Mitral Regurgitation: Diagnosis and Management

SUMMARY: 

Mitral regurgitation (MR) of either primary or secondary cause is the most prevalent valvular disorder in the United States increasing in prevalence with advanced age. The 2020 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease provides a contemporary and comprehensive review of treating this condition. 

• Causes of MR 
• Signs and Symptoms  
• Diagnosis and Follow-Up 
• Stages of MR 
• Exercise testing in patients  
• Medical Therapy  
• Prevention of Rheumatic Heart Disease and Secondary Rheumatic fever  
• Procedural Interventions  
• Antiplatelet/Anticoagulant therapy post MVR 

Causes Of Mitral Regurgitation 

• Acute MR 
  • Disruption of different parts of the mitral valve apparatus such as from infective endocarditis|, spontaneous chordal rupture|papillary muscle rupture 
  • May present with hemodynamic instability e.g., hypoxia | dyspnea due to pulmonary edema 
• Chronic MR 
  • Primary MR (degenerative): Disease of mitral valve apparatus (i.e. Rheumatic heart disease| mitral valve prolapse|myxomatous valve degeneration) 
  • Secondary MR (functional): Due to left atrium or left ventricular dilatation typically from systolic dysfunction 

Signs And Symptoms  

• Symptoms 
  • Exertional dyspnea | Decrease exercise tolerance | Heart failure symptoms 
• Physical exam signs 
  • Systolic murmur | Extra heart sound (S3) | Cardiac impulse is brisk and hyperdynamic 

Diagnosis and Follow-Up 

• Transthoracic echocardiogram (TTE) is indicated in patients with signs and symptoms of MR 
• Patients with MR  
  • When TTE does not provide sufficient information, a transesophageal echocardiogram (TEE) is indicated to evaluate MR severity and to guide mitral valve interventions intraoperatively 
  • Cardiac MRI is indicated to assess LV/RV volumes, function and assess MR severity if discrepant findings on clinical assessment and echocardiography 

Frequency Of TTE in Asymptomatic Patients With MR 

• Mild severity: Every 3 to 5 years 
• Moderate severity: Every 1 to 2 years 
• Severe: Every 6 months to 1 year (more frequently with dilating LV) 

Stages of MR 

• Stage A: At risk of MR: Mild mitral valve prolapse or mild valve thickening  
• Stage B: Progressive MS: Mild to moderate MR 
• Stage C: Asymptomatic Severe MR 
• Stage D: Symptomatic Severe MR 

Exercise Testing  

• In patients with primary MR with symptoms that may be attributable to MR 
  • Hemodynamic exercise testing with echocardiography or invasive assessment is reasonable to correlate severity of MR with patient’s exertional symptoms 

Medical Therapy 

• Acute MR 
  • Vasodilators | Mechanical support devices (i.e., intra-aortic balloon pump) 
• Chronic MR 
  • Primary: Vasodilators for blood pressure control. No indication if patient is normotensive. 
  • Secondary: Heart failure guideline directed medical therapy (GDMT) due to LV systolic dysfunction. 

Prevention of Rheumatic Heart Disease and Secondary Rheumatic Fever 

• Prompt treatment of Group A Strep infections i.e., impetigo or tonsillar pharyngitis with antibiotics decreases the changes of developing rheumatic valve disease by 70% 
• In patients that do develop rheumatic valve disease, secondary prevention of rheumatic fever is indicated typically with penicillin 
• Duration for secondary prophylaxis for Rheumatic Fever depends on presence/absence of carditis during acute rheumatic fever and development of persistent valvular disease post-acute phase 
• Carditis: Valvulitis (Manifested early as mitral regurgitation with/without aortic regurgitation). Myocarditis or pericarditis can also be seen 
• Rheumatic fever with carditis and persistent valvular heart disease 
  • 10 years or until patient is 40 years of age (whichever is longer) 
• Rheumatic fever with carditis and no valvular disease 
  • 10 years or until patient is 21 years of age (whichever is longer) 
• Rheumatic fever without carditis 
  • 5 years or until patient is 21 years of age (whichever is longer) 

Procedural Interventions  

Acute MR 

• Prompt mitral valve surgery, preferably mitral valve repair 

Chronic MR 

• Primary MR 
  • Symptomatic with severe primary MR: MV intervention is recommended irrespective of LV systolic function 
  • Asymptomatic with severe primary MR and LV systolic dysfunction (LVEF ≤ 60%, LV end systolic diameter ≥ 40 mm): MV surgery is recommended 
  • Severe primary MR where surgery is indicated: MV repair should be performed if feasible over mitral valve replacement 
  • Asymptomatic patients with primary severe MR with normal LV systolic function ≥ 60% and LV end systolic diameter ≤ 40 mm: MV repair is reasonable  
  • Symptomatic severe MR: Transcatheter edge-to-edge repair (TEER) (mitral clip) is reasonable if patient has high or prohibitive surgical risk 
• Secondary MR 
  • Symptomatic patients with severe MR related to LV systolic dysfunction (LVEF <50%) with persistent symptoms despite GDMT: Transcatheter edge-to-edge repair (TEER) (mitral clip) is reasonable if LVEF 20-50%, LV end systolic diameter ≤ 70 mm pulmonary artery systolic pressure ≤ 70 mmHg. 
  • If undergoing CABG for CAD/ischemia, mitral valve surgery is reasonable if patient with concomitant severe secondary MR 

Antiplatelet/Anticoagulant Therapy Post MVR 

Decision between a bioprosthetic vs mechanical mitral valve should consider patient’s values, preferences, co-morbid conditions, and risks of anticoagulant therapy 

• Bioprosthetic MVR 
  • Daily low-dose aspirin is recommended lifelong in addition to VKA anticoagulation with INR goal of 2.5 for first 3 to 6 months 
• Patients with a mechanical MVR 
  • Anticoagulation ONLY with vitamin K antagonist (VKA) is recommended with an INR goal of 3 

NOTE: DOACs (Direct Oral Anticoagulants) are currently not recommended after mitral valve replacement out of concern for increased risk of clot development  

LEARN MORE-PRIMARY SOURCES: 

ACC/AHA 2020: Guidelines for the management of patients with Valvular Heart DIsease  

Primary Prevention of Rheumatic Heart Disease 

Burden of valvular heart diseases: a population-based study 

Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial 

BACKGROUND AND PURPOSE:

• There are limited efficacious treatments available for Alzheimer disease. 
• Sims et al (JAMA 2023) assessed the efficacy of the monoclonal antibody donanemab, which is designed to clear brain amyloid plague, at providing clinical benefit to early symptomatic Alzheimer disease.  

METHODS: 

• Design, Setting, and Participants 
  • The study was a multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial from Jun 2020 to Nov 2021 (last patient visit for primary outcome in Apr 2023). 
  • 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging were enrolled. 
    • Mean age of 73.0 years; 57.4% women [996]; 68.1% with low/medium tau pathology [1182] and 31.8% with high tau pathology [552]. 
• Interventions 
  • Participants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blind manner if dose completion criteria were met. 
• Main Outcomes and Measures 
  • The primary outcome was the change in integrated Alzheimer Disease Rating Scale (IADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). 
  • There were 24 gated outcomes including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment).  

RESULTS:

• 76% of participants (1320/1736) completed the trial. 
• 23 of the 24 gated outcomes were statistically significant.  
• The least-squares mean (LSM) change in iADRS score at 76 weeks was −6.02 (95% confidence interval [CI], −7.01 to −5.03) in the donanemab group and −9.27 (95% CI, −10.23 to −8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population. 
• The LSM change in the combined population at 76 weeks was −10.2 (95% CI, −11.22 to −9.16) with donanemab and −13.1 (95% CI, −14.10 to −12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001). 
• LSM change in CDR-SB score at 76 weeks was 1.20 (95% CI, 1.00-1.41) with donanemab and 1.88 (95% CI, 1.68-2.08) with placebo (difference, −0.67 [95% CI, −0.95 to −0.40]; P < .001) in the low/medium tau population and 1.72 (95% CI, 1.53-1.91) with donanemab and 2.42 (95% CI, 2.24-2.60) with placebo (difference, −0.7 [95% CI, −0.95 to −0.45]; P < .001) in the combined population.  
• Amyloid-related imaging abnormalities of edema or effusion occurred in 205 participants (24.0%; 52 symptomatic) in the donanemab group and 18 (2.1%; 0 symptomatic during study) in the placebo group.  
• Infusion-related reactions occurred in 74 participants (8.7%) with donanemab and 4 (0.5%) with placebo.  
• Three deaths in the donanemab group and 1 in the placebo group were considered treatment related. 

CONCLUSION:

• Donanemab treatment significantly slowed clinical progression at 76 weeks in participants with early symptomatic Alzheimer disease and amyloid and tau pathology. 

Learn More – Primary Sources: 

Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial | Dementia and Cognitive Impairment | JAMA | JAMA Network 

Testosterone Treatment in Adult Men with Age-Related Low Testosterone 

Summary 

Testosterone levels in men begin to drop in their mid-30s, with over 50% of men having low levels of testosterone by the age of 80. This age-related low testosterone is sometimes accompanied by symptoms of androgen deficiency such as decreased libido and sexual dysfunction. There is no universally accepted level of testosterone below which it is considered pathologic, and instead providers must use their best judgement combining signs and symptoms with low laboratory levels of testosterone to diagnosis clinically significant low testosterone. While primary and secondary hypogonadism is always treated, there is still controversy regarding the treatment for low testosterone due to age. The American College of Physicians has published a guideline for the use of testosterone in men with age-related low testosterone. 

Clinical Signs and Symptoms 

• The signs and symptoms of androgen deficiency can be difficult to isolate in the setting of older male patients with multiple co-morbidities  
  • The clinician should consider whether symptoms are not more likely due to a comorbidity or medication side effect  
• Symptoms include:  
  • Reduced libido | Erectile dysfunction | Depressed mood | Fatigue  
• Signs include:  
  • Reduced muscle mass | Reduced strength | Increased adiposity | Osteoporosis/low bone mass | Cardiovascular disease | Decreased volume of ejaculate | Loss of body and facial hair | Anemia  

Diagnosis 

• Low Testosterone Syndrome 
  • Defined as at least 3 sexual dysfunction symptoms with a total testosterone level < 11.1 nmol/L (< 320 ng/dL) 
• Endocrine Society recommends measuring total testosterone concentrations on two separate mornings between 7-10 AM when the patient is fasting  
  • Testosterone levels can vary depending on: Time of day | Glucose intake | sex 
    hormone binding globulin levels | Recent illness | Medications 
  • Clinicians should not test levels following recent illness or if patient is on a short course of medication that can alter SHBG levels (e.g., opiates, glucocorticoids)  
  • In men whose total testosterone is near the lower limit of normal or who have a chronic condition or medication that cannot be halted that alters SHBG, obtain a free testosterone concentration using either equilibrium dialysis or estimating it using an accurate formula 

Treatment 

• Treatment with testosterone can be offered to men with sexual dysfunction due to age-related low testosterone who wish to improve sexual dysfunction  
  • Patients should be counseled on possible risks and side effects of taking testosterone  
  • Evidence shows small improvements in sexual dysfunction symptoms with testosterone replacement therapy 
  • This improvement was found regardless of starting testosterone level (as long as level was low)  
  • There is no improvement in other symptoms including: Strength | Stamina| Mood| Energy | Cognition  
• ACP suggests using intramuscular formulation of testosterone instead of transdermal due to similar efficacy and greatly decreased price ($156.32 vs. $2135.32 per year)  

Risks and Adverse Effects

• For patients on testosterone therapy, clinicians should reevaluate symptoms within 12 months and then again on subsequent follow ups  
• Testosterone should be discontinued if there is no improvement in sexual dysfunction  
• Studies of harms from long term testosterone use are inconclusive but there is concern for increased risk of: Heart attacks | Strokes | Prostate cancer | Polycythemia 
• Monitoring PSA and CBC while on testosterone is recommended  
  • Increases in either level should prompt discussion of drug discontinuation  

Key Points

• Low testosterone is very common in older men due to physiologic decreases with increasing age 
• Not all men with low testosterone will develop symptoms of androgen deficiency, and should not be offered treatment in the absence of symptoms  
• Testosterone therapy can be offered to patients with low T who wish to improve sexual dysfunction, as long as patient is willing to accept possible risks of therapy 
• If giving testosterone, intramuscular formulations are preferred to transdermal 

Primary Sources – Learn More  

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians 

Choosing Wisely: American Urological Association on Testosterone Therapy for Erectile Dysfunction 

Testosterone Therapy in Men With Hypogonadism: An Endocrine Society* Clinical Practice Guideline 

Pharmacologic and Non Pharmacologic Treatment of Type 2 Diabetes 

• Background
• A1C target
• ADA Treatment Recommendations
• Lifestyle Modification  
• Medications  
• Management Summary (Initiation) 
• Self-Monitoring of Blood Glucose (SMBG) 
• Hypoglycemia 
• Additional Notes  

Background 

Treatment of Type 2 Diabetes, whether new onset or persistent, requires multimodal, comprehensive management. Diabetic treatment includes lifestyle changes, weight management, and pharmacologic approaches. Newer drugs in the GLP-1 receptor agonist (GLP-1 RA) drug class have very high efficacy for both glycemic control and weight management and are now the preferred starting agents for patients with newly diagnosed diabetes. Aside from antihyperglycemic agents, patients may also require lipid-lowering and antihypertensive medications  

Management should be individualized based on numerous factors, such as age, life expectancy, comorbid conditions, duration of diabetes, risk of hypoglycemia or adverse consequences from hypoglycemia, patient motivation, and adherence. The ADA states that  

“A patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include comorbidities (e.g., atherosclerotic cardiovascular disease | heart failure | chronic kidney disease) | hypoglycemia risk | impact on weight | cost | risk for side effects | and patient preferences” 

A1C target (See ‘Related  PCMed Topic’ below): Currently, there are different professional guideline thresholds  

• ACP: Aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes and consider de-intensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%  
• ADA: Recommends <7% for the general population and to consider more stringent goals (<6.5%) for selected patients without significant hypoglycemia (e.g., long life expectancy, no CVD and treated with lifestyle or metformin only)  
• AACE/ACE: ≤6.5% if target can be achieved safely  

ADA Treatment Recommendations Include the Following  

• Metformin is no longer the only preferred first-line agent for glycemic control, but given its low cost and accessibility is still often used for initial therapy 
• The ADA recommends starting patients on “high efficacy” diabetes medications based on ability to lower glucose and achieve glycemic control 
• ACP recommends adding a SGLT-2 inhibitor or GLP-1 agonist to metformin and lifestyle modifications in adults with T2DM and inadequate glycemic control
• Consider combination therapy at treatment initiation to shorten time to glycemic control 
• Very high efficacy: 
  • Dulaglutide (Trulicity) | Semaglutide (Ozempic) | Tirzepatide (Mounjaro) 
  • Insulin 
  • Combination oral | Combination injectable (e.g., GLP-1 + Insulin)  
• High efficacy 
  • GLP-1 RA not listed above e.g., Exenatide (Byetta) | Liraglutide (Victoza) 
  • Metformin  
  • SGLT2-I e.g., Empagliflozin (Jardiance) | Canagliflozin (Invokana) 
  • Sulfonylurea 
  • Thiazolidinedione e.g., Pioglitazone (Actos) | Rosiglitazone (Avandia) 
• Encourage weight loss 
  • 3% to 7% weight loss improves glycemia and CV risk factors 
  • > 10% total body weight loss may have disease-modifying effects, including diabetes remission, and may improve long-term cardiovascular outcome 
  • Options for weight loss depend on patient’s BMI and co-morbid conditions: Lifestyle changes| Evidenced-based structured weight management programs | Pharmacotherapy | Metabolic surgery 
  • Very high efficacy pharmacotherapy diabetes medications for weight loss include: Semaglutide (Ozempic) | Tirzepatide (Mounjaro) 
  • These GLP-1 RA drugs should be first-line therapy for patients needing weight management and glycemic control  
  • High efficacy weight management drugs include: Liraglutide (Victoza) | Dulaglutide (Trulicity) 
• Consider early introduction of insulin  
  • Evidence of catabolism: Weight loss | Hypertriglyceridemia | Ketosis  
  • Hyperglycemic symptoms  
  • A1C levels >10% (86 mmol/mol) or blood glucose levels ≥300 mg/dL (16.7 mmol/L)  
  • As glycemic control improves, simplifying the regimen or changing to noninsulin agents is possible 
• Dual therapy: Consider in newly diagnosed patients if A1C ≥1.5% (12.5 mmol/mol) above target  
  • Initial dual therapy extends time to treatment failure (compared to sequential addition of medications) 
  • High costs and tolerability issues are important barriers to the use of GLP-1 receptor agonists 
  • If there are cost-related barriers consider use of lower cost medications e.g metformin | sulfonylureas | TZDs | insulin 
• Continue metformin for as long as tolerated and not contraindicated  
  • Add other agents, including insulin, to metformin 
  • Glucagon-like peptide 1 receptor agonist is preferred to insulin when possible  

With Comorbidities in addition to Type 2 Diabetes  

• In patients that are overweight or obese 
  • GLP-1 RA or dual GLP-1RA/GIP are recommended 
  • Once weight loss is attained continue therapy to maintain health benefits. Sudden discontinuation can lead to rebound weight gain and worsening of cardiometabolic risk factors 
• In patients with known atherosclerotic cardiovascular disease or high cardiovascular risk, kidney disease, or heart failure, the following are recommended 
  • Sodium–glucose cotransporter 2 inhibitors (SGLT2i) 
  • Glucagon-like peptide 1 receptor agonists with demonstrated CVD benefit 
  • If A1c remains above target for patients on SGLT2i considering adding GLP-1 RA or vice versa 
• In patients with concomitant biopsy-proven MASLD or high risk for liver fibrosis based on non-invasive tests 
  • Encourage weight loss via lifestyle changes and obesity pharmacotherapy 
  • Choose diabetes medications that assist with weight loss (such as GLP-1-RA or  GIP or dual GLP-1-RA/GIP ) or decrease liver fibrosis (Pioglitazone) 
• Consideration of these medications in the setting of these co-morbidities is independent of HbA1C or HbA1C target 

Lifestyle Modification  

• Lifestyle interventions can improve quality of life | promote weight loss | optimize glucose management| reduce CV risk factors | lead to deprescribing of medications
• ACCE/ACE/ACLM list the following as key areas for lifestyle modification
  • Advocacy for lifestyle interventions in the 6 pillars of lifestyle medicine e.g., restorative sleep| stress management | adequate physical activity |social connections | whole-food and plant predominant diet| avoiding as 1st line management
  • Assessment of baseline lifestyle habits in above 6 pillars and readiness to change
  • Setting SMART goals
  • Nutrition: Weight management | plant-based diet
  • Prescribing physical activity: 150 min/week exertion such as walking or stair climbing | Strength training using SMART goals e.g., FITT (Frequency | Intensity | Time | Type)
  • Discuss sleep quality and quantity | screening for sleep disorders | advocate: 6 to 8 hours/night
  • Behavioral support: Community engagement | Avoidance of excessive alcohol | Impact of tobacco and recreational drug usage moderation
  • Smoking cessation: No tobacco products
• The ADA additionally recommends  
  • Diabetes self-education and support 
  • Take into consideration social determinants of health (e.g., Health literacy | Access to medications | Access to housing and food)  
  • Avoidance of therapeutic inertia (e.g., Reassess and modify therapy every 3 to 6 months)  
• Patients with diabetes should also be assessed for diabetic complications 
  • ASCVD Risk | Heart disease history | Staging/screening of CKD | Hypoglycemia risk | Retinopathy | Neuropathy | Screening for MASLD/NASH 

Medications  

• Noninsulin Glucose-Lowering Agents 
  • GLP1 receptor agonists (GLP-1-RA) or GIP
  • Biguanides 
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i)
  • Dipeptidyl peptidase 4 inhibitors (DPP4i)
  • Thiazolidinediones (TZDs)
  • Insulin-secretagogues
• Insulin 

Noninsulin Glucose-Lowering Agents  

• GLP1 receptor agonists (GLP-1-RA) or GIP : Dulaglutide (Trulicity) | Semaglutide (Ozempic) | Tirzepatide (Mounjaro) 
  • Very high to high efficacy drugs (see above) considered first-line therapy 
  • Preferred agent for patients needing glycemic control and assistance with weight management  
  • Recommended for patients with comorbid cardiovascular disease or chronic kidney disease  
  • ACP recommends using GLP-1 agonist to reduce risk for all-cause mortality|major adverse cardiovascular events| stroke 
  • Preferred to insulin when possible 
  • When insulin is started GLP1-RA should be continued for greater efficacy, weight and hypoglycemia benefit 
  • Strong A1C-lowering properties: Associated with decreased weight, lipid and BP 
  • Risks and adverse events include: Pancreatitis | Thyroid cancer (in rodent models) | Ileus | GI side effects 
• Biguanides  
  • Metformin is a high efficacy medication that is generally affordable and accessible  
  • Benefits: Low hypoglycemia risk | May help with modest weight loss | Good antihyperglycemic efficacy at doses of 1,000 to 2,000 mg/day  
  • Side effects: GI intolerance (e.g., bloating| abdominal discomfort| diarrhea) 
  • Renal disease: Can be used with reduced estimated glomerular filtration rates (eGFR) ≥30 mL/min/1.73 m²  
  • Vitamin B12 deficiency: Periodically test for vitamin B12 levels 
• Sodium-glucose cotransporter 2 inhibitors (SGLT2i): Ertugliflozin | Dapagliflozin | Canagliflozin | Empagliflozin  
  • Intermediate to high efficacy  
  • Glucosuric effect: Associated with decreased A1C, weight, and systolic BP  
  • Recommended for patients with concomitant CKD or cardiovascular disease  
  • ACP recommends using an SGLT-2 inhibitor to reduce the risk for all-cause mortality| major adverse cardiovascular events| progression of CKD | hospitalization due to CHF 
  • Risks and adverse events include: DKA (rare) |Genital mycotic infections | Necrotizing fasciitis of the perineum  
• Dipeptidyl peptidase 4 inhibitors (DPP4i): Alogliptin | Saxagliptin | Linagliptin | Sitagliptin  
  • Inhibit DPP4 and increase GLP1 and other incretin hormones | Modestly lower A1C | Intermediate potency | low risk of hypoglycemia  
  • Combination pills available with metformin, SGLT2 inhibitors, and a TZD  
  • Weight neutral; does not assist with weight management  
  • Do not add DDP-4 to GLP-1 RA or GIP/GLP-1 RA combination medication due to lack of additional glucose lowering than that of GLP-1 RA alone 
  • Note: ACP does NOT recommend adding a (DPP-4) inhibitor to metformin and lifestyle modifications in adults with T2DM and inadequate glycemic control  
• Thiazolidinediones (TZDs): Pioglitazone | Rosiglitazone  
  • Directly reduce insulin resistance | High efficacy A1C-lowering properties | Low risk of hypoglycemia  
  • Caution recommended due to associated risk factors: Weight gain | Increased bone fracture risk in postmenopausal females and elderly males | Elevated risk for chronic edema or heart failure  
• Insulin-secretagogues  
  • Sulfonylureas (SUs): Glimepiride | Glipizide | Glyburide  
    • Relatively potent A1C-lowering effects  
    • Effects may not last | May increase weight | Risk for hypoglycemia and CVD  
  • Glinides: Nateglinide | Repaglinide  
    • Shorter half-life than SUs, with lower A1C-lowering effects but also lower risk of prolonged hypoglycemia  

Insulin  

• Most potent antihyperglycemic agent  
• Considerations prior to use  
  • Patient motivation | CVD, comorbidities and complications | Age | Risk for Hypoglycemia | Overall health |Cost considerations  
• Basal analogs: Glargine | Detemir | Degludec  
  • Flat serum insulin concentration for 24 hours or longer  
• Human Neutral protamine Hagedorn (NPH) insulin  
  • More likely to cause hypoglycemia than basal analogs  
• Addition of human NPH or long-acting insulin analogs to oral agents is “well-established approach that is effective for many patients” (ADA)  
• Rapid acting Insulin: Glulisine | Lispro | Aspart | Inhaled insulin  
  • Rapid acting formulations are preferable to regular human insulin 
  • May be necessary at mealtime if glycemia uncontrolled despite combination of oral medications and insulin/GLP1-RA  
• Premixed insulins combining longer and shorter action insulin available but less flexible and greater risk of hypoglycemia  
• Monitor for signs of overbasalization e.g. significant bedtime-to-morning or postprandial-to-preprandial glucose differential | A1C not at target despite normal fasting glucose, etc 

Management Summary (Initiation)  

• Recent onset T2D and A1C <9.0%  
  • Monotherapy (with a very high efficacy drug (GLP-1 RA) or metformin and lifestyle changes 
• A1C ≥9.0%  
  • Symptomatic (polyuria, polydipsia, or polyphagia): May need to initiate insulin to control glucose toxicity symptoms 
  • Asymptomatic: Consider starting combination therapy with two drugs picked based on efficacy and comorbid conditions (e.g., Obesity | CKD | CVD) 

Note: Link to detailed ACE/ACCE Glycemic Control algorithm available in ‘Learn More – Primary Sources’ below)  

Self-Monitoring of Blood Glucose (SMBG) 

• Recommended for patients on intensive insulin therapy (basal plus prandial insulin)  
  • Check prior to meals/snacks, prior to exercise, and at bedtime 
  • Once-daily fasting glucose in patient on basal insulin only 
  • Limited benefit for patients on oral therapy only 
• Continuous glucose monitoring (CGM) devices are emerging as a complement to SMBG  
  • Strong recommendation to use in adults on any insulin therapy 
  • Consider using for patients on non-insulin glucose lowering therapy 
  • Strong correlation between “time in range” (TIR) and HbA1c (70% TIR equates to HbA1c ~7%) 
  • Should be considered in patients who remains above their A1c target to identify therapeutic gaps and tailor therapy 
  • Educate patients on substances that can interfere with glucose readings 
• Patients not on insulin  
  • Routine glucose monitoring likely limited in clinical value  
  • For some, may provide insight regarding exercise, diet and medication management  

Hypoglycemia  

• Risk for antihyperglycemic agents, especially insulin  
• Some classes have lower risk for hypoglycemia  
  • Metformin | GLP1 receptor agonists | SGLT2 inhibitors | DPP4 inhibitors | TZDs  
  • However, hypoglycemia can still occur in combination with an insulin secretagogue or exogenous insulin 
• Screen patients for evidence of hypoglycemia unawareness  
  • Young children with type I diabetes and elderly are particularly vulnerable 
  • Interventions include: Medication or diet adjustments | Patient education | Individualized glycemic goals | Continuous glucose monitoring devices  
• Educate patients regarding symptoms  
  • Tremors or feeling shaky | Nervous or anxious | Sweating, chills and clamminess | Irritability | Confusion | Tachycardia | Lightheaded or dizziness | Pallor | Drowsy or weakness | Blurred/impaired vision | Tingling or numbness in the lips, tongue, or cheeks | Headaches | Lack of coordination | Seizures (severe)  
• “15-15 Rule”: Raise glucose to >70 mg/dL with 15 grams carbohydrate intake and check glucose at 15 minutes | Repeat if glucose still <70  
  • Glucose tablets or gel tube | 4 ounces (1/2 cup) of juice or regular (non-diet) soda | 1 tablespoon of sugar, honey, or corn syrup | Hard candies, jellybeans, or gumdrops (based on labelling)  
• Severe hypoglycemia (patient cannot treat herself or unconscious): Glucagon  
  • Available by injection (buttock, arm or thigh) or nasal powder (does not require inhalation)  
  • Educate family members or caregivers on how to administer 

Additional Notes  

• GLP1-RA is preferable to insulin for those patients who may require an injectable medication  
• Patients who require a 3rd medication and who have A1C >8.0% and/or long-standing disease are less likely to reach their target A1C with a third oral antihyperglycemic agent  
  • While adding GLP1-RA may initially work, many patients will still require insulin  
• Reevaluate medications regularly to avoid therapeutic inertia  
  • Every 3 to 6 months  
  • Adjust as needed based on new patient factors  
  • Yearly visits (or more frequent depending on clinical findings) to ophthalmologist and podiatrist  
• Important to prevent complications and slow CVD / renal disease  
  • Manage risk factors for atherosclerosis (e.g., BP, cholesterol, smoking, obesity)  
  • Early referral to nephrology for worsening albuminuria even in setting of stable creatinine 
• Patients with diabetes are at high risk for complicated infectious illnesses and routine vaccinations and annual dental visits should be encouraged  

Learn More – Primary Sources 

FDA List of Approved Type 2 Diabetes Medications

AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm

ADA 2025 Standards of Care

ACP Newer Pharmacologic Treatments for T2DM: A Clinical Guideline

Lifestyle Interventions for Treatment and Remission of Type 2 Diabetes and Prediabetes in Adults: A Clinical Practice Guideline From the American College of Lifestyle Medicine

Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians

Hyperthyroidism: Diagnosis and Management  

SUMMARY: 

Hyperthyroidism is a form of thyrotoxicosis caused by the excessive production and secretion of thyroid hormones from the thyroid. In iodine-sufficient countries, such as the United States, the majority of cases of hyperthyroidism are due to Graves’ disease, followed by toxic multinodular goiter and solitary toxic adenoma. Diagnosis is made based on symptoms at presentation followed by further imaging and antibody testing. Treatment ranges from antithyroid drugs to reduce hormone secretion, radioactive iodine therapy, and definitive surgery via thyroidectomy.  

Clinical Presentation 

• Hyperthyroidism affects roughly 1.2% of Americans  
  • Less than half of these cases will have signs and symptoms of overt hyperthyroidism  
• Increasing prevalence of hyperthyroidism with: 
  • Older age | Female sex | White race | Family history  
• Common reported symptoms: 
  • Palpitations | Fatigue | Tremor | Anxiety | Disturbed sleep | Weight loss (despite increased appetite) | Heat intolerance | Sweating | Polydipsia | Changes in menstruation  
• Physical exam findings include: 
  • Tachycardia | Extremity tremor | Weight loss | Tachypnea | Warm and moist skin 
• Graves’ disease may have additional physical exam findings such as: 
  • Ophthalmopathy (i.e., Graves’ orbitopathy) occurs in 25% of patients with Graves’ disease | Proptosis | Periorbital edema | Diplopia  
  • Thyroid dermopathy: Slightly pigmented thickened skin over the pretibial area 
  • Acropachy: Rare | Clubbing of fingers and toes  
• Patients with multinodular goiter may additionally present with:  
  • Globus sensation | Dysphagia | Orthopnea  
• Older patients are more likely to develop cardiovascular complications such as atrial fibrillation and heart failure 
• Serious complications of hyperthyroidism include 
  • Osteoporosis  
  • Decreased fertility  
  • Thyrotoxic periodic paralysis (e.g., Triad of acute muscle paralysis | Hypokalemia | Thyrotoxicosis)  

Diagnosis 

• Patients presenting with signs and symptoms of hyperthyroidism should have a TSH checked  
  • TSH has high sensitivity and specificity for thyroid disorders  
• If TSH is abnormal, T4 and T3 levels should be checked to distinguish between overt and subclinical hyperthyroidism  
  • Subclinical hyperthyroidism: Normal T3/T4 levels + Low TSH 
  • Overt hyperthyroidism: High T3/T4 + Low TSH 
• TSH may be normal in the case of hyperthyroidism caused by: 
  • TSH-producing pituitary adenoma 
  • Thyroid hormone resistance  
• Patients taking high doses of biotin may also have inaccurate TFT results and should repeat testing 2 days after stopping biotin 
  • If thyroid function tests (TFTs) suggest hyperthyroidism, then further testing should be obtained to determine etiology and guide treatment 
  • Thyroid ultrasound + TSH-receptor Antibodies (TRAb, i.e., thyroid-stimulating immunoglobulins or thyroid stimulating antibodies) OR 
• Radioactive iodine uptake test (RAIU) 
  • Thyroid US + TRAb 
  • May be preferred over RAIU due to lower cost and absence of radiation exposure  

• Graves’ disease: Positive TRAb and doppler US of the thyroid showing increased blood flow with a diffusely enlarged thyroid  
• Radioactive iodine uptake test  
  • Graves’ disease: Diffusely increased uptake  
  • Multinodular goiter: Normal or high uptake with an irregular and asymmetric pattern 
  • Toxic adenoma: Localized and focal increased uptake with suppression in the remaining thyroid tissue 
  • Thyroiditis | Drug-induced | Factitious: Diffuse low uptake  

Treatment 

• Symptomatic patients should be started on beta-adrenergic blockade while awaiting improvement in thyroid hormone levels with the below therapies  
  • Propranolol (Inderal) 10 to 40mg 3 to 4 times per day 
  • Atenolol (Tenormin) 25 to 100mg 1 to 2 times per day  
  • Metoprolol (Lopressor) 25 to 50mg 2 to 3 times per day 
  • Nadolol (Corgard) 40 to 160mg daily 
• Anti-thyroid drugs (ATD): Propylthiouracil (PTU, Propycil) | Thiamazole (Methimazole) 
  • Inhibit production of thyroid hormones within the thyroid | 1^st line therapy for hyperthyroidism due to Graves’ disease  
  • PTU dosing: 50 to 150mg three times daily  
  • Thiamazole dosing: 10 to 40mg daily  
  • Thiamazole is preferred in most cases due to its longer duration of action and better side effect profile  
  • Recommended to titrate to lowest effective dose to maintain TFTs within normal range 
  • Dosing depends on: Severity of symptoms | Size of thyroid gland  
  • Check TFTs 4 to 6 weeks after starting therapy | Repeat TFTs every 2 to 3 months afterwards 
  • Continue maintenance dosing of ATD for ≥ 12 to 18 months 
  • Cessation of ATD is associated with high rates of relapse within the first 6 months but is uncommon after 4 to 5 years 
  • Common side effects: Pruritis | Arthralgias | GI distress 
  • Less common side effects: Agranulocytosis | Hepatotoxicity | Vasculitis 
  • Agranulocytosis: Generally occurs within 90 days of ATD initiation  
  • Obtain baseline CBC and CMP prior to starting therapy 
• Radioactive iodine therapy 
  • Safe and cost effective  
  • Can be 1^st line therapy for: Graves’ disease | Toxic multinodular goiter | Toxic adenoma  
  • Contraindicated in: Pregnancy (or planning to become pregnant | Breastfeeding | Inability to adhere to radiation safety guidelines | Concern for thyroid cancer | Moderate to severe Graves’ orbitopathy 
  • Radioactive iodine therapy may worsen Graves’ orbitopathy | Give prophylactic steroids for patients with mild Graves’ orbitopathy following treatment  
  • Some patients might need treatment with an ATD while awaiting radioactive iodine therapy planning | ATD should be stopped 3 to 5 days prior to procedure and restarted 3 to 7 days later until TFTs normalize 
  • Monitor TFTs 1 to 2 months after radioactive iodine therapy | Repeat every 4 to 6 weeks until patient is euthyroid 
  • Patients who relapse or have persistent hyperthyroidism after 6 months can  repeat therapy  
  • Side effects: Acute thyroiditis | Worsening of ophthalmopathy  
• Total thyroidectomy  
  • Definitive and most successful therapy for Graves’  
  • Recommended for: Large goiters | Suspected or documented thyroid cancer | Moderate to severe ophthalmopathy | Patients who prefer surgery 
  • Patients should be treated with an ATD to achieve a euthyroid state prior to surgery 
  • After surgery patients will need supplemental levothyroxine  
  • Repeat TFTs after 6 to 8 weeks post surgery  
  • Complications include: Hypocalcemia (due to hypoparathyroidism)| Recurrent laryngeal nerve injury  

Thyroid Storm 

• Rare disorder of thyrotoxicosis with a high mortality rate requiring inpatient treatment  
• Can be triggered by: Discontinuation of ATD | Infection  
• Diagnosis is clinical when patient presents with signs and symptoms of thyroid hormone excess such as:  
  • Fever | AMS | Diarrhea | Jaundice | Tachycardia | Heart failure | Atrial fibrillation  
• Burch-Wartofsky Point Scale (BWPS) for Thyrotoxicosis (see Learn More below) can be helpful for diagnosis 
• Treatment includes: 
  • High dose anti-thyroid drugs: PTU 500 to 1000mg loading dose + 250mg every four hours | Thiamazole 20mg every 6 hours  
  • Inorganic iodine: 5 drops of saturated solution of potassium iodide every 6 hours PO 
  • Cholestyramine (Questran): 4g every 6 hours  
  • Beta blockers (e.g., Propanolol (Inderal)): For symptom management  
  • Glucocorticoids: Treat risk of adrenal insufficiency caused by severe thyrotoxicosis  
  • Acetaminophen (Tylenol) | External cooling: For symptom management  

KEY POINTS: 

• Hyperthyroidism in the US and other iodine-sufficient regions is most commonly due to Graves’ disease, followed by toxic multinodular goiter and solitary toxic adenoma 
• Diagnosis depends on abnormal thyroid function testing (e.g., Low TSH + Elevated T3/T4) in the setting of signs of and symptoms of hyperthyroidism  
• Further testing can be obtained to delineate the cause of hyperthyroidism including TRAb + Thyroid ultrasound OR radioactive iodine uptake testing 
• Treatment options include anti-thyroid drugs, radioactive iodine therapy or thyroidectomy  
• Thyroid storm is a potentially lethal complication of thyrotoxicosis, often triggered by infection or lack of adherence to ATD therapy, and warrants inpatient treatment  

Primary Sources – Learn More 

2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis  

The Lancet: Hyperthyroidism 

The American Association of Endocrine Surgeons: Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults 

Burch-Wartofsky Point Scale (BWPS) for Thyrotoxicosis 

Your PrEP Options

There are currently three forms of PrEP (Pre-Exposure Prophylaxis medication to prevent HIV infection.) Which one is right for you?

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The Three PrEP Medications

Transcript:
Dr. Raffaele Bernardo:  

So there are currently three FDA-approved medications for HIV pre-exposure prophylaxis. Two come in the form of pills. 

Each of those is taken as one pill once a day every day, whether or not you’re having sex. Those two pills go by the brand names of Descovy and Truvada, and they’re both single tablets that are taken once a day every day.  

The third is the first long-acting, injectable medication, called Apretude. Apretude is given in a provider’s office healthcare provider’s office. It’s given as an injection during one month, one month, two, and then every two months thereafter. 

It reduces the need to remember to take a pill every day. It helps around the situation of disclosure, since you don’t have to, you don’t have to keep a medicine bottle around the house, and it minimizes the need for additional medications you have to take every day for those who are already taking several different medications. So it is a great option. 

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Recorded on November 4th, 2024 at 8 pm ET

Watch the full webinar here

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Commercial Support

This educational activity is supported by an independent educational grant from Gilead Sciences

Webinar: PrEP for Primary Care Physicians 

Recorded on September 30th, 2024 at 8 pm ET

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Faculty: Jonathan Shuter, MD, Uriel Felsen, MD, and Raffaele M. Bernardo, DO
Moderator: Rasika Karnik, MD

Transcript Summary:

Key Highlights:

• Who is PrEP for?
  PrEP is recommended for any individual who is HIV-negative and at risk of acquisition through sexual contact or injection drug use. It is not limited to specific populations.
• PrEP Options and Efficacy:
  Three FDA-approved medications are available:
  • Truvada (oral)
  • Descovy (oral; not approved for vaginal sex)
  • Apretude (injectable, given bi-monthly)
    All are highly effective when taken as prescribed, with adherence being the strongest predictor of efficacy.
• Clinical Workflow and Screening:
  Initiating PrEP involves a comprehensive sexual history, baseline labs (including HIV, STI screening, hepatitis B status), and ongoing monitoring. Renal function should be assessed periodically depending on the medication.
• Adherence and Follow-up:
  The panel emphasized the importance of adherence counseling and support tools (e.g., reminders, pill organizers). Routine follow-ups every three months include repeat HIV and STI testing.
• Side Effects and Safety:
  PrEP is generally well-tolerated. Mild nausea may occur initially with oral options, and injection-site pain is common with Apretude. PrEP is safe during pregnancy and should be continued if risk remains.
• Special Populations and Scenarios:
  • PrEP for people who inject drugs is effective (~75%) but slightly less so than for sexual transmission.
  • Discontinuation of PrEP, especially injectable forms, should be done under provider guidance to mitigate risks (e.g., viral resistance, hepatitis B reactivation).
• Practice Integration Tips:
  Suggestions included telehealth adoption, staff training, EMR templates, and creating a welcoming clinic environment—especially for LGBTQ+ patients.
• Looking Ahead:
  Promising developments include twice-yearly injectable agents like lenacapavir and potential subcutaneous implants. Broadening access through pharmacies, EDs, and OB/GYN practices is also being explored.

Takeaway Messages:

• Normalize and routinize discussions of sexual health and HIV prevention.
• PrEP is a simple, safe, and effective tool—primary care providers can and should lead its implementation.
• HIV screening is foundational—both for treatment and prevention strategies.

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Transcript:

PrEP for Physicians webinar 

Rasika Karnik: Good evening, everyone. Thank you for joining us tonight for our PcMED Connect, where tonight we’re going to focus on learning about PrEP or pre-exposure prophylaxis for HIV. I am joined tonight by three infectious disease and HIV specialists. And my name is Rasika Karnik. By the way, I’m a physician. I do primary care at the University of Chicago. And I’m going to let my panelists, my esteemed panelists, introduce themselves, and we’ll go in alphabetical order. So how about Dr. Bernardo. 

Raffaele Bernardo:  Hi! Good evening, everyone. My name is Ralph Bernardo. I am an internist and an infectious disease specialist, currently practicing in New Jersey. 

Rasika Karnik:  All right. Dr. Felson. 

Uriel R. Felsen:  Hi, everyone! I’m Uriel Felson. I’m an infectious disease doctor. I work at the Montefiore Health System in the Bronx, New York, affiliated with the Albert Einstein College of Medicine, and I work with patients who are living with HIV, and I work with patients who are trying to prevent HIV and I do research on HIV treatment and prevention. 

Rasika Karnik:  Wonderful! Dr. Shuter. 

Jonathan Shuter:  Hi, I’m Jon Shuter. I also work at Montefiore Medical Center at Albert Einstein College of Medicine in the Bronx. I think I’m the senior person on this panel, and I have the dubious honor of having seen my first patient with HIV in 1985. So that is close to 40 years ago, and I have been taking care of patients with HIV ever since. I have an active patient panel in our clinic in the Bronx, and I continue to care for patients to this day. 

Rasika Karnik:  Wow! I’m so glad to have all of you here tonight. And we’re going to do this. This is pretty casual session. We’re going to be having a lot of questions and answers for our panelists from the audience. If you have any questions that pop up, please feel free to shoot them in the in the chat, and we’ll certainly get to them. So let’s get started. And Dr. Felson, who is PrEP for? 

Uriel R. Felsen:  It’s a great question, Rasika, and I think, you know, for this audience it’s really important to understand that PrEP is for anyone that isn’t already living with HIV, and is at risk for acquiring HIV. So there are some ways to think about some populations who may be more at risk for HIV. But I think the most important take home point for everyone to come home, you know, everyone who’s watching this to understand is that it’s really for anyone that doesn’t already have HIV, and that is interested in protecting themselves from acquiring HIV, either through sex or through intravenous drug use. 

Rasika Karnik:  Got it. That’s a good overview. So it almost feels like anybody who is interested. And then what about insurance coverage. How does that work out for folks? Because a lot of times people are concerned about payment for and coverage for the medication. 

Uriel R. Felsen:  The really nice thing about PrEP coverage at this point is that it has a grade A recommendation from the US Preventive Services Task Force, the USPSTF. And so, because there’s a grade A recommendation for it, all insurances are required to cover it without any contributions from the patient. And for those who are uninsured. There are a lot of access programs through the drug companies themselves, and some States also have assistance programs. So pretty much anyone who is interested in being on PrEP should have minimal financial barriers to being able to get it, at this point. 

Jonathan Shuter: Can I just chime in. 

Rasika Karnik:  Please. 

Jonathan Shuter:  Yes, so we have a very American-centric view here, but it ought to be added that there has been a fairly massive rollout of PrEP internationally, and even though there may not be the range of choices available everywhere that we have in the United States, there’s increasingly improved access to PrEP throughout the world at this point. 

Rasika Karnik:  Speaking of choices, what options are there for PrEP? Dr. Bernardo. 

Raffaele Bernardo:  Sure. So there are currently three medications that are FDA approved for HIV pre-exposure prophylaxis. Two of these medications come in the form of an oral tablet that’s taken once daily, and the third is actually the first long-acting injectable for HIV pre-exposure prophylaxis. But all three  are FDA approved, and all three, as long as they’re taken as prescribed, are highly effective at preventing HIV infection. The two tablets are single fixed-dose combination tablets of two different medications of the brand names. One is Truvada, the other is Descovy, and the long acting injectable goes by the brand name Apretude. Apretude is given one month back to back for the first two months, and then every other month thereafter. 

Rasika Karnik:  Are they equal in effectiveness? 

Raffaele Bernardo: So, the thing about PrEP is that we know it works. In every study that’s looked at the efficacy of PrEP, there was a direct correlation between adherence and efficacy. So if you take it, it works, and it’s largely up to the patient to determine that. But we know from study after study that there is a direct correlation between the two. So yes, if it’s taken as prescribed, PrEP, all three types, are highly effective at preventing HIV infection. 

Rasika Karnik: Gotcha, and how might one decide between the two, you know, like the two pill oral options or the injectable. And that question could be for anybody. 

Uriel R. Felsen:  I think it’s important to remember that there are three choices, but not all choices are necessarily for all different folks. There’s an option, anybody that’s interested in PrEP, there is an option, but asyou know, Dr. Bernardo mentioned Descovy and Truvada. Both of them contain tenofovir and emtricitabine, but they contain different formulations of the tenofovir. 

And currently, it’s really Truvada that is approved for cis men, cis women, and transgender men and transgender women, whereas Descovy is actually not approved for HIV prevention for anyone that’s at risk for acquiring HIV through vaginal sex. So that would be for cis women or potentially trans men. 

Rasika Karnik:  And is that because there haven’t been studies that have been done in the those populations, or it’s physiologically, does not work for some reason? 

Jonathan Shuter:  Well, there are ongoing studies looking at Descovy in women. There is some concern that the drug might not accumulate either as much or as rapidly in the vaginal mucosa. So there are concerns about it, although there are ongoing studies to try to prove its efficacy in women. 

Rasika Karnik:  Got it, that’s good to know.  So let’s say, you know, I told you I’m a primary care physician. Let’s say, I’ve got a patient who comes to my office, and brings it up themselves, or I bring it up. What happens next, you know, like, what do I have to do to get them started on PrEP? 

Raffaele Bernardo: I can start with that. So anytime someone brings it up in the office, I always take advantage of that opportunity, because we, as providers may may occasionally miss the opportunity to talk about PrEP or other preventative services. So in a when a patient is sort of bringing it up themselves. I really take that as a signal to sort of seize the opportunity and talk about PrEP. I think one of the first things to discuss are any sort of barriers related to PrEP.  Be it financial adherence, for example, if there’s any other concurrent issues like mental health issues, for example, substance use, lack of housing, financial coverage, although, as already mentioned earlier, that really shouldn’t be an issue, since PrEP can be obtained at little to no cost for most patients.  

The second thing to do is really have a conversation around sexual practices. Who are your sexual partners? What body parts are you using to have sex? And the reason why these questions are important is because, again, as Uri mentioned, not all forms of PrEP are approved for all types of sex. So it’s important to get a sense of who your patients are, who they’re having sex with and what body parts they’re using to have sex. That’s also important. When you talk about testing for sexually transmitted infections, you want to make sure that you’re offering comprehensive testing. And this includes three site testing, perhaps, for gonorrhea and chlamydia, again depending on body parts that a patient may use to have sex. For example, oropharyngeal swabs, rectal swabs which can be self-collected by the patient and/or vaginal swabs, which could also be self-collected by the patient, or urine sample, for example. And then we offer blood work for things like HIV, for example, to make sure that the patient at baseline is not living with HIV.  We do testing for syphilis and various forms of hepatitis. But most importantly, we have to test for the preexistence of hepatitis B. And the reason is because some of these medications do have activity against hepatitis B, particularly Truvada and Descovy. And so it’s very important to determine whether or not somebody may have an occult hepatitis B infection, because if you do start one of these oral forms of PrEP and then stop, you can actually cause a rebound hepatitis B viremia, and potentially could cause fulminant liver failure. So that definitely wants to be excluded. 

One of the other things that I think is imperative during these conversations is, yes, to talk about HIV prevention, but to talk about other things you can do to keep the patient healthy from a sexual standpoint. So this may include things like discussing vaccines against other sexually transmitted infections, such as hepatitis B and the human papillomavirus, or HPV. And for those patients at risk even the quadrivalent meningococcal vaccine. So I think it’s a great opportunity to discuss and update vaccinations, and then having a conversation around contraception. For example, for your patients who are capable of getting pregnant and who are having sex with sperm producing partners. I think it’s a great opportunity to talk about contraception and family planning, and if you don’t feel comfortable having that conversation to at least know where to refer them, to have those conversations a little bit more comprehensively. 

Jonathan Shuter:  I think that that’s a great review by Dr. Bernardo, I would just chime in one thing, and that so I agree with all of that. But I would almost lead off with the idea that the only way these medicines work is, if you adhere to them. So someone who is contemplating starting on PrEP. For him or herself, they have to be willing to take the medicine that’s prescribed. If it is sitting in the medicine cabinet, it doesn’t accomplish anything. So so I think that’s an idea to introduce really early to the patient that these pills require one pill every day.Patients have to be reliable and consistent with that and the injectable. They have to show up every two months and get their injection. Otherwise it’s not going to go well. So I think that that’s a good message to start with. And having these conversations. 

Raffaele Bernardo:  Definitely. And I’ll actually, I’ll even add, I think Dr. Shuter’s point about making sure patients are ready and willing to take their medications as prescribed, talking about things that may prevent that from happening. So, for example, I’ve had patients who have had concerns about disclosure. They have roommates, or maybe they live with family, and they’re worried about having a pill bottle with the label of these medications lying around the house. We talk about things to do there. But that might be a candidate, for example, for Apretude, coming into the office for an injection every other month rather than storing medications at home, just as an example. So when it comes to talking about adherence, trying to really get a sense of what those barriers might be to adhere to these medications, because it might help you steer the conversation toward one medication or another. 

Uriel R. Felsen:  And I think it’s also important to add, just building off what Doctors Shuter and Bernardo have said that you know a lot of the folks that you may be having this conversation with are people that are have not, don’t already carry other diagnoses, and aren’t necessarily used to being on a chronic medication. So this could be a big change for them. And that’s why, having that conversation is so important upfront. 

Rasika Karnik:  Yes, there’s a  ot to unpack in those responses, you know. And so it sounds like, when the idea of PrEP comes into play, there’s a lot of things that you can address. I mean, it sounds like you can address sexual health, which is health in general and then, talking to people about their social situation as well.  And so when taking a sexual history, when bringing that up and trying to glean information from your from your patients, do you have helpful dialogue that you have used in the past? Because sometimes it can be awkward, right there can be generational differences, and perhaps people may not, may feel shy. So what are some of the language? You know some of the ways that you discuss this with patients. If you have any tips for us. 

Raffaele Bernardo:  Sure I can start with it. So I think there are a few different approaches here, but I think the theme to the takeaway is, you want to be consistent, and I think by doing that it will make having these conversations easier as you have them with patients. These are important conversations we should be having with all of our patients, regardless of age, sex, race gender. Because once you standardize it, it becomes easier, I think, more natural when you’re having these conversations, and how you start off having these conversations is largely a personal preference. I usually will start off by saying something like, the next thing I would like to talk about is your sexual health. I feel like this is a topic that often goes unaddressed, and is just as important as every other part of your health. So if you don’t mind, I’d like to ask you some questions. 

And then from there I try to start off with open, ended questions. I try to let the patients lead the conversation themselves, because number one, sometimes it’s more natural that way, and sometimes patients are more comfortable sort of just ad lib talking about their sexual history, but if you find that they are stuttering, or they have a hard time giving you the information you need, you can start asking some more pointed questions, and this could be something as simple as can you tell me a little bit about who you’re having sex with? What are the genders of the people that you’re having sex? With? What body parts are you using to have sex? What methods are you using to prevent pregnancy? What methods are you using to prevent HIV infection? 

There’s also a method called the P’s method, I think at one point. It was the Five P’s. Now, it’s probably the Six or Seven P’s to help strategize your sexual history taking. So this is things like, for example, partners practices protection, like I mentioned, from other sexually transmitted infections, past history of STIs, pregnancy, plans. Pleasure, I think, is another one in the expanded P’s history. 

There are lots of these different things online that you can look for to help organize your sexual history taking to make it easier. But I think the important thing is that you try to create consistency with having these conversations because they’ll eventually happen more naturally. But it’s important to be comprehensive, because the question you don’t ask leads to the answer you don’t get, and it’s a missed opportunity to perhaps talk about some sort of preventative strategy with your patient. 

Rasika Karnik:  Absolutely and you know, when you brought up the Five P’s. I was just thinking about from medical school how these acronyms keep on evolving or mnemonic. Sorry, not acronyms. 

And so it’s it’s helpful to build templates in your electronic medical record, if you can. If you’re able to do that. So those are those those are great tidbits, for to use in practice. 

Raffaele Bernardo:  The other thing that I will add as well. The questions you ask are part of it. But I think the environment you create is just as if not more important than the questions you’re asking. Because anyone in this audience can think about perhaps being asked these questions in two very different scenarios, right? A very sort of whitewashed office, very sort of sterile environment versus an environment that perhaps has some signage on the wall sort of promoting sexual health, you know, depending on the population you’re serving. For example, I’m the medical director for a comprehensive LGBTQ-plus practice in New Jersey. So in our office, although we serve all types of individuals, we do have very subtle gestures of support toward the community. So we have, for example, a pride flag in the waiting room. We have nice modern pieces of art that tie-in the LGBTQ-plus colors as well. So these these subtle hints of support, I think, are also very important. You want to create an environment that welcomes these conversations. So I think again, the environment you’re creating is just as important, if not more important, than the actual questions that you’re asking your patients. 

Rasika Karnik:  That’s very true. So the nonverbal cues. 

Raffaele Bernardo:  Correct. 

Rasika Karnik:  And so now you’ll suppose I’ve got a patient that decides to start PrEP. What next? You know, like, we’ve done some of the screening, testing for concomitant STIs. No hepatitis B. What happens after that? Dr. Felson. 

Uriel R. Felsen:  Like you said, there’s some testing that we would do first. Very importantly, we want to make sure that the person is not already living with HIV. And so as long as you have either a negative, rapid test in front of you, or and you’ve sent off a lab-based HIV test, you can go ahead and you know, counsel the patient about adherence, and you can initiate PrEP. You may have renal function labs pending. That’s okay. For people that are on Truvada, it’s important to monitor their renal function on Truvada or Descovy so you can have that pending. You can always call somebody back if something needs to change based on that result. But then the idea is that people that are on PrEP, that if they’re taking oral PrEP, the general routine is every three month visits, and at those visits you would have repeat HIV testing, and you would do assessments for STI screening and you would repeat STI screening at that point, and repeat an HIV test. And that important thing to remember, once somebody has already been exposed to PrEP, or any other form of antiretroviral therapy, whether they’re coming off of a course of post-exposure prophylaxis, or they’re continuing, this is somebody that’s already been on PrEP pre-exposure prophylaxis. When you are repeating the HIV testing, the CDC at this point recommends sending an HIV viral load along with the antibody test to make sure that you aren’t missing early HIV acquisition. 

Raffaele Bernard:  One of the things that I think also many offices have implemented as well, which is one of the things for example we do, is same starts for PrEP as well. So actually having patients, for example, leave with a prescription, or even a sample in hand to get started the same day, we find that that often helps with adherence. So some offices do have the availability of doing point of care testing for HIV. There is a slightly longer window period for many of these point of care tests, but if you exclude an acute HIV infection clinically so, people who come in without any recent flu, like syndromes, for example, fevers, chills, swollen lymph nodes rash, etc, and their point of care for HIV is negative. You can actually even start same day PrEP, particularly the oral forms of PrEP. 

Rasika Karnik:   I’m actually gonna take this question from the chat which applies what we’re talking about. But one of our audience members wants to know, are there any specific side effects to counsel patients on when they start prep? So anything that patients should be aware of. 

Jonathan Shuter:  These medications are extremely well tolerated.So almost anyone who puts any new pill in their mouth and swallows it could get some nausea. So there is, you know, a certain incidence of nausea and GI upset, associated with the two oral preparations. There were larger earlier concerns with the potential for renal effects and for bone effects with the tenofovir-containing preparations which are both of the oral medications. But most of those fears and concerns have been allayed by the collective experience that that significant renal toxicity or bone toxicity are rare. And so those are really the common side effects with the pills. With the injection, it is basically what you would expect. With the injection, they get injection in site pain, and it is rare that that is severe enough that it causes discontinuation of the medicine, and that tends to get less with subsequent injections. 

Raffaele Bernardo:  I’ll add, with the nausea that’s occasionally seen,  almost always is self limiting, and within a week or so of daily use, the nausea actually goes away without any particular intervention. So I will often counsel my patients and say, while it’s rare, you may experience some nausea in the first few days. If it’s not too uncomfortable, keep taking your pill daily, and almost invariably the nausea self resolves within a couple of days when it happens. But to Dr. Shuter’s point, these side effects are typically very rare. 

Rasika Karnik Is it better if patients take it with food? 

Raffaele Bernardo:  Your patients could take it with or without food. It’s up to them. In my personal experience, I have seen patients prefer taking it with food when they do get some of those Gi side effects. But it’s a personal preference. 

Jonathan Shuter:  We have learned through painful experience in the HIV treatment world that patients getting any oral medication should always be told not to take the pill dry. So always take every pill. There’s nothing specific about these medicines for that, but always take every pill with adequate water or other liquid. 

Rasika Karnik:  Gotcha. Thank you for that question, to our audience member. And you had mentioned that, you know, monitoring for renal function.  And why is that? Is it just based? I mean, it sounds like there used to be more concerns with potential renal toxicity, but that has kind of gone away as time has gone on, so are there any specific patients that are more at risk for renal toxicity? 

Uriel R. Felsen: So Truvada was, was the first approved PrEP medication, and Truvada has the older form of tenofovir. And so the recommendation for Truvada is that people that when prescribing it the eGFR should be above 30 or 60, Ralph. Sorry I’m I’m blanking. 

Raffaele Bernardo:  For Truvada, 60. 

Uriel R. Felsen:  60. I’m sorry. So Truvada is 60, and for  Descovy it’s 30, the estimated GFR. And so you know, people that you might be concerned about starting Truvada on are people that have comorbidities that might be affecting their kidneys, diabetics, hypertensives. So you might be more concerned about the effects of Truvada on their kidneys, and consider Descovy, especially if they already have some early CKD. 

Rasika Karnik:  Got it. And putting my primary care hat on here just another time to sort of tell people how to explain how important blood pressure control is hypertension, and diabetic control is, so we can prevent those kidney side effects. So 

Raffaele Bernardo: I’ll also add to that the earlier guidelines for PrEP did recommend three month testing for renal function.  But with more and more experience, Truvada was actually found to be safer than was once thought, and so the most recent guidelines for PrEP have actually extended that interval from every three months to every six months, I believe, if not at least annually. So with more real world data, we’re actually finding that it’s actually safer than we once thought the caveat again, being, like Dr. Felson had mentioned, these are individuals who are otherwise healthy, with no other pre-existing comorbidities that may be affecting their kidney function, like uncontrolled hypertension, diabetes, etc. 

Rasika Karnik:   So monitoring my patients, and they’re coming in regularly. They’re adhering to their the PrEP medication, whichever option they’ve chosen. What happens if you decide you want to come off of PrEP,  you know. Like, what is it easy? Can you just stop one day, or is there any specific protocol that needs to be followed. 

Raffaele Bernardo:  So people’s situations change all the time. There may be a change in one’s perceived risk for HIV infection. So people come on and off PrEP all the time.  But it’s important that this is done under the guidance of a provider for a few different reasons. One is, you sort of want to remind the individual that if they do stop PrEP, there is going to be, if they do engage in any risks, any sexual activities or intravenous drug use where they could be exposed to HIV, that they no longer have that medication in their body. And so an alternative form of HIV prevention should be used. 

The second thing is, you again want to make sure that you’ve at least addressed the hepatitis B thing at some point, because, again, if there is a missed underlying hepatitis B infection, by stopping these medications abruptly, you can cause a viral rebound, hepatitis B viremia, and potentially fulminant liver failure. For those people who are incidentally found to have chronic hepatitis B, they do have to stay on treatment, at least in the beginning, until they are sort of staged and determine whether or not they need ongoing medication. So we’ll typically narrow them from Truvada, which contains tenofovir and emtricitabine to just tenofovir. 

Uriel R. Felsen:  I think there’s one other special consideration, which is the folks that are that are on the injectable, for when they want to come off, because  it’s a long-acting injectable, and the idea of stopping it would be to sort of let the drug levels peter out. But of course, during that period when the drug levels are petering out, you have some amount of of the medication in you, but not necessarily enough to offer protection. And so there is a small risk during that period, if somebody was to acquire HIV, that their strain of HIV that they’ve acquired could become resistant to the cabotegravir. So some people in that scenario have opted to start an oral medication, one of the oral PrEP options, while the cabotegravir is sort of petering out from their system. 

Raffaele Bernardo:  And that’s particularly important, because the resistance mutation that occurs sometimes with cabotegravir renders a lot of these single tablet regimens we use to treat HIV ineffective. So not to say that you couldn’t treat somebody now living with HIV. But your options will be somewhat limited. So that’s a great point, Dr. Felson for bringing that up. 

Rasika Karnik:  Yes, thank you. So it sounds, you know. It seems like there’s certainly a little bit more nuance when you want to stop cabotegravir, want to stop the injectable. And then what if you do develop HIV while you’re on PrEP. So what if what happens then? 

Raffaele Bernardo:  We like to think that that doesn’t happen. It’s exceedingly rare that that would happen for somebody who has been taking their medication consistently. So we’d like to say that that doesn’t happen, but we know that adherence isn’t always perfect. And so it will happen occasionally that somebody will develop or become infected with HIV while they’re taking PrEP,  perhaps intermittently, or you know, maybe missing several doses during the week. That’s not to say that you should stop treating them. But you are going to have to intensify the regimen now to treat them for HIV. One of the things to look out here for, and I’m not sure if this is really for this particular audience. But maybe it is. We often will send an HIV genotype in this case, because we are looking for some resistance mutations that could be associated with the two drugs in the oral formulations of PrEP mor cabotegravir, if that’s what the patient was on., for example. So we do want to look for those resistance mutations, because that may alter the treatment regimen that we ultimately use to treat somebody living with HIV. 

Jonathan Shuter:  Right. So if we were having this conversation twenty years ago, the idea of becoming resistant to one or two medicines was much more ominous, so there is the potential of becoming resistant to the tenofovir or the emtricitabine or to the cabotegravir. But even in the unlikely event that that happens, there are almost always good regimens that patients can resort to that will suppress their HIV infection very well. 

Raffaele Bernardo:  I actually think it’s a good opportunity to mention now that you sort of mentioned this, Rasika, is that you know you’re talking about a situation that as long as your patients are taking their medications, this again seldom happens, and I don’t want to scare anyone away from thinking about or going out there and prescribing PrEP. 

There are very few things in medicine that we can sort of guarantee patients are 100%. But PrEP, as long as it’s taken as prescribed, is one of those few things in medicine that we can get pretty close, so I don’t want the fear of somebody acquiring HIV while they’re on PrEP to prevent anyone from offering it. As long as patients are taking it every day, the chances of that happening are exceedingly exceedingly exceedingly rare. 

Rasika Karnik: Got it. No, that’s very helpful to know. I think I sort of provided this opportunity to discuss a doomsday scenario, so to speak. So. But yes, so people are taking it as prescribed it should. do its job. 

I was kind of curious here, and I think it might help our audience members, as well as you know from just from your clinics and your experience. What are what are some of the main hiccups that patients come back to you with, or some complaints or something, just practically speaking, when they start PrEP. What are some of the things that you hear from patients? 

Raffaele Bernardo:  So for me, I would say, the majority of the patients that, the community that I do serve is a largely a younger population. So one of the things because I think Dr. Felson had mentioned this earlier, a lot of these individuals aren’t on medications for anything else. And now, all of a sudden, you’re entrusting them to take a pill every day.  And so one of the big things that comes up during follow up appointments is adherence, and not because they want to miss their medication. They just forget, because it hasn’t been part of their daily routine to take a pill every day. So one of the things we talk about are strategies to remember. We talk about setting daily reminder alarms on their cell phones, for example, or I tell them to put their pill bottle next to something that they will reach for every morning, for example, like their toothbrush or their coffee machine, just to help with adherence. But I think the one most common thing that I will hear from patients in terms of quote unquote issues with PrEP, is just remembering to take their pill. 

And, conversely, I do have a handful of patients that have lots of other medical comorbidities, and they have the other problem. They develop what we call the medicine pill fatigue. So now you’re kind of inundating them with another pill they have to take every day, and so it becomes a similar but not so similar conversation. So both ends of the of the spectrum. 

Jonathan Shuter:  And, needless to say, for folks who are on their first chronic medicine, we shouldn’t assume that they know how to get a refill or know what a refill even is. They should leave the clinic or your office with a phone number to call if they’re having problems, if they lose their pills if they have questions about it, because if you don’t give them that and they have a problem, they’re not going to know what to do if they haven’t been trained in the medical system already. 

Raffaele Bernardo:  That actually just came up. The other day I sent three refills to a pharmacy, three months worth of PrEP for a patient, and after a month’s supply received the message that they were waiting to have a new script sent for their refill, not realizing that there had been three already sent to the pharmacy. So what you’re mentioning Dr. Shuter is very, very real. 

One of the other strategies I mentioned to patients is, I will often offer them if I have available, or I’ll tell them to go pick one up on online, is a little pill key chain, and I will tell my patients to keep one or two. I like to call them emergency pills on them. Put it on their backpack, on their keychain. So, for example, let’s say it’s a night out, they spend the night at a friend’s house, or whatever the case is, they go to work the next day. They forget they have one or two extra pills on them to just sort of take in the event that they forget. But I remind my patients, if you forget, just take it when you remember, never double up on a dose, and then just resume your normal schedule. The following day. 

Jonathan Shuter:  And I would say that this conversation keeps circling back to adherence, which is absolutely critical. And I think that there’s actually a shocking lack of research that’s been done on factors that promote good adherence to PrEP therapy. But there is a little bit of research and I think that we can extrapolate from what we know from adherence to other medications. So I think it could be summarized as simply this. The more strategies that you employ, the more likely they are to sink in so adherence. Counseling is good. You should tell the patient how important that it is, although that often, or even usually is not enough. So give them other recommendations. There’s a million adherence apps that that could be downloaded for free on people’s phones. There are pill boxes. There are other options, and the weight of the evidence out there is, the more strategies you offer, the more likely they are to adhere. So you know, I think a keychain thing, a pill box, an app, good counseling. All of those things are important, and they should be piled one on top of the other. 

Rasika Karnik:  Absolutely that’s critical. And I mean, it’s a good lesson, for managing any disease process, or any sort of, counseling your patients about adherence. Those are all great points. We do have another question from the audience. So I want to insert that in here and ask it. So this audience member wants to know., do you have any experience prescribing PrEP for patients whose primary risk factor for HIV acquisition is injection drug use. And how might that change some of the things that we’re talking about. 

Raffaele Bernardo:  So yes, I think I think we all do to to varying extents. I actually have prescribed PrEP for individuals who actually have had concurrent risk factors for HIV, largely sexual and injection drug use, and suffice to say, the approach remains relatively the same. You’re having the same conversations in terms of adherence, quarterly testing for HIV. But what changes here are the additional tools that you’re going to be giving your patients. You’re going to be talking about risk reduction strategies for other things. So, for example, people whose risk factor for HIV is injection drug use, you want to talk about risk reduction strategies to prevent or minimize risk of other things that can be transmitted through blood like hepatitis C, for example. So here’s an opportunity to talk about needle exchange programs, for example, or to remind your patients never to share needles or other drug paraphernalia, making sure you’re only using needles on yourself. If patients don’t have access to needle exchange programs or new needles, there are protocols online where you can actually use bleach solution to clean needles as well, and those can be found on the Internet pretty readily. But again, suffice to say, you’re still following these patients quarterly. It’s just your conversation is, gonna change a little bit about what else you’re going to be offering them. 

Rasika Karnik: Great. Thank you. 

Uriel R. Felsen:  Just also important to point out that the effectiveness of PrEP in the context of injection drug use is actually different from in the context of sexual acquisition. So Ralph was talking about, you know there are few things that are as effective as PrEP  if folks are taking it regularly. And if their risk factor is sexual acquisition, you know, we’re talking about like 99% effectiveness in preventing HIV acquisition. I believe the number in the context of injection drug use is more like 75% effectiveness. So it’s not exactly the same. 

Rasika Karnik:  And is the, is there knowledge as to why?  

Uriel R. Felsen:  Not something that I’m aware of. I mean, I think one thing to consider would be the burden of how much virus is introduced, you know, in a single act might have something to do with it. 

Jonathan Shuter:  And also the journey that the virus has to take to get into the body. So if someone injects 10,000 viral particles into their directly into their bloodstream, that’s a different situation than a viral inoculation that has to cross a mucosal barrier. 

Rasika Karnik:  And we’ve got another question in the audience. So if a single dose of PrEP is missed, how long should a patient wait before engaging? Is there a timeframe? I’m sort of changing the question a bit, but it sounds like the person wants to know when will the PrEP be as effective as it was, had you not missed the dose? Does that make sense? So at what point can patients still engage in sexual encounters and be protected? 

Jonathan Shuter:  So we wouldn’t want to advertise this to our patients. But there’s not really an expectation or necessity to be 100% adherent to the pill. So I don’t know these numbers off hand, but I think that the weight of the evidence shows that men who take their PrEP pills, these are just the oral preparations, three or 4 times a week get adequate protection, and the number is a bit higher for women. So more like 5 or 6. Getting 5 or 6 doses in per week is associated with very high levels of protection. So I would think that missing a single dose probably wouldn’t have a negative impact on the level of a patient’s protection, although once again I wouldn’t advertise that to my patients. 

Uriel R. Felsen:  I think it also does get to a different question, though, that, I think, would be useful. For this audience, which is like, how long after initiating PrEP can somebody expect to be able to enjoy the protection that it offers? And so for those at risk of acquisition through anal sex, it’s about 7 days, for those at risk for acquisition through vaginal sex, it’s more like three weeks. So twenty one days is the idea. So continue using other methods of protection during that period while you’re waiting to achieve the therapeutic levels or the protective levels of PrEP. 

Rasika Karnik:  A great point. Thank you for bringing that up. So we do have another question from our audience, for your patients who carry a pregnancy. If they get pregnant, what do you tell them about the safety of PrEP, and when to stop, if at all. 

Raffaele Bernardo:  That’s a great question. And whoever asked that question, I’d like to thank you for not gendering the question. So for patients who can carry a pregnancy, yes, absolutely, patients who have any ongoing risk for HIV, or perceived risk for HIV should continue taking their PrEP as prescribed throughout their pregnancy. We know that these medications are safe in pregnancy both to the mom and the developing fetus and for whatever it’s worth, you know, we do use these medications in combination with other medications, to treat individuals living with HIV throughout their pregnancy as well. So by providing PrEP,  I will argue, you’re not only protecting the individual carrying the pregnancy. But you’re also protecting the developing fetus from HIV infection as well. 

Jonathan Shuter:  So I agree. And the good news is that that there’s not really much of a safety signal with any of these medicines in pregnancy. Someone who is practicing receptive vaginal sex wouldn’t be on Descovy for for PrEP. So really, the discussion of Descovy is irrelevant here. So you’re talking about either Truvada or cabotegravir. So there’s really a mountain of evidence showing that Truvada is a safe drug to take through pregnancy. 

Cabotegravir, there’s less data on. There are emerging data from a variety of studies. It is looking to be safe, although I don’t think anyone has made that declaration yet. 

Rasika Karnik:  Wonderful. We’ve got great questions from our audience tonight, so keep them coming. But while we’re waiting for more questions from our audience, Dr. Bernardo, I wanted to ask you for more tips on, like how to integrate PrEP into your practice. So you had mentioned the welcoming environment. Are there any other things to consider with your practice? 

Raffaele Bernardo:  So I think a lot of it depends on the practice that you already have established. So if you are working, for example, in a sexual health setting, I think it’s very different than if you’re working in a general primary care setting. You could talk about, for example, scheduling certain days to do PrEP,  you can talk about integrating it throughout your regular workday. One of the other nice things about PrEP is that it can also be done through a telemedicine sort of modality as well. And I think that this is particularly important for our younger population for various reasons. So offering PrEP through a telemedicine platform, I think, is very, very helpful. You can even have the patients go to a local laboratory close to their home to perform their STI and HIV testing, and then you can send their prescriptions to their local pharmacy, and it definitely helps with adhering to medical visits in that regard. But there, there’s not a one size fits all on how to integrate a sort of PrEP program into your day to day practice. A lot of it depends on your pre-existing practice. Your providers, if you have help from support staff, for example, some offices are fortunate to also have peer to peer navigators, patient navigators, for example, or peers to help patients navigate the system to sort of take away some of that additional burden from the provider. So a lot of it depends on what you have established already. But the good news is that once you do it, it’s actually very, very easy. PrEP visits can be done very easily, very effectively, and I think can be integrated in anyone’s sort of pre-existing clinical practice. 

Rasika Karnik:  Great, and then, the hours kind of winding down a bit. So I wanted to, while we had some time, just ask Dr. Shuter what he thought about the future ofPrEP. You know, where are we going? Are we going to once a year? Injectables? What’s next? What’s on the horizon. 

Jonathan Shuter:  So this is a dynamic field. It is really making progress. And there are exciting possibilities on the horizon. So I just in my mailbox today, with the New England Journal of Medicine paper, the October 3^rd 2024 Issue of the New EnglandJjournal publishing the results of the purpose study that looked at lenacapivir, that was given as an every 6-month injection in a population of that included women, including adolescent women, because there’s really been a dearth of research done on adolescents, and they just had spectacular results that were a bit of a tidal wave in in the medical community with with basically,  not basically, but exactly 0 cases occurring in patients who were receiving lenacapivir over the course of the study. So unless something catastrophic happens with that drug, I think that that is something that is on the horizon, a realistic possibility of taking an injection every 6 months. And I think that would be a very big improvement over every two months. There’s a great deal of interest in new categories of medicines, oral medicines that can be taken once a month, and there are ongoing trials of that. Those are early. There is interest in developing subcutaneous implants the same way that certain contraceptives are administered with subcutaneous implants that can really last a long time, even potentially, out to a year. So there are a number of studies going on, and I think that we are going to see some of these exciting developments in the years to come. 

Uriel R. Felsen:  I would just want to add that it’s extremely exciting, what’s happening on the pharmaceutical front. But I think another area of excitement in PrEP is also the different environments or the different clinical settings where patients will be able to get it. And that’s another area of research. And I think, actually, a webinar like this is really important for disseminating the information to primary care physicians. But one of them challenges with PrEP has been, you know., in whose purview does it belong, and who should be providing it? It has sort of ended up with infectious disease doctors in large part, because we are used to using antiretroviral therapy. However, you know, once somebody has acquired HIV, the horse is already out of the barn as far as prevention goes. So I think a really exciting area of research is, where can we start introducing PrEP so that patients have better access to it and don’t have to necessarily find their way to an infectious disease doctor. So primary care physicians are great. There’s been work looking at pharmacists being the ones to prescribe PrEP.  I do work about trying to introduce PrEP into emergency department settings where there are high risk populations, urgent care settings. Certainly the Obgyn, there are opportunities for introducing PrEP as well. So I think you know, it doesn’t necessarily sound as novel as some of the pharmaceutical stuff. But it’s a really important way for increasing the footprint that up can have for prevention. 

Raffaele Bernardo:  And if I can, I also just want to take the opportunity to also remind the audience that none of this, none of these conversations can can happen without an HIV test. We know that HIV testing is the gateway to both treatment and prevention. And similar to how PrEP had been, has been given a grade, a recommendation by the USPSTF, so has HIV testing. So I will implore the members of the audience that if you are not already implementing, screening for all of your patients for HIV at your offices, I would implore you to start doing that at least a one-time test for everyone that you do see. 

Rasika Karnik:   And you know that sort of brings me to my last question or opportunity for our panelists. Any last minute or last words as our hour comes down, advice that you’d like to give our audience. You know common mistakes. You might see anything you want to add  about PrEP. I’ll start with you, Dr. Shuter. 

Jonathan Shuter:  So this is a bit of a tangent, but I think that it’s an important one that people who work with me know that I’m an anti-smoking zealot, and that all of my research pertains to smoking in people with HIV and people at risk for HIV. So people who show up in clinic to obtain PrEP probably smoke at higher rates than the general population. Although I don’t have evidence to back that up, because I don’t think there is such data, I would suspect that that is the case, and even if they don’t, even if they smoke at the same rate as everyone else, I think that certain medical issues are so weighty that if you ignore them on a comprehensive medical visit, you have to think about what a patient walks away thinking I went to a doctor, and he asked me all kinds of questions, and we spent a long time together. And and I guess smoking is okay, because it never came up.  Or the blood pressure came back 160, over 80, and all we talked about was PrEP and STD risk, and the blood pressure got ignored. So my blood pressure is probably not much of a problem, or my cholesterol is probably not much of a problem. Or if I’m at a certain age group, that screening for colon cancer is probably not a priority. I think that everyone on this call is an internist, and also in addition to what they do with their PrEP, and I think that there’s a real effort to normalize sexual health. And I think that that’s a good thing, but normalizing it means that it is in there against the background of all the rest of someone’s health. You have to be really careful about what you what you leave out. And you know to me, since smoking is the most, the most common, preventable cause of death in our society, that’s a really important target. But blood pressure and depression and substance use, none of these things can be ignored, if you’re going to be offering good medical care to somebody. 

Rasika Karnik:  And just a plug, for you know, primary care providers out there, physicians and advanced practitioners.

So it’s tough to kind of address every single thing at in one go. So, Dr. Shuter, I know I agree with you. All those things are important, but sometimes the 15 minutes just don’t quite cut it.  And it helps build patient rapport having those multiple visits.Dr. Felson, I wanted to offer you the same opportunity, any last suggestions, questions, comments. 

Uriel R. Felsen:  I think something that Ralph was saying earlier sort of struck me, which is you have to just make it routine in order to get good at it and to get comfortable with it. And I think, you know, I think it’s the same sort of mantra for routinizing HIV, testing, normalizing the conversation about sexual health. You’re not going to know unless you ask. And there are some patients that will come and ask you for it, and will start the discussion about their sexual health, and and may ask you about PrEP. But for those that don’t, it’s a really important opportunity for us to to address that aspect of their health, and and many patients are waiting for us to open that door. 

Rasika Karnik: Absolutely. And finally, Dr. Bernardo, your turn. 

Raffaele Bernardo:  So I’ll pretty much reiterate what Dr. Shuter and Dr. Felson already mentioned. A lot of your patients probably want to have these conversations. They just don’t know how to have them so normalize sexual health. Screen all of your patients for HIV. Prescribe PrEP.  And don’t forget vaccinations, please. There are catch-up vaccination, there are catch-up vaccination schedules available as well. So even if your patients missed their HPV vaccines, for example, it wasn’t available when they were born, it is available, I think, based on risk up until the age of 46. I think. You can vaccinate your patients, even if they miss those vaccines as younger adults or children. 

Jonathan Shuter:  And can I just add one last thing. I think that this has been said, but not very directly, in the course of the hour. We’ve talked about a lot of nuance here in the prescribing of these different medicines and a lot of cautionary tales about adherence, and we talked about side effects. But I think particularly for the primary care providers out there who aren’t doing this every day, that it’s really important to point out that in general, in your average patient, particularly if they can be adherent to medicines and follow up, that this is very easy thing to do. You’re just prescribing a simple, very non-toxic medicine one pill once a day, and you’re good. You have to follow the patient up, but it’s extremely easy in most cases. 

Rasika Karnik:  Thank you for that. So PrEP is easy. So that’s sort of the take home message. But thank you. And any other questions from the audience? I don’t think so. So thank you all for joining us today to our audience members. We hope that you learned something tonight and that you take back the information you have learned and incorporate it into your practice. 

Commercial Support

This educational activity is supported by an independent educational grant from Gilead Sciences

Faculty Disclosures

Dr. Shuter has no relevant financial relationships to disclose

Dr. Felsen has no relevant financial relationships to disclose

Dr. Bernardo has no relevant financial relationships to disclose

Dr. Karnik has no relevant financial relationships to disclose

Screening for Cervical Dysplasia

Recorded on August 13th, 2024 at 8 pm ET

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Faculty: Emma Grabinski, MD
Moderator: Rasika Karnik, MD

• Highlights
  • How Effective is Cervical Screening?
  • Whose Rates of Cervical Cancer are Increasing?
  • What Percentage of Women are Getting Screened?
  • Screening, Surveillance, and Diagnosis. What’s the Difference?
  • Current Guidelines for Cervical Cancer Screening
  • Clinical Benefits of Co-Testing
  • General Concerns about HPV
  • Self Swabs- Who Are They For?
  • How Often Should Primary Care Physicians do Pelvic Exams?
  • At What Age Should Screening End?
• Full Webinar

Highlights

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Full Webinar

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What is PcMED Connect™?  

PcMED Connect is a monthly, virtual Grand Rounds experience jointly provided by Postgraduate Institute for Medicine and the PcMED Project

• Free!
• Including top speakers with panel discussions and Q&A opportunity  
• Women’s Health topics that are practical and will impact your practice  
• Can’t make the live event?  It will be recorded

Management of Patients with Chronic Coronary Disease (CCD): PART 2 (Medical therapy and Revascularization)  

SUMMARY

Chronic coronary disease (CCD) affects 20 million persons in the United States. CCD includes patients with obstructive and nonobstructive coronary artery disease with or without previous heart attacks or revascularization.  

• Antiplatelet Therapy 
• Beta Blockers 
• Renin-Angiotensin-Aldosterone Inhibitors 
• Lipid Therapy 
• Blood Pressure Management 
• Diabetes Management 
• Angina Management 
• Revascularization 
• Women, Pregnancy and Postmenopausal Therapy 
• HIV and Autoimmune Disorders 

Antiplatelet Therapy 

• Aspirin (81mg) is recommended as secondary prevention to reduce recurrent atherosclerotic events (if no indication for oral anticoagulation) 
• Post percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT)- aspirin and clopidogrel for 6 months post PCI is recommended 
• Without recent ACS or PCI, DAPT is NOT recommended. 
• PPI can be effective in reducing GI bleeding risk in patients on DAPT 
• Prasugrel should NOT be used due to increased risk of bleeding in patients with previous stroke or TIA  
• In patients who have undergone elective PCI who also require oral anticoagulation, DAPT for 1-4 weeks followed by clopidogrel alone for 6 months in addition to DOAC is advised. 
• Chronic non-steroidal anti-inflammatory drugs should NOT be used due to increased cardiovascular and bleeding complications. 

Beta Blockers

• In patients with CCD and LVEF <50% with or without previous heart attacks, use of sustained release metoprolol succinate, carvedilol or bisoprolol is recommended 
• In patients with prior heart attacks WITHOUT history or current LVEF <50%, angina, arrhythmias, or uncontrolled hypertension, it may be reasonable to stop beta blocker after 2 years since heart attack event 

Renin-Angiotensin-Aldosterone Inhibitors 

• In patients with CCD who also have hypertension, diabetes, LVEF <40% or chronic kidney disease, use of Angiotensin-converting enzyme inhibitors or Angiotensin II receptor blockers is recommended to reduce cardiovascular events 

Lipid Therapy

• High-intensity statin is recommended with goal of achieving >50% reduction of LDL levels to reduce risk of major adverse cardiovascular events (MACE) 
• Effects of statins should be assessed with lipid panel in 4 to 12 weeks after statin initiation or dose adjustment and every 3 to 12 months thereafter to assess response or adherence to therapy 
• Addition of non-statin medications (ezetimibe | PCSK9 monoclonal antibody) can be beneficial to further reduce risk of MACE in patients on maximally tolerated statin therapy at high risk with LDL-C >70 mg/dl 
• The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended in patients with chronic coronary disease given the lack of benefit in reducing cardiovascular events. 

Blood Pressure Management

• Blood pressure goal in patients with CCD is <130/<80 mmHg to reduce cardiovascular events and all-cause death. 
• Nonpharmacological strategies are recommended as first-line therapy to lower BP 

Weight Loss	1 mmHg drop for every 1 kg reduction in body weight.
Healthy Diet(heart healthy diet rich in fruits in vegetables, Mediterranean diet)	11 mmHg drop in hypertensive patients
Dietary Sodium	Goal <1.5 grams/day. Expect 5 mmHg drop in hypertensive patients
Dietary Potassium	Aim for 3.5-5 grams/day (if no issues with hyperkalemia). Expect 5 mmHg drop in hypertensive patients
Physical Activity	Depending on type of exercise, expect between 4 to 8 mmHg drop in hypertensive patients
Alcohol Consumption	Limit to ≤ 1 drink per day for women and ≤ 2 drinks per men. Expect 4 mmHg drop in hypertensive patients

Diabetes Management

• Use of sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists with proven cardiovascular benefit is recommended 
• In patients with CCD and heart failure (reduced or preserved LVEF), SGLT2 inhibitors is recommended, regardless of diabetes status 
• Hemoglobin A1c goal of <7% or <8% for older patients at risk of hypoglycemia 

Angina Management 

• Anti-anginal management includes either monotherapy or combination of beta blocker, calcium channel blocker or long-acting nitrates to achieve symptomatic relief 
• In persistently symptomatic patients with angina despite above treatment, ranolazine is recommended.  
• In medically refractory angina, enhanced external counter pulsation (EECP) can be considered. 

Revascularization

• In patients with CCD with LIFESTYLE-LIMITING angina despite guideline directed medical therapy, revascularization is recommended to improve symptoms 
• In patients with significant left main or multivessel disease and severe LV dysfunction (LVEF <35%, coronary artery bypass grafting (CABG) is recommended to improve SURVIVAL. 
• In patients with significant left main disease, CABG is recommended to improve SURVIVAL.  
• In patients with CCD that are poor surgical candidates, reasonable to choose percutaneous coronary intervention (PCI) to improve symptoms and reduce major adverse cardiac events 
• In patients with CCD, diabetes and multivessel CAD with involvement of left anterior descending artery, CABG is recommended over PCI to reduce mortality and repeat revascularizations 
• Routine periodic anatomic or ischemic testing without a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making in patients with chronic coronary disease 

Women, Pregnancy and Postmenopausal Therapy

• ACE-inhibitors |ARB| Direct renin inhibitors| Angiotensin receptor neprilysin inhibitors |Aldosterone antagonist in women with CCD during pregnancy or when contemplating pregnancy is contraindicated  
• Continuation of statin during pregnancy is debatable 
• Systemic postmenopausal hormone therapy is not advised due to increased risk of venous thromboembolism 

HIV and Autoimmune Disorders

• Antiretroviral therapy is beneficial to decrease risk of cardiovascular events in patients with CCD and HIV 
• Lovastatin and simvastatin should NOT be used concomitantly with protease inhibitors 
• In patients with CCD and autoimmune disorders, use of immune modulating therapies to decrease inflammatory disease activity is helpful at decreasing risk of CV events 
• In patients with CCD and rheumatoid arthritis, high dose steroids (≥ 5 mg prednisone) should NOT be used long term if alternative therapies available due to increased cardiovascular risk 

Learn More – Primary Sources

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines 

Hepatocellular Carcinoma: From Prevention to Treatment  

SUMMARY: 

Primary liver cancer is the third leading cause of cancer-related deaths in the United States. The majority of primary liver cancers are due to hepatocellular carcinoma (HCC) in the setting of cirrhosis or chronic hepatitis infections. Any disease process that contributes to cirrhosis formation increases the risk of HCC regardless of the underlying etiology, and patients with cirrhosis have an annual risk of roughly 2% of developing HCC. In the United States most cases of cirrhosis and HCC occurrence are due to chronic hepatitis infection (HCV | HBV), alcohol use, and metabolic dysfunction-associated steatotic liver disease. Incidence and mortality of HCC have both declined since their peak in 2010, likely due to improved prevention, screening, and treatment strategies. The American Association for the Study of Liver Diseases (AASLD) has created a practice guideline to assist healthcare professionals in the prevention of HCC.  

Prevention 

• Primary prevention strategies focus on treating and preventing disease processes that contribute to cirrhosis formation before cirrhosis occurs  
  • Hepatitis B Virus (HBV): Universal vaccination for babies and high-risk adults who have not been immunized | HBV anti-viral therapy for viral suppression 
  • Hepatitis C Virus (HCV): Anti-viral therapy to eradicate infection  
  • Lifestyle recommendations: Maintain healthy weight | Avoid tobacco | Limit alcohol use | Treat co-morbid metabolic syndrome conditions (e.g., Diabetes | Hyperlipidemia) | Eat a balanced diet  
• Emerging strategies that require further study for the prevention of HCC in patients with chronic liver disease (CLD) include 
  • Coffee consumption 
  • Pharmacotherapy: ASA | Statin | Metformin  
• Secondary prevention strategies focus on screening and early diagnosis of HCC to reduce disease impact and improve treatment success  

Screening 

• HCC surveillance should be done in all high-risk patients 
  • High-risk groups include patients with: Child-Pugh A–B cirrhosis | Child-Pugh C cirrhosis AND transplant candidate | Non-cirrhotic chronic hepatitis B   
• Patients listed for liver transplant should undergo HCC screening every 6 months 
  • Diagnosis of early-stage HCC can change the patient’s position on liver transplant list  
• Target screening to patients who could benefit from and would be eligible for HCC therapy  
  • Avoid screening in patients with life-limiting comorbid conditions that cannot be treated (e.g., Life expectancy less than 1 to 2 years)  
• AASLD recommends against routine surveillance in patients with advanced fibrosis but without progression to cirrhosis  
• Screening includes semiannual (e.g., roughly every 6 months) measurement of AFP AND liver ultrasound  
  • CT and MRI-based technology should not be routinely used for screening, but may be considered in select patients when ultrasound-based surveillance is suboptimal  
• Screening findings and adequacy of ultrasound visualization (e.g., VIS score A through C) can alter timing of follow up surveillance  
  • Normal AFP + VIS score A + no lesions seen on US: Repeat screening in 6 months  
  • Normal AFP + VIS score B or small lesion on US (e.g., < 1cm): Repeat screening in 3 to 6 month and if lesion is growing proceed with diagnostic CT/MRI 
  • VIS score C (e.g., Poor visualization on US): Proceed with screening contrast enhanced MRI or multi-phase CT  
  • Lesion ≥ 1 cm on US or AFP ≥ 20 ng/mL or AFP increasing: Proceed with diagnostic contrast enhanced CT or MRI 
• If diagnostic CT or MRI is negative for HCC and AFP is low patients may return to semiannual US/AFP screening  

Diagnosis  

• Diagnosis of HCC is generally done with imaging findings using the LI-RADS criteria  
  • LI-RADS criteria do not apply in patients with liver nodules in the absence of cirrhosis or HBV infection, and pathologic diagnosis should be obtained 
  • Sensitivity of liver biopsy drops in smaller nodules, and a negative biopsy does not rule out HCC  
  • If findings are inconclusive liver biopsy should be repeated 
• LI-RADS scores of 4 or greater indicate likely HCC and multidisciplinary team should be engaged to determine next steps of care  
  • These patients will often proceed with biopsy for further histological and immunohistochemical analyses 
• Patients with confirmed HCC should undergo further staging with: High-quality multiphase CT or contrast-enhanced MRI for assessment of tumor extent | Non-contrast CT chest to assess for lung metastasis  
  • PET scan and bone scans should be avoided due to low sensitivity for HCC 

Treatment  

• Patients with HCC should be cared for by a multidisciplinary team including: Hepatology | Surgery | Oncology | Transplant surgery | Palliative care  
• Surgical resection is the treatment of choice for localized HCC in the absence of cirrhosis or in patients with limited tumor burden and well compensated cirrhosis  
  • Surveillance for HCC should resume post-operatively with repeat CT or MRI imaging every 3 to 6 months to monitor for recurrence  
• In patients with early-stage HCC and decompensated cirrhosis, liver transplantation is the treatment of choice in transplant eligible patients  
  • Surveillance for HCC should resume post-transplant with CT or MRI imaging, though optimal timing is uncertain in this population  
• Other treatment options include: Ablation | Targeted radioembolization | EBRT | Transarterial chemoembolization | Chemotherapy | Immunotherapy  
• Advanced care planning should be offered to all patients receiving palliative-intent therapy or best supportive care for HCC  

KEY POINTS: 

• Hepatocellular carcinoma is a primary liver cancer that typically occurs in the setting of cirrhosis or chronic hepatitis B infection  
• Incidence and mortality of HCC have decreased in the past decade due to improved awareness and implementation of prevention and screening strategies  
• Patients with cirrhosis or chronic HBV infection should undergo semiannual screening for HCC with AFP measurement and liver US 
• Patients with concerning findings for HCC on screening should obtain further imaging with CT or MRI to help diagnose HCC 
• Once HCC is confirmed, a multidisciplinary team should be engaged to develop a treatment plan  

Primary Sources – Learn More  

AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma 

National Cancer Institute (NCI): Liver (hepatocellular) cancer screening 

Heat-Related Illnesses 

SUMMARY: 

Climate change is causing unprecedented extreme heat events throughout the globe, with greater shares of the world population exposed to dangerous levels of heat. Critical heat waves are predicted to occur with greater frequency in the next few decades as the earth’s atmosphere continues to warm to previously unseen levels. This extreme heat has led to an increase in heat-related illnesses and deaths, as well as exacerbations of heat-sensitive conditions. Heat-related illnesses are preventable, and prompt recognition and treatment can decrease morbidity and mortality.  

General Principles  

• Heat-related illness incidence has been on the rise 
  • In the past 20 years, there has been a 54% increase in heat-related mortality among persons > 65 years of age 
• The clinical presentation of heat-related illnesses varies depending on severity  
• Mild to moderate heat related illnesses can generally be treated in clinic or at home 
• Severe heat related illness requires prompt treatment in a hospital setting  
• Heat-related illnesses can be present in the absence of a heat wave and clinicians should have a high index of suspicion for diagnosis  
• Clinicians can help identify patients at risk for heat-related illnesses and counsel them prior to the hotter seasons on methods to stay cool 
  • Use of evaporative coolers | Heat pumps | Air conditioning | Fans 
  • Check a weather app for the heat index and adjust outdoor exposure on hot days 
  • Increased water intake on hot days  
  • Develop a heat plan for hot days (e.g., Plan to seek shelter)  
  • If able, have a social worker check on patients at risk for heat-related illnesses 

Risk Factors 

• Susceptibility to heat-related illnesses is dependent on individual patient, societal and environmental factors 
• Individual susceptibility 
  • Age (e.g., Older than 65 years | Infants | Young children) 
  • Pregnant people  
  • Outdoor workers | Athletes  
  • Pre-existing medical conditions (e.g., Cardiac disease | Kidney disease | Obesity | Disabilities)
  • Social isolation | Immobility
  • Medications (e.g., Diuretics | Anticholinergics | Weight loss supplements) | Drugs (e.g., Cocaine | Amphetamines) | Alcohol  
• Heat exposure 
  • Humidity | Indoor heat sources | Lack of access to cooling | Heat amplification (e.g., Concrete spaces)  
• Sociocultural factors 
  • Poverty  
  • Structural and environmental racism (e.g., Urban heat islands due to history of red lining neighborhoods)  
  • Housing status | Literacy  
  • Limited worker protections  

Mild Heat-Related Illness 

Heat rash 

• Inflammatory disorder of the epidermis due to blockage of sweat glands 
• May develop superimposed bacterial infection 
• Treatment  
  • Remove patient’s clothing 
  • Evaporative cooling (e.g., Fanning + Misting)  
  • Topical glucocorticoids | Topical antibiotics 
  • Avoid topical emollients which may further occlude sweat glands  
  • Advise patient to wear loose clothing and avoid hot environments  

Heat cramps  

• Painful muscle cramps and spasms throughout the body 
• Typically occurs during or following activity in the heat 
• Results from excess loss of salt from sweating 
• Treatment 
  • Remove patient from heat | Rest  
  • Oral hydration that includes electrolytes 

Heat edema 

• Swelling of the limbs due to the physiologic compensatory mechanism of peripheral vasodilation in the setting of heat exposure 
• Treatment 
  • Elevated lower extremities | Remove patient from heat 
  • No indication for diuretics  

Heat syncope 

• Brief loss of consciousness due to pooling of blood in extremities from heat edema  
• Treatment 
  • Remove patient from heat | Rest in a supine position 
  • Passive cooling (e.g., Air conditioning | Fans | Remove clothes) 
  • Oral or IV rehydration  
  • Monitor mental status  
  • If no clinical improvement with above, or if concern for cardiac cause of syncope, then further work up is necessary  

Sunburns/Thermal Burns  

• Sunburns occur following sun exposure, generally after 4 hours 
  • Symptoms include: Erythema | Warm and tender skin | Swelling  
  • More serious sunburns can lead to: Blistering | Headaches | Fever | Fatigue | Nausea  
• Thermal burns are a serious skin injury caused by contact with excessively high heat sources  
• Serious burns require admission to the hospital for wound care and IV hydration  

Moderated Heat-Related Illness 

Heat exhaustion 

• Caused by a decrease in body water content or blood volume due to excessive salt and/or fluid losses in the setting of heat exposure  
• Body temperature may be mildly elevated (< 40°C)  
• Characterized by: Profound fatigue | Weakness | Headache | Dizziness | Nausea/vomiting  
• Notably, no changes in mental status or neurologic symptoms 
  • Lack of neurologic changes helps differentiate heat exhaustion from heat stroke 
• Treatment  
  • Remove patient from heat | Rest in supine position 
  • Evaporative cooling  
  • Intravenous or oral rehydration 
  • Monitor mental status  
  • If no clinical improvement with above, then consider further work up and possible hospital-based treatment 

Severe Heat-Related Illness  

Heat Stroke  

• Medical emergency that requires prompt diagnosis and treatment  
  • Take complete history 
  • Check core body temperature  
• Presentation classically composed of a triad of signs and symptoms:  
  • Hyperthermia (e.g., Internal temperature > 40°C) | Neurologic changes | Recent exposures to hot weather and/or physical exertion 
  • Neurologic changes and an elevated core body temperature help differentiate heat stroke from heat exhaustion  
• Other common signs: Tachycardia | Tachypnea | Hypotension 
• Two categories of heat stroke 
  • Classic heat stroke: More common in patients during a heat wave with pre-existing conditions | Mortality nearly 80% if untreated 
  • Exertional: Healthy patients who preform demanding tasks | Mortality 33% if untreated  
• Hot and dry skin a feature of classic heat stroke 
• Sweating is more common in exertional heat stroke  
• Severe neurologic symptoms may occur such as: Seizures | Incontinence  
• Presents in three phases:  
  • Acute phase: Hyperthermic-neurologic 
  • Hematologic–enzymatic phase: Peaking 24 to 48 hours later | Inflammation | Coagulopathy  
  • Late hepatic–renal phase: Occurring ≥ 96 hours after symptom onset | Organ failure  
• While treating for heat illness, consider differential diagnosis in these critically ill patients: 
  • Sepsis | Stroke | Toxicological emergencies (e.g., Serotonin syndrome | Anticholinergic toxidrome) | Endocrinologic emergencies (e.g., Thyroid storm) 
• Treatment 
  • Move patient to cool environment and immediately work to lower body temperature 
  • Assess and manage: Airway | Breathing | Circulation  
  • Diagnostic tests: CBC | CMP | U/A | Urine Drug Screen | PT/PTT | CK | EKG  CXR if any respiratory symptoms 
  • If outside of hospital setting: Pour copious amounts of cool water on patient | Use evaporative cooling 
  • Insider the hospital: Rapidly cool patient to 38°C to 39°C within 30 minutes of presentation 
  • Effective methods for cooling: Cold water/Ice water immersion (most effective) | Cold fluid infusion | Ice packs to neck, groin and axilla | Evaporative cooling 
  • Benzodiazepines may be used for: Agitation | Discomfort | Shivering  
  • Antipyretics are NOT recommended can worsen coagulopathy and end organ damage 
  • ICU admission is needed for management of end organ failure if present 

KEY POINTS: 

• Climate change has led to increasing extreme heat events and an increase in heat-related illness incidence and mortality  
• Clinicians can help prevent heat-related illnesses by identifying and counseling high risk patients on strategies to stay cool  
• Heat-related illnesses can range from mild, which can be treated at the home or office, to severe, which requires prompt hospital evaluation 
• Treatment of heat-related illnesses generally relies on prompt cooling and hydration  

Primary Sources – Learn More 

NEJM: Treatment and Prevention of Heat-Related Illness 

NEJM: Overview of Heat-Related Illnesses 

ACSM Expert Consensus Statement on Exertional Heat Illness: Recognition, Management, and Return to Activity 

Annals of Internal Medicine: Heat-Related Illnesses

Podcasts for Physicians: All About PrEP

• From Daily Pills to Long-Acting Injectables: What’s New in PrEP?
• Overcoming Barriers- Implementing and Maintaining a PrEP Program in Your Clinic
• Taking a Sexual History
• PrEP Guidelines for Healthcare Professionals

THIS INFORMATION WAS PREPARED FOR YOU BY: 

Raffaele M. Bernardo, DO, an Assistant Professor of Medicine in the Division of Infectious Diseases at Montefiore Medical Center and the Albert Einstein College of Medicine

Rasika Karnik, MD, an Assistant Professor of Medicine in the Biological Sciences Division at the University of Chicago

Summary

From Daily Pills to Long-Acting Injectables: What’s New in PrEP?

Runtime: 28 minutes

Summary

Listen as Dr. Bernardo and Dr. Karnik discuss implementing and maintaining a PrEP Program in your clinic.

Runtime: 20 minutes

Summary

Listen as Dr. Bernardo and Dr. Karnik discuss tips and recommendations for taking a comprehensive sexual history.

Runtime: 21 minutes

Summary

Listen as Dr. Bernardo and Dr. Karnik discuss what Healthcare professionals need to know about PrEP guidelines.

Runtime: 22 minutes

Learn More

Implement and Maintain a PrEP Program in Your Clinic

Sexual History Taking 101: How Do I Start the Conversation with My Patients?

The PrEP Guidelines Center

Commercial Support

This educational activity is supported by an independent educational grant from Gilead Sciences

Age-Related Hearing Loss 

SUMMARY: 

Age-related hearing loss (ARHL) is the most common sensory deficit in older adults, with nearly two thirds of American adults over the age of 71 reporting some degree of hearing loss. While there are many etiologies of hearing loss, ARHL refers to progressive bilateral sensorineural hearing loss (SNHL) associated with aging. Despite its ubiquity it remains underdiagnosed and undertreated, leading to increased social isolation and impacting the mental and physical wellbeing of patients with hearing loss. The American Academy of Otolaryngology – Head and Neck Surgery Foundation (AAO-HNSF) has published guidelines to assist healthcare practitioners in screening, diagnosing, and treating ARHL.  

• Screening
• Diagnosis
• Treatment
• Follow Up
• Key Points

Screening 

• Clinicians should screen all adults ≥ 50 years old for hearing loss during healthcare encounters  
  • Screening can be simple, such as with the prompt, “Do you have any difficulty with your hearing?” 
  • Screening can also be more complex, such as using questionnaires (e.g., HHIE-S | SAC. See “Learn More”)  
  • Exam techniques that may be used to screen include: Whispered voice | Finger rub | Watch tick test  
• For patients who screen negative, repeat testing should be done at regular intervals 
  • The World Health Organization (WHO) recommends screening every 5 years for ages 50 to 65 and every 1 to 3 years after age 65  
• If a patient reports hearing loss during screening, otoscopic exam should be done to rule out anatomic causes 
  • Cerumen impaction | Infection (e.g. Otitis media) | Tympanic membrane disease | Otitis media with effusion | Foreign bodies | Structural abnormalities (e.g., Stenosis | Atresia)  
• If screening for hearing loss is positive and otoscopic exam is unrevealing, clinicians should obtain an audiogram, either in office or via referral  
• When screening is positive, clinicians should also consider patient’s social determinants of health that may influence their access and utilization of hearing related health care 

Diagnosis 

• Patients with suspicion for ARHL should undergo audiometric evaluation via audiogram  
• Determining degree and type of hearing loss requires comprehensive testing 
  • Measurement of pure tone thresholds | Speech audiometry | Tympanometry | Acoustic reflex testing 
• Pure tone average (PTA) is considered the gold standard for detecting hearing loss 
  • Measures hearing sensitivity to various frequencies via bone and air conduction pathways  
  • Can be repeated and compared to previous testing to monitor for changes in hearing loss 
• Online (e.g., Pure tone testing | Word recognition) and at home screening tests may be helpful for patients without access to audiometric testing  
  • Online hearing tests can detect degree of hearing loss but cannot distinguish between types of hearing loss 
• Patients with hearing loss not due to ARHL (e.g., Patients with significant asymmetric hearing loss | Conductive or mixed hearing loss | Poor word recognition on diagnostic testing)  
  • Should receive further evaluation and treatment via their primary care provider 
  • Consider referral to ENT or hearing loss specialist   

Treatment  

• Patients with ARHL should be counseled on the impact of hearing loss  
  • Decreased situational awareness | Difficulty in communication with peers | Difficulty hearing safety warnings | Increased fall risk | Difficulty orienting to external environment  
  • ARHL is also associated with: Increased cardiovascular and all-cause mortality | Declines in bone mineral density | Increased risk of rheumatoid arthritis | More common in patients with diabetes | Difficulty with ADLs | Cognitive loss  
  • Decreased quality of life due to listening effort and fatigue | Increased risk of depression | Difficulty with employment and relationships 
• Family members should also receive guidance on expectations and impact of ARHL 
• Treatment focuses on: Communication strategies to improve hearing | Auditory rehabilitation | Assistive listening devices (ALDs) 
• Patients and partners should be counseled on communication strategies  
  • Communication strategies for patient: Facing a person when speaking | Moving away from noise | Take turns speaking 
  • Communication strategies for speaking partners: Do not talk as you walk away or from another room | Speak clearly and slowly | Get person’s attention prior to starting communication | Avoid complex sentences | If message is not understood, rephrase  
  • Communication strategies for healthcare workers: Avoid masks when there is not a concern for infectious diseases | Give important information in writing  
• Assistive listening devices (ALDs) are devices that solve specific listening challenges and can be broken down into four main groups 
  • Solutions targeted at a specific listening situation without the use of hearing aids (e.g., Amplification devices in doctors’ offices)  
  • Accessories to hearing aids to improve hearing in noise (e.g., Remote microphone)  
  • Telephone communication assistance (e.g., A federally funded program provides free landline amplified and captioned phones to any individual in the United States with hearing loss) 
  • Alerting devices (e.g., Phone flashes and vibrates for texts and calls) 
• Hearing aids are also grouped in as ALDs and should be appropriately fitted and programmed by a professional 
  • First line treatment for patients with mild-moderate ARHL 
• Patients with persistent hearing difficulty and poor speech comprehension despite appropriately fitting amplification devices should be referred for cochlear implantation consideration  
• Cochlear implants are surgically implanted hearing devices that bypass damaged cochlear hair cells to directly stimulate the cochlear nerve 
  • Standard of treatment for patients with severe hearing loss 
  • Safe and effective, even for elderly patients (e.g., > 80 years old)  

Follow Up 

• Patients with hearing loss 
  • Assess for improvement in quality of life, communication and hearing goals at subsequent health encounters, at least withing one year 
  • Reassess hearing via audiometric testing at least every 3 years, or more often if new hearing related concerns arise  

KEY POINTS: 

• Clinicians play a vital role in the diagnosis and treatment of ARHL, and should screen all older patients (i.e., ≥50 years old) for hearing loss 
• Patients who screen positive for hearing loss with no mechanical explanation identified on otoscopic exam should be referred for audiometric testing to determine degree and cause of hearing loss 
• Patients should be offered communication strategies to cope with hearing loss, as well as properly fitted assistive listening devices to improve hearing 
• If hearing fails to improve or if hearing loss is severe, patients should be referred for cochlear implant consideration  
• Follow up encounters should reassess hearing goals and quality of life, as well as intermittent repeat hearing testing via audiogram  

Primary Sources – Learn More: 

AAO-HNSF: Clinical Practice Guideline: Age-Related Hearing Loss 

USPSTF: Hearing Loss in Older Adults: Screening 

American College of Radiology ACR Appropriateness Criteria – Hearing Loss and/or Vertigo 

HHIE-S

Laboratory Evaluation of Functional Diarrhea and IBS-D 

SUMMARY: 

Chronic diarrhea, or watery diarrhea that has lasted for more than 4 weeks, has a wide differential including infectious etiologies, inflammatory bowel disease (IBD), and functional diarrhea or irritable bowel syndrome – diarrhea predominant (IBS-D). In evaluating immunocompetent patients with chronic diarrhea and suspected IBS-D or functional diarrhea, it is important to rule out these other potentially life-threatening etiologies. To that end, the American Gastroenterological Association (AGA) has developed recommendations for the laboratory evaluation of patients with chronic diarrhea and suspected functional diarrhea or IBS-D.  

Who to Test  

• Immunocompetent patients with chronic (> 4 weeks) watery diarrhea with suspected functional diarrhea or IBS-D should undergo laboratory evaluation prior to confirming the diagnosis of IBS-D/functional diarrhea 
  • These recommendations exclude immunosuppressed patients and patients with diarrhea and “red flag” symptoms including: Bloody diarrhea | Steatorrhea | Weight loss | Anemia | Hypoalbuminemia  
  • Additionally, these recommendations exclude patients with risk factors for infectious or inflammatory diarrhea including: Family history of IBD | Family history of colon cancer | Family history of celiac disease | Travel to a region with endemic diarrheal illnesses  

Laboratory Evaluation  

• Fecal calprotectin | Fecal lactoferrin  
  • AGA suggests the use of these tests in all patients presenting with chronic diarrhea as defined above  
  • Either test may be used to screen for inflammation in the GI tract  
  • These tests are regularly used in the evaluation and follow up of patients with IBD and a negative test can help rule out IBD 
  • AGA recommends a screening cut-off value of 50 µg/g for fecal calprotectin and threshold values in the range of 4.0 to 7.25 µg/g for fecal lactoferrin to optimize sensitivity  
  • A positive result should prompt the provider to obtain further testing to evaluate for IBD  
• Giardia antigen testing | Giardia PCR 
  • Giardia is a common diarrheal causing pathogen throughout the United States 
  • Giardia antigen or PCR testing should be checked in all patients presenting with chronic diarrhea  
  • In the absence of travel from high-risk areas, routine testing for other ova and parasites is not recommended   
• Celiac serologies 
  • Celiac disease should be ruled out in all patients presenting with chronic diarrhea 
  • Screen with IgA tissue transglutaminase and IgA levels 
  • In patients with concomitant IgA deficiency, then IgG tissue transglutaminase and IgG or IgA deaminated gliadin peptides should be checked in lieu of IgA tissue transglutaminase 
  • Positive testing should prompt GI referral for EGD and biopsy 
• Bile acid diarrhea 
  • Patients with chronic diarrhea should be evaluated for bile acid diarrhea  
  • Excess production or decreased absorption of bile acids can lead to increased concentration of bile acids in the colon and resultant watery diarrhea 
  •  Tests available in the United States include: Measurement of total bile acids in a 48-hour stool collection | Serum fibroblast growth factor 19 
  • If testing is unavailable, it is reasonable to trial bile acid binders in patients with suspected bile acid diarrhea and monitor for clinical improvement to confirm diagnosis  
• ESR | CRP  
  • AGA suggests AGAINST the routine use of ESR/CRP in patients with chronic diarrhea to evaluate for possible IBD given their lack of specificity  
  • If unable to obtain fecal calprotectin or lactoferrin, then checking CRP may be considered  
  • CRP is preferred over ESR given its higher sensitivity and specificity when using a recommended cut-off of 5 to 6 mg/L 
• Serologic testing 
  • Serologic testing for IBS-D currently lacks convincing data and is not recommended by the AGA 

KEY POINTS:  

• Immunocompetent patients with chronic diarrhea in the absence of concerning “red flag” symptoms or worrisome family history should undergo laboratory evaluation to rule out other infectious and inflammatory/autoimmune etiologies of chronic diarrhea prior to making a diagnosis of functional diarrhea or IBS-D 
• Recommended testing includes Celiac serologies, Giardia testing, fecal inflammatory markers, and testing for bile acid diarrhea  

Learn More – Primary Sources:  

AGA: Laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome (IBS-D) 

ACG Clinical Guideline: Management of Irritable Bowel Syndrome 

Chronic Hepatitis B Treatment  

SUMMARY: 

Chronic hepatitis B (CHB) is caused by the persistent infection and failure to develop sustained immunity to the hepatitis B virus (HBV), a double-stranded DNA virus transmitted through blood and other bodily fluids. Following infection with HBV, most immunocompetent adults will clear the virus, but roughly 1 to 5% of adults will go on to develop CHB. Nearly a quarter of a billion people in the world have CHB, with estimates in America ranging from 700,000 to 2.2 million adults living with CHB. Chronic hepatitis B infection can lead to cirrhosis, hepatocellular cancer, fulminant liver failure, and death. While immunization remains a cornerstone of HBV and thus CHB prevention, treatment options are available for select patients with CHB to reduce the morbidity and mortality associated with chronic hepatitis B infection.   

CHB Disease Phases  

• CHB is defined as HBsAg positivity for ≥ 6 months along with measurable HBV DNA  
• CHB is a dynamic and variable disease that is traditionally split into four different phases based on viral replication and the host immune response 
  • Immune tolerant phase: Normal ALT | Elevated HBV DNA | + HBeAg | Minimal fibrosis and inflammation 
  • Immune active phase: Elevated ALT | Elevated HBV DNA | + HBeAg | Moderate to severe fibrosis or inflammation 
  • Inactive CHB phase: Normal ALT | Low or undetectable HBV DNA | -ve HBeAg | Minimal inflammation | Variable fibrosis  
  • Immune reactivation phase: Elevated ALT | Mildly elevated HBV DNA | -ve HBeAg | Moderate to severe fibrosis or inflammation 
• Approximately 0.5% of patients with inactive CHB will clear their HBsAg yearly, with most developing HBsAb consistent with immunity 
  • Clearance of HBsAg improves survival and decreases risk of hepatic decompensation  

Evaluation 

• Initial evaluation in patients with CHB should include 
  • Thorough history with emphasis on risk factors such as: Alcohol use | Family history of liver cancer | Risk factors for co-infection (e.g., IV drug use) | Metabolic risk factors | Vaccination status  
  • Physical exam, with special attention paid to signs and symptoms of cirrhosis (e.g., Ascites | Palmar erythema | Splenomegaly | Encephalopathy | Asterixis)  
  • Laboratory testing: CBC | LFTs | INR | Albumin | Serum fibrosis panel (e.g., APRI | FIB‐4 | FIbroTest) 
  • Imaging: Abdominal ultrasound | Vibration‐controlled transient elastography 
  • Serology: HBeAg/anti‐HBe | HBV DNA quantitation | Anti‐HAV Ab (for vaccination) | HBV genotype | HCV | HIV  

When to Treat 

• The goal of antiviral treatment in HBV is to reduce the morbidity and mortality related to CHB via immunological cure 
  • Immunological cure is defined by HBsAg loss and sustained HBV DNA suppression 
  • Virological cure, defined as the complete eradication of HBV, is not currently attainable 
• Elevated serum ALT and HBV DNA are associated with increased morbidity and mortality from CHB 
  • Additional risk factors for CHB morbidity and mortality include: Older age | Male sex | Family history of HCC | Alcohol use | HIV infection | Diabetes | HBV genotype C | HBV precore and core promoter variants 
• Patients that should undergo HBV treatment include 
  • Patients with immune active CHB: Defined as ALT > 2x upper limit of normal or evidence of significant histological disease + elevated HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive) 
  • Patients with cirrhosis and detectable HBV DNA 
  • Select patients over the age of 40 years with elevated HBV DNA and evidence of liver fibrosis or inflammation  
  • Select patients with risk factors for increased morbidity and mortality from CHB 
  • Health care providers who preform exposure-prone procedures  
  • Patients with hepatocellular carcinoma  
• Prophylactic treatment should be given to patients with CHB who 
  • Are undergoing HBV-related liver transplantation to prevent recurrence  
  • Pregnant patients with elevated viremia in the final trimester to prevent vertical transmission 
  • Patients undergoing immunosuppressive therapy or chemotherapy to prevent the reactivation of HBV 

Treatment  

• Patients should be counseled prior to treatment that therapy for CHB will be long term and likely lifelong  
  • Exception to lifelong treatment includes: Patients with CHB in the absence of cirrhosis who seroconvert to anti-HBe while on therapy  
• Treatment for HBV includes pegylated interferon (e.g, Peg-IFN-a-2a (Pegasys)) and various nucleos(t)ide analogs (NAs), four of which are available in the United States  
  • NAs available in the United States include: Entecavir (Baraclude) | Tenofovir (Viread) | Lamivudine (Epivir) | Adefovir (Hepsera) 
• In patients with HIV coinfection, treatment of HBV needs to be coordinated with HIV therapy  
  • Several HBV drugs have anti‐HIV activity (e.g., Tenofovir | Entecavir | Lamivudine)   
• Preferred initial therapies for adults with immune-active CHB include 
  • Peg-IFN-a-2a (Pegasys): 180 mcg weekly  
  • Entecavir (Baraclude): 0.5mg daily  
  • Tenofovir (Viread): 300mg daily  
• NAs are generally better tolerated than peg-interferon, which is associated with common side effects (e.g., Flu-like symptoms | Cytopenias | Fatigue | Mood disturbances)  
• NAs can cause lactic acidosis, and lactic acid levels should be checked if there is clinical concern  

Monitoring  

• All patients with CHB should have regular follow up and blood work including 
  • CBC | LFTs | Albumin | Creatinine | INR 
• Patients on interferon therapy should additionally have their TSH checked every 3 months  
• Liver function tests should be repeated at least every 6 months in patients with immune tolerant CHB to monitor for transition to another phase of CHB 

KEY POINTS:  

• Chronic hepatitis B infection is caused by the continued replication of HBV DNA without the development of lasting immunity by the host, and can lead to cirrhosis, hepatocellular carcinoma, and death  
• Treatment is indicated in select patients who CHB to decrease morbidity and mortality, and is often continued lifelong as there is yet no cure for HBV  
• The preferred initial treatment for CHB includes: Peg-IFN-a-2a (Pegasys) | Entecavir (Baraclude) | Tenofovir (Viread) 
• Patients with CHB should be monitored regularly for the development of cirrhosis and HCC  

Primary Sources – Learn More:

Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance 

2016: AASLD guidelines for treatment of chronic hepatitis B 

WHO: Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection 

World Gastroenterology Organisation: Hepatitis B 

Hepatitis B: Who and when to treat?  

APRI

FIB‐4

HCV: From Screening to Management  

SUMMARY:  

Hepatitis C virus (HCV) is the most common blood-borne pathogen in the USA. It is generally asymptomatic in its acute phase, often going unrecognized until chronic infection leads to cirrhosis and significant morbidity and mortality. With the advent of direct-acting antiviral (DAA) therapies, effective treatment options are now available that can cure patients of a disease that was once considered a chronic, life-threatening illness. Universal screening has become a cornerstone in the management of HCV, as patients can be diagnosed while asymptomatic and receive treatment before any lasting damage is done. The IDSA (Infectious Disease Society of America) and AASLD (American Association for the Study of Liver Disease) have released updated guidance on the screening, management and treatment of HCV.  

• Screening
• Diagnosis
• Management
• Treatment
• Key Points

Screening 

• IDSA/AASLD recommend universal screening at least once in all adults (age ≥ 18) 
  • Screening should be a one time, routine, opt out HCV-antibody testing with reflex HCV RNA polymerase chain reaction (PCR) 
  • HCV RNA testing should be considered in patients who are immunosuppressed (e.g., patients who may not develop HCV antibodies if infected)  
• More frequent screening should occur in special patient populations: Injection drug users | HIV-uninfected MSM presenting for HIV pre-exposure prophylaxis (PrEP) | HIV infected patients | Persons in correctional settings | Pregnant persons (during each pregnancy) 
• Additional high-risk activities, exposures, and conditions warrant periodic screening  
  • Long term hemodialysis  
  • Glass crack pipe use  
  • Intranasal illicit drug use 
  • Persons who were ever incarcerated  
  • HBV infection  
  • Solid organ donors and recipients  
  • Patients with chronic liver diseases or chronic hepatitis  
  • Men who have sex with men 
  • Persons with exposure to percutaneous or parenteral blood (i.e. healthcare workers following needlestick injuries)  
  • Recipients of prior blood transfusion or organ donations  

Diagnosis  

• Positive HCV Ab AND positive HCV RNA PCR testing indicates active infection  
• Positive HCV Ab AND negative HCV RNA PCR indicates prior infection that has been cleared (e.g., Patient cleared the virus following previous exposure or patient previously treated for HCV and cured)  
  • Patients found to have evidence of prior infection should be told that they are NOT protected from reinfection  
• Quantitative HCV-RNA testing is recommended prior to initiation of antiviral therapy to document the baseline level of viremia  
• HCV genotype should also be obtained in patients in whom it may alter treatment (e.g., prior treatment failure)  

Management  

• Patients found to have active HCV infection should receive counseling on reducing transmission and decreasing liver disease progression  
  • Encourage abstinence from alcohol 
  • Check patients for HIV and HBV coinfection  
  • Evaluate patients for other conditions that may contribute to liver disease  
  • Evaluation for advanced hepatic fibrosis using noninvasive testing (see below) 
  • Vaccination for HAV and HBV, as well pneumococcal vaccine in patients with cirrhosis  
  • Counseling on how to decrease spread via blood transmission, especially for patients with IV drug use (e.g., use new sterile syringes and filters, clean injection sites with alcohol, dispose of needles in a safe place) 
• Routine testing to determine liver disease severity includes 
  • ALT | AST | Albumin | Bilirubin |INR | CBC with platelet count 
  • Serum fibrosis marker panels (e.g., FibroSure, Enhanced Liver Fibrosis Test) 
  • Transient elastography 
  • Liver US or CT  
• Calculate a Fibrosis-4 (FIB-4) Score  (see “Learn More”)
  • A FIB-4 score is >3.25 is consistent with cirrhosis  

Treatment  

• Prior to beginning treatment assess patient for evidence of cirrhosis (see above)  
  • US of the liver must be done prior to initiating treatment in patients with cirrhosis to exclude HCC or subclinical ascites 
• Complete a medication reconciliation, including review of supplements and over the counter drugs 
  • Check for potential drug-drug interactions, such as with the Liverpool drug interaction checker (see “Learn More”)
• IDSA/AASLD recommend a simplified HCV treatment pathway for qualifying patients 
  • Patients must be: Treatment naïve | No special circumstances (see below) | No current or former decompensation of their cirrhosis  
  • Compensated cirrhosis refers to patients with Child-Pugh A cirrhosis  

Treatment of Naïve Patients without Cirrhosis 

• Glecaprevir (300 mg) / Pibrentasvir (120 mg) (Mavyret)  
  • Once daily with food for 8 weeks 
• Sofosbuvir (400 mg) / Velpatasvir (100 mg) (Epclusa) 
  • Once daily for 12 weeks   
• While on treatment: 
  • Patients on diabetes medications should be counseled and monitored for symptomatic hypoglycemia 
  • Patients on Warfarin should have special monitoring of their INR to monitor for possible subtherapeutic levels  
  • No other laboratory monitoring is necessary 
• Follow up:  
  • Repeat HCV RNA and LFTs should be done 12 weeks following completion of therapy to confirm virologic cure and AST/ALT normalization  
  • Patient who do not achieve sustained virologic remission (SVR) should be referred to a specialist (see below – Special Circumstances)  

Treatment of Naïve Patients with Compensated Cirrhosis  

• The following regimens are not recommended for patients with cirrhosis AND eGFR <30 mL/min/m² 
• Glecaprevir (300 mg) / Pibrentasvir (120 mg) (Mavyret)  
  • Once daily with food for 8 weeks 
• Sofosbuvir (400 mg) / Velpatasvir (100 mg) (Epclusa) 
  • Once daily for 12 weeks 
  • If wishing to use Sofosbuvir/Velpatasvir (Epclusa), genotype testing must first be obtained in patients with cirrhosis  
  • Patients with genotype 3 require baseline NS5A resistance-associated substitution (RAS) testing; if negative they may proceed with Sofosbuvir/Velpatasvir (Epclusa) treatment 
• While on treatment: 
  • Patients on diabetes medications should be counseled and monitored for symptomatic hypoglycemia 
  • Patients on Warfarin should have special monitoring of their INR to monitor for possible subtherapeutic levels  
  • Consider monitoring LFTs as hepatic decompensation can rarely occur in patients with cirrhosis on DAA therapy  
• Follow up:  
  • Repeat HCV RNA and LFTs should be done 12 weeks following completion of therapy to confirm virologic cure and AST/ALT normalization  
  • Patient who do not achieve sustained virologic remission should be referred to a specialist (see below – Special Circumstances) 
  • Patients will need to continue their regular cirrhosis follow ups (e.g., Liver US every 6 months to evaluate for HCC) following HCV treatment, as sustained virologic remission (SVR) does not reverse cirrhosis  

Special Circumstances 

• Certain patients will require care from an infectious disease specialist or hepatologist and may not be eligible for the simplified HCV treatment pathway 
  • Retreatment and treatment failures  
  • HIV/HCV co infection 
  • HCV and pregnancy  
  • Acute HCV infection  
  • Decompensated cirrhosis  
  • HBsAg positive  
  • Known or suspected HCC 
  • Prior liver transplant  

KEY POINTS: 

• Universal one time opt out screening for HCV infection should be done in all adults  
• Certain at-risk patient populations should be screened periodically due to increased risk of HCV transmission 
• Cure rates are ≥95% with direct-acting antiviral (DAA) therapies for 8 to 12 weeks, and the drugs are generally well tolerated with few adverse effects  
• Simplified treatment pathways exist for uncomplicated, low risk patients to assist primary care doctors in their management of HCV  

Learn More – Primary Sources:  

Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection 

CDC: Testing Recommendations for Hepatitis C Virus Infection 

AASLD and IDSA: Recommendations for testing, managing, and treating Hep C 

Association of Direct-Acting Antiviral Treatment With Mortality Among Medicare Beneficiaries With Hepatitis C 

Fibrosis-4 (FIB-4) Score  

Liverpool Drug Interaction Checker 

Universal Screening for Hepatitis C 

SUMMARY:  

USPSTF has reviewed available evidence and has updated its hepatitis C screening guidance. HCV is the most common chronic blood-borne pathogen in the US with potential for significant morbidity and mortality if left untreated.  

• The incidence rate of acute hepatitis C has more than doubled since 2013, and increased 15% from 2019 to 2020,  
  • This increase is primarily due to increased testing and surveillance, as well as increased injection drug use  
• The USPSTF recommends screening for HCV infection in adults aged 18 to 79 years  
• Population: All asymptomatic adults aged 18 to 79 years without known liver disease  
• B level recommendation  
  • Offer or provide this service  
  • There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial  

The USPSTF concludes with moderate certainty that screening for HCV infection in adults aged 18 to 79 years has substantial net benefit  

Risk Assessment  

• Screen all adults ages 18 to 79 years  
• Risk factors to consider  
  • Injection drug use: Consider screening adolescents <18 years or >79 years  
    • Young adults (ages 18 to 30): Approximately 30% are infected  
    • Older adults: 70% to 90% are infected  
  • Pregnancy  
    • Screen pregnant adults during each pregnancy     
    • Due to increasing prevalence of HCV in women aged 15 to 44 years and in infants born to HCV-infected mothers, clinicians may want to consider screening pregnant persons younger than 18 years 

Screening Test  

• Anti-HCV antibody testing followed by polymerase chain reaction testing for HCV RNA  
  • HCV infection can be detected by anti-HCV screening tests (enzyme immunoassay) 4 to 10 weeks after infection  
  • Delayed seroconversion may occur in immunocompromised individuals (e.g., those with HIV infection)  
    • Consider addition of HCV RNA in these patients despite a negative antibody test 

Screening Intervals  

• “Most adults need to be screened only once”  
  • Consider more frequent screening for individuals with ongoing risk (e.g., ongoing injection drug use)  
  • See “Related Topics” below for further information 

KEY POINTS:  

Hepatitis C Overview  

• Acute Hepatitis C occurs within the first 6 months after exposure to HCV  
• Many individuals will remain asymptomatic  
• 15% of patients will spontaneously clear the virus within 6 months  
• Signs and symptoms of acute HCV infection  
  • Fever | Fatigue | Dark urine | Clay-colored stool | Abdominal pain | Loss of appetite | Nausea and vomiting | Joint pain | Jaundice  
  • Most individuals with newly acquired HCV infection will be asymptomatic | 20 to 30% will exhibit symptoms  
  • Symptoms will usually appear within 2 to 12 weeks (range: 2–26 weeks)   
• Symptoms of chronic HCV infection  
  • Most people are asymptomatic or have non-specific symptoms (e.g., chronic fatigue and depression)  
  • Many eventually develop chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer  
  • Chronic HCV infection is typically not recognized until asymptomatic people are identified as HCV-positive when screened for blood donation or liver function tests return an abnormal result (e.g., elevated ALT), often during routine evaluation   

Hepatitis C Treatment  

Acute  

• The same regimens recommended for chronic HCV infections are recommended for acute infection 

Chronic  

• Current antiviral therapies can result in sustained virologic response (SVR; absence of detectable virus 12 weeks after completion of treatment)  
  • SVR is indicative of a cure of HCV infection  
  • Over 90% of HCV infected persons can be cured of HCV infection regardless of HCV genotype with 8-12 weeks of oral therapy  
  • See “”Related Topics” below for information on HCV drug regimens  

Other Considerations 

• Advise abstinence from alcohol and acetaminophen during acute infection                  
• Evaluate for hepatitis B and HIV infection 
• Vaccinate against Hepatitis A and Hepatitis B, as well as pneumococcal vaccine in patients with cirrhosis  
• Evaluation for advanced hepatic fibrosis with  
  • Elastography or liver imaging (US or CT Scan) 
  • FIB-4 Score (see “Learn More” below)
  • Lab tests: ALT | AST | Albumin | Bilirubin | INR | CBC 
• Provide education on how to prevent HCV transmission to others 

Other Professional Recommendations  

• AASLD/IDSA  
  • One-time, routine, opt out HCV testing is recommended for all individuals aged 18 years and older  
  • One-time HCV testing should be performed for all persons less than 18 years old with behaviors, exposures, or conditions or circumstances associated with an increased risk of HCV infection  
  • Periodic repeat HCV testing should be offered to all persons with behaviors, exposures, or conditions or circumstances associated with an increased risk of HCV exposure  
  • Annual HCV testing is recommended for all persons who inject drugs and for HIV-infected men who have unprotected sex with men  
  • As part of prenatal care, all pregnant women should be tested for HCV infection, ideally at the initial visit, and test should be repeated with each pregnancy 
• CDC  
  • All adults 18 years and older (except in settings where the prevalence is <0.1%)  
  • All pregnant persons should be screened for HCV during each pregnancy (except in settings where the prevalence of HCV infection is < 0.1%)  
  • All persons with risk factors (e.g., persons with HIV, prior recipients of blood transfusions, persons who ever injected drugs and shared needles, and persons who are born to an HCV-infected mother) should be tested for HCV, with periodic testing while risk factors persist  

Learn More – Primary Sources:  

Screening for Hepatitis C Virus Infection in Adolescents and Adults – US Preventive Services Task Force Recommendation Statement 

AASLD / IDSA: HCV Testing and Linkage to Care  

CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020 

CDC Clinical Overview of Hepatitis C 

Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States 

Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection 

FIB-4 Score