As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.

In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.

Carol Renner/NDSU

Steroid fiasco sparked rule revisions

The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.

More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.

The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.

As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.

“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.

“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.

In-office mixing a top concern

Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.

Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.

Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.

Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”

USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.

“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.

Pediatric issues

Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.

They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.

“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.

Relevance of rules

None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.

Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.

Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”

Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.

Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.

He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.

But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.

The quinacrine problem

A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.

“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”

Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”

Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.

While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.

Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.

Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.

[email protected]

As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.

In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.

Carol Renner/NDSU

Steroid fiasco sparked rule revisions

The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.

More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.

The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.

As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.

“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.

“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.

In-office mixing a top concern

Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.

Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.

Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.

Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”

USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.

“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.

Pediatric issues

Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.

They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.

“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.

Relevance of rules

None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.

Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.

Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”

Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.

Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.

He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.

But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.

The quinacrine problem

A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.

“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”

Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”

Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.

While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.

Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.

Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.

[email protected]

As new rules about drug compounding get shaped, rheumatologists seek to protect their ability to combine injectable drugs – most commonly a steroid and a local anesthetic – in their own offices.

In a position statement sent to government agencies and members of Congress in February, the American College of Rheumatology voiced concerns that the practice, which it called “critical,” could become a casualty of drug-compounding regulations under revision by the United States Pharmacopeial Convention (USP), a nonprofit group whose standards are enforceable by state and federal regulators.

Carol Renner/NDSU

Steroid fiasco sparked rule revisions

The ACR’s concerns follow a tighter focus by state and federal agencies on drug compounding after a fungal meningitis outbreak in 2012 was traced to contaminated steroids produced in bulk by a compounding pharmacy.

More than 800 infections, 64 of them fatal, occurred after the New England Compounding Center in Framingham, Mass., sold contaminated methylprednisolone acetate that was used in epidural and intra-articular joint injections.

The following year Congress passed the Drug Quality and Security Act, which aims, in part, to prevent compounding pharmacies from engaging in what amounts to unregulated manufacturing.

As part of the law, the FDA created a list of drugs appropriate for compounding and a process by which larger compounding pharmacies must register with the FDA, and agree to inspections. The USP standards, meanwhile, address detailed technical and safety aspects of compounding and are enforceable by the FDA and state agencies.

“USP and FDA have had the ability to regulate compounding for over a decade, but only recently have the rules become actively enforced,” said Donald Miller, PharmD, of North Dakota State University, Fargo, who helped shape the ACR’s position statement on compounding with the help of rheumatologists in private practice.

“When you make guidelines for safety, they make sense, but then you can’t anticipate the way it’s going to affect individuals’ practice. And that’s where rheumatology got caught up,” said Dr. Miller, who was a member of the FDA Arthritis Advisory Committee in 2014-2016.

In-office mixing a top concern

Other specialties, including dermatology and immunology, also stand to be affected by various changes to compounding law and practice – and their societies have been active in voicing concerns.

Though the latest revisions of USP chapter 797, which impacts in-office mixing, are still being sorted out, it’s the No. 1 compounding-related concern for rheumatologists, Dr. Miller said.

Rheumatologists routinely mix an analgesic and a steroid for injection. The analgesic makes the steroids less viscous, and offers patients hours of immediate relief. They also add analgesics to hyaluronic acid injected for viscosupplementation. The mixing is usually conducted bedside, and the injections are administered right away.

Technically, combining these products amounts to sterile compounding, Dr. Miller explained. “And theoretically, under these rules, a physician could still do this, but they’d have to do it under a sterile hood like you find in a pharmacy, and that’s just not practical. It also becomes a matter of interpretation.”

USP chapter 797 sanctions in-office mixing for “immediate use” with individual patients – which is nearly always the case for the steroid injections used in rheumatology. But it’s unclear whether “immediate use” means emergency use only, or allows for routine use, as rheumatologists hope.

“One reason this came to rheumatology’s attention is that some state boards of medicine were inspecting and saying ‘Hey, you can’t do that,’ ” Dr. Miller said.

Pediatric issues

Pediatric rheumatologists, and adult rheumatologists who see children occasionally, use compounding pharmacies to create palatable oral medicines and adjusted doses of adult treatments.

They also use injections combining steroids with analgesics, and consider the addition of the analgesic a key aid to compliance.

“The biggest barrier we have is patient and parent anxiety about doing the procedure and the associated pain. We always administer our steroids mixed with lidocaine to help with the postprocedural discomfort,” said Adam Reinhardt, MD, chief of pediatric rheumatology at the University of Nebraska and Children’s Hospital and Medical Center in Omaha.

Relevance of rules

None of the rheumatologists interviewed questioned the need for tightened state and federal oversight of compounding practices overall – just the applicability of certain rules to their own practice.

Dr. Snow and Dr. Huffstutter noted that reports of infected joints – a potential result of a contaminated injection – are sporadic and rare. “There’s very little research in this, but [these types of injections] have been standard practice for decades,” Dr. Snow said.

Srikanth Mukkera, MD, a rheumatologist in Tupelo, Miss., agreed that “sporadic cases of joint infection do happen following injection, but it can be hard to show if an injection was the cause.”

Assuring that medicines are mixed only immediately prior to injection, and not stored, reduces the likelihood of contamination, Dr. Mukkera said. Moreover, he noted, epidural injections such as those that resulted in the 2012 meningitis outbreak carry different risks than those seen in intra-articular injections.

Dr. Miller, the lead author of the ACR statement, said that the rheumatologists on our committee “don’t know of anyone that’s had a knee or other joint infection from a contaminated injection. They feel that unless somebody finds some evidence of that, they should be allowed to continue” with their usual practice.

He said that he feels that the USP will ultimately heed the concerns of rheumatologists and hopefully provide a more relaxed interpretation of in-office compounding. “We’re hoping they’ll make some exceptions when they revise 797 standards or at least maybe leave room for organizations to create a best practice statement. We’ll see,” Dr. Miller said.

But this is in no way guaranteed. Dr. Huffstutter said he fears that, if the rules come to be interpreted more narrowly, even standard practices like reconstituting biologic drugs for infusion – something that’s also a routine part of in-office practice – could fall under the rubric of sterile compounding and come into question.

The quinacrine problem

A separate compounding-related issue in rheumatology is clinicians’ access to quinacrine, an antimalarial rheumatology drug that, while infrequently used, represents the only alternative to hydroxychloroquine for some lupus patients.

“There are no alternatives out there for hydroxychloroquine, so we need it as a backup,” Dr. Snow said. “If hydroxychloroquine isn’t an option, there’s nothing out there that we can use. There’s no easy replacement.”

Dr. Huffstutter said he currently had no patients on quinacrine. “It’s not very often that we use it, but in those patients that really need it, it can make a huge difference in how they do.”

Quinacrine is no longer manufactured commercially as a finished drug product but is available in a powder that compounding physicians put into 100-mg capsules. It is not on the FDA’s current list of drugs available for compounding except with special permission.

While the ACR has requested that the FDA add it the list of bulk drug substances that can be used in compounding, quinacrine remains off the list for now – and, providers say, hard to find.

Moreover, while rheumatologists may have previously been able to order and store quantities of quinacrine and other compounded nonsterile medications to dispense to their patients, they can no longer easily do so, as only the FDA-approved compounding “outsourcing facilities” are allowed to process larger orders; the rest can only respond to prescriptions for individual patients.

Dr. Miller said it’s likely that quinacrine will make it onto the FDA’s next list of bulk drugs available for compounding. “The FDA has kind of said, ‘Don’t worry about it,’ ” he said.

[email protected]

About 24% of women and 1% of men will experience military sexual trauma (MST) during their service.¹ Despite the higher percentage of women reporting MST, the estimated number of men (55,491) and women (72,497) who endorse MST is relatively similar. Military sexual trauma is associated with negative psychosocial (eg, decreased quality of life) and psychiatric (eg, posttraumatic stress disorder [PTSD], depression) sequelae. Surís and colleagues provided a full review of sequelae, with PTSD being the most discussed consequence of MST.² However, sexually transmitted infections (STIs) during or after MST are a consequence of growing concern.

Sexually Transmitted Infections

The link between sexual trauma and increased incidence of STIs is well established. Survivors of rape are at a higher risk of exposure to STIs due to unprotected sexual contact that may occur during the assault(s).³ Numerous studies have demonstrated that sexual trauma is directly related to greater engagement in risky sexual behaviors (eg, more sexual partners, unprotected sex, and “sex trading”).^2,4

This relationship is particularly concerning given that individuals in the military tend to report sexual trauma with greater propensity than that reported in civilian populations.⁴ Additionally, military personnel and veteran populations tend to engage in high-risk behaviors (eg, alcohol and drug use) more often than their civilian counterparts, increasing their potential susceptibility to predatory sexual trauma(s) and victimization.^2,5 Taken in aggregate, military personnel and veterans may be at increased risk for STIs compared with the civilian population due to the increased incidence of risky sexual behavior and sexual traumatization during military service.

Sexually transmitted infections potentially lead to immediate-term (eg, physical discomfort, sexual dysfunction) and long-term (eg, cancer, infertility) adverse health consequences.⁶ Early detection is crucial in the treatment of STIs because it can aid in preventing STI transmission and allow for early intervention. See Table for a list of common STIs and their prevalence, testing method, method of sexual transmission, and treatment. Early detection is also important because many STIs may be asymptomatic (eg, HIV, human papillomavirus [HPV]), which decreases the likelihood of seeking testing or treatment as well as increases the likelihood of transmission.⁷

Current Research

To date, only 1 study has explicitly examined the relationship between MST and STIs. In 2011, researchers analyzed a large national database of 420,725 male and female Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans.⁶ In the study, both male and female OEF/OIF veterans who endorsed MST were significantly more likely than those who did not endorse MST to have a STI diagnosis. The researchers noted that this finding underscored the necessity for sexual health assessment in survivors of MST, to facilitate early detection and treatment.

STI Risk Assessment

Because military personnel and veterans often initially disclose their MST to a mental health provider (MHP), these providers operate in a unique circumstance where they may be the individual’s first point of contact for determining STI risk. In these circumstances, the MHP should consider the utility of briefly assessing the patient’s sexual health and making subsequent medical referrals as necessary.

To accurately assess a patient’s STI risk, the MHP should gather information regarding both current/acute risk (eg, “Have you had unprotected sexual contact, for instance, genital contact without a condom or oral sex without a dental dam, in the past month?”) as well as longer standing (eg, “Have you had unprotected sexual contact... in the past year?”) STI risk. Providers also should consider oral, anal, and genital modes of sexual contact as well as common STI symptoms (eg, warts, sores, genital discharge, and/or pain or burning sensation when peeing or during sex). Additionally, psychoeducation should be provided, especially information regarding the asymptomatic nature of certain STIs, such as HIV and HPV, and the risk of transmission in all forms of sexual contact, including nongenital anal contact. Appropriate referrals to sexual health education, including safe sex practices, also should be considered in order to minimize risk of future STI transmission.

Mental health providers also should determine the date of patient’s most recent STI test. Not all STIs can be detected via a blood test or routine yearly Papanicolaou (Pap test) physicals. Additionally, MHPs should be aware that risky practices, including substance misuse, are more common in survivors of MST and that there is an association between substance misuse and STIs.^2,6 If testing has not occurred recently, MHPs should strongly encourage the individual to access STI testing and provide resources as necessary, such as access to low-cost STI testing. Further, if the MHP has reason to suspect the presence of an STI after the brief assessment (eg, individual endorses unprotected sexual contact or risky behaviors, including substance misuse, sex trading, and STI symptomatology; a positive STI test but the patient has not accessed treatment), an appropriate sexual health referral should be made.

During the assessment and psychoeducation processes, terminology and language plays an integral role. If a MHP assumes an individual has sexual contact only with opposite sex partners (eg, asking a male “How many women have you had sexual contact with in the past 30 days?” vs “How many partners have you had sexual contact with in the past 30 days?”), the MHP will not accurately assess the individual’s level of current risk. Additionally, it is important to remember that sexual behavior does not always align with sexual identity: A man who identifies as heterosexual may still have sexual contact with men. Due to the sensitive nature of sexual health, MHPs should be careful to use nonjudgmental language, such as using the term sex work rather than the more pejorative term prostitution, to avoid offending patients and to increase their likelihood to disclose sexual health information.

Nonjudgmental language is especially relevant when working with gender-minority veterans (eg, transgender, gender nonconforming, gender transitioning), because this clinical population has a higher risk of victimization and lower rates of help-seeking health behavior.⁷ In particular, a sizable portion of individuals who identify as transgender do not seek services out of fear that they will be discriminated against, humiliated, or misunderstood.⁷ To assuage these concerns, MHPs should ensure they refer to the veteran with the veteran’s preferred pronouns. For example, a MHP could ask “I would like to be respectful, how would you like to be addressed?” or “What name and pronoun would you like me/us to use?” Providers also should consider nonbinary pronouns when appropriate (eg, singular: ze/hir/hirs; plural: they/them/theirs). Providers also should recognize that making a mistake is not uncommon, and they should apologize to maintain rapport and maximize the patient’s comfort during this distressing process. Further, MHPs should consider additional training, education, and/or consultation if they feel uncomfortable or ill prepared when working with gender-minority veterans.

Future Research

Research has attempted to understand the consequences of MST on sexual health; however, despite these efforts, more research is necessary. The majority of published studies have focused on females even though a similar number of males have reported MST.² This dearth of published studies likely is due to hesitation by male active-duty personnel and veterans to disclose or seek treatment for MST and because the percentage of females reporting MST is much higher. Males are less likely to report or seek treatment for MST because of stigma-based concerns (eg, shame, self-blame, privacy concerns).^8,9 Therefore, it is difficult to acquire a sizable research sample to study. As previously noted, a single study has specifically examined MST and STI risk. Although this study included a sizable population of male OEF/OIF veterans, results have yet to be replicated in other clinical populations of interest, such as male military personnel and male veterans of other service eras.

Research is even more limited regarding lesbian, gay, bisexual, transgender, and other gender-minority military personnel and veterans. Although researchers propose that these populations may experience a similar, or even heightened, likelihood of MST during their service, no empirical research yet exists to fully examine this hypothesis.^10,11 It is important to note that the paucity of research attention may be related to the Don’t Ask, Don’t Tell (DADT) policy, which obstructed the open discussion and empirical examination of sexual and gender minorities within military populations.¹¹ The DADT policy led to limited awareness and greater stigmatization among sexual- and gender-minority personnel, resulting in poorer sexual health outcomes in these populations.^10,11 With the end of DADT in 2011, it is now imperative for future research to examine the prevalence and associated consequences of MST in sexual- and gender-minority military personnel and veterans.

Conclusion

The DoD and VA should be commended for their continued focus on understanding the health consequences of MST. These efforts have yielded substantial information regarding the negative effects of MST on sexual health; in particular, increased risk for STIs. These findings suggest that MHPs may, at times, be the first point of contact for MST-related sexual health concerns. These providers should be aware of their ability to assess for STI risk and make appropriate referrals to facilitate early detection and access to treatment. Despite the presence of MST-related sexual health research, continued research remains necessary. In particular, a broader focus that includes other genders (eg, male, transgender) and sexual minorities would further inform research and clinical practice.

About 24% of women and 1% of men will experience military sexual trauma (MST) during their service.¹ Despite the higher percentage of women reporting MST, the estimated number of men (55,491) and women (72,497) who endorse MST is relatively similar. Military sexual trauma is associated with negative psychosocial (eg, decreased quality of life) and psychiatric (eg, posttraumatic stress disorder [PTSD], depression) sequelae. Surís and colleagues provided a full review of sequelae, with PTSD being the most discussed consequence of MST.² However, sexually transmitted infections (STIs) during or after MST are a consequence of growing concern.

Sexually Transmitted Infections

The link between sexual trauma and increased incidence of STIs is well established. Survivors of rape are at a higher risk of exposure to STIs due to unprotected sexual contact that may occur during the assault(s).³ Numerous studies have demonstrated that sexual trauma is directly related to greater engagement in risky sexual behaviors (eg, more sexual partners, unprotected sex, and “sex trading”).^2,4

This relationship is particularly concerning given that individuals in the military tend to report sexual trauma with greater propensity than that reported in civilian populations.⁴ Additionally, military personnel and veteran populations tend to engage in high-risk behaviors (eg, alcohol and drug use) more often than their civilian counterparts, increasing their potential susceptibility to predatory sexual trauma(s) and victimization.^2,5 Taken in aggregate, military personnel and veterans may be at increased risk for STIs compared with the civilian population due to the increased incidence of risky sexual behavior and sexual traumatization during military service.

Sexually transmitted infections potentially lead to immediate-term (eg, physical discomfort, sexual dysfunction) and long-term (eg, cancer, infertility) adverse health consequences.⁶ Early detection is crucial in the treatment of STIs because it can aid in preventing STI transmission and allow for early intervention. See Table for a list of common STIs and their prevalence, testing method, method of sexual transmission, and treatment. Early detection is also important because many STIs may be asymptomatic (eg, HIV, human papillomavirus [HPV]), which decreases the likelihood of seeking testing or treatment as well as increases the likelihood of transmission.⁷

Current Research

To date, only 1 study has explicitly examined the relationship between MST and STIs. In 2011, researchers analyzed a large national database of 420,725 male and female Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans.⁶ In the study, both male and female OEF/OIF veterans who endorsed MST were significantly more likely than those who did not endorse MST to have a STI diagnosis. The researchers noted that this finding underscored the necessity for sexual health assessment in survivors of MST, to facilitate early detection and treatment.

STI Risk Assessment

Because military personnel and veterans often initially disclose their MST to a mental health provider (MHP), these providers operate in a unique circumstance where they may be the individual’s first point of contact for determining STI risk. In these circumstances, the MHP should consider the utility of briefly assessing the patient’s sexual health and making subsequent medical referrals as necessary.

To accurately assess a patient’s STI risk, the MHP should gather information regarding both current/acute risk (eg, “Have you had unprotected sexual contact, for instance, genital contact without a condom or oral sex without a dental dam, in the past month?”) as well as longer standing (eg, “Have you had unprotected sexual contact... in the past year?”) STI risk. Providers also should consider oral, anal, and genital modes of sexual contact as well as common STI symptoms (eg, warts, sores, genital discharge, and/or pain or burning sensation when peeing or during sex). Additionally, psychoeducation should be provided, especially information regarding the asymptomatic nature of certain STIs, such as HIV and HPV, and the risk of transmission in all forms of sexual contact, including nongenital anal contact. Appropriate referrals to sexual health education, including safe sex practices, also should be considered in order to minimize risk of future STI transmission.

Mental health providers also should determine the date of patient’s most recent STI test. Not all STIs can be detected via a blood test or routine yearly Papanicolaou (Pap test) physicals. Additionally, MHPs should be aware that risky practices, including substance misuse, are more common in survivors of MST and that there is an association between substance misuse and STIs.^2,6 If testing has not occurred recently, MHPs should strongly encourage the individual to access STI testing and provide resources as necessary, such as access to low-cost STI testing. Further, if the MHP has reason to suspect the presence of an STI after the brief assessment (eg, individual endorses unprotected sexual contact or risky behaviors, including substance misuse, sex trading, and STI symptomatology; a positive STI test but the patient has not accessed treatment), an appropriate sexual health referral should be made.

During the assessment and psychoeducation processes, terminology and language plays an integral role. If a MHP assumes an individual has sexual contact only with opposite sex partners (eg, asking a male “How many women have you had sexual contact with in the past 30 days?” vs “How many partners have you had sexual contact with in the past 30 days?”), the MHP will not accurately assess the individual’s level of current risk. Additionally, it is important to remember that sexual behavior does not always align with sexual identity: A man who identifies as heterosexual may still have sexual contact with men. Due to the sensitive nature of sexual health, MHPs should be careful to use nonjudgmental language, such as using the term sex work rather than the more pejorative term prostitution, to avoid offending patients and to increase their likelihood to disclose sexual health information.

Nonjudgmental language is especially relevant when working with gender-minority veterans (eg, transgender, gender nonconforming, gender transitioning), because this clinical population has a higher risk of victimization and lower rates of help-seeking health behavior.⁷ In particular, a sizable portion of individuals who identify as transgender do not seek services out of fear that they will be discriminated against, humiliated, or misunderstood.⁷ To assuage these concerns, MHPs should ensure they refer to the veteran with the veteran’s preferred pronouns. For example, a MHP could ask “I would like to be respectful, how would you like to be addressed?” or “What name and pronoun would you like me/us to use?” Providers also should consider nonbinary pronouns when appropriate (eg, singular: ze/hir/hirs; plural: they/them/theirs). Providers also should recognize that making a mistake is not uncommon, and they should apologize to maintain rapport and maximize the patient’s comfort during this distressing process. Further, MHPs should consider additional training, education, and/or consultation if they feel uncomfortable or ill prepared when working with gender-minority veterans.

Future Research

Research has attempted to understand the consequences of MST on sexual health; however, despite these efforts, more research is necessary. The majority of published studies have focused on females even though a similar number of males have reported MST.² This dearth of published studies likely is due to hesitation by male active-duty personnel and veterans to disclose or seek treatment for MST and because the percentage of females reporting MST is much higher. Males are less likely to report or seek treatment for MST because of stigma-based concerns (eg, shame, self-blame, privacy concerns).^8,9 Therefore, it is difficult to acquire a sizable research sample to study. As previously noted, a single study has specifically examined MST and STI risk. Although this study included a sizable population of male OEF/OIF veterans, results have yet to be replicated in other clinical populations of interest, such as male military personnel and male veterans of other service eras.

Research is even more limited regarding lesbian, gay, bisexual, transgender, and other gender-minority military personnel and veterans. Although researchers propose that these populations may experience a similar, or even heightened, likelihood of MST during their service, no empirical research yet exists to fully examine this hypothesis.^10,11 It is important to note that the paucity of research attention may be related to the Don’t Ask, Don’t Tell (DADT) policy, which obstructed the open discussion and empirical examination of sexual and gender minorities within military populations.¹¹ The DADT policy led to limited awareness and greater stigmatization among sexual- and gender-minority personnel, resulting in poorer sexual health outcomes in these populations.^10,11 With the end of DADT in 2011, it is now imperative for future research to examine the prevalence and associated consequences of MST in sexual- and gender-minority military personnel and veterans.

Conclusion

The DoD and VA should be commended for their continued focus on understanding the health consequences of MST. These efforts have yielded substantial information regarding the negative effects of MST on sexual health; in particular, increased risk for STIs. These findings suggest that MHPs may, at times, be the first point of contact for MST-related sexual health concerns. These providers should be aware of their ability to assess for STI risk and make appropriate referrals to facilitate early detection and access to treatment. Despite the presence of MST-related sexual health research, continued research remains necessary. In particular, a broader focus that includes other genders (eg, male, transgender) and sexual minorities would further inform research and clinical practice.

About 24% of women and 1% of men will experience military sexual trauma (MST) during their service.¹ Despite the higher percentage of women reporting MST, the estimated number of men (55,491) and women (72,497) who endorse MST is relatively similar. Military sexual trauma is associated with negative psychosocial (eg, decreased quality of life) and psychiatric (eg, posttraumatic stress disorder [PTSD], depression) sequelae. Surís and colleagues provided a full review of sequelae, with PTSD being the most discussed consequence of MST.² However, sexually transmitted infections (STIs) during or after MST are a consequence of growing concern.

Sexually Transmitted Infections

The link between sexual trauma and increased incidence of STIs is well established. Survivors of rape are at a higher risk of exposure to STIs due to unprotected sexual contact that may occur during the assault(s).³ Numerous studies have demonstrated that sexual trauma is directly related to greater engagement in risky sexual behaviors (eg, more sexual partners, unprotected sex, and “sex trading”).^2,4

This relationship is particularly concerning given that individuals in the military tend to report sexual trauma with greater propensity than that reported in civilian populations.⁴ Additionally, military personnel and veteran populations tend to engage in high-risk behaviors (eg, alcohol and drug use) more often than their civilian counterparts, increasing their potential susceptibility to predatory sexual trauma(s) and victimization.^2,5 Taken in aggregate, military personnel and veterans may be at increased risk for STIs compared with the civilian population due to the increased incidence of risky sexual behavior and sexual traumatization during military service.

Sexually transmitted infections potentially lead to immediate-term (eg, physical discomfort, sexual dysfunction) and long-term (eg, cancer, infertility) adverse health consequences.⁶ Early detection is crucial in the treatment of STIs because it can aid in preventing STI transmission and allow for early intervention. See Table for a list of common STIs and their prevalence, testing method, method of sexual transmission, and treatment. Early detection is also important because many STIs may be asymptomatic (eg, HIV, human papillomavirus [HPV]), which decreases the likelihood of seeking testing or treatment as well as increases the likelihood of transmission.⁷

Current Research

To date, only 1 study has explicitly examined the relationship between MST and STIs. In 2011, researchers analyzed a large national database of 420,725 male and female Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans.⁶ In the study, both male and female OEF/OIF veterans who endorsed MST were significantly more likely than those who did not endorse MST to have a STI diagnosis. The researchers noted that this finding underscored the necessity for sexual health assessment in survivors of MST, to facilitate early detection and treatment.

STI Risk Assessment

Because military personnel and veterans often initially disclose their MST to a mental health provider (MHP), these providers operate in a unique circumstance where they may be the individual’s first point of contact for determining STI risk. In these circumstances, the MHP should consider the utility of briefly assessing the patient’s sexual health and making subsequent medical referrals as necessary.

To accurately assess a patient’s STI risk, the MHP should gather information regarding both current/acute risk (eg, “Have you had unprotected sexual contact, for instance, genital contact without a condom or oral sex without a dental dam, in the past month?”) as well as longer standing (eg, “Have you had unprotected sexual contact... in the past year?”) STI risk. Providers also should consider oral, anal, and genital modes of sexual contact as well as common STI symptoms (eg, warts, sores, genital discharge, and/or pain or burning sensation when peeing or during sex). Additionally, psychoeducation should be provided, especially information regarding the asymptomatic nature of certain STIs, such as HIV and HPV, and the risk of transmission in all forms of sexual contact, including nongenital anal contact. Appropriate referrals to sexual health education, including safe sex practices, also should be considered in order to minimize risk of future STI transmission.

Mental health providers also should determine the date of patient’s most recent STI test. Not all STIs can be detected via a blood test or routine yearly Papanicolaou (Pap test) physicals. Additionally, MHPs should be aware that risky practices, including substance misuse, are more common in survivors of MST and that there is an association between substance misuse and STIs.^2,6 If testing has not occurred recently, MHPs should strongly encourage the individual to access STI testing and provide resources as necessary, such as access to low-cost STI testing. Further, if the MHP has reason to suspect the presence of an STI after the brief assessment (eg, individual endorses unprotected sexual contact or risky behaviors, including substance misuse, sex trading, and STI symptomatology; a positive STI test but the patient has not accessed treatment), an appropriate sexual health referral should be made.

During the assessment and psychoeducation processes, terminology and language plays an integral role. If a MHP assumes an individual has sexual contact only with opposite sex partners (eg, asking a male “How many women have you had sexual contact with in the past 30 days?” vs “How many partners have you had sexual contact with in the past 30 days?”), the MHP will not accurately assess the individual’s level of current risk. Additionally, it is important to remember that sexual behavior does not always align with sexual identity: A man who identifies as heterosexual may still have sexual contact with men. Due to the sensitive nature of sexual health, MHPs should be careful to use nonjudgmental language, such as using the term sex work rather than the more pejorative term prostitution, to avoid offending patients and to increase their likelihood to disclose sexual health information.

Nonjudgmental language is especially relevant when working with gender-minority veterans (eg, transgender, gender nonconforming, gender transitioning), because this clinical population has a higher risk of victimization and lower rates of help-seeking health behavior.⁷ In particular, a sizable portion of individuals who identify as transgender do not seek services out of fear that they will be discriminated against, humiliated, or misunderstood.⁷ To assuage these concerns, MHPs should ensure they refer to the veteran with the veteran’s preferred pronouns. For example, a MHP could ask “I would like to be respectful, how would you like to be addressed?” or “What name and pronoun would you like me/us to use?” Providers also should consider nonbinary pronouns when appropriate (eg, singular: ze/hir/hirs; plural: they/them/theirs). Providers also should recognize that making a mistake is not uncommon, and they should apologize to maintain rapport and maximize the patient’s comfort during this distressing process. Further, MHPs should consider additional training, education, and/or consultation if they feel uncomfortable or ill prepared when working with gender-minority veterans.

Future Research

Research has attempted to understand the consequences of MST on sexual health; however, despite these efforts, more research is necessary. The majority of published studies have focused on females even though a similar number of males have reported MST.² This dearth of published studies likely is due to hesitation by male active-duty personnel and veterans to disclose or seek treatment for MST and because the percentage of females reporting MST is much higher. Males are less likely to report or seek treatment for MST because of stigma-based concerns (eg, shame, self-blame, privacy concerns).^8,9 Therefore, it is difficult to acquire a sizable research sample to study. As previously noted, a single study has specifically examined MST and STI risk. Although this study included a sizable population of male OEF/OIF veterans, results have yet to be replicated in other clinical populations of interest, such as male military personnel and male veterans of other service eras.

Research is even more limited regarding lesbian, gay, bisexual, transgender, and other gender-minority military personnel and veterans. Although researchers propose that these populations may experience a similar, or even heightened, likelihood of MST during their service, no empirical research yet exists to fully examine this hypothesis.^10,11 It is important to note that the paucity of research attention may be related to the Don’t Ask, Don’t Tell (DADT) policy, which obstructed the open discussion and empirical examination of sexual and gender minorities within military populations.¹¹ The DADT policy led to limited awareness and greater stigmatization among sexual- and gender-minority personnel, resulting in poorer sexual health outcomes in these populations.^10,11 With the end of DADT in 2011, it is now imperative for future research to examine the prevalence and associated consequences of MST in sexual- and gender-minority military personnel and veterans.

Conclusion

The DoD and VA should be commended for their continued focus on understanding the health consequences of MST. These efforts have yielded substantial information regarding the negative effects of MST on sexual health; in particular, increased risk for STIs. These findings suggest that MHPs may, at times, be the first point of contact for MST-related sexual health concerns. These providers should be aware of their ability to assess for STI risk and make appropriate referrals to facilitate early detection and access to treatment. Despite the presence of MST-related sexual health research, continued research remains necessary. In particular, a broader focus that includes other genders (eg, male, transgender) and sexual minorities would further inform research and clinical practice.

Photo by Chad McNeeley

The use of autologous transplant after a 3-drug induction regimen for multiple myeloma (MM) prolongs progression-free survival (PFS) but not overall survival (OS), according to new research.

In a phase 3 trial, newly diagnosed MM patients who received lenalidomide, bortezomib, and dexamethasone (RVD) followed by an autologous hematopoietic stem cell transplant (HSCT) had significantly better PFS but similar OS when compared to patients who only received RVD.

In addition, HSCT recipients had significantly higher rates of high-grade blood and lymphatic system disorders, gastrointestinal events, and infections.

The study also showed that OS outcomes were similar for patients who received HSCT after completing treatment with RVD and patients who were in the RVD-only treatment arm but underwent HSCT later, as salvage therapy.

Researchers believe this suggests MM patients can potentially choose when to undergo a transplant.

The team reported their findings in NEJM. The study was supported by grants from Celgene and Janssen and by funds from the French Ministry of Health Programme Hospitalier de Recherche Clinique and from the French National Research Agency.

“Over the past decade, drugs that modulate the immune system and agents known as proteasome inhibitors have shown a great deal of promise in patients with multiple myeloma, when used in combination with chemotherapy,” said study author Paul Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This led us to propose that these combinations could be used selectively with established modalities such as transplant for patients with newly diagnosed myeloma, and this, in turn, raised questions about where and how transplant should be fit into the therapeutic paradigm. Our trial sought to comprehensively address these issues in a prospective fashion, and provide a foundation for future studies as the next generation of agents, such as monoclonal antibodies, impact the field.”

The study enrolled 700 adult patients under the age of 65 who were newly diagnosed with MM. They were treated at 69 centers in France, Belgium, and Switzerland.

The patients were randomized to 2 treatment arms. Both groups received 3 initial cycles of RVD.

One group then received 5 more cycles of RVD. The other received high-dose chemotherapy (melphalan) followed by an autologous HSCT and 2 additional cycles of RVD.

Patients in both groups then received lenalidomide as maintenance therapy for 1 year or until they progressed, experienced unacceptable adverse events (AEs), or withdrew consent.

Response and survival

The complete response rate was significantly higher in the HSCT arm than the RVD-alone arm—59% and 48%, respectively (P=0.03).

And there was a significantly higher percentage of patients who were negative for minimal residual disease in the HSCT arm than in the RVD arm—79% and 65%, respectively (P<0.001).

The median PFS was significantly longer in the HSCT arm than the RVD arm—50 months and 36 months, respectively (P<0.001). The researchers said this benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk.

There was no significant between-group difference in the rate of OS at 4 years, which was 81% in the HSCT arm and 82% in the RVD arm.

Subsequent therapy

In the RVD arm, 207 patients progressed, and 172 received second-line therapy, which was followed by salvage HSCT in 136 patients (79%).

In the HSCT arm, 149 patients progressed, and 123 received second-line therapy, which was followed by a second HSCT in 21 patients (17%).

Safety

Nine percent of patients in the RVD arm and 11% in the HSCT arm discontinued treatment due to AEs. There were 2 treatment-related deaths in the RVD arm and 6 in the HSCT arm.

Grade 3/4 AEs with a significantly higher incidence in the HSCT arm than the RVD arm were blood and lymphatic system disorders (95% and 64%, respectively, P<0.001), gastrointestinal disorders (28% and 7%, respectively, P<0.001), and infections (20% and 9%, respectively, P<0.001).

Thirteen patients in the RVD arm and 17 in the HSCT arm had at least 1 invasive second primary malignancy (P=0.36). Acute myeloid leukemia occurred in 1 patient in the RVD arm and 4 in the HSCT arm (P=0.21).

The researchers said these results suggest the benefits of HSCT plus RVD must be weighed against the increased risk of toxicity associated with high-dose chemotherapy plus HSCT, particularly since HSCT after progression might be as effective as early HSCT for ensuring long-term OS. 

Photo by Chad McNeeley

The use of autologous transplant after a 3-drug induction regimen for multiple myeloma (MM) prolongs progression-free survival (PFS) but not overall survival (OS), according to new research.

In a phase 3 trial, newly diagnosed MM patients who received lenalidomide, bortezomib, and dexamethasone (RVD) followed by an autologous hematopoietic stem cell transplant (HSCT) had significantly better PFS but similar OS when compared to patients who only received RVD.

In addition, HSCT recipients had significantly higher rates of high-grade blood and lymphatic system disorders, gastrointestinal events, and infections.

The study also showed that OS outcomes were similar for patients who received HSCT after completing treatment with RVD and patients who were in the RVD-only treatment arm but underwent HSCT later, as salvage therapy.

Researchers believe this suggests MM patients can potentially choose when to undergo a transplant.

The team reported their findings in NEJM. The study was supported by grants from Celgene and Janssen and by funds from the French Ministry of Health Programme Hospitalier de Recherche Clinique and from the French National Research Agency.

“Over the past decade, drugs that modulate the immune system and agents known as proteasome inhibitors have shown a great deal of promise in patients with multiple myeloma, when used in combination with chemotherapy,” said study author Paul Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This led us to propose that these combinations could be used selectively with established modalities such as transplant for patients with newly diagnosed myeloma, and this, in turn, raised questions about where and how transplant should be fit into the therapeutic paradigm. Our trial sought to comprehensively address these issues in a prospective fashion, and provide a foundation for future studies as the next generation of agents, such as monoclonal antibodies, impact the field.”

The study enrolled 700 adult patients under the age of 65 who were newly diagnosed with MM. They were treated at 69 centers in France, Belgium, and Switzerland.

The patients were randomized to 2 treatment arms. Both groups received 3 initial cycles of RVD.

One group then received 5 more cycles of RVD. The other received high-dose chemotherapy (melphalan) followed by an autologous HSCT and 2 additional cycles of RVD.

Patients in both groups then received lenalidomide as maintenance therapy for 1 year or until they progressed, experienced unacceptable adverse events (AEs), or withdrew consent.

Response and survival

The complete response rate was significantly higher in the HSCT arm than the RVD-alone arm—59% and 48%, respectively (P=0.03).

And there was a significantly higher percentage of patients who were negative for minimal residual disease in the HSCT arm than in the RVD arm—79% and 65%, respectively (P<0.001).

The median PFS was significantly longer in the HSCT arm than the RVD arm—50 months and 36 months, respectively (P<0.001). The researchers said this benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk.

There was no significant between-group difference in the rate of OS at 4 years, which was 81% in the HSCT arm and 82% in the RVD arm.

Subsequent therapy

In the RVD arm, 207 patients progressed, and 172 received second-line therapy, which was followed by salvage HSCT in 136 patients (79%).

In the HSCT arm, 149 patients progressed, and 123 received second-line therapy, which was followed by a second HSCT in 21 patients (17%).

Safety

Nine percent of patients in the RVD arm and 11% in the HSCT arm discontinued treatment due to AEs. There were 2 treatment-related deaths in the RVD arm and 6 in the HSCT arm.

Grade 3/4 AEs with a significantly higher incidence in the HSCT arm than the RVD arm were blood and lymphatic system disorders (95% and 64%, respectively, P<0.001), gastrointestinal disorders (28% and 7%, respectively, P<0.001), and infections (20% and 9%, respectively, P<0.001).

Thirteen patients in the RVD arm and 17 in the HSCT arm had at least 1 invasive second primary malignancy (P=0.36). Acute myeloid leukemia occurred in 1 patient in the RVD arm and 4 in the HSCT arm (P=0.21).

The researchers said these results suggest the benefits of HSCT plus RVD must be weighed against the increased risk of toxicity associated with high-dose chemotherapy plus HSCT, particularly since HSCT after progression might be as effective as early HSCT for ensuring long-term OS. 

Photo by Chad McNeeley

The use of autologous transplant after a 3-drug induction regimen for multiple myeloma (MM) prolongs progression-free survival (PFS) but not overall survival (OS), according to new research.

In a phase 3 trial, newly diagnosed MM patients who received lenalidomide, bortezomib, and dexamethasone (RVD) followed by an autologous hematopoietic stem cell transplant (HSCT) had significantly better PFS but similar OS when compared to patients who only received RVD.

In addition, HSCT recipients had significantly higher rates of high-grade blood and lymphatic system disorders, gastrointestinal events, and infections.

The study also showed that OS outcomes were similar for patients who received HSCT after completing treatment with RVD and patients who were in the RVD-only treatment arm but underwent HSCT later, as salvage therapy.

Researchers believe this suggests MM patients can potentially choose when to undergo a transplant.

The team reported their findings in NEJM. The study was supported by grants from Celgene and Janssen and by funds from the French Ministry of Health Programme Hospitalier de Recherche Clinique and from the French National Research Agency.

“Over the past decade, drugs that modulate the immune system and agents known as proteasome inhibitors have shown a great deal of promise in patients with multiple myeloma, when used in combination with chemotherapy,” said study author Paul Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This led us to propose that these combinations could be used selectively with established modalities such as transplant for patients with newly diagnosed myeloma, and this, in turn, raised questions about where and how transplant should be fit into the therapeutic paradigm. Our trial sought to comprehensively address these issues in a prospective fashion, and provide a foundation for future studies as the next generation of agents, such as monoclonal antibodies, impact the field.”

The study enrolled 700 adult patients under the age of 65 who were newly diagnosed with MM. They were treated at 69 centers in France, Belgium, and Switzerland.

The patients were randomized to 2 treatment arms. Both groups received 3 initial cycles of RVD.

One group then received 5 more cycles of RVD. The other received high-dose chemotherapy (melphalan) followed by an autologous HSCT and 2 additional cycles of RVD.

Patients in both groups then received lenalidomide as maintenance therapy for 1 year or until they progressed, experienced unacceptable adverse events (AEs), or withdrew consent.

Response and survival

The complete response rate was significantly higher in the HSCT arm than the RVD-alone arm—59% and 48%, respectively (P=0.03).

And there was a significantly higher percentage of patients who were negative for minimal residual disease in the HSCT arm than in the RVD arm—79% and 65%, respectively (P<0.001).

The median PFS was significantly longer in the HSCT arm than the RVD arm—50 months and 36 months, respectively (P<0.001). The researchers said this benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk.

There was no significant between-group difference in the rate of OS at 4 years, which was 81% in the HSCT arm and 82% in the RVD arm.

Subsequent therapy

In the RVD arm, 207 patients progressed, and 172 received second-line therapy, which was followed by salvage HSCT in 136 patients (79%).

In the HSCT arm, 149 patients progressed, and 123 received second-line therapy, which was followed by a second HSCT in 21 patients (17%).

Safety

Nine percent of patients in the RVD arm and 11% in the HSCT arm discontinued treatment due to AEs. There were 2 treatment-related deaths in the RVD arm and 6 in the HSCT arm.

Grade 3/4 AEs with a significantly higher incidence in the HSCT arm than the RVD arm were blood and lymphatic system disorders (95% and 64%, respectively, P<0.001), gastrointestinal disorders (28% and 7%, respectively, P<0.001), and infections (20% and 9%, respectively, P<0.001).

Thirteen patients in the RVD arm and 17 in the HSCT arm had at least 1 invasive second primary malignancy (P=0.36). Acute myeloid leukemia occurred in 1 patient in the RVD arm and 4 in the HSCT arm (P=0.21).

The researchers said these results suggest the benefits of HSCT plus RVD must be weighed against the increased risk of toxicity associated with high-dose chemotherapy plus HSCT, particularly since HSCT after progression might be as effective as early HSCT for ensuring long-term OS. 

ANSWER

The radiograph shows a large, round hyperdensity within the right lower lobe. This lesion is highly concerning for malignancy and warrants further work-up.

With his gastrointestinal bleed and hypercoagulability from warfarin toxicity, the patient required admission anyway. Subsequent biopsy confirmed the presence of a primary lung carcinoma. 

ANSWER

The radiograph shows a large, round hyperdensity within the right lower lobe. This lesion is highly concerning for malignancy and warrants further work-up.

With his gastrointestinal bleed and hypercoagulability from warfarin toxicity, the patient required admission anyway. Subsequent biopsy confirmed the presence of a primary lung carcinoma. 

ANSWER

The radiograph shows a large, round hyperdensity within the right lower lobe. This lesion is highly concerning for malignancy and warrants further work-up.

With his gastrointestinal bleed and hypercoagulability from warfarin toxicity, the patient required admission anyway. Subsequent biopsy confirmed the presence of a primary lung carcinoma. 

Transferring fewer embryos in appropriate clinical conditions reduces the rate of multiple gestations without impacting live birth rates, according to new recommendations from the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology.

The recommendations are the first update since 2013.

javi_indy/ Thinkstock

Transferring fewer embryos in appropriate clinical conditions reduces the rate of multiple gestations without impacting live birth rates, according to new recommendations from the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology.

The recommendations are the first update since 2013.

javi_indy/ Thinkstock

Transferring fewer embryos in appropriate clinical conditions reduces the rate of multiple gestations without impacting live birth rates, according to new recommendations from the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology.

The recommendations are the first update since 2013.

javi_indy/ Thinkstock

Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.

The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.

Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.

The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.

Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.

The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.

NEW YORK – A pair of new monoclonal antibodies have dramatically changed treatment for patients with acute lymphoblastic leukemia to prepare them for a stem cell transplant, Daniel J. DeAngelo, MD, said at a conference held by Imedex.

“We don’t use standard chemotherapy for reinduction anymore; we use blinatumomab or inotuzumab,” said Dr. DeAngelo, a hematologist oncologist at Dana-Farber Cancer Institute in Boston.

Blinatumomab (Blincyto), approved by the Food and Drug Administration in 2014, has produced “exceptional” response rates, becoming “standard of care” for patients with relapsed acute lymphoblastic leukemia (ALL) that does not have a Philadelphia chromosome, Dr. DeAngelo said in a video interview.

Approved based on results from a phase II study, blinatumomab’s efficacy and safety were recently further delineated in results from the first phase III trial (N Engl J Med. 2017 Mar 2;376[9]:836-74), with 376 treated patients. In that trial, blinatumomab more than doubled the complete remission rate, compared with control patients (34% vs. 16%), and nearly doubled median overall survival – 7.7 months with blinatumomab, compared with 4.0 months for control patients treated with standard chemotherapy.

These findings “further substantiated” blinatumomab’s role, he said.

Blinatumomab’s big limitations are certain adverse effects and the logistics of its dosing. The major adverse effect is “cytokine release syndrome,” which manifests as fever, low blood pressure, and neurologic toxicities that can range from tremors to encephalopathy and seizure. These are manageable by close observation of patients by experienced nurses, Dr. DeAngelo said.

Dosing involves 4 weeks of continuous infusion, starting with 10 days done entirely in the hospital, with the remaining 18 days with patients going home but needing to return every 48 hours to have their infusion bag changed. “Depending on how far the patient lives from the clinic, it can be a logistical challenge,” he said.

A second new antibody he has used on many patients is inotuzumab, which was accepted for review for approval by the FDA in February 2017, with action expected by August.

Dr. DeAngelo served as a coinvestigator in a phase III trial reported in 2016 with 218 evaluable patients. In that trial, investigators reported an 81% complete remission rate with inotuzumab treatment, compared with a 29% among control patients on chemotherapy (N Engl J Med. 2016 Aug 25;375[8]:740-53).

Inotuzumab was effective against patients with Philadelphia chromosome positive ALL, but it will not work for the roughly 5%-10% of ALL patients who lack CD-22 expression in their B-cell ALL.

Inotuzumab is easier to administer than blinatumomab, requiring a once a week infusion, and causes little immediate toxicity – although thrombocytopenia and liver-function abnormalities can occur with continued use, and the risk of veno-occlusive disease is increased when patients later receive a stem cell transplant, Dr. DeAngelo said.

“It’s nice to have options” when choosing antibody-based treatment, he said. Blinatumomab is a good choice for patients with a lower tumor burden – either patients with early relapse or with minimal residual disease – while inotuzumab works better for patients with more bulky disease, as well as those who are not able to accommodate the logistic demands of blinatumomab infusions.

Dr. DeAngelo also highlighted several trials now underway that are testing the efficacy of both antibodies when used as part of first-line treatment.

Dr. DeAngelo has been a consultant to Amgen, the company that markets blinatumomab (Blincyto); to Pfizer, the company developing inotuzumab; and to Ariad, InCyte, and Novartis.

[email protected]

On Twitter @mitchelzoler

NEW YORK – A pair of new monoclonal antibodies have dramatically changed treatment for patients with acute lymphoblastic leukemia to prepare them for a stem cell transplant, Daniel J. DeAngelo, MD, said at a conference held by Imedex.

“We don’t use standard chemotherapy for reinduction anymore; we use blinatumomab or inotuzumab,” said Dr. DeAngelo, a hematologist oncologist at Dana-Farber Cancer Institute in Boston.

Blinatumomab (Blincyto), approved by the Food and Drug Administration in 2014, has produced “exceptional” response rates, becoming “standard of care” for patients with relapsed acute lymphoblastic leukemia (ALL) that does not have a Philadelphia chromosome, Dr. DeAngelo said in a video interview.

Approved based on results from a phase II study, blinatumomab’s efficacy and safety were recently further delineated in results from the first phase III trial (N Engl J Med. 2017 Mar 2;376[9]:836-74), with 376 treated patients. In that trial, blinatumomab more than doubled the complete remission rate, compared with control patients (34% vs. 16%), and nearly doubled median overall survival – 7.7 months with blinatumomab, compared with 4.0 months for control patients treated with standard chemotherapy.

These findings “further substantiated” blinatumomab’s role, he said.

Blinatumomab’s big limitations are certain adverse effects and the logistics of its dosing. The major adverse effect is “cytokine release syndrome,” which manifests as fever, low blood pressure, and neurologic toxicities that can range from tremors to encephalopathy and seizure. These are manageable by close observation of patients by experienced nurses, Dr. DeAngelo said.

Dosing involves 4 weeks of continuous infusion, starting with 10 days done entirely in the hospital, with the remaining 18 days with patients going home but needing to return every 48 hours to have their infusion bag changed. “Depending on how far the patient lives from the clinic, it can be a logistical challenge,” he said.

A second new antibody he has used on many patients is inotuzumab, which was accepted for review for approval by the FDA in February 2017, with action expected by August.

Dr. DeAngelo served as a coinvestigator in a phase III trial reported in 2016 with 218 evaluable patients. In that trial, investigators reported an 81% complete remission rate with inotuzumab treatment, compared with a 29% among control patients on chemotherapy (N Engl J Med. 2016 Aug 25;375[8]:740-53).

Inotuzumab was effective against patients with Philadelphia chromosome positive ALL, but it will not work for the roughly 5%-10% of ALL patients who lack CD-22 expression in their B-cell ALL.

Inotuzumab is easier to administer than blinatumomab, requiring a once a week infusion, and causes little immediate toxicity – although thrombocytopenia and liver-function abnormalities can occur with continued use, and the risk of veno-occlusive disease is increased when patients later receive a stem cell transplant, Dr. DeAngelo said.

“It’s nice to have options” when choosing antibody-based treatment, he said. Blinatumomab is a good choice for patients with a lower tumor burden – either patients with early relapse or with minimal residual disease – while inotuzumab works better for patients with more bulky disease, as well as those who are not able to accommodate the logistic demands of blinatumomab infusions.

Dr. DeAngelo also highlighted several trials now underway that are testing the efficacy of both antibodies when used as part of first-line treatment.

Dr. DeAngelo has been a consultant to Amgen, the company that markets blinatumomab (Blincyto); to Pfizer, the company developing inotuzumab; and to Ariad, InCyte, and Novartis.

[email protected]

On Twitter @mitchelzoler

NEW YORK – A pair of new monoclonal antibodies have dramatically changed treatment for patients with acute lymphoblastic leukemia to prepare them for a stem cell transplant, Daniel J. DeAngelo, MD, said at a conference held by Imedex.

“We don’t use standard chemotherapy for reinduction anymore; we use blinatumomab or inotuzumab,” said Dr. DeAngelo, a hematologist oncologist at Dana-Farber Cancer Institute in Boston.

Blinatumomab (Blincyto), approved by the Food and Drug Administration in 2014, has produced “exceptional” response rates, becoming “standard of care” for patients with relapsed acute lymphoblastic leukemia (ALL) that does not have a Philadelphia chromosome, Dr. DeAngelo said in a video interview.

Approved based on results from a phase II study, blinatumomab’s efficacy and safety were recently further delineated in results from the first phase III trial (N Engl J Med. 2017 Mar 2;376[9]:836-74), with 376 treated patients. In that trial, blinatumomab more than doubled the complete remission rate, compared with control patients (34% vs. 16%), and nearly doubled median overall survival – 7.7 months with blinatumomab, compared with 4.0 months for control patients treated with standard chemotherapy.

These findings “further substantiated” blinatumomab’s role, he said.

Blinatumomab’s big limitations are certain adverse effects and the logistics of its dosing. The major adverse effect is “cytokine release syndrome,” which manifests as fever, low blood pressure, and neurologic toxicities that can range from tremors to encephalopathy and seizure. These are manageable by close observation of patients by experienced nurses, Dr. DeAngelo said.

Dosing involves 4 weeks of continuous infusion, starting with 10 days done entirely in the hospital, with the remaining 18 days with patients going home but needing to return every 48 hours to have their infusion bag changed. “Depending on how far the patient lives from the clinic, it can be a logistical challenge,” he said.

A second new antibody he has used on many patients is inotuzumab, which was accepted for review for approval by the FDA in February 2017, with action expected by August.

Dr. DeAngelo served as a coinvestigator in a phase III trial reported in 2016 with 218 evaluable patients. In that trial, investigators reported an 81% complete remission rate with inotuzumab treatment, compared with a 29% among control patients on chemotherapy (N Engl J Med. 2016 Aug 25;375[8]:740-53).

Inotuzumab was effective against patients with Philadelphia chromosome positive ALL, but it will not work for the roughly 5%-10% of ALL patients who lack CD-22 expression in their B-cell ALL.

Inotuzumab is easier to administer than blinatumomab, requiring a once a week infusion, and causes little immediate toxicity – although thrombocytopenia and liver-function abnormalities can occur with continued use, and the risk of veno-occlusive disease is increased when patients later receive a stem cell transplant, Dr. DeAngelo said.

“It’s nice to have options” when choosing antibody-based treatment, he said. Blinatumomab is a good choice for patients with a lower tumor burden – either patients with early relapse or with minimal residual disease – while inotuzumab works better for patients with more bulky disease, as well as those who are not able to accommodate the logistic demands of blinatumomab infusions.

Dr. DeAngelo also highlighted several trials now underway that are testing the efficacy of both antibodies when used as part of first-line treatment.

Dr. DeAngelo has been a consultant to Amgen, the company that markets blinatumomab (Blincyto); to Pfizer, the company developing inotuzumab; and to Ariad, InCyte, and Novartis.

[email protected]

On Twitter @mitchelzoler

Improved education could keep clinicians from ordering laxatives and stool softeners just prior to ordering Clostridium difficile tests, improving the specificity of such testing.

In a 4-month prospective cohort study of pediatric inpatients, most clinicians were aware that their patients were receiving laxatives or stool softeners before they were sent for C. difficile tests.

Darrin Klimek/Thinkstock

[email protected]

Improved education could keep clinicians from ordering laxatives and stool softeners just prior to ordering Clostridium difficile tests, improving the specificity of such testing.

In a 4-month prospective cohort study of pediatric inpatients, most clinicians were aware that their patients were receiving laxatives or stool softeners before they were sent for C. difficile tests.

Darrin Klimek/Thinkstock

[email protected]

Improved education could keep clinicians from ordering laxatives and stool softeners just prior to ordering Clostridium difficile tests, improving the specificity of such testing.

In a 4-month prospective cohort study of pediatric inpatients, most clinicians were aware that their patients were receiving laxatives or stool softeners before they were sent for C. difficile tests.

Darrin Klimek/Thinkstock

[email protected]

WASHINGTON – Reducing the amount physicians are paid for drugs administered in their offices and introducing shared savings could save Medicare up to $5 billion over 5 years, according to recommendations from the Medicare Payment Advisory Commission.

Those MedPAC recommendations to Congress include cutting physicians’ average sales price add-on percentage, as well as an alternative purchasing initiative called the Drug Value Program that would allow shared savings through more effective pharmaceutical utilization.

Mathier/Thinkstock

[email protected]

WASHINGTON – Reducing the amount physicians are paid for drugs administered in their offices and introducing shared savings could save Medicare up to $5 billion over 5 years, according to recommendations from the Medicare Payment Advisory Commission.

Those MedPAC recommendations to Congress include cutting physicians’ average sales price add-on percentage, as well as an alternative purchasing initiative called the Drug Value Program that would allow shared savings through more effective pharmaceutical utilization.

Mathier/Thinkstock

[email protected]

WASHINGTON – Reducing the amount physicians are paid for drugs administered in their offices and introducing shared savings could save Medicare up to $5 billion over 5 years, according to recommendations from the Medicare Payment Advisory Commission.

Those MedPAC recommendations to Congress include cutting physicians’ average sales price add-on percentage, as well as an alternative purchasing initiative called the Drug Value Program that would allow shared savings through more effective pharmaceutical utilization.

Mathier/Thinkstock

[email protected]

Cutting back on antibiotic courses in intensive care unit settings can significantly reduce the number of multidrug-resistant organism (MDRO) transmissions, according to the findings of a modeling study.

“Significant opportunities exist to optimize and reduce antibiotic usage, [but] the impact of reducing overall antibiotic usage on antibiotic resistance is not known and would be difficult to assess using traditional study designs,” wrote Sean L. Barnes, PhD, of the University of Maryland, College Park, and his colleagues. “Therefore, we applied mathematical modeling to estimate the effect of reducing antibiotic usage on antibiotic resistance.”

Using an agent-based model – which allows for a realistic prediction of interactions between patients and health care workers, while also allowing for heterogeneity in the characteristics of each distinct “person” – Dr. Barnes and his coinvestigators simulated the transmission of MDROs from health care workers to patients.

Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci were deemed “high-prevalence pathogens;” carbapenem-resistant Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa were deemed low-prevalence pathogens. These designations were based on transmission rates found in existing literature.

Patients on antibiotic courses were set at 75% (0.75) at baseline, which was then adjusted to determine its effect on overall MDRO transmission. The number of patients at baseline was 18, with nine nurses, two physicians, and six other health care workers. Mean length-of-stay was 3.5 days, hand hygiene rates were set at 80% for nurses and 50% for physicians, with a 0.83 (83%) efficacy rate when followed. The probability of worker-to-patient transmission was set at 0.025 (2.5%), and set at 0.075 (7.5%) for transmission going the other way.

“We simulated the transmission of the high- and low-prevalence MDROs for 1 year [and] performed 200 replications each for 33 parameter-based scenarios,” the authors said.

When the number of patients on an antibiotic course was dropped from 75% to 65% (a drop of 10%), the rate of high-prevalence MDRO transmission dropped by 11.2% (P < .001). When reduced from 75% to 50% (a drop of 25%), the high-prevalence MDRO transmission rate fell by 28.3% (P < .001), according to the model.

Low-prevalence MDROs also reduced by significant amounts when antibiotic regimens were cut back by the same percentages, with transmission rates falling by 14.3% (P < .001) and 29.8% (P < .001), respectively.

In terms of microbiome effects, the 10% reduction in antibiotics lowered high-prevalence rates by an effect of 1.5, and low-prevalence rates by 1.7; those numbers were 1.2 and 1.4, respectively, when antibiotics were dropped by 25%.

“These reductions are statistically significant and proportionally similar for both high- and low-prevalence MDROs,” the authors concluded, “and they can potentially decrease MDRO acquisition among patients who are receiving antibiotics, as well as among patients who are not receiving antibiotics.”

The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.

Cutting back on antibiotic courses in intensive care unit settings can significantly reduce the number of multidrug-resistant organism (MDRO) transmissions, according to the findings of a modeling study.

“Significant opportunities exist to optimize and reduce antibiotic usage, [but] the impact of reducing overall antibiotic usage on antibiotic resistance is not known and would be difficult to assess using traditional study designs,” wrote Sean L. Barnes, PhD, of the University of Maryland, College Park, and his colleagues. “Therefore, we applied mathematical modeling to estimate the effect of reducing antibiotic usage on antibiotic resistance.”

Using an agent-based model – which allows for a realistic prediction of interactions between patients and health care workers, while also allowing for heterogeneity in the characteristics of each distinct “person” – Dr. Barnes and his coinvestigators simulated the transmission of MDROs from health care workers to patients.

Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci were deemed “high-prevalence pathogens;” carbapenem-resistant Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa were deemed low-prevalence pathogens. These designations were based on transmission rates found in existing literature.

Patients on antibiotic courses were set at 75% (0.75) at baseline, which was then adjusted to determine its effect on overall MDRO transmission. The number of patients at baseline was 18, with nine nurses, two physicians, and six other health care workers. Mean length-of-stay was 3.5 days, hand hygiene rates were set at 80% for nurses and 50% for physicians, with a 0.83 (83%) efficacy rate when followed. The probability of worker-to-patient transmission was set at 0.025 (2.5%), and set at 0.075 (7.5%) for transmission going the other way.

“We simulated the transmission of the high- and low-prevalence MDROs for 1 year [and] performed 200 replications each for 33 parameter-based scenarios,” the authors said.

When the number of patients on an antibiotic course was dropped from 75% to 65% (a drop of 10%), the rate of high-prevalence MDRO transmission dropped by 11.2% (P < .001). When reduced from 75% to 50% (a drop of 25%), the high-prevalence MDRO transmission rate fell by 28.3% (P < .001), according to the model.

Low-prevalence MDROs also reduced by significant amounts when antibiotic regimens were cut back by the same percentages, with transmission rates falling by 14.3% (P < .001) and 29.8% (P < .001), respectively.

In terms of microbiome effects, the 10% reduction in antibiotics lowered high-prevalence rates by an effect of 1.5, and low-prevalence rates by 1.7; those numbers were 1.2 and 1.4, respectively, when antibiotics were dropped by 25%.

“These reductions are statistically significant and proportionally similar for both high- and low-prevalence MDROs,” the authors concluded, “and they can potentially decrease MDRO acquisition among patients who are receiving antibiotics, as well as among patients who are not receiving antibiotics.”

The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.

Cutting back on antibiotic courses in intensive care unit settings can significantly reduce the number of multidrug-resistant organism (MDRO) transmissions, according to the findings of a modeling study.

“Significant opportunities exist to optimize and reduce antibiotic usage, [but] the impact of reducing overall antibiotic usage on antibiotic resistance is not known and would be difficult to assess using traditional study designs,” wrote Sean L. Barnes, PhD, of the University of Maryland, College Park, and his colleagues. “Therefore, we applied mathematical modeling to estimate the effect of reducing antibiotic usage on antibiotic resistance.”

Using an agent-based model – which allows for a realistic prediction of interactions between patients and health care workers, while also allowing for heterogeneity in the characteristics of each distinct “person” – Dr. Barnes and his coinvestigators simulated the transmission of MDROs from health care workers to patients.

Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci were deemed “high-prevalence pathogens;” carbapenem-resistant Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa were deemed low-prevalence pathogens. These designations were based on transmission rates found in existing literature.

Patients on antibiotic courses were set at 75% (0.75) at baseline, which was then adjusted to determine its effect on overall MDRO transmission. The number of patients at baseline was 18, with nine nurses, two physicians, and six other health care workers. Mean length-of-stay was 3.5 days, hand hygiene rates were set at 80% for nurses and 50% for physicians, with a 0.83 (83%) efficacy rate when followed. The probability of worker-to-patient transmission was set at 0.025 (2.5%), and set at 0.075 (7.5%) for transmission going the other way.

“We simulated the transmission of the high- and low-prevalence MDROs for 1 year [and] performed 200 replications each for 33 parameter-based scenarios,” the authors said.

When the number of patients on an antibiotic course was dropped from 75% to 65% (a drop of 10%), the rate of high-prevalence MDRO transmission dropped by 11.2% (P < .001). When reduced from 75% to 50% (a drop of 25%), the high-prevalence MDRO transmission rate fell by 28.3% (P < .001), according to the model.

Low-prevalence MDROs also reduced by significant amounts when antibiotic regimens were cut back by the same percentages, with transmission rates falling by 14.3% (P < .001) and 29.8% (P < .001), respectively.

In terms of microbiome effects, the 10% reduction in antibiotics lowered high-prevalence rates by an effect of 1.5, and low-prevalence rates by 1.7; those numbers were 1.2 and 1.4, respectively, when antibiotics were dropped by 25%.

“These reductions are statistically significant and proportionally similar for both high- and low-prevalence MDROs,” the authors concluded, “and they can potentially decrease MDRO acquisition among patients who are receiving antibiotics, as well as among patients who are not receiving antibiotics.”

The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.