Care of Acute HIV in the Hospital (Fenning, 11/29/2023)

  A recording of this presentation is available HERE.

***

Many thanks to Dr. Reece Fenning for an excellent presentation this week on Acute HIV in the Hospital. A recording of his presentation is available above. 

My notes:

  • 75% of the HIV+ population in Sonoma County is >40 years old
  • HIV disproportionately affect African American and Latinx people, who make up 65% of the new diagnoses each year
  • Whereas in California 73% of people living with HIV are engaged in care and 64% are virally suppressed, in Sonoma County, 86% are engaged in care, and 82% are virally suppressed
  • Patients with HIV have 1.5x the hospitalization rate as their HIV- counterparts
The CDC recommends that ALL US adults receive a one time HIV screening. People who should be tested more frequently (annually) include: 1) people with partners who are known HIV+ or have a known exposure, 2) pregnant patients, 3) patients who use IV drugs, and 4) people who exchange money (or other goods) for sex. 

Luckily, our HIV testing sensitivity has improved in the last decade, and the so-called "window period" is now much shorter than the past -- it is only around 10 days (but up to 3 weeks) between viral acquisition and possibility of a false negative test. 

When seeing patients with HIV in the hospital and/or outpatient, you should check their CD4 count AND their viral load. Also, screen for common co-morbid infections: TB (the most common worldwide), acute viral hepatitis (A, B, C), and other STI testing (RPR, GC/CT), and lipids.

HIV is staged based on CD4 count and/or CD4 percentage:
  • Stage 1: CD4 count >500
  • Stage 2: CD4 count 200-500
  • Stage 3: CD4 count <200 and/or CD4 percent <14%
Newly diagnosed HIV should be treated immediately (rapid tx induction), except in rare cases of specific comorbidities. These exceptions include Cryptococcus meningitis and active TB. Both require initiation of treatment of these conditions prior to treating the HIV disease. (see chart below):

Standard anti-retroviral treatment for HIV includes 2NRTIs and 1 NSF. You ideally want to know the viral load and genotype prior to starting treatment, but this may not always be possible.
  • Biktarvy (bictegravir/emtricitabine/TAF) is a single pill containing all three meds
  • Alternate options includes a couple of different dolutegavir-containing regimens
    • Trivicay + Descovy (2 pills)
    • Trovicay + Truvada (2 pills)
    • Triumeq (only one pill, but requires HLA testing, so not great for rapid treatment)
What about empiric prophylaxis Opportunistic Infections (OIs)? 
You should be worried about OIs if CD4<200 and/or CD4 percentage<14%. The most common OIs for which to consider ppx are PCP pnuemonia (aka PJP) if CD4<200-- ppx is TMP-SMX daily,  and MAC (if CD4<50) -- ppx is azithromycin once weekly.

How should we think about OIs in the acute setting? There are a couple of different ways to think about OIs:

Time with HIV
  • newly acquired (<6 months)
  • previously on treatment but now stopped
  • on treatment, but its not working
Presenting symptoms:
  • AMS --> think CNS infection (Crypto
  • respiratory symptoms --> think PCP, MAC
  • dermatologic symptoms --> think HSV, VZV, MRSA, KS
Random acute HIV symptoms and pearls:
  • Acute HIV: The large majority of patients will have viral/flu-like symptoms with acute HIV that will self-resolve. Most are not sick enough to present to the ER during this acute illness.


  • Immune reconstitution inflammatory syndrome (IRIS) usually appears 2-4 weeks after starting tx, it is a diagnosis of exclusion. Greatest risk with high viral load and very low CD4 (<50). Treatment is NSAID (outpatient) or steroids (inpatient)
  • HIV wasting syndrome: acute weight loss (>10% of body weight), often with acute diarrhea. Looks like cancer. May need an EGD and/or colonoscopy for biopsy to diagnose. See testing algorithm below.



  • Odynophagia: pain with eating may be a sign of oral thrush and/or esophageal candidiasis
  • Dermatologic infections in HIV are very confusing and also often require a biopsy (see images)
  • (L>R clockwise: Kaposi's Sarcoma, HSV, MRSA Shingles)

  • Respiratory illness in HIV disease should be evaluated like non-HIV with CXR, blood work, but also add beta-D-glucan (for fungal infections). You likely will need tissue (bronchoscopy or induced sputum) to get a diagnosis. 
  • Neurologic symptoms in someone with HIV require a head CT, followed by CSF studies. Also don't forget a fundoscopic exam (CMV retinitis)

Additional resources:


Primary Care for Patients with Alcohol Use Disorder (Lund, 11/15/2023)

A recording of this presentation is available HERE

***

Deep gratitude to our Assistant Program Director and local expert, Dr. Erin Lund, for an excellent presentation on Primary Care Management of Alcohol Use Disorder (AUD). Living in the wine country, this is a medical problem that sometimes hides in the shadows of social acceptability and cultural norms. 

Dr. Lund covered a broad range of topics related to AUD, including healthy drinking, screening for risky drinking, assessing severity of the use disorder and treatment (both acute withdrawal and chronic management). Alcohol, consumed around the world, is one of the oldest-used psychoactive substances, 2/2 only to caffeine.  There is documentation of humans indulging in alcohol dating back 9,000+ years.

(Note: much of the ETOH literature includes gender-based nomenclature. In an effort to be gender inclusive, I will use the following terms in this blogpost: AMAB: assigned male at birth, AFAB: assigned female at birth)

Healthy drinking

Standard drinks vary based on alcohol content and volume: 12 oz beer, 8-9 oz malt liquor, 5 oz wine, 1.5oz distilled spirits (see image below). Healthy drinking guidelines are based on age and gender assigned at birth: for adults under age 65, no more than 4 drinks for AMAB or 3 drinks for AFAB on any one day AND no more than 14 drinks/week for AMAB and 7 drinks/week for AFAB.


Risky Drinking

Rates of risky drinking and AUD are shockingly high in the US: 12-month prevalence of 13.9% of AUD (7% mild, 3% moderate and 3% severe) and a lifetime overall prevalence of 29%. Typically people AMAB have higher rates than people AFAB, but this is changing, as alcohol becomes more socially acceptable for AFAB patients. People ages 18-35 have the highest prevalence. 

A binge episode is defined as: 

  •  >4 drinks for AFAB >5 drinks for AMAB,
  • at least one day in the last 30 days

>5 days of binge drinking=HEAVY USE

Heavy use is NOT the same as AUD, but intervention should be considered, as heavy use is associated with increased all-cause mortality, earlier death, increased automobile accidents, increased accidental and intentional injuries, and social and legal problems.

Alcohol Use Disorder

DSMV outlines AUD* as "a maladaptive pattern of alcohol use" within the past 12 months, as defined by at least two of the following criteria:

  • Drinking larger amounts/longer periods than intended
  • Efforts/desire to cut down
  • Great deal of time spent obtaining, using, recovering
  • Craving
  • Recurrent failure to fulfill role
  • Continued use despite social/interpersonal problems related to drinking
  • Activities given up (social, occupational, recreational)
  • Recurrent physically hazardous behavior
  • Continued use despite physical or psychological problems
  • Tolerance
  • Withdrawal

*Mild AUD: 2-3 criteria, moderate 4-5, severe ≥ 6

Screening for AUD

USPSTF gives a grade B recommendation to screen ALL adults for unhealthy alcohol use. Here's the good news: when we screen, it makes a difference! Patients actually cut back and change their use habits. People live longer. 

There are a variety of standardized screening tools; these include:

  • 1Q screen: How many times in the past year have you had more than 4 drinks/day (AFAB) or 5 drinks/day (AMAB). Positive with answer of >1
  • AUDIT-C (which is what is used at SRCH, see image below)
A nice thing about using the AUDIT-C is that the results can be used to guide treatment. An AUDIT-C score of 0-3 indicates low risk drinking (no intervention needed), a score 4-5 is moderate risk (brief intervention indicated). A score 6-7 merits a brief intervention + psychotherapy and consideration of pharmacotherapy. A score of 8-9 is an indication for pharmaceutical intervention + psychosocial intervention+/-specialty care management. A score of 10+ merits urgent specialty referral.

Treatment of AUD
Treatment of AUD includes both psychosocial and pharmacological treatments. It also involves both an acute stage (active use, withdrawal) and a chronic stage (maintenance, harm reduction, reduction).

Psychosocial support involves both formal treatment programs (inpatient and outpatient programs), many of which are based in Peer Support. These include but are not limited to AA, smart recovery, etc.
Pharmacological management involves, at the minimum, 1 of 3 FDA-approved medications. These meds can be started in the inpatient or outpatient setting. We have great room to improve in this area. A study in 2012 found that only 8% of US patients with AUD were being treated with medications. 

Considerations in starting meds for patients should include goals (e.g. abstinence vs. reduced use), relevant health factors (e.g. comorbidities like chronic pain, cirrhosis, etc.), and external barriers. 

Alcohol Withdrawal Syndrome (AWS)

The slide pasted below demonstrates the timeline for Alcohol withdrawal and some recommendations in terms of who can withdraw in an outpatient setting vs. those who need inpatient support.

Alcohol withdrawal is most likely to occur in patients who have been drinking for more than 2 weeks and who have abruptly stopped drinking. Once a person is 5 days past their last drink, they are outside the window of acute withdrawal. And one can move onto the maintenance stage of management of AUD. 

Providers should use standardized scores to keep an objective assessment of a patient's alcohol withdrawal. There are several, including the CIWA (10q, objective + subjective report), the SAWS (10q, patient-completed), and the SEWS (7q, clinical assessment)

CIWA: <10: very mild AWS, 10-15 mild AWS, 16-20 modest AWS, >20 severe (DTs)


SAWS: patient scores their own symptoms in past 24 hours, <12 is mild AWS, >12 is moderate to severe AWS


SEWS

The severity of AWS dictates the level of care the patient needs. Patients with mild-moderate withdrawal can be managed in the outpatient setting, assuming they can also 1) have consistent follow-up 2) take PO meds 3) have friend/relative/support person 4) have no prior hx of DTs 5) have no high risk comorbidities (physical or psychiatric) that would make home withdrawal unsafe (e.g. extreme anemia, decompensate cirrhosis) 6) do NOT have polysubstance use.

All other patients should be managed in an inpatient setting.

Pharmacotherapy for AWS

Goal of treatment of AWS is to help patients withdraw safely (prevent DTs, seizures, death) and reduce likelihood of relapse. This can be accomplished using either benzodiazepines (e.g. chlordiazepoxide or lorazepam), which was the previous gold standard, and/or with benzo-sparing protocols, most of which use anticonvulsants and anti-adrenergic medications. 

Anticonvulsants: phenobarbital, gabapentin, valproic acid, carbamazepine

Anti-adrenergic: clonidine, propranolol, guanfacine, precedex

Everyone with AWS should get folic acid (1gm/day) and vitamin B1 (thiamine, 100mg/day)

The idea behind the benzo-sparing protocols is that these medications are AS effective in safe withdrawal with less abuse potential than benzos. There are still evolving studies in this area, and some agents have more evidence than others. These protocols vary based on location and experience. 

See below the draft algorithm (not yet live) at SRCH, which screens for patients who may safely withdraw outpatient and uses fixed dose gabapentin (300mg TID vs. 600mg TID).


Older algorithms use fixed vs. on demand dosing of lorazepam and/or chlordiazepoxide. You can find a link to those older guidelines HERE

Chronic Management of AUD

Okay, finally, moving onto medications that prevent relapse and/or help people cut back and/or help people remain abstinent. Most studies look at a period of time of 12-16 weeks of reduced use and/or abstinence, but in clinical practice a minimum of a year of maintenance therapy is recommended, particularly if there is a high risk of relapse.

FDA approved: naltrexone, Acamprosate, disulfiram

  • Naltrexone: 50mg PO daily OR 380mg IM monthly, reduces risk to any drinking (NNT 10) and heavy drinking (NNT 12), injectable has evidence for reducing number of heavy drinking days. Reduces craving and pleasurable effect of drinking. Contraindicated in liver failure, concomitant opiate use (within 7 days). Pregnancy is relative contraindication.
  • Acamprosate 333mg, 2 tabs TID daily. Reduces return to any drinking (NNT 12), reduces withdrawal associated dysphoria. Has mixed evidence on efficacy compared to placebo. Contraindicated in renal failure (GFR<30) and pregnancy. 
  • Disulfiram: oldest med on the market for AUD (1949), anticipation of feeling sick discourages use. Blinded studies don't show great effect, but open label studies do show reasonable effect. 

Non-FDA approved but have some evidence: topiramate, baclofen, gabapentin, ondansetron, sertraline, semaglutide

  • Topiramate: non-FDA approved, may reduce cravings, impulsivity and post-withdrawal dysphoria, 100-300mg/day (titrated up over 6 weeks from 25mg day starting dose, increase by 50 mg per week), BID dosing recommended. Contraindicated in pregnancy and renal failure.
  • Gabapentin: non-FDA approved, may be continued after using for treatment of AWS, 300mg-600mg TID for maintenance dosing to reduce cravings and return to drinking

Endometrial Cancer (Delic 11/8/2023)

A link to a recording of this presentation is available HERE

***
Many, many thanks to our speaker this week, Dr. Lejla Delic, a local gynecologist-oncologist, who works with our local oncologists and gynecologists to care for patients in our community with gyn cancers. Her presentation was excellent -- so good, in fact, that we we want her back for a Part 2, on ovarian cancer. Stay tuned. We will get her scheduled in the winter/spring.



In the meantime, my notes:

Gynecological cancers occur in the uterus (most common, aka endometrial cancer), cervix, fallopian tubes, ovaries, peritoneal cavity, vulva and vagina.

In the US, there are ~65,000 new cases of uterine cancer  per year --> 12,000 deaths
In the US, there are ~19,000 new cases of ovarian cancer per year--> 12,000 deaths

Unfortunately, mortality from uterine/endometrial cancer is on the rise

Endometrial cancer, the most common type of gyn cancers, has a lifetime prevalence of 3%. Women are average age 60 years old at the time of diagnosis and, because endometrial cancer typically presents with post-menopausal bleeding, 75% are diagnosed in the early stage (stage I and II). When it does metastasize, endometrial cancer typically spreads via local lymphatics to the pelvic nodes and then to the aortic lymph nodes. 

Unfortunately, black women in this country are dying at disproportionate rates of endometrial cancer and are diagnosed with more aggressive cancers, younger than white women. 

Risk factors for endometrial cancer:
  • Obesity (endogenous unopposed estrogen). In fact, every 5 points of BMI increases your risk of being diagnosed with endometrial cancer by 50%. 
  • Chronic anovulation (obesity, PCOS)
  • Nulliparity, infertility, early menarche, late menopause
  • Exogenous unopposed estrogen (e.g. HRT without progesterone)
  • Tamoxifen (2x risk of uterine cancer)
  • Hereditary: these present earlier than sporadic cancers, more typically in non-obese younger women (<50 years old), including genetic syndromes like Lynch Syndrome and MLH1, 2, 6, etc. 
Risk reduction for endometrial cancer:
  • OCPs (combined)
  • Weight loss
  • Hysterectomy (offered to women with Lynch syndrome after age 45 or when fertility is accomplished)
NEJM: Association with race and BMI and endometrial cancer


Historically, endometrial cancers have been divided in two groups: Type 1-- or non-aggressive, more excess estrogen type--  and Type 2, more aggressive, poorly differentiated, frequently metastasize (40% of women with Type 2 have +LN at time of diagnosis. Increasingly, however, new molecular characterization studies are changing the way we think about and treat endometrial cancer and are being integrated into the categorization. This is because prognosis is variable depending on these molecular characteristics.

90% of women with endometrial cancer present with post-menopausal (PMP) uterine bleeding. All cases of PMP bleeding should be investigated but it is important to note that only 9-14% of women with PMP bleeding have cancer.  Abnormal uterine bleeding (AUB) in premenopausal women may present more like "intermenstrual" bleeding.

Evaluation of AUB:
1) Pelvic ultrasound: in PMP women, >4mm endometrial stripe necessitates and EMB. Of note, endometrial stripe thickness in premenopausal women is totally useless. Also, in someone with repeated bleeds, even a thin stripe should not prevent you from getting an EMB.
2) Endometrial biopsy (EMB)

Of note, Type 2 Endometrial cancers, an EMB has a 25% false negative rate.
If the patient has recurrent bleeding, even if they have a normal EMB, refer for hysteroscopy and D&C

Treatment of endometrial cancer:

1) Surgery
All gyn cancers (except for cervical, trophoblastic and vaginal) need surgery to be staged.
Surgery includes hysterectomy, bilateral salpingectomy, and lymph node assessment (sential LN mapping).

Stage I: cancer confined to uterus
Stage II: cancer extends to cervix
Stage III: LN involvement/ovaries/tubes
Stage IV: distant mets (omentum, lungs)

Robotic/minimal invasive surgery has best outcomes (but NOT in cervical cancer). With robot, conversion to open only happens 3% of the time (whereas its 20% of the time with typical surgery). This is really important for patients with elevated BMI who have a much better/easier recovery with minimally invasive surgery and way less bad outcomes.

2) Immunotherapy may be indicated for Stage III or IV or recurrent endometrial cancer 
Historically, chemo was used (Carboplatin and paclitaxil) but with new molecular studies, immunotherapy is showing increasing promise.

Fertility preservation in young women with endometrial cancer is important to many women! 14% are pre-menopausal at diagnosis and may not be done building their families. Low Grade (1) and non-invasive cancers (as determined by MRI) can sometimes be treated temporarily with high dose progesterone (either oral Megace 80mg BID or Mirena IUD). Informed consent is important. About 50% respond, but 20-30% will either progress or return. Some women hate the side effects of high dose progesterone, which include increased appetite, weight gain, and blood clots. 

***

On a final note, Dr. Delic recommends TWO passes with your EMB pipelle when doing an EMB to ensure you get a good amount of tissue. And without a tenaculum whenever possible. 

Stay tuned for the spring for Part 2: Ovarian cancers

Functional Medicine: when the symptoms don't match the textbook (Walton 11/1/2023)

 A recording of this presentation is available HERE.

***

Many thanks to senior resident, Dr. Rebecca Walton, for a thought-provoking Grand Rounds presentation this week on Functional Disorders. Such an important and challenging topic!

What are functional disorders, you ask? As the name implies, functional disorders is not one entity; it is an umbrella term for a group of syndromes including functional GI disorders (e.g. IBS), fibromyalgia, interstitial cystitis, chronic pelvic pain, chronic headaches, and chronic fatigue.

Functional disorders are all disorders that do not have an identifiable disease label (at least not in our world of allopathic medicine) and feature "normal labs" but negatively impact the functioning of the body. They tend to be chronic and some are relapsing.

Functional disorders can be challenging to treat, cause patients and providers frustration and distress, and are steeped in bias. Functional disorders have their roots in psychiatric disorders: Freud's conversion disorder, substitution of a somatic symptoms for a mental one; hysteria, medically unexplained symptoms in multiple organ systems, often tied to the presence of a uterus; and somatic symptom disorder, a significant focus on physical symptoms that results in major distress or problems functioning.

Functional disorders are common in primary care and impose an impressive healthcare burden:

  • Functional GI disorders represent 12% of the workload in primary care and 30% of outpatient GI consultations
  • Fibromyalgia affects 2-4% of the population, and can lead to up to 10 outpatient visits per person per year
  • Chronic headaches, one of the most common complains for neurological referral, are found in 4-5% of the population and results in, on average, 9 days of missed work per year
Patient groups who are already marginalized and at risk for poor outcomes are at highest risk for functional disorders; these include women, rural populations, less educated patients, lower SES, and those with a history of physical or sexual abuse. 

There are much higher rates of functional disorders in female-identified persons than male-identified: interstitial cystitis (14x), fibromyalgia (6x), IBS (2x), chronic headache (2-3x), TMJ (1.5x). Healthcare provider bias plays a role in diagnosis and treatment. 

Dr. Walton wants us to be careful not to tell patients that it is "all in their head". In fact, the second part of Dr. Walton's presentation was an effort to educate us on the many ways in which these functional disorders are not just in people's heads.

Chronic Pain and Central Sensitization
Central Sensitization is a state of persistent neuronal dysregulation that leads to allodynia (pain to non-painful stimuli), hyperalgesia (abnormally heightened pain), and widespread pain. These symptoms seem to occur due to increased responsiveness to stimuli by the CNS. This is super interesting!

Attributes of patients with central sensitization:
  • no objective tissue or laboratory findings
  • a genetic and/or environmental predisposition
  • stress as triggering or exacerbating symptoms
  • dysfunctional pain or sensory processing
  • do not respond to therapies used for pain (e.g. acetaminophen)
See the image below for a description of how this plays out pathophysiologically in both the central and peripheral nervous systems:

IBS
Moving on to IBS. There are many theories as to how IBS comes about. Many have biologic plausibility and evolving understanding. These include post-infectious IBS (e.g. after a bad gastroenteritis with shigella, salmonella and e coli), autoimmune theories (including anti vinculin and anti-CdtB antibodies), and dysbiosis. Did you know, for example, that people with IBS tend to have higher levels of bacteroides in their guts compared to healthy controls who tend to have higher levels of prevotella?

SIBO, which is characterized by abnormal bacterial growth in the small intestine (most of our gut microbiome resides in our LARGE intestine), can occur due to IBS and other motility issues. Common symptoms include bloating, flatulence, abdominal pain, and diarrhea, weakness, and fatigue. 

There is absolutely bidirectional communication between our gut and our CNS. Animal studies have shown the extreme stress leads to lifelong alterations in gut microbiome and the HPA access. Also CBT can not only increase serotonin levels in the gut but also decrease bacteroides (crazy cooL!!)

There is little argument that early trauma and adverse childhood events (ACEs) have a huge influence on IBS, and prevention of these events is key in preventing leaky gut, microbiome changes, and lifelong GI upset. 
***

I will leave you with Dr. Walton's own takeaways
The brain matters, but it isn’t the whole picture
Those who are already facing healthcare discrimination are prone to having functional disorders and thus experience further neglect
There is ongoing research into these syndromes, and I hope that soon the “lack of biomedical markers” changes
Even without biomedical markers, these symptoms matter
Here is a list of references and further reading provided by Dr. Walton:
  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479361/

  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695775/

  3. https://www.ncbi.nlm.nih.gov/books/NBK532253/

  4. https://pubmed.ncbi.nlm.nih.gov/33479067/

  5. https://pubmed.ncbi.nlm.nih.gov/32294476/

  6. https://www.sciencedirect.com/science/article/abs/pii/S0049017222001111?via%3Dihub

  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040193/

  8. https://pubmed.ncbi.nlm.nih.gov/35156215/

  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902126/

  10. https://www.sciencedirect.com/science/article/abs/pii/S0049017207001473?via%3Dihub

  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268359/

  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708662/

  13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430499/

  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039952/

  15. https://pubmed.ncbi.nlm.nih.gov/22180058/

  16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860136/

  17. https://pubmed.ncbi.nlm.nih.gov/34847963/

  18. https://pubmed.ncbi.nlm.nih.gov/28888668/

  19. https://www.nature.com/articles/mp201644

  20. https://pubmed.ncbi.nlm.nih.gov/33268363/

  21. https://www.nature.com/articles/mp201644

  22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507713/


Climate Change in Medicine (Murphy, 4/24/2024)

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