<v ->Welcome. My name is Jeanette Tetrault.</v> I'm a Professor of Medicine and Public Health at Yale School of Medicine, and today, I'm going to be presenting a module on Medical Considerations for Patients with Opioid Use Disorder. I have no relevant financial disclosures. The overall goal of the PCSS is to train healthcare professionals in evidence-based practices for the prevention and treatment of opioid use disorders, particularly in prescribing medications, as well as for the prevention and treatment of substance use disorder. At the conclusion of this activity, participants should be able to recognize acute and chronic injection-related infections related to substance use, define epidemiologic trends of injection drug use related infective endocarditis in the US, consider treatment seeking for complications for substance use as an opportunity for healthcare teams to engage individuals in addiction treatment and implement harm reduction strategies, and review treatment and prevention opportunities for healthcare teams to address hepatitis C and HIV in patients with substance use disorder. We'll start off the discussion with a case. NC is a 30-year-old woman with a history of opioid use disorder. She was initially treated with buprenorphine, has intermittent primary care, and has ongoing injection opioid use. She presents to the ED with fever and a warm, indurated area in her left antecubital fossa. She also complains of severe back pain and generalized malaise. It's important to note that injection drug use comes with a related host of infectious complications. And I really like this particular graphic, which is taken from a recent edition in the "Medical Clinics of North America" focusing on substance use and substance use disorder. And it shows a variety of clinical syndromes, their associated pathogens, and potential exposures or risk factors related to injection drug use. So, wound botulism or tetanus may occur from spore-forming bacteria through the environmental contamination of drugs. With regard to the host, soft tissue, osteoarticular, and endovascular infections can occur from a variety of pathogens, including gram negative bacteria related to water that's required to dissolve drugs prior to injection. It can occur with candid albicans, and that may be seen when lemon juice is used as an acidification agent to dissolve either brown heroin or crack cocaine. You may see other bacteria that can be related to practices such as licking needles, when saliva is introduced when one licks needles, and certainly gram positive bacteria when non-sterile injection equipment or technique is used. And then certainly, we can see acquired immunodeficiency syndrome or viral hepatitis occurring when viruses are introduced through needle-sharing transmissions of blood-borne pathogens. So with regard to skin and soft tissue infections in people who inject drugs, this is the most common cause of hospitalization for people who inject drugs. Cutaneous and subcutaneous abscesses may occur, and they're the most common skin and soft tissue infections in this population. They're often found at the sites of frequent injection, including the antecubital fossa, the groin, the feet. Honestly, wherever the individual is injecting their drugs or has access to veins to inject their drugs. Oftentimes you have to think about your treatment approach based on the skin and soft tissue infection that presents. So if the patient's presenting with a cellulitis, the general approach is using antibiotics directed towards Staph and Strep species initially, and then narrowing as identification and sensitivities are back on the patient. One must have special consideration for coverage of methicillin-resistant Staph aureus at the outset, and again, antibiotic coverage can be tailored later on. When the patient presents with an abscess, the treatment needs to be focused on incision and drainage initially, and may often need to be done frequently. And when a patient presents with abscesses, it's important to note that polymicrobial infections are common and present in over 50% of cases, and treatment should include coverage of anaerobic bacteria, again, when abscesses are the presentation. So when we're thinking about our patient, some things to think about right when you're starting to put your treatment plan together for this patient. If wound care or packing is needed, having an understanding of where the patient lives and who they live with. So, do they live in an environment where sterile conditions can be met, or near sterile conditions can be met, if the wound needs to be packed? Who lives with the patient, and could they be trained to do the packing, or do we need to engage nursing services or find an urgent care place where the patient can present frequently? So beyond packing, it's important to think about vaccines and prevention. So is this a patient who's had vaccination for tetanus in the past? And consider administering if it's not been performed within the last 10 years, so certainly asking your patient if they've had this vaccination, or reviewing their health record. Given our patient, NC's, intermittent primary care, it's vital at the outset to think about linking this patient not only to primary care services, but also thinking about addiction treatment and harm reduction services as we're putting our initial treatment plan together. So I'm really trying to hit home the point that, yes, the antibiotic and incision and drainage plan is important, but these other factors need to be considered at the outset, because it can sometimes be complicated to get all of these things set up. What screening tests should we perform for this particular patient? So we should certainly get a sense of her blood counts and chemistries. Checking a urinalysis to see if there's any kidney damage. Checking a patient's liver enzymes can be helpful to think about our treatment plan and ongoing management. And then certainly screening for this patient, screening for viral hepatitis, including hep C, HIV, hepatitis B, and a urine pregnancy test for our patient who is a woman of childbearing age. Offer screening for sexually transmitted infections. Consider screening for latent tuberculosis infection in this particular patient. And then thinking about age-appropriate primary care screening is important. Now, again, we know this patient has intermittent primary care, and she is here seeking intervention from the healthcare system, so whether or not we're doing this from the ED, we're at least starting to think about linking this patient to primary care services, and letting her know what to expect is important. What complications do we need to consider in our patient? Now, remember, in addition to her presenting complaints, she also is complaining of severe back pain, so what are some of the things that we need to be thinking of as we broaden out our differential diagnosis to explain all of her symptoms? So could there be an underlying bacteremia or sepsis in this patient above and beyond the skin and soft tissue infection? We should think about, if that is the case, is there seeding of various parts of her body? So thinking about an underlying osteomyelitis or discitis. Could she have a mycotic aneurysm, either in this patient or other patients? When we see patients with underlying skin and soft tissue infections, we always need to be concerned about necrotizing fasciitis, especially if our initial treatment plan does not seem to be addressing the skin and soft tissue infection. Additionally, thinking about paraspinal abscesses and bacterial seeding of deep tissue spaces, so joint infections, and certainly cannot take endocarditis off the list in a patient who's presenting in this manner. These are graphics, representations, similar that were seen in this particular case, but not the exact data from this particular patient. So you can see the blood culture results showing gram positive cocci in clusters, and she underwent a transthoracic echocardiogram showing a vegetation on her valve, on her tricuspid valve. Infectious endocarditis, especially that related to injection drug use, is increasing, and this is a graphic showing an increased rate between 2008 and 2014, showing the prevalence of infective endocarditis related admissions in young folks. And you can see a steady increase. This has not leveled off. So we know that injection drug use related endocarditis is associated with a worse three-year survival. So this is a Kaplan-Meier curve showing the survival estimate for all-cause mortality in injection drug use related endocarditis versus non-injection drug use related endocarditis. And you can see in the red line, a three-year survival is 47% for injection drug use related endocarditis, compared with 60% among non-injection drug use related endocarditis. That all-cause mortality can be improved among those folks who receive continuous medications for opioid use disorder after a diagnosis of injection drug use related endocarditis, so again, hitting home the point that when a patient presents with a substance use related complication, this is a prime moment to initiate treatment for substance use disorder. And not only can it affect their quality of life, but it can affect their mortality. So we know, again, patients presenting to the hospital with complications of substance use disorder, specifically opioid use disorder, initiating treatment in the hospital is effective. So this is a summary showing four retrospective cohort studies, two prospective cohort studies, and one randomized clinical trial that all show that initiation of medication for opioid use disorder in the hospital increases entry into treatment, retention in treatment, and completion of medical treatment. Additionally, it decreases opioid use and both 30 and 90-day readmission to the hospital. It's vital that when we're working in hospital settings and interfacing with patients who present with complications related to opioid use and opioid use disorder, thinking about initiating treatment in the hospital and linking them to care is vital. Other considerations that we need to think about. Getting patients initiated on treatment and linking them to care is important, but we also need to think about keeping them in the hospital, and initiating medications for opioid use disorder can effectively treat opioid craving and withdrawal symptoms, it can help us adequately address pain control in patients who are presenting in this fashion, and it gives us the opportunity to discuss options for prolonged IV antibiotic treatment with our patient and with their multidisciplinary team. And so there are opportunities to think about how to carry out treatment plans with long-term IV antibiotics not only in the hospitalized setting. So you can consider the use of a nine-point risk assessment tool for clinical decision making for patients who are in the hospital and initiated on IV antibiotics, and implementing these tools to then think about their discharge planning and safety of discharge planning. So again, our patient, NC, she is a 30-year-old woman with a history of opioid use disorder, and she was diagnosed with a tricuspid valve injection drug use related infective endocarditis. She began IV antibiotic treatment and underwent evaluation for valve replacement surgery while in the hospital. She was also started on medications to address her opioid craving and pain control. Her viral screening results showed that she had hep C antibody positive or reactive, her HIV ELISA was non-reactive, and screening for hepatitis B was similarly non-reactive. When we think about patients who use injection drugs, we have to counsel them about underlying viral etiologies. So the epidemiology of hepatitis C is common in this country. About one-third of folks who use injection drugs between the age of 18 and 30 have a seroprevalence positivity for hepatitis C. Those over 30 years of age, variable prevalence, but certainly, we see high seroprevalence. In some series, up to 75% of those infected with hepatitis C are unaware, and in this country, it is the leading cause of cirrhosis, hepatocellular cancer, and reason for liver transplantation. Who is at risk? So there are certain risk factors and risk groups for hepatitis C transmission. So with regard to risk factors, both intravenous and intranasal drug use are risk factors, and we have to think about any blood-to-blood contact, and so thinking about the nasal mucosa as potentially friable and a site of entry for blood-to-blood contact. Other risk factors include multiple sexual partners, other chronic viral infections, and blood transfusion or organ transplantation pre-1992, before widespread screening was done of blood products. In terms of risk groups, certainly children born to mothers who are infected with hepatitis C, chronic hepatitis C infection, can be exposed at birth through blood-to-blood contact. Occupational exposure is a risk group, though, with universal precautions, this has certainly decreased. Patients with kidney disease on hemodialysis again may be a risk group, just because of blood-to-blood contact, and incarcerated populations as well. So with regard to that natural history of hepatitis C, so anyone who is exposed to hepatitis C develops an antibody, and this is how we screen for hepatitis C infection. Of those who are exposed, up to 80 to 85% go on to develop chronic hepatitis C infection, as evidenced by viral particles in the blood. That being said, about 15 to 20% resolve the infection on their own, meaning they don't have detectable virus in their blood, but do have a positive antibody for hepatitis C. Around 10 to 15% of individuals with chronic hepatitis C infection can go on to develop irreversible scarring of the liver, or liver cirrhosis. While the majority of people with chronic hepatitis C infection have stable, indolent disease, patients with cirrhosis are at risk for the development of hepatocellular carcinoma or liver failure. And folks who have cirrhosis, about a quarter of them can go on to develop these really significant and potentially costly to the healthcare system complications. The remainder of individuals with cirrhosis have, again, slowly progressive disease, and may go on to develop decompensations related to their cirrhosis. With regard to the natural history, going from exposure to the development of cirrhosis may take 10 to 20 years, and that progression may be expedited when there are other threats to an individual's liver health. The point of this is that there really is opportunity to engage people and think about intervention and treatment for their hepatitis C. And as we'll talk about shortly, there are very effective treatments for this condition. So with regard to screening, again, hepatitis C antibody testing by immunoassay is the gold standard for screening. There are various ways that this can be done. Oftentimes it's done serologically, but rapid testing and self collection kits are available. For individuals who are found to have a positive antibody, there may be opportunities to reflex testing directly to viral load, either qualitatively or quantitatively, so is the virus present? And if it is present, how much virus is in the bloodstream, and what is the genotype of the hepatitis C that is present? This used to be vitally important information, because treatment depended on genotype many years ago. Nowadays, we have pangenotypic treatment options, but the genotype can still be helpful for us in terms of staging and following patients. So there is a myth about hepatitis C in that a lot of my patients will tell me, "My doctor or healthcare worker that I have interfaced with told me I don't need to worry about hepatitis C because my liver function tests are okay." And I think it's important to recognize that patients with hepatitis C may have various patterns in their liver function tests. So this is an old study, but telling nonetheless, looking at over a thousand individuals with known chronic hepatitis C that were followed in a liver clinic, and over two years duration looking at serum ALT measurements. So this is including patients with greater than four measurements over that two-year period of time. And basically, this is, again, all patients with known chronic hepatitis C. About 40% of them had persistently normal ALT levels throughout that two-year period of time. So again, they have known chronic hepatitis C, but persistently normal levels throughout. Another 40% had intermittent elevations and back to normal levels of their ALT. But only about 15% had persistently elevated ALT levels, again hitting home the point that most individuals with chronic hepatitis C will oftentimes have normal LFTs, so the point being, do not necessarily use those levels as indications of the patient's underlying liver health. So patients who screen positive for hepatitis C should be offered further workup. That would include hepatitis C viral load testing. A quantitative measurement is important for patients who are going to undergo treatment. Genotype testing can also be helpful for monitoring. Patients should undergo complete blood count testing, basic metabolic profile, liver function test, TSH, an INR, which is an important marker for the patient's underlying synthetic function, and for all individuals of childbearing age, a urine HCG should be obtained. Patients should also undergo screening for HIV and other viral hepatitis panels, hepatitis A and hepatitis B. For patients who screen negative, they should be offered vaccination for hepatitis A and hepatitis B. The treatment plan should be altered for those who have concomitant HIV or hepatitis A or B. An assessment of the individual's degree of liver fibrosis should be obtained. In this day and age, noninvasive testing is widespread and easily obtained. This can either be a serologic test or ultrasound transient elastography. Biopsy is rarely indicated at this point unless we have concerns that there may be other conditions affecting the patient's liver that need to be diagnosed. For patients who have evidence of cirrhosis, either through biopsy or noninvasive testing, we can then implement screening for other complications, including esophageal varices and hepatocellular carcinoma. Similar to thinking about treatment for infective endocarditis when we diagnose a patient with underlying hepatitis C, if substance use or substance use disorder is a condition that we also have diagnosed in this patient, we must review their addiction and harm reduction treatment plan. Patients should reduce alcohol and other substance use to keep their liver healthy. We can promote abstinence through treatment, but this should not be a limitation to treatment. So any patient who has hepatitis C should be considered for treatment, and we should consider keeping them healthy and safe. And then implementing prevention messaging with regard to preventing HIV, further hep C transmission to others, limiting hepatotoxins, including alcohol, and implementing harm reduction. So the goal of hepatitis C treatment is to reduce all-cause mortality and liver-related health adverse consequences by the achievement of virologic cure as evidenced by a sustained virologic response. What's a sustained virologic response? That is after a patient completes hepatitis C treatment, and three months later, if they have no evidence of virus in their bloodstream, they're considered to have a sustained virologic response or virologic cure. Treatment is recommended for all patients with chronic hep C infection, except those with short life expectancies owing to comorbid conditions. So there are no exclusions for patients who are on treatment for opioid use disorder or for those who have ongoing active opioid or other substance use. That being said, there continues to be a treatment cascade, and while this data is a little bit on the older side, the graphic is still true nonetheless. So there's a universe of people who have chronic hepatitis C infection who really are not diagnosed or not aware of their disease. For those who have chronic hep C, access to outpatient care is another drop-off in this cascade. Once engaged in outpatient care, there's a drop-off for those who actually undergo RNA confirmation testing or viral load testing. Some of those individuals may get tested, but may not return, or may not be given that information, so may be unaware that they have it. Then there's a drop-off for those who undergo ongoing assessment of their liver fibrosis, drop-off for those who are prescribed treatment, and further drop-off for those who achieve virologic cure. So this presents a real opportunity for primary care providers, for general psychiatrists, general psychiatry providers, for emergency physicians, to educate and think about treatment. And really, there is a real opportunity for addiction treatment providers to be involved in limiting these drop-offs on this cascade. So hep C treatment has changed substantially over the last several years. So the first phase of treatment was interferon, which then went to pegylated interferon and Ribavirin. So this was an injection that a patient would need to take once a week, and pills that they would need to take daily for upwards of a year of time. The treatment was brutal. Lots of side effects, hair loss, feelings of nausea, vomiting, fatigue, and the cure rate was only on the order of 50 to 70%. Treatments evolved substantially. There were some first-generation direct acting antivirals, rather than just killing fast, turning over cells. There were treatment that really directly targeted the viral particles. The first generation still needed interferon and Ribavirin as a backbone, and these medications were added to it. But fast forward to this day and age, we have excellent treatments that are all oral. No need for interferon or Ribavirin. The treatment can last eight to 12 weeks, and the cure rate is 95%. And side effects are really quite minimal, potentially a little bit of nausea, some headaches, which usually get better with time. I want to bring your attention to a wonderful resource online called HCVguidelines.org that is put out through the AASLD and IDSA, and it really talks about treatment recommendations, treatment protocols, things to monitor, and it can be a very useful tool, whether you're planning on offering hepatitis C treatment in your clinical setting or just want to be able to educate patients and set expectations when you're referring them for treatment. So coming back to our patient, you'll recall she screened positive for hepatitis C with an antibody. Further workup showed she did have chronic hep C infection, as evidenced by a viral RNA. She had genotype 1a. She underwent 12 weeks of treatment with the direct acting antiviral agent ledipasvir/sofosbuvir, which is one pill, once a day medication. And she established an SVR, sustained virologic response, meaning that she had no evidence of viremia three months after treatment was completed. So now that we've got this patient engaged in care, how do we protect her from acquiring other infections, as well as from a hepatitis C reinfection? So these are things that we really need to be thoughtful of at this point so that we can keep our patient as safe and healthy as possible. So, when thinking about this... So again, hitting home the point of screening, so screening for HIV, hep C, other viral hepatitis, and one-time screening may not be enough. This may be something we need to offer this patient very periodically, depending on her substance use patterns, not making assumptions that if she is engaged in medications for opioid use disorder treatment that she's no longer exposed. Offering screening for sexually transmitted infections and tuberculosis, depending, again, on several of her risk factors. Offering immunizations, so immunizing patients for hepatitis A and hepatitis B, regardless of whether they have hep C infection. Immunizing for COVID, COVID-19, in terms of general vaccinations and boosters as appropriate. Immunizing for influenza, tetanus, diptheria, and pertussis. Immunizing for human papillomavirus if indicated, pneumonia if indicated, with pneumovax and meningococcus if indicated. And then I can't hit home the point hard enough that any healthcare provider should be talking to our patient, NC, and all patients, about reducing harm and optimizing their safety. So thinking back to that original graphic that I shared at the very beginning of this talk, offering education and local resources with regard to the use of clean needles and works, syringes, thinking about and educating on how the patient is dissolving their substances if they are injecting, employment of hand hygiene, cleaning skin prior to use to decrease skin flora introduction into the bloodstream, never sharing needles, syringes, works, or water with individuals, really having their own equipment, and locating local agencies that provide safe supplies, and linking your patient to these agencies. And while they may not be necessarily immediately available, being sure that we can link them through mail order and other opportunities. So thinking about HIV screening, there are guidelines for screening. One-time screening should be offered for all individuals age 13 to 64 unless there's a very, very, very low prevalence. Any patient initiating tuberculosis treatment and any patient seeking treatment for a sexually transmitted infection should be offered one-time screening. But really, the populations that we treat with opioid use and opioid use disorder, at least annual screening. Any person who exchanges sex for money or drugs should be offered screening periodically. Sexual partners of HIV infected persons should be offered screening, and we'll talk about other prevention measures. Men who have sex with men and heterosexual individuals who themselves or their partner have more than one sex partner since the last HIV test should be offered more frequent screening than one time. And really, screening should be opt-out, especially in treatment settings where we're working with patients who use substances. So this shows our screening algorithm, which no longer relies on Western blot testing. Our fourth generation tests have very good sensitivity and specificity, though we still may miss individuals within 10 days of HIV acquisition. So again, if you have a high level of concern about exposure, repeat testing may be necessary. For patients who are diagnosed with HIV, again, the goals of treatment are to reduce HIV associated morbidity and prolong duration and quality of survival, and to prevent HIV transmission to others. Treatment is recommended for all HIV infected patients, regardless of biomarkers or CD4 cell count. Baseline evaluation should include, as we mentioned, CD4 count, viral load testing, genotype testing, complete blood count, chemistries, transaminases, screening for viral hepatitis if not done already, assessment of blood glucose and lipids, because these may be altered by certain treatment regimens, the genotype, as mentioned, and screening for sexually transmitted infections, and depending on CD4 count, thinking about screening for opportunistic infections as well. This table shows the recommended treatment algorithms for patients who are treatment-naive, and can be found at the website listed at the bottom of this slide, ClinicalInfo.hiv.gov, which is, again, continually updated based on new data. So with regard to prevention, it's important to note that we have lots of avenues towards prevention of hep C and HIV. Addiction treatment is prevention, and so when we are interfacing, again, with patients who use substances, getting them involved in addiction treatment is prevention. We'll talk a little bit more about this. Behavioral risk reduction counseling is important. Don't make assumptions about your patient's practices. Don't make assumptions about if they're using or not using, ask, and thinking about opportunities where they can reduce their risk. And for HIV, there are antiviral-based interventions which can prevent HIV transmission, so we'll go over these in a little more detail. So as I said, addiction treatment is prevention, and this is data showing that opioid agonist therapy can prevent HCV transmission. So this is looking at individuals who present for drug treatment three months prior to the assessment, and they're looking at the adjusted hazard ratio of incident hep C infection three months into the study period. And for those who have no drug treatment, they're considered the referents group. For patients who are enrolled in non-opioid agonist treatment, so not enrolled in buprenorphine or methadone, but other treatment options, their risk of incident hep C infection is 0.71, but certainly not necessarily significant. In terms of those entering opioid agonist detox regimens, the hazard ratio of incident HCV infection after three months of treatment, again, increased but not significant. But those who enroll in opioid agonist treatment, buprenorphine or methadone, in an ongoing way have a decreased risk of incident HCV infection. So again, opioid agonist treatment is prevention of hepatitis C seroconversion. So similarly, opioid agonist treatment is prevention against HIV seroconversion, and this slide shows a systematic review of nine studies over 23,000 person years. And this is looking specifically at methadone, but the pool data showed that there was a 54% reduction in HIV incidence among individuals who were enrolled in methadone treatment, looking at this particular systematic review. Again, methadone prevents HIV seroconversion among people with opioid use disorder. So what about behavioral risk reduction for hep C and HIV prevention? This should be part and parcel with everything we do in addiction treatment. So, thinking about linking individuals to needle and syringe programs, whether they're involved in addiction treatment or not, these should be things that we're talking to our patients about. Pharmacy programs for safe supplies if needle and syringe programs are not available, knowing what your local pharmacies engage in, and referring patients. There are locales now that have vending machines for various supplies, and this is something that we hope to see more of. Certainly, supervised consumption sites are known to decrease risk, and we've got lots and lots of data from multiple other countries, and now have some sites here in the US, and we'll see more and more data coming out of these and other pilot and larger scale projects. And then again, what can we do on a day-to-day basis? Counseling and education on safe injection practices. This is the same as counseling and education for our patients with diabetes, hypertension, mood disorders. How do we arm our patients and work with them to keep them safe and healthy? So for HIV prevention, we do have a very effective tool, pre-exposure prophylaxis, or PrEP, which is an antiviral-based intervention, and the table on this slide shows clinical indications and eligibility, dosage, and followup care. This table can be found at cdc.gov, and can walk you through how to initiate PrEP, especially for patients that, again, we interface with every day who may be injecting drugs. So for patients who have an HIV positive injecting partner, or those who are sharing injection equipment, we should really be thinking about either providing PrEP or referring patients for PrEP. So in summary, acute and chronic serious injection-related infections are important to recognize among individuals with substance use. These infections include skin and soft tissue infections, injection drug use related infective endocarditis, chronic hepatitis C infection, and HIV. The time of presentation for complications related to injection drug use present a vital opportunity for us to screen and employ prevention strategies for other complications, and really to engage individuals in addiction treatment and implement harm reduction strategies. Comprehensive prevention interventions for hepatitis C and HIV include effective addiction treatment, behavioral risk reduction counseling, and antiviral-based interventions, for HIV specifically. Here are the references used in today's talk. Please note that there is a PCSS-related Mentoring Program, which is designed to offer general information to clinicians about evidence-based clinical practices in prescribing medications for opioid use disorder. There's a national network of providers with expertise, and really a unique approach that allows every mentor-mentee relationship to be catered to the specific needs of the mentee, and it comes at no cost. The PCSS also offers a discussion question where you can enter a clinical question and receive a simple and direct answer, especially related to medications for opioid use disorder, from colleagues. PCSS is a collaborative effort led by the American Academy of Addiction Psychiatry in partnership with multiple other organizations, and we really hope you'll engage with our network, which focuses on education, training, and mentorship. Thank you very much.

Opioid Use Disorder

Prevention

Treatment

Substance Use Disorder

Infectious Complications

HCV

HIV

Addiction Treatment