolute difference 3.9%).

Among the 1,588 patients who had their percentage of time in the therapeutic range (PTTR) calculated, genotyping improved PTTR time by 3.4% overall. The effect was especially strong from days 4 to 14, when it improved PTTR by 5.7% relative to clinical guidance.

Three other studies have examined the effect of a genotype-based warfarin dosing regimen, Dr. Gage and his coauthors noted: Two found no benefit, and a third found that such guidance improved INR control. GIFT has several advantages over those trials, which the authors said lend credence to its results.

“Compared with previous studies, this trial was larger, used genotype-guided dosing for a longer duration, and incorporated more genes into the dosing algorithm …The longer period of genotype-guided dosing likely prevented cases of supratherapeutic INR that were common in these trials,” they wrote.

Dr. Gage reported no financial disclosures, but several coauthors reported ties with pharmaceutical and imaging companies.

[email protected]

Genotype-guided warfarin dosing reduced anticoagulation-related adverse events by almost 4% compared with a clinically based warfarin-dosing regimen in a randomized trial of 1,650 elderly patients undergoing hip or knee arthroplasty.

The difference in the composite endpoint (major bleeding within 30 days, international normalized ratio [INR] of 4 or greater within 30 days, venous thromboembolism within 60 days, or death within 30 days) in the Genetic Informatics Trial of Warfarin to Prevent Deep Vein Thrombosis (GIFT) trial was mainly driven by a significant difference in episodes of elevated INR, reported Brian F. Gage, MD, and his colleagues (JAMA 2017;318[12]:1115-1124. doi: 10.1001/jama.2017.11469).

A total of 1,597 patients completed the trial. Of 808 patients in the genotype-guided group, 10.8% met one of the endpoints. Of 789 in the clinically guided warfarin dosing group, 14.7% met at least 1 of the endpoints. There were no deaths in the study.

“Widespread use of genotype-guided dosing will depend on reimbursement, regulations, and logistics. Although several commercial platforms for warfarin-related genes have been approved by the Food and Drug Administration and the European Medicines Agency, routine genotyping is not yet recommended,” wrote Dr. Gage of Washington University, St. Louis, and his coauthors.

The Centers for Medicare and Medicaid Services used its Coverage with Evidence Development program to fund genotyping in this trial and will review the results to determine future coverage, the researchers added.

In GIFT, patients were randomized to an 11-day regimen of warfarin guided either by a clinical algorithm or by their individual genotype. The team tested for four polymorphisms known to affect warfarin metabolism: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. The treatment goal was an INR of 1.8-2. After 11 days, physicians could administer warfarin according to their own judgment.

The absolute difference of 3.9% in the composite endpoint was largely driven by a 2.8% absolute difference in the rate of an INR of 4 or greater. The rate difference between the two groups was 0.8% for major bleeding, and 0.7% for VTE.

About 41% of the cohort was considered to be at high risk of bleeding complications, and this group accrued the highest benefit from genotype-based dosing. Among them, the composite endpoint was 11.5% compared with 15.2% in the clinical algorithm group – an absolute difference of 3.76%.

The benefit was consistent among black patients, and those with CYP2C9.

By day 90, one VTE had occurred in each group. An intracranial hemorrhage occurred in one patient in the clinically guided group, 2 months after stopping warfarin.

The clinical benefit of genotype-based dosing influenced 90-day outcomes as well, with the composite endpoint occurring in 11% of the genotype group and 15% of the clinically guided group (absolute difference 3.9%).

Among the 1,588 patients who had their percentage of time in the therapeutic range (PTTR) calculated, genotyping improved PTTR time by 3.4% overall. The effect was especially strong from days 4 to 14, when it improved PTTR by 5.7% relative to clinical guidance.

Three other studies have examined the effect of a genotype-based warfarin dosing regimen, Dr. Gage and his coauthors noted: Two found no benefit, and a third found that such guidance improved INR control. GIFT has several advantages over those trials, which the authors said lend credence to its results.

“Compared with previous studies, this trial was larger, used genotype-guided dosing for a longer duration, and incorporated more genes into the dosing algorithm …The longer period of genotype-guided dosing likely prevented cases of supratherapeutic INR that were common in these trials,” they wrote.

Dr. Gage reported no financial disclosures, but several coauthors reported ties with pharmaceutical and imaging companies.

[email protected]

New and persistent opioid use is a common complication of surgery in patients with early-stage cancer, according to results of a retrospective cohort study.

The risk of new persistent opioid use was 10.4% (95% confidence interval, 10.1%-10.7%) among patients undergoing curative-intent cancer surgery, according to the report, which was based on examination of 68,463 deidentified insurance claims from employer health plans from 2010 to 2014.

“This problem requires changes to prescribing guidelines and patient counseling during the surveillance and survivorship phases of care,” wrote Jay Soong-Jin Lee, MD, and his colleagues at the University of Michigan, Ann Arbor (J Clin Oncol. 2017 Oct 19. doi: 10.1200/JCO.2017.74.1363).

One year after the surgery, patients who developed new persistent opioid use were still filling prescriptions at high daily opioid doses, equivalent to six hydrocodone 5-mg tablets per day, according Dr. Lee and his colleagues.

“This dose is similar to intermittent and chronic opioid users [in the insurance claim data], suggesting that patients with new persistent opioid use may transition to chronic opioid use,” they said in the study report.

Adjuvant chemotherapy was a “strong risk factor” for new persistent opioid use, they added, though use was still common among patients who had no adjuvant chemotherapy. Rates of new persistent opioid use ranged from 15% to 21% for adjuvant therapy patient groups, compared with 7%-11% for no advjuvant therapy, data show.

Previous studies suggested a 6%-8% risk of new persistent opioid use among surgical patients, but those studies either did not focus on cancer patients or excluded them entirely, Dr. Lee and his coauthors noted.

Strategies are needed to combat new persistent opioid use after curative-intent surgery, they added.

They recommended further study to develop evidence-based guidelines to reduce excessive opioid prescribing and screening tools to identify at-risk patients (e.g., those with psychosocial factors).

Surgeons should be more active in counseling patients on the potential risks of opioids and how to keep use to a minimum after surgery, they added.

“Given the high risk of new persistent opioid use in this population, physicians should consider universal precautions … including educating patients on safe use, storage, and disposal,” they wrote.

Dr. Lee disclosed no relationships relevant to the study, while several coauthors reported relationships with Neuros Medical, Merck, and Anesthesia Associates of Ann Arbor.

New and persistent opioid use is a common complication of surgery in patients with early-stage cancer, according to results of a retrospective cohort study.

The risk of new persistent opioid use was 10.4% (95% confidence interval, 10.1%-10.7%) among patients undergoing curative-intent cancer surgery, according to the report, which was based on examination of 68,463 deidentified insurance claims from employer health plans from 2010 to 2014.

“This problem requires changes to prescribing guidelines and patient counseling during the surveillance and survivorship phases of care,” wrote Jay Soong-Jin Lee, MD, and his colleagues at the University of Michigan, Ann Arbor (J Clin Oncol. 2017 Oct 19. doi: 10.1200/JCO.2017.74.1363).

One year after the surgery, patients who developed new persistent opioid use were still filling prescriptions at high daily opioid doses, equivalent to six hydrocodone 5-mg tablets per day, according Dr. Lee and his colleagues.

“This dose is similar to intermittent and chronic opioid users [in the insurance claim data], suggesting that patients with new persistent opioid use may transition to chronic opioid use,” they said in the study report.

Adjuvant chemotherapy was a “strong risk factor” for new persistent opioid use, they added, though use was still common among patients who had no adjuvant chemotherapy. Rates of new persistent opioid use ranged from 15% to 21% for adjuvant therapy patient groups, compared with 7%-11% for no advjuvant therapy, data show.

Previous studies suggested a 6%-8% risk of new persistent opioid use among surgical patients, but those studies either did not focus on cancer patients or excluded them entirely, Dr. Lee and his coauthors noted.

Strategies are needed to combat new persistent opioid use after curative-intent surgery, they added.

They recommended further study to develop evidence-based guidelines to reduce excessive opioid prescribing and screening tools to identify at-risk patients (e.g., those with psychosocial factors).

Surgeons should be more active in counseling patients on the potential risks of opioids and how to keep use to a minimum after surgery, they added.

“Given the high risk of new persistent opioid use in this population, physicians should consider universal precautions … including educating patients on safe use, storage, and disposal,” they wrote.

Dr. Lee disclosed no relationships relevant to the study, while several coauthors reported relationships with Neuros Medical, Merck, and Anesthesia Associates of Ann Arbor.

New and persistent opioid use is a common complication of surgery in patients with early-stage cancer, according to results of a retrospective cohort study.

The risk of new persistent opioid use was 10.4% (95% confidence interval, 10.1%-10.7%) among patients undergoing curative-intent cancer surgery, according to the report, which was based on examination of 68,463 deidentified insurance claims from employer health plans from 2010 to 2014.

“This problem requires changes to prescribing guidelines and patient counseling during the surveillance and survivorship phases of care,” wrote Jay Soong-Jin Lee, MD, and his colleagues at the University of Michigan, Ann Arbor (J Clin Oncol. 2017 Oct 19. doi: 10.1200/JCO.2017.74.1363).

One year after the surgery, patients who developed new persistent opioid use were still filling prescriptions at high daily opioid doses, equivalent to six hydrocodone 5-mg tablets per day, according Dr. Lee and his colleagues.

“This dose is similar to intermittent and chronic opioid users [in the insurance claim data], suggesting that patients with new persistent opioid use may transition to chronic opioid use,” they said in the study report.

Adjuvant chemotherapy was a “strong risk factor” for new persistent opioid use, they added, though use was still common among patients who had no adjuvant chemotherapy. Rates of new persistent opioid use ranged from 15% to 21% for adjuvant therapy patient groups, compared with 7%-11% for no advjuvant therapy, data show.

Previous studies suggested a 6%-8% risk of new persistent opioid use among surgical patients, but those studies either did not focus on cancer patients or excluded them entirely, Dr. Lee and his coauthors noted.

Strategies are needed to combat new persistent opioid use after curative-intent surgery, they added.

They recommended further study to develop evidence-based guidelines to reduce excessive opioid prescribing and screening tools to identify at-risk patients (e.g., those with psychosocial factors).

Surgeons should be more active in counseling patients on the potential risks of opioids and how to keep use to a minimum after surgery, they added.

“Given the high risk of new persistent opioid use in this population, physicians should consider universal precautions … including educating patients on safe use, storage, and disposal,” they wrote.

Dr. Lee disclosed no relationships relevant to the study, while several coauthors reported relationships with Neuros Medical, Merck, and Anesthesia Associates of Ann Arbor.

SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.

Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).

juststock

[email protected]

On Twitter @karioakes

*Correction 11/14/17: An earlier version of this article misstated the P values.

SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.

Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).

juststock

[email protected]

On Twitter @karioakes

*Correction 11/14/17: An earlier version of this article misstated the P values.

SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.

Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).

juststock

[email protected]

On Twitter @karioakes

*Correction 11/14/17: An earlier version of this article misstated the P values.

Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.

Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.

©bbbrrn/Thinkstockphotos.com

Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.

Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.

©bbbrrn/Thinkstockphotos.com

Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.

Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.

©bbbrrn/Thinkstockphotos.com

I am not going to tell you about the dangers of lead, as it is well known and publicized, but I will tell you my family’s story with lead.

In 2012, 1 year after my younger daughter was born, I took her for her 1-year checkup. As I would do with any of my pediatric patients at this age, I took her for a lead level check. Never during my residency training or my first few years of practice as a pediatrician have I encountered a positive lead level. So when I opened the lab result sheet, I thought I would be shredding it the next moment. Well, that didn’t happen. It turned out that her lead level was 7 mcg/dL! Not too high, but detectable. The only question that kept on coming back over the next month or so was a big WHY? Why my child? Now my older daughter’s lead level was normal at her 1-year visit. We had just moved into a new house before my youngest daughter was born. I thought, it has to do with the house, and since my 1-year-old was putting everything in her mouth at this stage, then she must be getting the lead that way.

Dr. Faddoul is a private practice pediatrician in La Canada Flintridge, Calif.

I am not going to tell you about the dangers of lead, as it is well known and publicized, but I will tell you my family’s story with lead.

In 2012, 1 year after my younger daughter was born, I took her for her 1-year checkup. As I would do with any of my pediatric patients at this age, I took her for a lead level check. Never during my residency training or my first few years of practice as a pediatrician have I encountered a positive lead level. So when I opened the lab result sheet, I thought I would be shredding it the next moment. Well, that didn’t happen. It turned out that her lead level was 7 mcg/dL! Not too high, but detectable. The only question that kept on coming back over the next month or so was a big WHY? Why my child? Now my older daughter’s lead level was normal at her 1-year visit. We had just moved into a new house before my youngest daughter was born. I thought, it has to do with the house, and since my 1-year-old was putting everything in her mouth at this stage, then she must be getting the lead that way.

Dr. Faddoul is a private practice pediatrician in La Canada Flintridge, Calif.

I am not going to tell you about the dangers of lead, as it is well known and publicized, but I will tell you my family’s story with lead.

In 2012, 1 year after my younger daughter was born, I took her for her 1-year checkup. As I would do with any of my pediatric patients at this age, I took her for a lead level check. Never during my residency training or my first few years of practice as a pediatrician have I encountered a positive lead level. So when I opened the lab result sheet, I thought I would be shredding it the next moment. Well, that didn’t happen. It turned out that her lead level was 7 mcg/dL! Not too high, but detectable. The only question that kept on coming back over the next month or so was a big WHY? Why my child? Now my older daughter’s lead level was normal at her 1-year visit. We had just moved into a new house before my youngest daughter was born. I thought, it has to do with the house, and since my 1-year-old was putting everything in her mouth at this stage, then she must be getting the lead that way.

Dr. Faddoul is a private practice pediatrician in La Canada Flintridge, Calif.