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Do New Internists Who Received Better Scores on Residency Assessments Provide Better Patient Care?

BACKGROUND AND PURPOSE:

  • US internal medicine residents are assessed with milestone assessments and American Board of Internal Medicine (ABIM) internal medicine certification examination
  • The relationship between resident graduates’ scores on these two assessment metrics and their patients’ outcomes is not well understood
  • Gray et al. (JAMA Network Open, 2024) examined the association between physicians’ milestone ratings and certification examination scores and hospital outcomes for their patients

METHODS:

  • Retrospective cohort analysis
  • Population
    • Hospitalists completing training in US hospitals in 2016 to 2018
    • Caring for Medicare fee-for-service beneficiaries during hospitalizations in 2017 to 2019
  • Exposures
    • Certification examination score quartile
    • Milestone ratings
      • Overall core competency rating, defined as
        • Mean of the end of residency milestone subcompetency ratings (Low | Medium | High)
      • Knowledge core competency measure (same categories)
  • Study design
    • Overall core competency defined as
      • Mean of the end of residency milestone subcompetency ratings (Low | Medium | High)
    • Analyses accounted for hospital fixed effects
    • Adjustments: Patient characteristics | Physician years of experience | Year
  • Primary outcomes
    • Patient 7-day mortality and readmission rates
  • Secondary outcomes
    • Patient 30-day mortality and readmission rates | Length of stay | Subspecialist consultation frequency

RESULTS:

  • 455,120 hospitalizations
    • Median patient age: 79 years (IQR, 73 to 86) | Female: 56.5%
  • A high vs low overall or knowledge milestone core competency rating was not associated with any of the outcome measures
    • E.g. 7.-day mortality
      • 2.7% nonsignificant increase among high competency rated physicians (95% CI, −5.2 to 10.6) | P=0.51
  • Top vs bottom examination score quartile was associated with differences in patients’ outcomes
    • 7-day mortality rates
      • 8.0% reduction among top scoring physicians (95% CI, –13.0 to –3.1) | P=0.002
    • 7-day readmission rates
      • 9.3% reduction among top scoring physicians (95% CI, _6.7 to –0.4) | P=0.03
  • Top examination score quartile was also associated with more consultations
    • 2.4% more among top scoring physicians (95% CI, 0.8 to 3.9) | P<0.003
  • There was no association between length of stay or 30-day readmission rates

CONCLUSION:

  • For recent graduates of internal medicine residency programs, higher certification examination score was associated with improved patient outcomes
  • Residency milestone ratings, on the other hand, were not associated with differences in patient outcomes
  • The authors state

Among newly trained hospitalists, certification examination score, but not residency milestone ratings, was associated with improved outcomes among hospitalized Medicare beneficiaries, suggesting that formally incorporating standardized examinations into residency ratings might improve their validity

Learn More – Primary Sources:

Associations of Internal Medicine Residency Milestone Ratings and Certification Examination Scores With Patient Outcomes

Consider Inherited MEN1 for Familial Hyperparathyroidism and Other Endocrine Tumors

SUMMARY:

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition involving predisposition to various types of endocrine tumors. Although most MEN1-related tumors do not become malignant, they can cause significant morbidity due to the excess secretion of various hormones. Primary hyperparathyroidism causing hypercalcemia due to parathyroid tumors is the most common clinical manifestation in individuals with MEN1.

Tumor Risks

  • Parathyroid tumors: up to 90% by age 50
  • Pituitary tumors: 30%
  • Pancreatic neuroendocrine tumors and other endocrine tumors of the GEP tract: 75%
  • Thymic, bronchial, and gastric carcinoid tumors: 3 to 10%
  • Adrenocortical tumors: 20 to 73%
  • Non-endocrine tumors:
    • Facial angiofibromas: 85%
    • Collagenomas: 70%
    • Lipomas: 30%
    • Meningiomas: 8%
    • Leiomyomas: 30 to 40%

Genetics 

Symptoms/Diagnosis

  • More than 20 types of endocrine and non-endocrine tumors are associated with MEN1
    • Symptoms vary based on the type of hormones produced by each individual tumor
  • The first symptom is often hyperparathyroidism, presenting as asymptomatic hypercalcemia in the 20’s
  • Diagnosis is confirmed for any of the following:
    • An individual with more than one MEN1-related tumor
    • An individual with an MEN1-related tumor and a family history of MEN1
    • Any individual with a pathogenic variant in the MEN1 gene
  • Targeted genetic testing for the familial MEN1 variant is appropriate when a family member has been diagnosed with MEN1

Management

  • Referral to cancer genetics and endocrinology for counseling and management
  • Follow-up generally includes
    • Regular surveillance for new tumors with tumor-associated markers such as calcium, PTH, insulin, growth hormone, and prolactin
    • MRI or CAT scans to follow the size, number, location, and growth of tumors or to identify new ones
    • Treatment of hyperparathyroidism with parathyroidectomy
    • Some hormone-secreting adenomas are able to be treated with specific medications (eg. somatostatin analogs for GH-secreting adenomas); others require surgical excision
    • Prophylactic thymectomy may be considered

Note: Because early medical interventions can prevent severe morbidity and mortality, MEN1 is on the ACMG list of secondary findings | The ACMG document on reporting such findings makes the following recommendations

  • In the course of genetic testing for research or clinical care, the laboratory may identify variants in genes unrelated to the initial indication for testing, but nevertheless may have important health implications
  • Results of such secondary findings should be communicated to the individuals who may benefit from this knowledge
  • An individual can ‘opt out’ of receiving secondary findings

KEY POINTS:

  • MEN1 is associated with a broad spectrum of endocrine tumors, particularly
    • Parathyroid (typically multiglandular)
    • Anterior pituitary
    • Pancreatic neuroendocrine
  • Consider MEN1 and referral to genetics for patients who present with
    • Multiple MEN1-related tumors in the same individual
    • Gastrinoma
    • Parathyroid adenoma before age 30 or involving multiple glands
  • Management includes thorough surveillance with biomarkers associated with endocrine tumors and medical or surgical treatments for specific tumors as needed
    • Recommended surveillance begins as early as age 5, thus, genetic testing should be offered for at-risk children

Learn More – Primary Sources:

ACMG and NSGC Joint Practice Guidelines: Referral Indications for Cancer Predisposition Assessment

NIH: Multiple Endocrine Neoplasia Type 1

GeneReviews – Multiple Endocrine Neoplasia type 1

Locate a Genetic Counselor or Genetics Services: 

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC 

Genetic Services Locator-CAGC 

Positive Prenatal Carrier Screening Result for Hemophilia: Obstetric Management Considerations

SUMMARY:

Hemophilia A and B are inherited bleeding disorders caused by a deficiency of clotting factor VIII (hemophilia A) or IX (hemophilia B) activity. Because they are X-linked, these conditions primarily affect males. Female carriers have varying levels of clotting factor activity and are at risk for excessive bleeding. In pregnancy, factor VIII levels rise which may reduce the risk of bleeding in hemophilia A carriers. There are special considerations for the care of hemophilia A and B carriers in pregnancy and childbirth due to potential bleeding in both the mother and the neonate.

Background

  • Hemophilia A affects 1 in 6,500 males | Hemophilia B affects 1 in 30,000 males
  • Symptoms in affected males range from mild to severe
    • Prolonged bleeding
    • Poor healing after injury or trauma
    • Intracranial hemorrhage
    • Spontaneous bleeding in joints
  • Genetic female (46, XX) hemophilia carriers are at risk for
    • Spontaneous bruising
    • Menorrhagia
    • Delayed healing after major trauma
    • Postpartum hemorrhage
  • Hemophilia A and B are included in the ACMG’s “Tier 3” recommendations for carrier screening, which should be offered to all patients who are pregnant or are considering pregnancy (see ‘Related ObG Topics’ below)

Genetics

  • Hemophilia A and B are X-linked conditions
  • Associated with pathogenic variants in the F8 (Hemophilia A) and F9 (Hemophilia B) genes
  • For the offspring of female carriers
    • Males have a 50% chance to be affected
    • Females have a 50% chance to be carriers
  • All daughters of affected males will be carriers

Diagnosis and Carrier Testing

  • Diagnosis in affected males is established by clotting factor assays and may include genetic testing
    • Hemophilia A: deficiency of clotting factor VIII with normal von Willibrands factor
    • Hemophilia B: deficiency of clotting factor IX
  • Genetic testing of F8 or F9 is required to confirm carrier status in at-risk females
    • An affected male should be the first person tested in a family in order to guide testing of other family members
    • Normal factor levels do not rule out carrier status or risk for bleeding complications in at-risk females

Pregnancy Management for Hemophilia Carriers

  • Factor VIII or IX clotting activity should be measured
    • Prior to pregnancy
    • Before any diagnostic procedures
    • In the third trimester prior to delivery
  • Hemophilia carriers are at an increased risk for bleeding with procedures or after spontaneous pregnancy loss, as well as during delivery and postpartum
    • Prophylactic treatment with desmopressin or clotting factor concentrate is recommended prior to any uterine evacuation procedure
  • Carrier status is not associated with increased risk of miscarriage
  • Iron deficiency should be corrected early in pregnancy
  • Referral for consultation with a high-risk obstetrician/hematologist and consideration of a multidisciplinary team at delivery if indicated
  • Counsel about risk to offspring
    • If fetus is male (by ultrasound or NIPS), offer prenatal diagnosis for familial hemophilia variant via CVS or amniocentesis
  • External cephalic version is not recommended

Delivery Management

  • Use of neuraxial anesthesia and mode of delivery should include
    • Input from multidisciplinary team
    • Shared patient decision making for obstetrical care
  • Plan for administration of clotting factor concentrate (VIII or IX) at delivery if third trimester factor levels are <50%
    • TXA or DDAVP (used to raise factor VIII levels) if clinically indicated
  • The use of thromboprophylaxis (if indicated) should be discussed with hematology service
  • Continue clotting factor replacement at least 5 days postpartum

If Fetus Affected Male or Prenatal Diagnosis Was Declined

  • No fetal scalp electrodes or fetal blood sampling
  • Consider unassisted vaginal delivery (no forceps or vacuum extractions) or planned cesarean delivery
  • Collect cord blood at delivery for factor level and/or genetic testing
  • Avoid circumcision until hemophilia A is excluded
  • Postpartum vaccines
    • Should be administered unless not recommended by hematology service  
    • Prolonged pressure should be given to the injection site

KEY POINTS:

  • Hemophilia carriers are at increased risk for hemorrhage during delivery and postpartum
  • Delivery should occur in a medical center with available support from a multidisciplinary team
  • Male infants of hemophilia carriers have a 50% chance of being affected
  • Neonates should be treated as if they are at risk for bleeding until affected status is ruled out

Learn More – Primary Sources:

GeneReviews—Hemophilia A

GeneReviews—Hemophilia B

National Hemophilia Foundation Medical and Scientific Advisory Counsel (MASAC): Guidelines for Pregnancy and Perinatal Management of Women with Inherited Bleeding Disorders and Carriers of Hemophilia A or B

Locate a Genetic Counselor or Genetics Services: 

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC 

Genetic Services Locator-CAGC 

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

COVID-19 Rebound: No Increased Risk with Antiviral Use

SUMMARY:

COVID-19 Rebound occurs between 2 – 8 days after the initial illness recovery and is described by the CDC as a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative. High profile cases of COVID-19 rebound following the use of antiviral medications has led to growing concern that the use of these agents may prolong illness or paradoxically worsen outcomes. Two recent studies, one comparing symptomatic and viral rebound in untreated outpatients, and another examining differences in rebound rates of hospitalized patients, have shown reassuring results, with no increased risk of rebound due to antiviral use, and no increased morbidity or mortality associated with COVID-19 rebound.

KEY POINTS:

Annals of Internal Medicine

  • Outpatients with COVID-19
    • Retrospective analysis of previous RCT
    • 563 patients in the placebo arm were followed for symptom and viral (laboratory) rebound
    • 13 different symptoms recorded daily during the study
    • Patients underwent RNA testing on days 0 to 14, and then again on days 21 and 28
    • Median onset of symptom rebound was on day 11 and occurred in 26% of participants
    • Viral rebound occurred in 31% of participants
    • Only 3% of participants had BOTH viral and symptom rebound
    • Most rebounds were transient

The Lancet Infectious Diseases

  • Hospitalized patients with COVID-19 during the omicron wave in Hong Kong  
    • Retrospective study | Viral rebound and composite outcomes were assessed
    • 4,592 patients who did not initially require supplemental oxygen
    • 563 received Molnupiravir (Lagevrio)| 242 received Nirmatrelvir–Ritonavir (Paxlovid) | 3787 did not receive any oral antiviral treatment (control group)
    • Viral burden rebound was observed in 4 to 7% of hospitalized patients and there was no statistically significant difference between each group
    • Viral rebound was more common in certain groups: Younger adults (age 18–65 years) | Fully Vaccinated | Prior poor health | Immunocompromised | Patients on corticosteroids
    • Viral rebound was not associated with increased adverse clinical outcomes
    • Researchers in conclusion suspect that COVID-19 rebound may be due to the natural biphasic course of the disease or that the course of antiviral medications may not be adequate for certain patient populations (e.g., the immunocompromised)

Learn More – Primary Sources

ACP: COVID-19 rebound occurs with or without antivirals, doesn’t affect outcomes, studies find

Annals of Internal Medicine: Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection

The Lancet ID: Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study

EMAS Position Statement: Use of Vitamin D Among Postmenopausal Women

SUMMARY:

EMAS, an international society that promotes health in women and men at midlife and beyond, has produced a position statement targeting the use of vitamin D in postmenopausal women. The literature suggests “an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality.” The document includes an extensive literature review.

‘Vitamin D’ Overview

What is it?

  • Group of lipophilic hormones
  • Regulates calcium homeostasis via kidney, gastrointestinal tract, skeleton and parathyroid
  • Critical for skeletal health but impacts multiple tissues
  • Two major forms
    • Vitamin D2 (ergocalciferol)
    • Vitamin D3 (cholecalciferol)
      • Major source through cutaneous synthesis through exposure to sunlight
      • Small amount from animal diet (fatty fish, eggs and milk)

Measurement

  • Vitamin D status: Measure serum 25-hydroxyvitamin D levels
    • <20 ng/ml (<50 nmol/l): Vitamin D deficiency
    • <10 ng/ml (<25 nmol/l): Severe Vitamin D deficiency

Vitamin D Deficiency and Associated Health Outcomes

  • Skeletal
    • Increased fracture risk
  • Menopausal Symptomatology  
    • Evidence is inconsistent
    • Some studies have demonstrated increased risk
      • Hot flashes | Depression | Sexual dysfunction | Sleep disturbances
  • Cardiac
  • Cancer
    • Increased risk for cancers: Colorectal | Lung | Breast
    • Overall and cancer-specific mortality rates are increased in postmenopausal women
    • No evidence for ovarian or other gyn cancers
  • Infections and Inflammation
    • Increased risk for respiratory infection
    • Increased risk for autoimmune disorders

Vitamin D Supplementation Recommendations for Postmenopausal Women

Skeletal Health

  • No vitamin D deficiency or low fracture risk
    • No evidence to support vitamin D supplementation
  • Vitamin D deficiency with osteoporosis and/or high fracture risk (FRAX model)
    • Vitamin D: 2000 to 4000 IU (4000 to 6000 IU in obese patients)
    • Calcium: 1000 to 1200 mg of calcium (dietary or supplements)
    • Encourage Vitamin D and calcium use for minimum 3 to 5 years
    • Check vitamin D levels 3 to 6 months with target above 20 ng/ml (<50 nmol/l)

Menopausal Symptomatology

  • Vitamin D supplementation is not recommended to improve menopausal symptoms

Cardiovascular Disease

  • No effect of vitamin D supplementation on decreasing CVD risk

Cancer

  • No effect of vitamin D supplementation on cancer incidence although some studies identified a small reduction in cancer-related mortality

Infections and Inflammation

  • Vitamin D supplementation may ‘modestly’ decrease the risk for acute respiratory tract infections including COVID-19
  • Concerns regarding study design such as “heterogeneity in design, duration, population and vitamin D dosage among studies must be underscored”

KEY POINTS:

  • Typical daily dose of 1000 to 1200 mg of calcium is not associated with increased risk for cardiovascular disease or nephrolithiasis
  • Studies on vitamin D supplementation have significant limitations due to heterogeneity regarding dose, inclusion of calcium and baseline vitamin D status
  • More research needed to
    • Discriminate between vitamin D replacement and supplementation
    • Determine the need for universal vitamin D screening in postmenopausal women

Learn More – Primary Sources:

EMAS position statement: Vitamin D and menopausal health

IDSA Clinical Practice Guidelines: Seasonal Influenza

Summary:

Seasonal influenza is a respiratory illness caused by the Influenza A and B viruses. Virus outbreaks typically occur in the winter season, and symptoms can range from mild to life threatening. While most patients recover from uncomplicated influenza, the illness can progress to severe disease and death. Young children, older adults, pregnant and postpartum patients, and those with certain medical conditions such as immunosuppression, are at highest risk of complications. While influenza rates declined markedly during the COVID-19 pandemic, the virus returned aggressively in 2022 with unprecedented rates of infection compared to recent years. The cornerstone of influenza treatment remains prevention with yearly vaccination. The IDSA last released a clinical practice guideline in 2018 to assist with diagnosis, treatment, chemoprophylaxis and outbreak management.

Diagnosis:

Signs and Symptoms

  • Commonly: Fever | Myalgia | Non-productive cough
  • Also typical: Sore Throat | Rhinorrhea | Headache | Nausea | Weakness
  • Complications: Pneumonia | Respiratory failure | ARDS | Multiorgan failure | Sepsis | Liver inflammation| Rhabdomyolysis | Myocarditis | Encephalitis | AKI
  • Laboratory, physical exam, and imaging findings are not specific for the flu and generally do not clarify diagnosis in the absence of flu testing

Outpatient Testing

  • Clinicians should preform outpatient testing for the flu during an influenza outbreak in patients who:
    • Are high risk (e.g. older age, immunocompromise, pregnant) and present with acute respiratory illness or flu-like symptoms if testing will alter clinical management
    • Develop acute respiratory symptoms, with or without fever, in addition to exacerbation of chronic medical conditions or known complication of the flu (e.g. pneumonia) and testing will alter clinical management
    • Are not high risk but present with flu-like illness, pneumonia or respiratory illness and are likely to be discharged or reduce the use of antibiotics in the setting of a positive flu test, or otherwise alter clinical management
  • Clinicians can consider outpatient testing for the flu in the absence of high local flu activity if a patient presents with acute respiratory symptoms, prioritizing those with immunocompromise or high-risk conditions

Inpatient Testing

  • Clinicians should preform inpatient testing for the flu during an influenza outbreak in patients who:
    • Are being admitted with acute respiratory illness, with or without fever
    • Are being admitted for acute worsening of chronic cardiopulmonary disease (e.g. asthma, CHF, COPD)
    • Are being admitted with respiratory symptoms, with or without fever, in the setting of immunocompromise or high-risk comorbidities
    • Develop respiratory symptoms while hospitalized in the absence of a clear alternative diagnosis
  • Clinicians should test for the flu during low local influenza activity if the patient is being admitted for acute respiratory illness and has: Known exposure to the flu | Exposure to a respiratory illness outbreak of uncertain cause | Traveled from an area with high flu activity
  • Clinicians can consider testing for influenza in patients who present with acute febrile respiratory illness and are at high risk of complications, if testing will alter management

Modes of Testing

  • Clinicians should obtain upper respiratory specimens for testing as soon as symptoms develop, and preferably within 4 days to improve yield and accuracy
  • Nasopharyngeal specimens are preferred
    • Endotracheal aspirate or BAL specimens can be used for inpatients on mechanical ventilation        
  • Outpatient testing:
    • Rapid molecular assays (e.g. nucleic acid amplification tests) are preferred over rapid diagnostic tests
  • Inpatient testing:
    • Reverse-transcription polymerase chain reaction (RT-PCR) or other molecular assays are preferred
    • RT-PCR targeting multiple respiratory pathogens should be used in immunocompromised patients or in immunocompetent patient’s if it will influence care
  • Consider resistance testing for:
    • Patients who develop influenza infection while on chemoprophylaxis
    • Immunosuppressed patients or patients with severe disease with evidence of ongoing disease after 7 to 10 days
    • Patients who received subtherapeutic doses of NAI therapy

Treatment:

  • Start antiviral therapy as soon as possible in all patients with positive flu testing who meet the following criteria:
    • Inpatients hospitalized for influenza infection, regardless of duration
    • Outpatients with severe or progressive illness, regardless of duration
    • Outpatients at high risk for complications
    • Children < 2 years old and adults ≥ 65 years old
    • Pregnant patients and those within 2 weeks postpartum
  • Consider antiviral therapy in all patients not at risk for complications who the meet the following criteria:
    • Outpatients who present within 48 hours of symptom onset
    • Outpatients with symptoms who are household contacts of those at high risk of complications
    • Outpatient symptomatic healthcare workers who care for patients
      who are at high risk of developing complications if infected with influenza
  • Antiviral therapy is with: Oral oseltamivir | Inhaled Zanamivir | Single dose of intravenous Peramivir
  • Oral and inhaled therapies should be given for 5 days, but course may be extended for immunosuppressed and hospitalized patients
  • Further work up for alternative causes and antibiotics for bacterial coinfection should be added for patients who: Present with severe disease | Improve but then deteriorate | Fail to improve after 3 to 5 days of antiviral therapy

Chemoprophylaxis:

  • Oral and inhaled NAIs are the preferred drugs for chemoprophylaxis
  • Post exposure prophylaxis should be given with 48 hours of exposure and last for 7 days since last contact with known exposure
  • If a patient on chemoprophylaxis tests positive for the flu they should be switched to antiviral treatment dosing

Preexposure Chemoprophylaxis

  • Preexposure chemoprophylaxis for the length of flu season may be considered for:
    • Patients at high risk of flu complications who are unable to be vaccinated (e.g., the severely immunosuppressed) or unlikely to respond to vaccines (e.g., recent stem cell transplant patients)
  • Short term preexposure chemoprophylaxis and administration of inactivated flu vaccine may be considered for:
    • Patients at high risk for flu complications in whom the vaccine is expected to be effective during times of high flu activity 

Postexposure Chemoprophylaxis

  • Consider giving postexposure chemoprophylaxis to Asymptomatic high-risk patients who are unable to be adequately vaccinated with a household exposure
  • Consider giving postexposure chemoprophylaxis and the inactivated influenza vaccine to unvaccinated patients with household members at high risk for complications

Institutional Outbreak Control:

  • Outbreak control measures include: Chemoprophylaxis for residents/patients for 14 days and at least 7 days after last symptom onset of last identified case| Surveillance testing | Testing for all patients who develop respiratory symptoms | Empiric treatment dose antiviral therapy for patients who develop symptoms prior to test results

Primary Sources – Learn More:

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa

CDC Flu Information for Health Professionals

Annals of Internal Medicine: Influenza