AFP Journal Review

1. AFP Journal Review October 15, 2009 Issue Lianne Beck, MD Assistant Professor Emory Family Medicine

2. Articles Reviewed • Envenomations: An Overview of Clinical Toxicology for the Primary Care Physician • Mental Status Examination in Primary Care: A Review • Diagnosis and Management of Adnexal Masses • Evaluation of the Solitary Pulmonary Nodule • Recognition and Management of Vitamin D Deficiency

3. Envenomations: An Overview of Clinical Toxicology for the Primary Care Physician • Epidemiology • Globally, an estimated 1.2 million persons are bitten by snakes each year; 20,000 to 100,000 die • Of the 4,000 to 6,000 venomous snakebites that occur each year in the US, approximately 70% require antivenom and about 5 are fatal • 40 to 100 persons who die each year from anaphylaxis after hymenopteran stings • Most snakes in the US are nonvenomous or only mildly toxic colubrid species, and these snakes are responsible for most bites

4. Snake and Lizard Envenomations • Pit vipers and Gila monster (Heloderma suspectum) • Coagulopathic/Hemorrhagic/Para-lytic • Edema (rapidly progressive) • Systemic effects (lymphadenopathy, lymphangitis, n/v/d, perioralparesthesia, metallic taste, hypotension, hypertension [particularly in Gila monster envenomation], vertigo, shock, hyperreactive airway, loss of consciousness) • Labs: CBC, CMP, LFT’s, PT/PTT, Fibrinogen, d-dimer, ABG , CPK, UA, CE’s http://timberrattlesnake89.tripod.com/venomouspage.html

5. First Aid • Limit ambulation, splint affected limb below heart level • Except for Gila monster, copperhead, water moccasin, or pygmy rattlesnake envenomations, consider pressure and immobilization if substantial delay in treatment or neurotoxic features are expected • Remove constrictive clothing, jewelry • Give fluids as tolerated (not orally, if possible) and acetaminophen; withhold other medications until after medical evaluation • Contraindicated: cryotherapy, ice, NSAIDs (may cause bleeding), constricting ligatures, incision and/or suction, illicit drugs, alcohol

6. Treatment • IVF; provide fluid bolus and repeat as indicated • Anaphylaxis protocol • Intubation and ventilation may be necessary in envenomations with paralytic features • Wound care, tetanus prophylaxis and supportive management (non-sedating analgesia, monitoring of patients with comorbidities) • General treatment considerations: • Compartment syndrome requires surgical intervention • Coagulation factor and platelet replacement (controversial; currently under investigation) • Dialysis for established renal failure, urine alkalinization for myoglobinuria (uncertain value) • After administration of antivenom, a short, nontapered course of prednisone (40 to 60 mg daily for five days) should be given to decrease the incidence of type III immune complex disease. • Antibiotics are indicated only if evidence of infection is present.

7. Antivenom Indications • Grading system • 0 = nonenvenomation ("dry" bite). Fang marks may or may not be visible; no local or systemic effects. Antivenom is not indicated. • 1 = minimal envenomation. Local effects (pain, edema) are limited to the bite site; no systemic effects or laboratory abnormalities. Antivenom is not usually needed, but may be given if clinical progression occurs. • 2 = moderate envenomation. Extension of local effects, but the entire bitten extremity is not involved; systemic signs (n/v, metallic taste); some laboratory abnormalities (thrombocytopenia, prolonged INR, elevated CPK level). Antivenom is required. • 3 = severe envenomation. Rapidly progressing edema; blistering and ecchymoses; shock; altered sensorium; multiple laboratory abnormalities (markedly prolonged INR, severe thrombocytopenia [platelet count < 20,000 mm3]); fibrin degradation products; renal insufficiency or failure. Antivenom is required with a high initial dose. Large subsequent doses are often required.

8. Antivenom dosing and administration • Crotalidae polyvalent immune Fab (ovine): 4 to 6 vials, diluted in 250 mL saline, initial infusion of 20 to 60 mL per minute; increase to 250 mL per hour if no adverse reactions occur. • Additional 4 to 6 vials, followed by 2 vials every six hours for 18 hours (14 to 18 vials total) as indicated; higher doses may be required for severe envenomations. • Presynaptic envenomation by species such as Mojave rattlesnakes may require higher doses and may be ineffective in late presentations, requiring intubation and ventilation. • Delayed absorption of sequestered venom is possible; because of the variably short half-life of the antivenom (12 to 23 hours), serial assessment of INR is essential (reversal of prolonged INR is sufficient to withhold further antivenom, but INR must be monitored for 24 to 48 hours [sometimes longer]). • Counsel on risk of antivenom anaphylaxis, immune complex disease, and possible loss of function, regardless of treatment effectiveness. • No antivenom is available for Gila monster envenomations.

9. ¶- The coral snake antivenom formerly manufactured by Wyeth is no longer in production; an alternative formulation (Coralmyn) is being tested.

17. Management • The decision to administer antivenom is guided by clinical findings, but indications differ by species. • In patients with envenomations from nonnative species, the choice and availability of antivenom may be an issue. • The Antivenom Index (http://www.pharmacy.arizona.edu/avi/index#top) identifies the availability of antivenom and locations of stock for zoos and poison control centers • Clear guidelines are often lacking for envenomations involving nonnative species. • Seek advise from poison control center (1-800-222-1222) and medical expert Web sites, such as Clinical Toxinology Resources (http://www.toxinology.com).

19. Quiz • In which one of the following situations is antivenom therapy clearly warranted?  (check one) A. When there are late paralytic features after rattlesnake envenomation. B. When there is mild localized swelling but no systemic symptoms. C. When the bite is from a pit viper, regardless of symptoms. D. In the presence of rapidly developing edema of the bitten limb, with fluid shifts.

20. A patient is bitten by a coral snake, but is far from a medical center. Which one of the following first aid methods is most likely indicated?  (check one) A. Immediate incision of the bite wound. B. Application of pressure to the bite site. C. Application of papain or permanganate. D. Application of an arterial tourniquet. E. Immediate dosing with a nonsteroidal anti-inflammatory drug.

21. For which of the following animals is antivenom currently available in the United States?  (check all that apply) A. Recluse spiders. B. Black widow spiders. C. Pit vipers. D. Scorpions from the southwestern United States. E. Sting rays.

22. Mental Status Examination in Primary Care: A Review • Components of MSE • Appearance and Behavior • Motor Activity • Speech • Mood and Affect • Thought Process • Thought Content • Perceptual Disturbances • Sensorium and Cognition • Judgement • Insight

24. Which one of the following questions assesses patient insight?  (check one) A. “Do you ever feel that life is not worth living?” B. “Have you been angry or on edge lately?” C. “Do you think your thoughts and moods are abnormal?” D. “Who is the president of the United States?”

25. Which one of the following is a U.S. Preventive Services Task Force screening recommendation for mental health disorders?  (check one) A. There is insufficient evidence to recommend for or against screening for depression. B. Screening for dementia is not recommended. C. Screening for illicit drug use is recommended. D. There is insufficient evidence to recommend for or against screening for dementia

26. Impairment in which components of the mental status examination may be a sign of depression? (check all that apply) A. Mood and affect. B. Thought process. C. Speech. D. Appearance.

27. Diagnosis and Management of Adnexal Masses • Ovarian cancer is the leading cause of death from gynecologic malignancy. • It is the fifth leading cause of cancer death in women in the United States, accounting for 15,280 deaths in 2007. • The risk of ovarian cancer increases steadily with age, with the greatest risk occurring after menopause. • Although most masses in prepubescent girls are benign, 5 to 35 % are malignant. • In postmenopausal women, 30 % of adnexal masses are malignant. • No effective screening method for ovarian cancer that has been shown to significantly improve clinical outcomes.

28. Diagnosis and Management of Adnexal Masses • In pregnant women, the most common cause of an adnexal mass is a corpus luteum cyst. • In nonpregnant patients, the most common etiologies are functional cysts and leiomyomata. • The most common benign ovarian neoplasm is the cystic teratoma.

29. Diagnosis and Management of Adnexal Masses • Adnexal masses are characterized on US as cystic, solid, or complex. • According to an ACR guideline, simple cysts in premenopausal women are considered benign. • Complex masses may rarely be malignant in premenopausal women. Most are likely to be hemorrhagic cysts or endometriomas; tubo-ovarian abscess, ectopic pregnancy, and ovarian torsion can also present as a complex mass. • Solid masses are most commonly pedunculated fibroids, but can be benign ovarian tumors, fibromas, thecomas, malignant ovarian tumors, or an ovarian torsion.

31. Risk Factors for Ovarian Cancer • Age older than 60 years • Early menarche • Late menopause • Nulliparity • Infertility • Personal history of breast or colon cancer • Family history of breast, colon, or ovarian cancer.

32. Hereditary cancer syndromes • Occur in less than 0.1 % of the population • Comprise less than 10 % of patients with ovarian cancer • Hereditary nonpolyposis colorectal cancer, an autosomal dominant genetic disorder, increases the risk of gastrointestinal, urologic, ovarian, and endometrial cancers. • Associated with BRCA1 mutations: • Ashkenazi Jewish heritage, young age at breast cancer diagnosis, bilateral breast cancer, family history of breast and ovarian cancer, multiple cases of breast cancer in the family, and a male family member with breast cancer.

34. Evaluation • Targeted PE • Urine HCG -> Quantitative β-hCG and transvaginal US • CBC • CA 125 • Imaging • Transvaginal US (the standard) similar sn and sp as CT, but more cost effective • MRI and PET future role

36. Finding Suggesting Malignancy • CA 125 level greater than 35 U per mL (postmenopausal) or 200 U per mL (premenopausal) • Evidence of abdominal or distant metastasis • Family history of first-degree relative with ovarian or breast cancer • Nodular or fixed pelvic mass (postmenopausal) • Concerning US findings: solid component, thick septations (greater than 2 to 3 mm), bilaterality, Doppler flow to the solid component of the mass, and presence of ascites • Women with any of these findings should be referred to a gynecologist or gynecologic oncologist. • All prepubescent girls with adnexal masses should be referred.

40. In which one of the following patients is an adnexal mass most likely to be cancerous?  (check one) A. A two-day-old infant girl. B. A six-year-old girl. C. A 24-year-old woman. D. A 28-year-old pregnant woman.

41. A 42-year-old premenopausal woman presents for a well-woman examination. She has been having urinary incontinence with coughing. You feel a mass in the left adnexa during bimanual examination. A pregnancy test is negative. Transvaginalultrasonography shows an 8-cm cyst with thin walls, no septae, and no excrescences. Which one of the following steps is most appropriate?  (check one) A. Order computed tomography of the pelvis. B. Measure her cancer antigen 125 level. C. Repeat ultrasonography in four to six weeks. D. Refer her to a gynecologist.

42. Which of the following is/are risk factors for ovarian cancer? (check all that apply) A. Age older than 60 years. B. Nulliparity. C. Early menopause. D. Family history of breast cancer

43. Evaluation of the Solitary Pulmonary Nodule • Lung cancer screening is not recommended by the American College of Chest Physicians (ACCP) for the general population, nor for smokers, because it has not been shown to prevent mortality. • Solitary pulmonary nodules are isolated, spherical radiographic opacities that measure less than 3 cm in diameter and are surrounded by lung parenchyma. • Noted in roughly 0.09 to 0.2% of all CXRs • Prevalence of solitary pulmonary nodules in the literature ranges from 8 to 51%

47. Imaging • CXR • visualize nodules as small as 5 to 6 mm; high false-negative rate • CT (thin slice) • imaging modality of choice to reevaluate pulmonary nodules seen on CXR and to follow nodules on subsequent studies for change in size. • FDG-PET • FDG is selectively taken up by malignant tumor cells • used in oncology for tumor diagnosis, staging, and assessment of response to therapy. • high sn and sp for evaluating nodules greater than 8 to 10 mm in diameter. • most cost-effective for patients with discordant pretest probability and CT results