The Stark (Law) Reality of Self-Referral in Medicine

As of 1992, the Stark law contains provisions that govern physician self-referral for Medicare and Medicaid patients. The law is named for United States Congressman Pete Stark, who sponsored the initial bill in 1989.

What is Physician Self-Referral?

Physician self-referral is the practice of physicians referring a patient to a medical facility in which they or an immediate family member have a financial interest. It could be ownership, investment, or a structured compensation arrangement. Critics of the practice allege an inherent conflict of interest exists because the physicians can benefit from the referral. They believe that such arrangements may encourage over-utilization of services that drives up health care costs. They also assert that it limits or eliminates competition from other providers. On the other hand, in medically underserved areas, a physician may be providing a service that otherwise is not readily available.

What Constitutes a Referral?

A referral includes a request by a physician for an item or service payable under Medicare or Medicaid (including the request by a physician for consultation with another physician and any test or procedure ordered or performed by such other physician), or a request by a physician for the establishment of a plan of care that includes the provision of Designated Health Services (DHS). The DHS list can be found at the CMS website and is extensive, including ultrasound and other imaging services as well as outpatient pharmacy and physical and occupational therapy.

Are there exceptions?

The law contains numerous exceptions that add to its complexities. For example, the referral-source physicians who are members of a physician group practice can refer a patient for imaging services or other DHS to be provided within the group practice without violating Stark. Qualifying as a “group practice” under Stark enables physicians to take advantage of certain exceptions, including the physician services exception and the in-office ancillary services exception. Group practices that provide DHS should review Stark’s group practice requirements to make sure they qualify under the definition, in order to protect their referrals under the in-office ancillary services exception.

Penalties for violating Stark can be quite harsh.  They include denial of payment, refund of payment, imposition of a $15,000 per service civil monetary penalty and imposition of a $100,000 civil monetary penalty for each arrangement considered to be a circumvention scheme.

Learn More – Primary Sources:

Fraud & Abuse Laws | Office of Inspector General | Government Oversight | U.S. Department of Health and Human Services (hhs.gov)

Becker’s Hospital Review: 15 Things to Know About Stark Law

Stark Law Website

Training community hospital residents for a future in the hospital’s community – what program directors should know about Stark Laws

AAFP: The Stark Truth About the Stark Law: Part I

CMS: Code List for Certain Designated Health Services (DHS)

Diagnosis and Management of Primary Hypothyroidism

• Summary
• Key Points
  • Definitions
  • Clinical Presentation
  • To Screen or Not to Screen?
  • Diagnosis
  • Pharmacologic Therapy
  • When to Consider Treating Subclinical Hypothyroidism
  • Monitoring Treatment and Endpoints
  • When to Consult an Endocrinologist
  • Other Considerations
• References

SUMMARY:

Hypothyroidism is a common and easily treatable condition encountered in primary care. The most common cause of hypothyroidism worldwide is iodine deficiency, particularly in developing nations; in the US, it is chronic autoimmune (Hashimoto’s) thyroiditis. Hypothyroidism is 5 to 10 times more common in women and is often associated with other autoimmune disorders (type I diabetes, Addison’s disease, lupus). In many cases it is iatrogenic, caused by radioactive iodine therapy or surgery for hyperthyroidism or thyroid cancer, or drugs such as lithium, amiodarone, interferon alpha, or tyrosine kinase inhibitors. The American Thyroid Association (ATA), in conjunction with the American Association of Clinical Endocrinologists (AACE), offers a useful practice guideline for managing this prevalent endocrine disorder. Of note, the following summary applies to primary hypothyroidism and does not address management of central hypothyroidism or hypothyroidism in pregnancy, which are considered separate topics.

KEY POINTS:

Definitions

• Overt hypothyroidism
  • High TSH (usually above 10 mU/L)
  • Low free T4
• Subclinical hypothyroidism
  • TSH above the upper reference range (4.5 to 10 mU/L)
  • Normal free T4

Clinical Presentation 

• Dry skin
• Sensitive to cold
• Fatigue
• Muscle cramps
• Voice changes
• Constipation
• Weight gain/obesity
• Thinning hair
• Impaired Memory
• Irregular menses
• Depression
• Findings associated with severe hypothyroidism
  • Carpal tunnel syndrome | Sleep apnea | Pituitary hyperplasia (causing hyperprolactinemia and associated galactorrhea) | Hyponatremia

To Screen or Not to Screen?

Controversial—Recommendations Vary by Organization

• ATA: Screen all adults every 5 years beginning at age 35
• AACE: Screen “older” patients (age not specified)
• USPSTF does not recommend routine screening
• However, there is strong evidence to support “case finding” (screening in selected populations)
  • Autoimmune disease | Pernicious anemia | First-degree relative with autoimmune thyroid disease | History of radiation to neck or thyroid surgery | Abnormal thyroid exam | Psychiatric disorder | Taking amiodarone or lithium

• Other disorders that can be used to support hypothyroid screening include
  • Adrenal insufficiency | Alopecia | Anemia | Cardiac dysrhythmia | Changes in skin texture | Congestive heart failure | Constipation | Dementia | Diabetes mellitus, type 1 | Dysmenorrhea and other menstrual disorders | Hypercholesterolemia | Hypertension | Mixed hyperlipidemia | Malaise and fatigue | Myopathy, unspecified | Prolonged QT interval | Vitiligo | Weight gain

Diagnosis 

Check serum TSH and free T4

• Multiple clinical scoring systems exist but are not recommended for diagnosis
• Not necessary or recommended to check T3 (total or free)
• Mild TSH elevation common in older people and does not necessarily represent subclinical hypothyroidism
• Do not check TSH in hospitalized patients unless suspicion for primary thyroid process (e.g. myxedema coma)

When to measure Thyroid peroxidase antibody test (TPOAb)

• Subclinical hypothyroidism | Nodular thyroid | Recurrent miscarriage
  • Patients with subclinical hypothyroidism and TPOAb+ are almost twice as likely to progress to overt hypothyroidism (annual risk 4.3% vs 2.6%)

Pharmacologic Therapy

• Levothyroxine (Synthroid)
  • Alternative therapies
    • Combination levothyroxine/L-triiodothyronine | Desiccated thyroid hormone
  • ‘Thyroid enhancing’ dietary supplements e.g. iodine in iodine sufficient areas and nutraceuticals are NOT recommended or endorsed
• Starting dose
  • Overt hypothyroidism: 1.7 mg/kg
  • Young, healthy adults: Full replacement dose
  • Patients 50 to 60 years old
    • Without cardiovascular disease: 50 mcg
    • With cardiovascular disease: 12.5 to 25 mcg, and monitor for development of angina
  • Subclinical hypothyroidism: start with 25 to 75 mcg
• When to take levothyroxine
  • 30 to 60 minutes before breakfast or
  • Bedtime 4 hours after last meal
  • Take with water and avoid other medications that interfere with absorption (e.g. calcium carbonate, iron supplements, aluminum containing antacids)

When to Consider Treating Subclinical Hypothyroidism

• Symptoms consistent with hypothyroidism
• TPOAb+
• Cardiovascular disease/heart failure
• Improvement in atherosclerotic risk factors (lipids, endothelial function) with treatment

Monitoring Treatment and Endpoints

• Initially: Check TSH and Free T4 four to eight weeks after initiation or change in dose
• Once therapeutic dose achieved: Check TSH at 6 months and then yearly thereafter
• If patient has initiated or stopped a drug that interferes with absorption or metabolism of levothyroxine
  • Check TSH and Free T4 four to eight weeks
  • Examples: Estrogen or androgen | Carbamazepine | Phenobarbital | Phenytoin | Rifampin | Sertraline | Tyrosine kinase inhibitors
• Avoid overtreatment
  • Happens in 20% of patients treated with levothyroxine
  • Adverse consequences include cardiovascular (angina, atrial fibrillation), skeletal (osteoporosis), psychiatric
• Therapeutic endpoint: Normalization of TSH and Free T4

Normalization of a variety of clinical and metabolic endpoints including resting heart rate, serum cholesterol, anxiety level, sleep pattern, and menstrual cycle abnormalities…are further confirmatory findings that patients have been restored to a euthyroid state

• Therapeutic goal:  TSH 0.45 to 4.12

When to Consult an Endocrinologist

• Children/infants
• Difficulty achieving or maintaining euthyroid state
• Pregnancy or women planning conception
• Cardiac disease
• Structural thyroid abnormality (goiter, nodule)
• Comorbid endocrine disease
• Unusual constellation of thyroid function test results

Other Considerations

Do Not Use Thyroid Hormone to Treat

• Symptoms of hypothyroidism without biochemical confirmation (TSH/free T4)
• Obesity
• Depression

Adrenal Insufficiency

• Often associated with concurrent hypothyroidism
• Treat adrenal insufficiency with steroids first, then reassess thyroid function

Interruptions in Treatment

• If <6 weeks with no intervening cardiac event or significant weight loss, can resume full dose
• Preop setting
  • Hypothyroidism affects perioperative outcomes
  • Levothyroxine should be given preoperatively

Patients taking Biotin

• Hold the supplement for ≥2 days prior to TFT’s especially if taking more than 10 mg

Factors that Alter Thyroxine and Triiodothyronine Binding in Serum

• Increased T4-binding globulin (TBG)
  • Inherited | Pregnancy| Estrogens| Hepatitis| Porphyria| Heroin| Methadone| Mitotane| 5-FU| SERMS (e.g., tamoxifen, raloxifene)

• Decreased TBG
  • Inherited| Androgens| Anabolic steroids| Glucocorticoids| Severe Illness| Hepatic failure| Nephrosis| Nicotinic acid| L-Asparaginase

• Binding inhibitors
  • Salicylates| Furosemide| Free fatty acids| Phenytoin| Carbamazepine| NSAIDs (variable, transient)| Heparin

References:

Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association

USPSTF Update: Screening for Abdominal Aortic Aneurysm

SUMMARY:

In December 2019, the USPSTF updated the 2014 recommendations for screening asymptomatic adults for abdominal aortic aneurysm (AAA), based on 4 large population-based clinical trials

A newly added feature is the importance of family history (first degree relative) of AAA as a risk factor for screening decision in women

USPSTF recommends the following

Men 65 to 75 years who have ever smoked

Recommendation Grade B (offer or provide this service)

• One-time screening ultrasound
  • Magnitude of net benefit of screening is moderate | Harms are small to moderate
• Ever smoker “commonly defined as ≥100 cigarettes”

Men 65 to 75 years who have never smoked

Recommendation Grade C (offer or provide this service for selected patients depending on individual circumstances)  

• Selectively offer one-time screening ultrasound rather than routinely to all men in this age group
• Magnitude of net benefit of screening is small | Harms are small to moderate
• Consider
  • Medical history | Family history | Other Risk Factors | Personal values

Women who have never smoked and have no family history of AAA

Recommendation Grade D (discourage the use of this service) 

• “Adequate evidence” that there is no benefit to screening ultrasound| Harms are small to moderate
• Moderate certainty that harms outweigh benefits

Women 65 to 75 years who have ever smoked or have a family history of AAA

I Statement (if the service is offered, patients should understand the uncertainty about the balance of benefits and harms)

• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined
  • Abdominal aortic aneurysm – there may be greater potential to prevent serious adverse outcomes
    • Compared to men, women with small AAAs have an increased risk of rupture
    • Approximately 25% to 33% of women have AAA with a diameter <5.5 cm surgical threshold at the time of rupture
  • However, women also experience higher risk of harms
    • Higher operative mortality | Longer hospital stay | Higher readmission rate       

KEY POINTS:

• AAA is defined as aortic enlargement with a diameter of ≥3.0 cm
• Due to the low uptake of screening in the USA the prevalence is unclear
• Recommendations are stratified by “men” and “women”
  • Benefit vs risk estimates are driven by biologic sex (ie, male/female) rather than gender identity
  • Persons should consider their sex at birth to determine which recommendation best applies to them
• Risk factors
  • Older age
  • Male sex
  • Smoking
  • First degree relative with AAA
  • Other vascular aneurysms | CAD | CAD | Cerebrovascular disease | Atherosclerosis | Hypercholesterolemia | Hypertension
• Protective factors
  • African American race | Hispanic ethnicity | Asian ethnicity | Diabetes  

Note: Above are risk factors for AAA | Risk factors for actual rupture include older age, female, smoking, and elevated BP                                             

Ultrasound Screening for AAA

• Screening test is a conventional abdominal duplex ultrasonography
• Screening intervals
  • 3 to 4 cm diameter: Reimage once a year
  • 4 to 5 cm diameter:  Reimage every 6 months
  • Enlargement > 0.5 cm within 6 months should be considered at high risk for rupture

Treatment for AAA

• Balance of risk of rupture vs operative mortality
• Most common approach is endovascular aneurysm repair (EVAR)
• Elective repair
  • Men: Diameter ≥5.5 cm
  • Women: 5.0 to 5.4 cm (Society for Vascular Surgery)

Recommendations by Other Organizations

ACC and AHA

• Recommend one-time screening for AAA with physical examination and ultrasonography for
  • Men 65 to 75 years who have ever smoked
  • Men ≥60 years are the sibling or offspring of a person with AAA
• Do not recommend screening for
  • AAA in men who have never smoked
  • Women

The Society for Vascular Surgery

• Recommends one-time ultrasonography screening for
  • All men and women 65 to 75 years with a history of tobacco use
  • Men ≥55 years with a family history of AAA
  • Women ≥65 years who have smoked or have a family history of AAA 

The American College of Preventive Medicine

• Recommends one-time screening for
  • Men 65 to 75 years who have ever smoked
• Does not recommend
  • Routine screening in women

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Learn More – Primary Sources:

Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force

Primary Care Screening for Abdominal Aortic Aneurysm Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Open versus endovascular repair of abdominal aortic aneurysm

USPSTF Releases Final Recommendation On Ovarian Cancer Screening

SUMMARY:

The USPSTF has posted its final recommendation regarding ovarian cancer screening on February 13, 2018. The Task Force is standing by previous guidance and considers the evidence sufficient to recommend against routine screening with transvaginal ultrasound and/or CA-125 for ovarian cancer.

KEY POINTS:

Reference Population

• Asymptomatic women
• This recommendation does NOT refer to women who are at increased risk for ovarian cancer, for example personal or family risk of the following:
  • Hereditary Breast Ovarian Syndrome (BRCA1 / BRCA2)
  • Lynch Syndrome
  • Li-Fraumeni Syndrome
  • Peutz-Jeghers Syndrome
  • Family History of Ovarian Cancer

Benefits

• Transvaginal ultrasound and/or CA-125 measurements do not reduce deaths due to ovarian cancer

Harms

• Excessive false positives in asymptomatic women lead to unnecessary surgical interventions
  • False positive rates range from 4.2% to 44.2%
• Magnitude of harm rated from moderate to substantial depending on the risk of the unnecessary surgery
  • Percentage of women who went for unnecessary surgeries range from 0.2% to 3.2%
• Insufficient evidence to determine if there are psychological harms as well

Other Professional Guidelines

ACOG

• Does not recommend screening for ovarian cancer in low-risk, asymptomatic women
• Evaluation of high-risk women may include transvaginal ultrasound and CA-125 testing, in addition to physical examination

ACS

• Does not recommend screening for ovarian cancer in average-risk women

ACR

• Does not recommend screening for ovarian cancer in average-risk women

AAFP

• Recommends against screening for ovarian cancer in asymptomatic women (consistent with USPSTF)

Conclusions

• There is at least moderate certainty that the harms of screening for ovarian cancer outweigh the benefits
• There is adequate evidence that screening for ovarian cancer does not reduce ovarian cancer mortality
• Based on 3 large good-quality studies, there does not appear to be any benefit in ovarian cancer mortality from annual screening in asymptomatic, non-high risk women
• The USPSTF assessed studies that included CA-125
  • Whether CA-125 was used as a single cut-off measure or within the framework of an age-adujsted algorithm, there was no difference in ovarian cancer mortality
• Based on the above, the Draft Recommendation is a ‘D’ Grade
  • The USPSTF recommends against screening for ovarian cancer in asymptomatic women

Learn More – Primary Sources:

Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement

Prophylactic Mastectomy and BRCA – Risk Reduction and Guidelines

CLINICAL ACTIONS:

A recent large prospective cohort study (see ‘Related ObG Project’ below) demonstrated that by age 80, the cumulative breast cancer risk for BRCA1 mutation carriers is 72% (95% CI, 65% to 79%) and 69% (95% CI, 61% to 77%) for BRCA2.  In the context of women with high risk for breast cancer, consider the following:

• Bilateral risk-reducing mastectomy (RRM) is an option for women at high risk for breast cancer
• High-risk includes carriers of deleterious mutations in BRCA1, BRCA2 and other genes associated with high risk of breast cancer such as TP53, PTEN, CH1 or STK11
• Prior to surgery, obtain the following
  • Multidisciplinary consultations with genetic counseling, surgical reconstructive and oncology teams
  • Clinical breast exam
  • Bilateral mammogram if not performed within past 6 months
• If no findings on clinical examination or imaging
  • Women may choose to undergo RRM with or without immediate reconstruction
  • Remove all breast tissue (total mastectomy)
  • Axillary node assessment has limited utility at the time of RRM and only required if cancer identified on pathology
• If patient at risk for occult primary cancer (abnormal imaging or positive family history without MRI imaging available)
  • Sentinel note biopsy may be performed for axillary staging

SYNOPSIS:

There are other management options aside from RRM for women who are at high risk for breast cancer due to pathogenic variants in BRCA and related genes.  Chemoprevention using risk reducing medications such as tamoxifen and raloxifene may be appropriate. Selection of these agents depends on age, race, breast cancer risk and history of hysterectomy. Aromatase inhibitors have also been investigated for use as risk reducing agents.  However, these medications are more effective at preventing ER+ disease which is more highly associated with BRCA2 compared to BRCA1.  Surveillance programs using imaging studies are also available.  Monitoring with MRI is not a preventative strategy but rather an approach that can be used for early detection.

KEY POINTS:

• RRM may not reduce the risk of all-cause mortality but can reduce the risk of breast cancer in BRCA carriers by 85 to 100%
• NCCN and ACOG recommend that RRM be offered to women who are BRCA mutation carriers to reduce the risk of breast cancer
• Shared decision making should include general health and life expectancy

Women at High Risk but Not BRCA Mutation Carriers

According to the National Cancer Institute, other women at high risk for breast cancer, aside from BRCA mutation carriers, who might consider risk reducing mastectomy include (see ‘Primary Sources – Learn More’ below)

Those with a strong family history of breast cancer (such as having a mother, sister, and/or daughter who was diagnosed with bilateral breast cancer or with breast cancer before age 50 years or having multiple family members with breast or ovarian cancer) 

Those with lobular carcinoma in situ (LCIS) plus a family history of breast cancer 

Those who have had radiation therapy to the chest (including the breasts) before the age of 30 years 

Learn More – Primary Sources:

ACOG Practice Bulletin 182: Hereditary Breast and Ovarian Cancer Syndrome

NCCN Guidelines For Detection, Prevention, & Risk Reduction: Breast Cancer Risk Reduction

NCI: Surgery to Reduce the Risk of Breast Cancer

USPSTF Guidance on Screening for Lung Cancer

SUMMARY:

The current USPSTF guidelines recommend annual cancer screening using low-dose CT. Lung cancer has a poor prognosis and is the third most common type of non-skin cancer in the United States. Lung cancer is the leading cause of cancer death in men and in women. The USPSTF recommends (Grade B – offer or provide this service)

Screen annually for lung cancer with low-dose computed tomography

Discontinue screening when the patient has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery

Population

Adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit smoking within the past 15 years

Risk Factors for Lung Cancer

• Most important factors
  • Age: Incidence relatively low in individuals under 50 and increases with age, especially >60 years
  • Total cumulative exposure to tobacco smoke
  • Years since quitting smoking
• Additional risk factors
  • Environmental exposures
  • Prior radiation therapy
  • Other (noncancer) lung diseases
  • Family history

Screening Tests

• Low-dose CT
  • High sensitivity and acceptable specificity in high-risk populations persons

Balance of Benefits vs Harms

• Annual screening for lung cancer with low-dose CT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking

KEY POINTS:

Evidence of Benefit for low-dose CT

• Large RCT – National Lung Screening Trial (NLST) is cited as the study demonstrating clinical utility
• Participants
  • 55 to 74 years
  • Cigarette smoking histories of ≥30 or more pack-years and who, if they are former smokers, have quit within the last 15 years
• Results: Low-dose CT
  • Reduces lung cancer mortality by 20% (95% CI, 6.8 to 26.7; P = .004)
  • Reduces all-cause mortality by 6.7% (95% CI, 1.2 to 13.6; P = .02)
  • Updated analysis: Lung cancer reduction of 16%

• Harms
  • Primarily harm is risk for false-positive low-dose CT
  • Majority of positive results do not lead to a diagnosis and up to 96% of positive exams may not result in cancer detection
  • In a high-quality screening program, further imaging can resolve most, although not all, false-positive results
  • Overdiagnosis can be up to 30% depending on screening population per heterogenous meta-analysis (NCI)
  • Radiation Exposure from CT 

The NELSON Trial (NEJM, 2020)

• The NELSON RTC demonstrated that at 10 years of follow-up, screening with volume CT imaging
  • Reduced lung-cancer mortality by 24% among men and by 33% among women in high-risk populations
  • Reduced overdiagnosis to 10%
  • Improved PPV to 43.5%

Calculating Pack-Years

• Calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked
  • 1 pack = 20 cigarettes
• Examples
  • 1 pack (20 cigarettes) per day for 1 year = 1 pack-year
  • 2 packs (40 cigarettes) per day for half a year = 1 pack-year
  • ½ pack (10 cigarettes) per day for 20 years = 10 pack-years

Recommendations of Other Professional Societies

• American Society of Clinical Oncology
  • Annual screening
  • People age 55 to 74 who have smoked for 30 pack-years or more | Also recommended for those age 55 to 74 who have quit within the past 15 years
  • CT screening not recommended: Smoked for less than 30 pack-years | Younger than 55 or older than 74 | Quit smoking more than 15 years ago | Have a serious condition that could affect cancer treatment or shorten a person’s life

• The American Association for Thoracic Surgery
  • Annual screening
  • Age 55 to 79 years with ≥30 pack-year smoking history
  • Long-term lung cancer survivors who have completed 4 years of surveillance without recurrence, and who can tolerate lung cancer treatment in order to detect second primary lung cancer until the age of 79
  • Age 50 to 79 years with a 20 pack-year smoking history and additional comorbidity that produces a cumulative risk of developing lung cancer ≥5% in 5 years
• American College of Chest Physicians
  • Annual screening
  • Age 55 to 77 years with ≥30 pack-year smoking history and either continue to smoke or have quit within the past 15 years
• NCCN
  • Annual screening Age 55 to 77 with ≥30 pack-year smoking history and smoking cessation <15 years
  • Age ≥50 years and ≥20 pack-year history of smoking and have at least 1 additional risk factor for lung cancer
• American Cancer Society
  • Annual screening
  • Age 55 to 74 years, currently smoke or have quit within the past 15 years, and
  • Have at least a 30-pack-year smoking history

Learn More – Primary Sources:

USPSTF: Lung Cancer Screening

Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening: The National Lung Screening Trial

NEJM: Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

NCI: Lung Cancer Screening (PDQ®)–Health Professional Version

Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers

NCI: Pack-Year Definition

Screening for Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Lung Cancer Screening Guidelines: Most Commonly Referenced Lung Cancer Screening Guidelines (Society of Thoracic Surgeons)

NCCN Lung Cancer Screening

ASCO Screening Information for Lung Cancer

Professional Guidelines: Colorectal Cancer Screening

CLINICAL ACTIONS:

Colorectal cancer (CRC) is the third most common new site and cause of cancer death in the US. Screening is recommended for all patients 50 to 75 years of age, based on USPSTF guidance. There are currently multiple screening strategies available and professional guidelines may differ in approach.

The USPSTF recommends the following

Who to Screen

• Asymptomatic adults ≥50 years
• Average risk of CRC
  • No family history of known genetic disorders predisposing to high lifetime risk of CRC (e.g., Lynch syndrome or familial adenomatous polyposis)
  • Note: An individual with a family history of multiple relatives with CRC, especially at an early age, may benefit from a genetic risk assessment for a heritable cancer syndrome
  • No personal history of IBD, previous adenomatous polyp, or previous CRC
  • No personal history of getting radiation to the abdomen or pelvic area to treat a prior cancer (ACS)
• Along with the above, the American Cancer Society considers a personal history of radiation cancer treatment to the abdomen/pelvic area or a family history of CRC to be above-average risk factors for CRC

When to Screen

• Adults 50 to 75 years
  • Screen for CRC starting at age 50
  • Grade A recommendation | Offer or provide this screening
• Adults 76 to 85 years
  • Grade C recommendation | Offer or provide this service for selected patients depending on individual circumstances
  • Adults in this age group who have never been screened for colorectal cancer are more likely to benefit
  • Screening most appropriate for the following
    • Healthy enough to undergo CRC treatment if cancer detected
    • No comorbid conditions that would significantly limit their life expectancy

Screening Tests

Stool-Based Tests

Tests other than colonoscopies that can be used for screening of average risk patients

• Guaiac based Fecal Occult Blood test (gFOBT)
  • Annual
  • Requires dietary restrictions and three stool samples
  • Does not require bowel preparation, anesthesia, transportation
• Fecal Immunochemical Test (FIT)
  • Frequency: Annual
  • Single stool sample
  • Does not require bowel preparation, anesthesia, transportation
• FIT- DNA/stool DNA test ‘Cologuard’ (identifies altered DNA and/or blood in stool)
  • Every 1 to 3 years
  • Single stool sample

Direct Visualization Tests

• Colonoscopy
  • Every 10 years
  • Requires bowel preparation, anesthesia or sedation and transportation to and from the screening examination
• CT colonography (radiographic)
  • Every 5 years
  • Requires bowel preparation, no anesthesia or transportation to and from the screening examination
• Flexible sigmoidoscopy (not commonly available)
  • Every 5 years
  • Only visualizes rectum and lower third of colon
  • Availability decreasing
• Flexible sigmoidoscopy with annual FIT (not commonly available)
  • Every 10 years
  • Only visualizes rectum and lower third of colon

Note: Colorectal cancer almost always develops from precancerous polyps in the colon or rectum | Direct visualization test only screening test that can remove precancerous lesions.

KEY POINTS:

Additional Guidelines

U.S. Multi-Society Task Force on Colorectal Cancer Recommendations (2017)

Note: Represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy

• Begin screening at age 50 | In African Americans begin at age 45
• Discontinue at age 75 or <10 years of life expectancy
• Test selection
  • First-tier: Colonoscopy every 10 years or annual FIT
  • Second-tier for patients who refuse colonoscopy: CT colonography every 5 years or FIT-fecal DNA every 3 years or Flexible sigmoidoscopy every 5 to 10
  • Third-tier for patients who refuse second tier: Capsule colonoscopy every 5 years

Note: Can consider sequential approach with colonoscopy the test of choice and FIT for those who decline colonoscopy | Colonoscopy or FIT when multiple options are presented

Canadian Guidelines (2016)

Recommendations apply to adults aged ≥50 years who are not at high risk for colorectal cancer (CRC)

• 50 to 59 years
  • gFOBT or FIT every two years or
  • Flexible sigmoidoscopy every 10 years
• 60 to 74 years
  • gFOBT or FIT every two years or
  • Flexible sigmoidoscopy every 10 years
• ≥75 years
  • Recommend against screening

Note: Recommend not using colonoscopy

American Cancer Society (2018)

• 45 to 75 years
  • Patients in good health with life expectancy of more than 10 years
  • Screen with stool-based or direct visualization test
• 76 to 85 years
  • Base screening decision on
    • Personal preferences | Life expectancy | Overall health | Prior screening history
• 85 years
  • Should no longer get CRC screening

ACP (2019)

• 50 to 75 years
  • Screen average-risk adults for CRC
• Suggested screening tests and intervals based on discussion of “benefits, harms, costs, availability, frequency and patient preferences”
  • FIT or high-sensitivity guaiac-based fecal occult blood testing: Every 2 years
  • Colonoscopy: Every 10 years
  • Flexible sigmoidoscopy every 10 years plus FIT every 2 years
• >75 years or life expectancy ≤ 10 years
  • Discontinue screening

Learn More – Primary Sources:

JAMA: Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement

USPSTF Final Recommendation Statement: Colorectal Cancer: Screening

JAMA Clinical Guidelines Synopsis: Colorectal Cancer Screening

Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer

Canadian Task Force on Preventive Health Care

American Cancer Society Guideline for Colorectal Cancer Screening

Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians

The relationship between Exercise and Heart Disease – Does Genetics Matter?

BACKGROUND AND PURPOSE:

• Previous studies on fitness and cardiovascular disease (CVD) tend to rely on small sample sets and rely on self-reporting
• Tikkanen et al. (Circulation 2018) determined the effectiveness of physical activity in preventing cardiovascular disease in those predisposed due to genetic factors

METHODS:

• Large longitudinal cohort study
  • Individuals 40 to 69 years of age enrolled in the UK Biobank cohort study (2006 to 2010)
  • Includes detailed health assessments and collection of blood, urine, and saliva samples
  • Participants agreed to have their future health/disease events followed and monitored
• Data collected include grip strength, objective and subjective physical activity, and cardiorespiratory fitness along with cardiovascular events and all-cause death
• Associations were further examined in individuals with different genetic burden by stratifying individuals based on their genetic risk score for coronary heart disease and atrial fibrillation
• Disease risk was compared between individuals in different tertiles (data broken down in to 3 parts each containing a 3^rd of the population) of fitness, physical activity, and genetic risk
• Statistical analysis was based using hazard ratio (HR)

RESULTS:

• The UK biobank incudes 502,635 participants and 54% were women
• Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events

Coronary Heart Disease

• Grip strength: HR 0.79 (95% CI, 0.77 to 0.81)
• Physical Activity: HR 0.95 (95% CI, 0.93 to 0.97)
• Cardiorespiratory fitness: HR 0.68 (95% CI, 0.63 to 0.74)

Atrial Fibrillation

• Grip strength: HR, 0.75 (95% CI, 0.73 to 0.76)
• Physical activity: HR 0.93 (95% CI, 0.91 to 0.95)
• Cardiorespiratory: HR 0.60 (95% CI, 0.56 to 0.65)
• Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group (Ptrend <0.001 in each genetic risk category)
• In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38 to 0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30 to 0.55) among individuals at high genetic risk for these diseases

CONCLUSION:

• Physical activity demonstrates inverse correlations with incident cardiovascular disease in not only in the overall population, but especially in those with genetic risk as well

Learn More – Primary Sources:

Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study

Herpes Zoster: Clinical Presentation and Treatment

SUMMARY:

Herpes zoster, more commonly known as shingles, is caused by a virus that establishes latency on dorsal root and cranial nerve ganglia after a varicella-zoster (chickenpox) infection. Eventual reactivation of the virus causes it to spread from a nerve root to a cutaneous dermatome and produce a characteristic painful rash. The incidence of herpes zoster increases with age, which is why the rash usually presents in elderly populations, with a median age of 64.

• Clinical presentation
• Differential diagnosis
• Complications
• Treatment

Clinical Presentation

• Painful prodrome typically precedes rash by 2 to 3 days
• Pain can be constant or intermittent—usually described as a “burning” or “throbbing”
• Rash manifests as erythema and macules, followed by papules
  • Papules develop into vesicles in 1 to 2 days
  • Vesicle formation continues for 3 to 4 days
  • All types of lesions (erythema, macules, papules, vesicles) may be present at 1 week
• Lesions tend to cluster at cutaneous nerve branches
• Only a single dermatome is typically affected in immunocompetent patients

Differential Diagnosis

• Can be confused with zosteriform herpes simplex and contact dermatitis
• Diagnostic tests such as PCR and immunohistochemical analysis of a skin scraping can be used to confirm diagnosis

Complications of Herpes Zoster

• Mostly limited to immunocompromised populations (e.g. AIDS, chemotherapy)
  • Encephalitis
  • Herpes zoster ophthalmicus with delayed contralateral hemiparesis
  • VZV retinitis
  • Myelitis
  • Persistent pain (postherpetic neuralgia)

Treatment

Antiviral Therapy Shortens Duration of Rash and Viral Shedding

• Acyclovir: 800 mg 5 times daily for 7 to 10 days
• Famciclovir: 500 mg 3 times daily for 7 days
• Valacyclovir: 1000 mg 3 times daily for days

Acute Pain

• Treat acute pain with OTC analgesics: Acetaminophen or NSAIDs
  • Keep lesions clean and dry
• If OTCs fails, consider longer term pain management
  • Gabapentin: Start with 100 mg capsule twice a day and titrate up 300 mg 3 times a day
  • Pregabalin: 75 mg daily titrated up to 300 mg in 3 divided doses
  • Nortriptyline: 10 mg and titrate up to 40 mg nightly
• There is no indication for systemic glucocorticoids
• Therapy during the acute phase does not prevent postherpetic neuralgia
• Lesions may take 2 to 4 weeks to heal

Secondary Bacterial Infections

• Treat with systemic antibiotics to cover staph and strep (such as cephalosporin)

Additional Considerations

• Transmission Risk
  • Patients with active lesions can transmit VZV to persons who have not had varicella infection, varicella-zoster vaccination or immunocompromise patients
  • Pregnant women who do not have adequate varicella titers are also at higher risk
  • Patients are considered contagious until all lesions have crusted over
• Varicella Vaccination
  • Adults who do not have antibodies to varicella should receive 2 doses of varicella vaccine 1 to 2 months apart
  • Exceptions: Pregnant woman or women planning pregnancy

Learn More – Primary Sources:

IDSA: Recommendations for the treatment of herpes zoster, Clinical Infectious Diseases 2007

AAFP: Herpes Zoster and Postherpetic Neuralgia: Prevention and Management

CDC: Shingles (Herpes Zoster)

Are Optimal Doses of Heart Failure Medications the Same for Men and Women?

BACKGROUND AND PURPOSE

• Medications for heart failure with reduced ejection fraction (HFrEF) include
  • Angiotensin-converting-enzyme (ACE) inhibitors | Angiotensin-receptor blockers (ARBs) | β blockers
  • Men and women are prescribed the same doses
• Santema et al. (Lancet, 2019) investigated whether there are sex differences in the optimal doses of these medications for HFrEF

METHODS

• Post-hoc analysis of prospective BIOSTAT-CHF study (11 European countries)
  • Study to evaluate heart failure treatment with left ventricular ejection fraction less than 40%
  • Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF
• Primary outcome
  • A composite of time to all-cause mortality or hospitalization for heart failure

RESULTS

• 1,308 men and 402 women
• Women were
  • Older (74 vs 70 years; p<0.0001)
  • Lower bodyweights (72 kg vs 85 kg; p<0.0001)
  • Heights (162 cm vs 174 cm; p<0.0001)
  • No difference in BMI
• A similar number of men and women reached guideline-recommended target doses
• Sex differences related to drug dosage and risk for death or hospitalizations for heart failure
  • Men: Lowest numbers of death or hospitalizations for heart failure occurred at 100% of the recommended medication dose
  • Women: 30% lower risk of death or hospitalizations at only 50% of the recommended doses and no further decrease in risk at higher dose levels
  • Adjusting for age and body surface area did not alter results
  • Findings were similar in the second ASIAN-HF study

CONCLUSION

• Women may require half the dose of heart failure medications compared to men
• This finding is particularly important as literature demonstrates that women may have more adverse drug reactions and these reactions may be more severe than those seen in men
• This study highlights the pervasive bias towards male-based medical guidelines in research and in addition the authors state

This study also underlines the importance of performing prespecified sex-specific analyses in all drug trials

Learn More – Primary Sources

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study