September 4, 2018, Medscape 

The US Food and Drug Administration (FDA) has approved two new oral treatments for adults with HIV-1 infection, Pifeltro and Delstrigo, both from Merck & Co, according to a company news release.

Pifeltro contains doravirine (100 mg), a new non-nucleoside reverse transcriptase inhibitor to be given in combination with other antiretroviral medicines.  Delstrigo is a once-daily fixed-dose combination of doravirine (100 mg), lamivudine (3TC; 300 mg), and tenofovir disoproxil fumarate (TDF; 300 mg).

Both drugs are indicated for the treatment of HIV-1 infection in adults with no prior antiretroviral treatment history and are taken once daily with or without food.

The FDA approved doravirine on the basis of the phase 3 DRIVE-FORWARD clinical trial, in which 766 patients with no antiretroviral treatment history were randomly assigned to once-daily treatment with doravirine or darunavir 800 mg plus ritonavir 100 mg (DRV+r), each in combination with emtricitabine (FTC)/TDF or abacavir (ABC)/3TC.

Treatment with doravirine led to sustained viral suppression through 48 weeks, meeting its primary endpoint of noninferiority compared with DRV+r, each in combination with FTC/TDF or ABC/3TC.

At week 48, 84% of the doravirine group and 80% of the DRV+r group had plasma HIV-1 RNA of less than 50 copies/mL.

Of the 20% of study participants with a high viral load at baseline (HIV-1 RNA > 100,000 copies/mL), 77% in the doravirine group and 74% in the DRV+r group achieved HIV-1 RNA of less than 50 copies/mL at week 48.

The rate of therapy discontinuation due to adverse events was low in both groups (2% in the doravirine group and 3% in the DRV+r group). Clinical adverse reactions of all grades occurring in at least 5% of participants in the doravirine group included nausea (7%), headache (6%), fatigue (6%), diarrhea (5%), and abdominal pain (5%). No adverse reactions of grade 2 or higher occurred in 2% or more of participants treated with doravirine.

The doravirine/3TC/TDF combination pill was approved on the basis of data from the phase 3 DRIVE-AHEAD trial, in which 728 patients naive to antiretroviral therapy were randomly assigned to once-daily treatment with doravirine/3TC/TDF or efavirenz (EFV)/emtricitabine/tenofovir disoproxil fumarate (EFV 600 mg/FTC 200 mg/TDF 300 mg).

The doravirine/3TC/TDF combination provided sustained viral suppression through 48 weeks, meeting its primary endpoint of noninferiority compared with EFV/FTC/TDF.

At week 48, 84% of the doravirine/3TC/TDF group had plasma HIV-1 RNA of less than 50 copies/mL, as did 81% of the EFV/FTC/TDF group.

Of the 21% of patients with a high viral load at baseline (HIV-1 RNA > 100,000 copies/mL), 77% in the doravirine/3TC/TDF group and 72% in the EFV/FTC/TDF group achieved HIV-1 RNA of less than 50 copies/mL at week 48.

A statistically significantly lower proportion of doravirine-treated patients reported neuropsychiatric adverse events in the three prespecified categories of dizziness (9% vs 37%), sleep disorders and disturbances (12% vs 26%), and altered sensorium (4% vs. 8%).

The rate of discontinuation of treatment due to adverse events was lower with doravirine/3TC/TDF than with EFV/FTC/TDF (3% vs 6%). Clinical adverse reactions of all grades occurring in at least 5% of patients in the doravirine group included dizziness (7%), nausea (5%), and abnormal dreams (5%). No adverse reactions of grade 2 or higher occurred in 2% or more of patients treated with doravirine.

Both of the new drugs "are contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of Delstrigo and Pifeltro. Delstrigo is contraindicated in patients with a previous hypersensitivity reaction to 3TC," the company said in its news release.

"As a result of the remarkable strides made in the fight against HIV, clinicians and their patients have the opportunity to work together to identify treatment regimens that may be best for each individual, taking into account other aspects of that person's health, including other medicines they may be taking," David Wohl, MD, from the AIDS Clinical Trials Unit at the University of North Carolina at Chapel Hill, said in the release. "Today's approvals of Delstrigo and Pifeltro provide two new options for the treatment of HIV-1 in appropriate treatment-naive adult patients."

Merck said it anticipates that both drugs will be stocked through wholesalers within 1 month.

 

August 30, 2018, MedPage Today 

Sexually transmitted disease (STD) diagnoses have increased every year since 2013, with the number of new STD diagnoses the highest ever in 2017, CDC researchers found.

There were 2.3 million cases of chlamydia, gonorrhea, and syphilis diagnosed in 2017, with syphilis diagnoses up by 76% and gonorrhea diagnoses up by 67% since 2013, according to preliminary data released by the CDC at the National STD Prevention Conference in Washington.

At a press briefing, Gail Bolan, MD, director of the CDC division of STD prevention, characterized this as a "continuation of a persistent and troubling trend," particularly noting that rates of diagnosis for gonorrhea "nearly doubled" among men and increased one-fifth among women, "something we haven't seen in a long time," she added.

The CDC reported that chlamydia remained the most common condition reported to the CDC, with more than 1.7 million cases diagnosed in 2017, with a little under half among women ages 15 to 24.

Bolan cited another troubling statistic about the looming threat of antibiotic resistance regarding gonorrhea treatment. The CDC currently recommends a two-dose therapy for gonorrhea consisting of an intramuscular dose of ceftriaxone -- the only "highly effective" antibiotic used to treat gonorrhea in the U.S. -- and oral azithromycin.

But Bolan reported that a "small, but growing fraction" of lab specimens of gonorrhea are showing "signs of antibiotic resistance." While she added that there has never been a "confirmed treatment failure" when using this recommended treatment, the worry is there may eventually be a strain of gonorrhea that does not respond to ceftriaxone.

"Our nation urgently needs new treatment options for gonorrhea," Bolan said. "But CDC alone cannot turn the tide on rising STDs. It requires new commitment from the healthcare sector, scientists, industry, state and local health departments."

"Commitment" usually means "money," and state and local health officials spoke candidly about the country's "eroding public health infrastructure" that they felt contributed to the tremendous increase in STDs. Specifically, officials cited years of cutbacks in funding for STD prevention, with state and local health departments who rely on federal funding to support their STD programs, working with budgets that are half of what they were 15 years ago.

"We maintain our bridges and roads, and we see them on TV when they crumble. You don't always see a crumbling public health infrastructure," said Michael Fraser, PhD, executive director, Association of State and Territorial Health Officials (ASTHO). "We know what works with STD prevention. We just don't want to pay for all of it."

David C. Harvey, MSW, executive director, National Coalition of STD Directors, called for an additional $70 million in funding to "immediately arm state and local health programs to combat this crisis." He said that treatment for STDs costs more than $16 billion a year.

"It is time that President Trump and Secretary Azar declare STDs in America a public health crisis," adding that emergency access to funding is also needed to bring these rates down.

In addition to cutbacks in federal and state funding, Harvey cited other factors for the rise of STDs in America, namely the "extreme lack of awareness and education about STDs and sexual health." But he also said providers and patients played a significant role as "doctors are not screening and testing for STDs and patients don't know they need to ask for screening and treatment."

Bolan added that screening needs to be "routine care" and that providers and patients need to be having that conversation about testing.

Harvey added a plea to Congress for more funding for provider training, through the CDC STD Prevention Training Centers, where funding has also been cut over the last 20 years.

But Fraser pointed out that the solution to the rising STD problem is not going to be "treating our way out of it," and that a solid public health infrastructure is also needed. He specifically noted that cuts in funding have affected programs that support "disease investigators," who meet with individuals, talk about their sexual behavior, do contact tracing, and try to prevent future infections.

"Expecting a physician in an already hurried day-to-day practice to do a slew of [recommended STD testing] is probably not realistic, given the way physicians practice," he said. "Public health can take some of the pressure off the clinical system. You don't need a medical degree to prevent an STD -- you need to talk with people about using condoms."

Bolan said that the full 2017 STD surveillance report is expected to be released in late September.

APAOG members may view recorded webinars at anytime. Please check out our latest addition, "When Sex Hurts: Identifying and Treating the Causes of Sexual Pain: presented by Alyse Kelly-Jones, MD.

Click here to view the webinar library. *Must be logged in to view webinar library. 

August 28, 2018, JAAPA 

Evaluating patients for infertility is common in the primary care setting and can involve multiple differentials and treatment options. This case report describes a 34-year-old woman whose infertility evaluation led to the diagnosis of a pituitary adenoma. 

Read the full article here.

August 23, 2018, MedPage Today 

Routine screening for cervical cancer substantially reduces disease incidence and mortality for average-risk women ages 21 to 65, and the benefits outweigh the harms, the U.S. Preventive Services Task Force (USPSTF) concluded in a final guidance statement on the issue.

The recommendations encompassed multiple screening strategies. The task force concluded "with high certainty" that the benefits of screening women ages 21 to 29 every 3 years with cytology alone (Pap test) "substantially outweigh the harms." The USPSTF panel also concluded that screening every 3 years with a Pap test alone, every 5 years with high-risk human papillomavirus (hrHPV) DNA testing alone, or every 5 years with both tests (cotesting) provides benefits that outweigh the harms for women ages 30 to 65.

The final recommendations differed from the draft guidance, published in September 2017, by recognizing cotesting as an acceptable screening option. However, cotesting every 5 years for women 30 to 65 is identified as an "alternative" to the "preferred" strategies of cervical cytology or hrHPV testing alone.

"Women should choose which strategy is right for them after a discussion with their clinician," according to a statement from the USPSTF.

The task force's review of evidence showed that women younger than 21 or older than 65 do not benefit from screening, provided that women at the upper end of the age range were adequately screened in the past.

The recommendations, published in JAMA, apply to women with an intact cervix, irrespective of sexual history, but do not apply to women with a history of cervical cancer or precancerous cervical lesions.

"Screening for cervical cancer saves lives and identifies the condition early when it is treatable," said task force member Carol Mangione, MD, of UCLA. "There are several effective screening strategies available, so women should talk to their doctor about which one is right for them."

Added panelist Melissa Simon, MD, of Northwestern University's Feinberg School of Medicine in Chicago: "Most cases of cervical cancer occur in women who have not been regularly screened or appropriately treated. That's why it's important for women to be screened regularly throughout their lifetime and receive follow-up and treatment when needed."

The authors of an accompanying editorial lauded the USPSTF for including cotesting as an option for cervical cancer screening.

"The USPSTF has shown a high degree of responsiveness to the concerns of clinicians and patients about cotesting," wrote Lee Learman, MD, PhD, of Florida Atlantic University in Boca Raton, and Francisco Garcia, MD, of the University of Arizona in Tucson.

"The current USPSTF recommendation statement preserves the greatest range of choices for practitioners and patients; in that sense, both will benefit," the editorial added.

The recommendations have the effect of achieving "an unprecedented degree of concordance across recommendations from a variety of professional organizations," Learman and Garcia continued. The USPSTF, American College of Obstetricians and Gynecologists (ACOG), American Cancer Society/American Society for Colposcopy and Cervical Pathology (ASCCP)/American Society for Clinical Pathology, and (to a lesser extent) the Women's Preventive Services Task Force of the Institute of Medicine "all arrived at very similar recommendations."

The author of a second editorial appearing in JAMA Internal Medicine noted that the USPSTF did not include cost-effectiveness in the review that led to the recommendations. "Although the USPSTF sets the standard for evidence-based recommendations and acknowledges the critical value of high-quality evidence in making recommendations, it might reasonably be asked, where is the evidence of value in cervical cancer screening?" wrote George Sawaya, MD, of the University of California San Francisco.

Sawaya pointed out that he is leading an ongoing evaluation of cost-effectiveness analyses "to determine the range of reasonable options for cervical cancer screening. Such analyses may inform future screening recommendations."

He also noted that the USPSTF recommendations differ in two ways from the Society of Gynecologic Oncology (SGO) guidance on the issue: (1) Starting hrHPV testing at age 30, rather than 25, as supported by SGO; and (2) testing at 5-year intervals and not more frequently.

ACOG, ASCCP, and SGO issued a joint statement, thanking the USPSTF for including multiple screening options in the recommendations and describing the task force guidance as "largely in line" with their own recommendations.

One or more members of the task force disclosed relationships with Healthwise, the National Area Health Education Center Organization, and the Merck Foundation.

Sawaya reporting having no relevant relationships with industry.

August 21, 2018, Medscape 

The standard of care for human papillomavirus (HPV)-positive oropharyngeal cancer remains radiation therapy and cisplatin, say experts, after interim results from a large phase 3 trial comparing another regimen showed worse outcomes. Patients who were treated with radiation and cetuximab had worse overall and progression-free survival, but overall rates of serious (grade 3 to 5) adverse events were similar for both study groups. These top-line results from RTOG 1016 were outlined in a press release issued by the National Cancer Institute (NCI), which funded the trial. 

August 15,2018, Healio 

Women in labor receiving IV remifentanil patient-controlled analgesia were half as likely to need a subsequent epidural than those receiving intramuscular pethidine injection, which is the current standard of care, according to data published in The Lancet.

“Previous studies have shown that at least one in three women given pethidine to manage pain during labor require a subsequent epidural as the drug is not always effective. It also has unwanted side effects such as sedation and nausea for the mother, and it may pass into the baby’s bloodstream through the placenta,” Matthew J.A. Wilson, MD, from the School of Health and Related Research at the University of Sheffield, England, said in a press release.

Remifentanil may be an alternative to pethidine but is not widely used or researched, according to Wilson and colleagues. Therefore, the researchers conducted a trial to investigate whether IV remifentanil patient-controlled analgesia during labor reduces the need for epidural analgesia and subsequent adverse maternal or neonatal events compared with intramuscular pethidine injection.

A total of 400 women aged 16 years or older, beyond 37 weeks’ gestation were randomly assigned to receive either remifentanil (n = 201) or pethidine (n = 199) during labor if they requested opioid pain relief. Patients in the remifentanil group controlled their own IV drip and could receive a 40-g bolus of remifentanil on demand every 2 minutes. Patients in the pethidine group were injected with 100 mg of pethidine every 4 hours for up to 400 mg in a 24-hour period.

All participants were able to request an epidural at any time. If patients received an epidural, the other form of pain relief was discontinued.

The allocated drug was received by 93% of participants in the remifentanil group and 77% of participants in the pethidine group.

The researchers found that 19% of patients in the remifentanil group and 41% of those in the pethidine group had an epidural (RR = 0.48; 95% CI, 0.34–0.66).

Women in the remifentanil group reported that their pain was less severe than those in the pethidine group. The need for forceps and vacuum during labor was less common among women receiving remifentanil than those receiving pethidine (15% vs. 26%).

The incidence of low oxygen levels was twice as likely among women in the remifentanil group than the pethidine group (14% vs. 5%). Additionally, supplementary oxygen was given to more patients in the remifentanil group.

No serious adverse events or drug reactions were observed in either group.

“Our findings challenge the routine use of pethidine for pain relief during labor,” Wilson said in the release. “Remifentanil reduced the need for an epidural by half and there were no lasting problems for the mothers and babies in our trial, although the effect of remifentanil on maternal oxygen levels needs to be clarified in further studies.” – by Alaina Tedesco

Disclosure: The authors report no relevant financial disclosures.

August 8, 2018, JAAPA 

Adverse reactions to hormonal contraceptives are a common patient concern. Alopecia, an adverse reaction to androgen activity caused by the progestin component of hormonal contraceptives, can cause considerable psychosocial distress for women. This article discusses how to identify the level of androgen activity in certain progestins, how increased androgen activity can lead to hair loss, and alternatives for patients experiencing androgenic alopecia due to high androgen index contraceptives.

Read more.

August 6, 2018, MultiBrief 

About 1.5 million Americans are diagnosed with diabetes every year. In 2015, 30.3 million Americans, or 9.4 percent of the population, had diabetes. Approximately 1.25 million American children and adults have type 1 diabetes.

Diabetes kills more Americans every year (2010: 69,201 deaths) than acquired immunodeficiency syndrome (21,601 deaths, 2009) and breast cancer (40,676 deaths, 2009) combined. Nearly half of American adults have diabetes or prediabetes.

Diabetes increases the risk of heart disease (the most common diabetes complication) by about four times in women but only about two times in men, and women have worse outcomes after a heart attack. Women are also at higher risk of other diabetes-related complications such as blindness, kidney disease and depression.

Diabetes is different among women as well. African American, Hispanic/Latina, American Indian/Alaska Native and Asian/Pacific Islander women are more likely to have diabetes than white women.

Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. In fact, diabetes and cancer often coexist in the same individuals. In a previous study, 8 percent to 18 percent of individuals suffering from cancer also had diabetes, and prevalence rates varied according to tumor sites.

A recent global review involving almost 20 million people has shown that having diabetes significantly raises the risk of developing cancer, and for women the risk is even higher. According to Dr. Toshiaki Ohkuma, research fellow with The George Institute for Global Health, the link between diabetes and the risk of developing cancer is now firmly established.

Ohkuma and researchers have also demonstrated for the first time that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral and stomach cancers, and leukemia.

This review indicated that women with diabetes were 27 percent more likely to develop cancer than women without diabetes, and for men the risk was 19 percent higher. Diabetes was a risk factor for the majority of cancers of specific parts of the body for both men and women. Overall, women with diabetes were 6 percent more likely to develop any form of cancer than men with diabetes.

There were significantly higher risks for women with diabetes for developing cancer of the kidney (11 percent higher), oral cancer (13 percent higher), stomach cancer (14 percent higher) and leukemia (15 percent higher) compared to men. For liver cancer, the risk was 12 percent lower for women with diabetes compared to men with diabetes. One explanation is that heightened blood glucose may have cancer-causing effects by leading to DNA damage.

Dr. Sanne Peters of The George Institute for Global Health at the University of Oxford believes that there are several possible reasons why women were subject to an excess risk of cancer. Women are in the pre-diabetic state of impaired glucose tolerance two years longer than men.

According to the researchers, the more gender-specific research indicates that women are not only undertreated, they have different risk factors for other diseases, including stroke, heart disease, as well as diabetes.

July 21, 2018, Medical News Today  

The Food and Drug Administration announce the approval of the commercial version of the drug elagolix for the treatment of endometriosis pain. This is the first time in over a decade that an oral treatment specifically designed for endometriosis pain has been approved.

Endometriosis is a condition affecting around 1 in 10 women in the United States, and around 200 million people worldwide.

The condition is characterized by an abnormal growth of endometrium, which is the tissue that normally lines the inside of the uterus.

This tissue growth causes pain in the pelvis, lower back, and abdomen. Other symptoms include heavy periods or bleeding in-between periods, extremely painful menstrual cramps, pain during intercourse, and infertility.

There is currently no cure for the condition, but surgery is often recommended to remove the tissue, which relieves the symptoms for a while. Birth controlpills are often prescribed to slow down the growth of abnormal tissue, and nonsteroidal anti-inflammatory drugs such as ibuprofen help ease the pain.

Now, the Food and Drug Administration (FDA) have approved a new drug to ease the pain of women living with moderate to severe endometriosis.

Elagolix is "the first and only oral gonadotropin-releasing hormone [...] antagonist" designed specifically for endometriosis.

The drug — which will be marketed at the beginning of August this year under the brand name Orilissa — is the first of its kind to have been approved by the FDA in more than a decade. 

Drug relieves pain in largest clinical trial yet 

The drug was approved based on the results of two studies that formed the largest phase 3 clinical trial program to have ever been conducted on endometriosis.

In total, the studies examined the effects of elagolix on almost 1,700 women who had moderate to severe endometriosis pain.

In the two studies, the women were administered either 150 milligrams of elagolix once daily or 200 milligrams twice daily.

Compared with the women who received placebo, those who received the treatment reported a significant reduction in three types of pain: nonmenstrual pelvic pain, menstrual pelvic pain, and pain during intercourse.

These results were noted at 3 months and 6 months from the beginning of the treatment.

The FDA approved the following recommended dosage and duration of use: the drug can be taken for up to 24 months in a dosage of 150 milligrams per day, or up to 6 months if the dose is 200 milligrams twice per day.

However, the clinical trials also revealed a range of side effects. The most common ones were hot flashes, night sweats, headache, nausea, trouble sleeping, anxiety, joint pain, depression, and mood swings.

The biopharmaceutical company AbbVie funded the clinical trials. Dr. Michael Severino, the vice president of the company, comments on the FDA approval, saying that it "represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease."

First study author Dr. Hugh S. Taylor — the chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine in New Haven, CT — also weighs in, saying, "Endometriosis is often characterized by chronic pelvic pain that can impact women's daily activities."