RSV Vaccines (Teng - 9/20/23)

 A recording of this presentation can be viewed HERE.

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Many thanks to Dr. Angelica Teng for a breaking-news Grand Rounds presentation on the brand new RSV vaccines that are rolling out just in time for the 2023-24 RSV season. A recording  of her presentation is available at the link above. 

My written notes below:

RSV, as you may already know, is an RNA virus that infects the lungs and leads to lower respiratory tract infections (LRTIs). It is the most common cause of LRTIs in infants and toddlers, leading to 2.1 million clinic visits per year in children <5 years old. RSV has less impact on adults, but does lead to 60-160K hospitalizations per year in adults >65.

Here is the link to an excellent video demonstrating classic findings in RSV bronchiolitis: https://www.youtube.com/watch?v=oOrty5PfhTY

RSV tends to be seasonal, with a typical RSV illnesses  starting in early fall (usually November in CA), peaking in winter (February), and then tapering off in early spring. It spreads mostly via droplets (cough) and can live up to six hours on hard surfaces

source: CDC

Here is the good news!

There are THREE new RSV vaccines approved in 2023

Abrysvo 

Arexvy

Nirsevimab 

There are THREE groups of patients we should consider for the new RSV vaccinations

1) Adults over 60 (Abrysvo or Arexvy)

2) Infants <8 months (Nirsevimab)

3) Pregnant women between 32-36 weeks EGA (Abrysvo)

Adults > 60: Abrysvo and Arexvy are recombinant vaccinations, each made slightly differently with inactivated proteins. Both were FDA approved in May 2023 for adults over 60. In RCTs, both vaccines were found to reduce the risk of RSV-lower respiratory tract infection by 82-89% in older adults in the first year after receiving the vaccine.  They are similar to one another, except for the inclusion of an adjuvant in Abrysvo formulation.

Infants < 8 months: In July 2023, the FDA approved a new monoclonal antibody called Nirsevimab for infants ages 1 week to 8 months during RSV season. Monoclonal antibody therapy is not technically a vaccine but can provide an infusion of prefabricated antibodies, giving temporary protection for up to five months to newly developing pediatric immune systems. In a clinical trial, nirsevimab was ~77% effective against both hospitalizations and cases of RSV requiring a doctor’s visit. The CDC is  recommending that all infants <8 months during RSV season  receive Nirsevimab and additionally children ages 8-24 months with high risk conditions (e.g. prematurity, congenital heart disease, cystic fibrosis, neuromuscular disorders).

Pregnant patients 32-36 weeks: Finally, in August of 2023, the FDA approved Abrysvo as the first-ever maternal vaccine intended to help protect newborns against RSV. It was studied in late third trimester (32-36 week EGA) with the idea that protective IgG from the RSV vaccine moves across the placenta and grant protection for newborn infants.  The vaccine was found to be 82% effective at protecting infants from severe illness during the three months after birth and waned to 69% effective over six months during a double-blind study. Of note, ACOG has not yet put out a formal statement about this vaccine. This is expected by late October.

A few key notes to consider:

1) Unlike a more traditional age-based recommendation for vaccination in adults >60, the CDC recommends for Abrexvy and Abrysvo that the decision to vaccinate be a shared decision between the physician and the patient. Consideration should be based on risk, and certain conditions are associated with higher risk of severe disease (e.g. lung disease, renal disease, nursing home and long term care facility residency). 

2) The RSV for pregnant woman is in no way intended to protect the mom from RSV infection and complications. It is purely meant for the infant.

3) There was a non-statistically significant outcome of low birth weight in women who received vaccination in the third trimester.

4) While there is no official statement, it is believed that guidelines will ultimately recommend that parents choose between the maternal vaccine at 32-36 weeks and the nirsevimab for infants. There is no current belief that children will need both. But this could change.

5) The only absolute contraindication to vaccination with Abrexvy or Abrysvo is anaphylaxis to any of its components.

6) It is okay to administer the RSV vaccine at the same time as either the flu or the COVID vaccine (local recommendation is to do 2 but not all 3 at the same time)

7) It is okay to administer the RSV vaccine when someone has mild cold symptoms

8) The monoclonal antibody nirsevimab is though to have a 5 month protective duration

9) It is unclear when/whether nirsevimab will replace palivizumab (synagis), the old very expensive monthly monoclonal ab that is currently used to treat high risk preemie babies during RSV season. It is likely that a single dose of nirsevimab will be more cost effective.

summary chart, source: A Teng

Oncologic Emergencies (Kanaan - 9/13/23)

 A recording of this presentation can be viewed HERE.

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Thank you to local SMGR Oncologist, Dr. Zeyad Kanaan, for an action-packed presentation this week on Oncologic Emergencies. His presentation focused on five major emergencies-- SVC syndrome, Tumor Lysis syndrome, Hypercalcemia of malignancy, Acute malignant cord compression, and Leukostasis. Sprinkled among the five oncologic emergencies was a necklace of pearls for the primary care provider caring for cancer patients. 

Here are a few general pearls:

• Primary care providers diagnose cancers; oncologists treat them. 
• Oncologists cannot begin treatment of any cancer without a biopsy (i.e. "tissue is the issue")
• It can be anxiety-producing to carry a patient through the process of a cancer discovery and arranging the appropriate plan for biopsy. 
• Oncologists can help guide us through this part, even if they are not yet managing the cancer.
• All cancer symptoms (e.g. chemo-related nausea and vomiting) are graded 0-5 (1 is mild, 5 is most severe). 
• Most people with Gr 1 &2 symptoms can be managed as outpatient. 
• Patients with Grade 3 sx should be sent to the ER. 
• Gr 4 is life-threatening (often means ICU).
• Aggressive cancers, by definition, replicate and grow rapidly, which means they also tend to respond quickly to treatments. 
• BUT aggressive cancers can also can come back quickly
• All oncologic emergencies require an urgent management plan, a plan for the next few days (less urgent). 
• Ultimate management is treatment of the underlying cancer.

SVC Syndrome

SVC syndrome is caused by obstruction of the SVC, leading to facial edema and sometimes arm edema. The most common cause of SVC syndrome is cancer (particularly lung cancer, lymphoma, germ cell tumors). But there are other less common things that can obstruct the SVC. 

Medial and perihilar masses are more likely to be squamous cell cancer and small cell lung cancers.

If you see "central necrosis" on imaging it means that the cancer is very aggressive and is growing too fast for its own blood supply.

As mentioned above, SVC Syndrome is graded 0-5. Grade 3 symptoms require ER/hospital management and definitive treatment of the underlying cancer, which means urgent initiation of chemotherapy.

Grade 4 requires a stent (rarely done).

SVC syndrome, regardless of Grade, is a bad prognostic sign. 

Tumor Lysis Syndrome (TLS)

TLS is an oncologic emergency caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. TLS is more common in solid tumors. TLS can lead to AKI, cardiac arrythmias and even seizures. TLS can be diagnosed either clinically or via lab tests (lab abnormalities: hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia). TLS can occur spontaneously with aggressive cancers and/or can also occur with initiation of chemotherapy.

Treatment of TLS:

1) Aggressive Hydration (1-2L bolus, followed by 200-300ml/hr crystalloids)

2) Urine alkalization (via bicarbonate drip)

3) Allopurinol -- allopurinol is a preventive drug for TLS, does nothing to an already elevated uric acid and cannot help urgently. Given PO. Dosed 100mg/m2 or 10mg/kg/day (divided q8h). Often started in solid tumors prior to chemo initiation.  Dose needs to be reduced by 50% with renal failure.

4) Rasburicase -- considered a rescue agent, very potent cleavage of uric acid, $$$, very effective within 30 minutes. Usually requires only one dose (3mg, which is half of the manufacturer recommended dose), check uric acid daily. Can repeat but hardly ever necessary.

Both allopurinol and rasburicase should be started together in cases of TLS. Of note, both allopurinol and rasburicase can (and should) be given prophylactically in cases where TLS is highly anticipated. 

Hypercalcemia of Malignancy

"moans, bones, and psychic overtones"

Lytic cancers that metastasize to bone are most likely to cause hypercalcemia. These include, most commonly breast cancer, multiple myeloma, lymphomas, and leukemias. Prostate cancer, e.g. while often spreading to bones, is less likely to be lytic.

Treatment of Hypercalcemia:

1) Aggressive hydration

2) Bisphosphonates (+Denosumab) take a little longer than calcitonin. Works in ~2 days. 

3) Calcitonin: is the acute treatment of choice, will drop the calcium quickly, but Ca will rise again quickly if otherwise left untreated

Once Ca starts dropping, goal is to treat the underlying cause.

Don't forget to check labs to be sure it's hypercalcemia of malignancy. A low intact PTH and elevated PTHrP is most consistent with malignant hypercalcemia. HyperCa in setting of elevated vitamin D levels, more often seen in lymphoma, is more likely to respond to steroids.

Mild hyper Ca (<12): oral hydration, treat the underlying cause

Mod hyper Ca (12-14): need IV hydration

Severe hyper Ca (>14): IVF, calcitonin, bisphosphonates, Hemodialysis can be helpful if Ca>18, desnosumab if renal failure. prednisone if elevated Vitamin D

In the end, once again you must treat the underlying cause. 

Acute Malignant Cord Compression

This is a true oncologic emergency.

The thoracic vertebrae is the most common spinal place for cancer to go (lumber spine is the next most common). The cancer spot may actually be very small, but it is the edema leading to the cord compression and symptoms of pain and weakness. A patient's pre-intervention neurologic status influences a patient's chance of regaining function

Hours can matter in terms of neurological preservation, so do not be afraid to start steroids. Primary care and ED's job is to 1) start steroids -- dexamethasone 4mg q6 hours (total 16 mg/day) and 2) call the neurosurgeon. 

The vasogenic edema will respond quickly to the steroids. 

Leukostasis = hyperviscosity (of Waldenstrom)

Most common symptoms: bleeding, blurred vision, headache, vertigo

Treatment is IVF to decrease viscosity

Check serum viscosity (>4 is significant)

Check IgM level 

Plasmapheresis is very effective

Local patients with acute leukemia are admitted for urgent chemo (either to Alta Bates or Sacramento)
Goal is to treat leukostasis (WBC<100K), end organ effects (e.g. CAD) and leukemia all at once

Thriving or Surviving: The Connection Between Chronic Stress, Chronic Disease, and Social Determinants of Health (Deol - 9/6/23)

 A recording of this presentation can be viewed HERE. 

***

Thank you to Dr. Navi Deol, PGY3, who gave an excellent presentation this week titled Thriving or Surviving: the intersection between chronic stress, chronic disease, and the social determinants of health. Each of the items in the subtitle is a HUGE topic, and Dr. Deol was able to weave them together beautifully and powerfully. I encourage you to watch yourself.

Image from https://www.glasbergen.com/stress-management-cartoons/cartoons/page/3

If you prefer the written word, see my notes:

• stress: how certain stimuli (stressors) affect a person's mind, body and spirit
• stress response: how our body reacts normal, a normal physiologic and psychologic response to stressors
• some stressors evoke positive emotions and can be beneficial (eustress); some evoke negative emotions and cause problems (distress)

A certain amount of stress is important and necessary to generate optimum productivity and performance, but too much stress can lead to anxiety, overload, and burnout (see image below of the Yerke's-Dodson Law).

Yerke's-Dodson Law, image fromhttps://stock.adobe.com/

Stress causes physiologic changes in our bodies. We are all familiar with the autonomic nervous system, which responds to acute stress with the sympathetic "fight or flight" and the balancing parasympathetic "rest and digest", but what happens when the stress response is constantly being activated? 

Image from: https://www.backtothebooknutrition.com/adrenal-fatigue-hpa-axis-dysregulation/

The answer is that our long-term stress response leads to a cascade of responses that make us more vulnerable to chronic diseases.

A 2019 study published in the Journal of ACC looked at the link between SES factors such as low income and higher crime on MACEs (cardiac death, myocardial infarction, unstable angina, cerebrovascular accident, peripheral artery disease with revascularization, or heart failure). This study suggests that a biological pathway contributes to this link, involving, in series, higher amygdala activation, increased activation of the bone marrow (with release of inflammatory cells), which in turn leads to increased atherosclerotic inflammation and its atherothrombotic manifestations

Patients were categorized according to quartiles of their neighborhood median income and neighborhood crime rates.  Amygdalar activity (A) and arterial inflammation (B) were lower as neighborhood median income increased. Amygdalar activity was higher (C) and arterial inflammation trended toward an increase (D) as neighborhood crime rate increased. One image from that study is seen below. For more information, click the link above or see the study link below the image.

https://www.jacc.org/doi/10.1016/j.jacc.2019.04.042

Chronic diseases are non-communicable illnesses that persist for long periods of time and result from a combination of genetic, environmental, and psychological factors. These include cardiovascular disease (e.g. hypertension, coronary artery disease, and strokes), metabolic disorders (e.g. type 2 diabetes and obesity), mental health issues (e.g. depression, generalized anxiety disorder), and substance use disorders.

We know that inflammatory cascades play an important (and damaging role) in the onset and progression of chronic disease. While acute inflammation is technically "good" for us because it cleans up disease states in our body, chronic inflammation is bad bad bad.

Financial stress

Are you aware that money (finances and inflation) is a tremendous source of chronic stress for a shocking number of US adults. A 2022 survey found that 57% of US adults reported not having enough money to pay for essential items; 43% reported that they are not saving enough, and 56% had to make different choices due to their lack of money. 

Violent stress

Mass shootings, gun violence, and crime are also sources of tremendous chronic stress, particularly for people living in poverty and disproportionately for BIPOC people. 

Social Determinants

This leads us directly into a discussion of the importance of the Social determinants of health (SDOH), the conditions into which individuals are born, grow, live, work and age. There is an unsurprising link between chronic stress and the SDOH. These include your neighborhood and built environment, healthcare, education, economic stability, and social and community context. 

image from Healthy People 2030

If this is news to you, check out this video about how zip codes influences an individual's health: A Tale of Two Zip codes.

And for something even closer to home, check our our local Sonoma County data on how the SDOH vary based on zip code in the report titled A Portrait of Sonoma County 2021 Update, available here:  https://upstreaminvestments.org/impact-make-a-change/portrait-of-sonoma-county

https://upstreaminvestments.org/impact-make-a-change/portrait-of-sonoma-county

What can we do about all this stress?

Dr. Deol encouraged us to take a deep breath and realize that we cannot tackle these complex issues alone. First, we must acknowledge the deep-rooted history of structural and systemic racism, oppression, and discrimination that have led to health inequities that require interventions at multiple levels to reduce disparities. 

When caring for individuals, we should be careful about using the term "non-compliance" and better recognize the daily barriers our patients face due to their own SDOH. In our communities, we should be screening for SDOH and get to know and refer to appropriate community services. And at the state level, she encouraged us to support CAFP Bill AB85, which requires SDOH screening and provides resources and education for providers in referring to community health workers. 

More information for AB85 can be found HERE. 

Eating Disorders in Teens (Buckelew - 8/30/23)

A recording of this presentation can be viewed HERE.

Thank you to Dr. Sara Buckelew, Director of the UCSF Eating Disorder Program, who gave an excellent presentation this week on Eating Disorders in Adolescents.  As usual, a recording of the presentation is available at the link above.

Below, my notes:

Anorexia Nervosa is the most lethal of all DSM-5 diagnoses. This is a diagnoses found in all sizes and weights. Denial of symptoms and ambivalence for change are often part of the disease. Clinicians must be aware of our weight bias and the sigma associated with talking about weight. 

There are a range of eating disorders (ED), including:

• Anorexia (including atypical anorexia, in which patient has all symptoms of anorexia but is not underweight)
• Bulimia
• Binge eating
• Avoidant/restrictive food intake (ARFID)

Without question, the COVID Pandemic exacerbated eating disorders. It was a perfect storm of increased risk (increased media, disruption of school and life routines, and social isolation) and lower protective factors and access to care (including increased food insecurity, challenges to seeing primary care, etc.). This storm then led to a huge treatment bottle neck with long wait times and patients presenting increasingly ill to care.

Key Point: Early intervention is important in ED, as a shorter duration of illness is associated with improved outcomes. 

The SCOFF Questionnaire is a screening instrument designed to suggest "likely cases". A positive SCOFF does not give an adolescent a diagnosis of ED, but if positive, suspicion for ED should be elevated and early intervention should be considered

S "Do you make yourself SICK because you feel uncomfortably full?"

C "Do you worry you have lost CONTROL  over how much you eat?"

O "Have you recently lost ONE stone (15 pounds) in a 3 month period?"

F "Do you consider your self FAT?"

F "Would you say that FOOD dominates your life?"

Answering YES to at least 2 of the above is a positive SCOFF screen

Key Point: Avoidant Restrictive Food Intake Disorder (ARFID), new in the DSM-5 about 10 years ago is a more heterozygous group of ED in which there is no body image component to the restriction.

The diagnosis of ARFID concerning weight patterns, concerning behaviors: avoidance of meals, excessive exercise. The question that excludes ARFID from you ddx during ED assessment is the following: Are your eating habits related to you thinking you are too big or too heavy? 

There are 3 subtypes of ARFID: 

1) Avoidant: sensory, textures

2) Aversive: fear-based  (usually pain, nausea)

3) Restrictive: general disinterest in eating

Medical Evaluation for ED includes:

1. Height/weight in a gown (all weights are blinded), watch for % change in body mass (not just total pounds lost or gained)
2. Growth curves
3. Vital signs: temperature, orthostatic BP and pulse
4. Physical exam
5. EKG/lab work, looking for signs of malnutrition, this can be falsely reassuring to providers and patients and families because are not uncommonly normal. Normal labs does not mean all okay. Use the UA look at specific gravity for water-logging (pts do this to add weight), the ESR typically abnormally low, and hormones can revert to prepubertal levels.

UCSF Admission Criteria for ED

• Bradycardia HR<50 when awake, HR<45 when asleep
• Orthostasis
• Hypotension <90/45
• Hypothermia T<36C or T<96F
• Other: BMI<75%, acute food refusal, electrolyte abnormalities

Inpatient treatment of ED involves feeding patients.

Key Point: Food is Medicine in management of hospitalized patients with ED

3 meals + 3 snacks per day

2000kCal/day

No food choices allowed except cow's vs. soy milk

Of note 2000kCal/day is safe and effective without risk of refeeding syndrome

Diet is advanced daily 200-300kcal/day

If cannot reach 2000kcal, Boost Plus or other supplement is added

In rare cases, an NGT

In order to minimize refeeding, check electrolytes (including Ca, Mg, Phos) 

Physical Activity is also limited in the hospital

Key Point: You can see cognitive changes with severe malnutrition

These cognitive changes include slowed thinking, obsessions/distortion, short-term memory loss, and difficulty with basic decision-making

Treatment of Eating Disorders has not changed a lot in the last two decades.

Family-Based Treatment is a mainstay of Anorexia treatment

It is basically parent coaching, empowering parents to not allow the ED to be "in charge"

Avoid blaming the child for the ED, separate the ED from the child

Involves eating meals with a therapist, who observes what is happening within a family at mealtime

The first session is often dubbed "the funeral session" which is meant to be a funeral for the ED

This type of therapy is often extremely uncomfortable, many families will concern, therapists are not warm and welcoming, and may be actively disliked by patients and families.

Medications are generally not helpful for Anorexia

You can rx SSRI if preceding comorbid anxiety/depression, but SSRIs do not help with weight loss and  don't help with relapse

Off label use of atypical antipsychotic (e.g. low dose olanzapine) has some low-quality evidence. 

Treatment for Bulimia Nervosa is slightly different

Therapies with some evidence include CBT, DBT, and FBT

Meds: SSRI may help

For ARFID there are even fewer evidence-based treatments

Evolving evidence for psychotherapy including ERP (exposure and response prevention), CBT, FBT

Meds can increase appetite, which cam be helpful (meds with some evidence: mirtazapine periactin)

OT/dietician

What is new in ED treatments?

Telehealth for ED has increased in the wake of COVID; there is still much to learn about the value of telehealth in ED management. It certainly can increase access particularly for those who are geographically isolated or lack transportation.

There are ongoing studies for psychedelic assisted therapies

Dr. Buckelew ended her presentation with some powerful debunking of the "SWAG Myth" --  that is the skinny white affluent girl being the only version of anorexia. She reminded us that ED can be seen (and are increasing) in men, older adults, BIPOC populations, adults with intellectual disabilities, etc. And while higher SES does predict higher rates of treatment seeking, this does not mean that they are the only ones who suffer from ED. There is also a lack of diversity in the ED Workforce.

And some final pearls from Dr. Buckelew: