WHAT'S NEW IN INTERNAL MEDICINE?
From 36th Annual Advances in Internal Medicine, sponsored by University of California, San Francisco, School of Medicine
Educational Objectives
| The goal of this program is to educate the listener about new information in primary care and geriatrics over the last
year. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Discuss the diagnosis of septic arthritis and evaluation of arthrocentesis fluid.
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| 2. Distinguish peripheral from central facial paralysis.
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| 3. List the benefits of vitamin D supplementation.
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| 4. Describe the role of zoledronic acid in the treatment of hip fractures.
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| 5. Discuss treatment of chronic constipation and describe benefits of treatment of hypertension in the elderly.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgements
Drs. Kohlwes and Johnston were recorded at 36th Annual Advances in Internal Medicine, held May 19-23, 2008, in
San Francisco, CA, and sponsored by the Department of Medicine, University of California, San Francisco, School of
Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production
of this program.
| Primary Care: Year in Review
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| Jeffrey Kohlwes, MD, Associate Professor of Clinical Medicine, University of California, San Francisco, School of Medicine,
and Director, PRIME Residency Program, Veterans Affairs Medical Center, San Francisco, CA
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| Monoarticular arthritis: differential diagnosis—gout; calcium pyrophosphate dihydrate deposition disease (CPPD);
connective tissue diseases; osteoarthritis; trauma; infectious; infectious—Neisseria gonorrhoeae (GC) most common
infection causing monoarticular arthritis; migratory
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| Septic arthritis: 8% to 27% of patients who present with monoarticular arthritis also have septic arthritis; ≤15% mortality
if untreated; cartilage destroyed within days; pathogenesis—no basement membrane to synovial lining; hematogenous
spread or bacteremia; inflamed extra-articular structures (eg, bursitis, cellulitis); direct inoculation;
procedures (eg, common after arthroscopic surgery); microbiology—mostly Staphylococcus or Streptococcus but
any bacteria can cause; 70% to 95% sensitivity and specificity with Gram stain and culture; study showed variable
presentation of septic arthritis; tests not sufficiently diagnostic to rule in or rule out disease; risk factors for developing
septic arthritis should raise awareness higher than for standard patient; likelihood ratios (LR)—defined as
sensitivity divided by 1 minus specificity; LR derived from test characteristics and can be applied directly to patient;
with LR of 2, probability increases by ≈15%, with LR of 5, probability increases by ≈30%, and with LR of
10, probability increases by ≈50%; ankle tap—have patient flex great toe; insert needle distal to medial malleolus
(can feel extensor hallucis longus) and aim for middle (avoids dorsalis pedis pulse); interpreting laboratory
findings—in arthrocentesis fluid, high white blood cell (WBC) count septic arthritis until proven otherwise; WBC
count in arthrocentesis most predictive value for septic joint (except for positive Gram stain); 20% of people who
present with gout have infection in joint (presence of crystals does not rule out septic arthritis); LR of 28 with
WBC count >100,000/µL diagnostic for septic joint; with WBC <25,000/µL, watch patient and follow up later;
speaker admits patients with WBC >50,000/µL to hospital and observes them on intravenous (IV) antibiotics until
culture comes back negative; patients with WBC between 25,000 and 50,000/µL and negative Gram stain, who
have previous crystalline disease, should be treated for gout and asked to return for follow-up; if WBC <25,000/
µL ask patient being treated for crystalline disease to return if condition worsens
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| Facial droop: acute facial paralysis with no other associated signs of stroke most commonly idiopathic (Bell’s
palsy; 66%); differential diagnosis—idiopathic; varicella virus infection (can detect herpes simplex virus (HSV)
in anyone who has had chickenpox; question whether part of pathogenesis or co-actor); diabetes (mononeuritis
multiplex and Bell’s palsy); Lyme disease (ask about tick bites; Bell’s palsy presents early in infection);
Sjogren’s syndrome; sarcoidosis; trauma
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| Bell’s palsy: idiopathic peripheral facial paralysis; fairly common; men or women; any age; 20% to 30% have residual
weakness, and 5% to 10% have disfiguring weakness after Bell’s palsy; physical findings—patients with
peripheral lesion, eg, Bell’s palsy, cannot wrinkle forehead (central crossover enables patient with central event,
eg, stroke, to wrinkle forehead); easiest test to determine peripheral vs central facial droop; patients with Bell’s
palsy also cannot close eyes and cannot smile (ask patient to suck on straw to unmask subtle facial droop);
treatment—antiviral agents; steroids; Scottish study—496 patients with Bell’s palsy for <72 hr received either
prednisolone plus placebo, acyclovir plus prednisolone, acyclovir plus placebo, or placebo plus placebo; study
found after 9 mo, those randomized to steroids (with or without acyclovir) had 96% rate of resolution, those
given acyclovir alone had 78% resolution (no better historically than placebo), and those taking placebo alone
had 85% resolution; number needed to treat (NNT) 9 in study; concluded that prednisolone effective if given
early; no evidence for acyclovir; another study found valacyclovir effective (warrants further study); speaker gives
prednisone 25 mg bid for 10 days
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| Antioxidants: long line of negative studies; Women’s Antioxidant Cardiovascular Study looked at vitamin C, vitamin
E, and beta carotene; no effects on cardiovascular (CV) outcomes shown
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| Vitamin D: get 90% from sun, remainder from some types of fish, eggs, and milk (assumes ability to absorb fat-soluble
vitamins); vitamin D deficiency—≤4% of populations of normal healthy children and ≤70% of patients in
nursing homes; reasons include lack of outdoor activity in winter and inability of elderly to absorb dietary vitamin
D; fracture prevention—meta-analysis of 5 randomized controlled trials (RCTs) found 25% reduction in relative
risk (RR) for hip fracture in patients who took adequate amounts of vitamin D; similar data on nonvertebral fracture
risk; studies used 700 to 800 IU of cholecalciferol daily (standard vitamin pill has between 200 and 400 IU; no
better than placebo in trials); prevention of falls—bone mineral density (BMD); improved muscle strength (vitamin
D receptors in muscle); meta-analysis showed 22% reduction in RR for falls (NNT 15); all-cause mortality—meta-
analysis of 18 RCTs (57,000 patients) found 8% reduction in RR for mortality in those receiving vitamin D supplementation
vs those who did not; biologic plausibility—mechanism unclear; not explained by reduced falls or fractures;
vitamin D receptors found in bone, muscle, kidney, endothelium, biliary tree, and immune cells; does not
reduce risk for CV disease or cancer, but patients who have CV disease or cancer do better on vitamin D; dose—
700 to 800 IU with 1.2 g calcium (not as well studied); side effects include kidney stones (1% in people taking
>800 IU) or gastrointestinal (GI) upset (rare)
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| Computed tomography (CT) in minor head injury: scan patients with depressed Glasgow Coma Scale
(GCS) score (rate of neurosurgical interventionable head trauma increases from 1% to 5% with depressed GCS
score); minor head trauma—≤7% of emergency department and acute care clinic visits nationwide; 6% to 21% of
patients have complications; 1% require neurosurgical intervention; CT prediction rules—New Orleans Criteria
(NOC) and Canadian CT Head Rule (CHR) looked at factors that enabled reduction in number of head CTs; found
that, in patients with loss of consciousness (LOC), CT had 100% sensitivity for neurosurgical intervention; head injury
without LOC—CT in Head Injury Patients (CHIP) rule states that any patient without LOC but with any major
criteria (eg, pedestrian or cyclist vs vehicle, ejection from vehicle, depressed GCS score, signs of skull fracture, age
>60 yr) or 2 minor criteria requires CT; look at criteria that put patient at increased risk for bleeding or complications
(aspirin, warfarin [Coumadin], age)
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| Human papillomavirus (HPV) vaccine: cervical cancer—20th leading cause of death in United States (1997);
Papanicolaou (Pap) tests reduced cervical cancer mortality by 70%; Pap tests detect early lesions (secondary prevention);
cervical cancer prevention—observational study of 82 college women showed hazard ratio of 0.3% or 70%
reduction with 100% condom use, compared to women whose partners did not use condoms; no case reports of cervical
intraepithelial neoplasia [CIN] with condom use; vaccines—2 with proven safety and efficacy (Gardasil
[quadrivalent]); Cervarix [bivalent]); vaccine does not have DNA or attenuated virus; ≥5 yr of protection; study—
quadrivalent vaccine; RCT of 12,000 women ages 15 to 26 yr; 3 doses and 4-yr follow-up; reduction in all lesions
(RR reduction 45%; NNT slightly <100); no significant difference in amount of carcinoma in situ but this outcome
rare; HPV vaccine guidelines (American Cancer Society)—routine vaccination for girls 11 to 12 yr of age; catch-up
vaccination for girls 13 to 18 yr of age; insufficient data on women 19 to 26 yr; Pap screening recommendations remain
same for vaccinated women; HPV testing before vaccination not recommended; vaccination not recommended
for women >26 yr or for boys; concerns—20 state mandates for vaccine; long-term efficacy not known;
influence beyond science (eg, money, politics)
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| Metabolic syndrome: definition—syndrome includes increased abdominal adiposity, increased insulin resistance,
proinflammatory state with elevated C-reactive protein, hypertension, prothrombotic state with elevated plasminogen
activator inhibitor-1, and atherogenic dyslipidemia; carbonated beverages—associated with obesity and diabetes in
children; 97 calories and 33 mg of sodium per 8 oz of Coke; Framingham Heart Study—6000 patients; adjusted analysis
for age, sex, smoking, and diet; examined risk of >1 carbonated beverage daily on development of metabolic syndrome;
study found increased risk, depending on number of carbonated beverages consumed; ≥1 soda daily conferred
30% to 40% increased risk for factors in metabolic syndrome; 44% increased risk overall for metabolic syndrome; no
difference between regular and diet beverage; possible reasons—catch-up eating; decreased fluid satiety leading to
overeating later; brown caramel syrup (may increase inflammation)
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| Geriatrics: Year in Review
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| C. Bree Johnston, MD, MPH, Associate Professor of Clinical Medicine, Division of Geriatrics, University of California,
San Francisco, School of Medicine
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| Dementia: screening—dementia often unrecognized in primary care; early detection allows opportunity for advance
care planning, promotion of safety (eg, driving, firearms, financial security, and elder abuse), and identification of
potentially reversible causes of dementia (treatment with medications may help modestly); United States Preventive
Services Task Force (USPSTF) states that “concept of detecting dementia at an early stage to allow interventions
is a good one”; review article—use Mini-Mental State Examination (MMSE) to find cognitive impairment of
at least moderate severity; use Hopkins Verbal Learning Test if mild impairment suspected or patient highly educated
(time-consuming and not practical in every setting); use clock-draw test when little time available (speaker
uses this with 3-item recall [“mini-cog”]; can essentially rule out dementia if patient can recall 3 items and draw
clock); clinical bottom line—reasonable to screen patients >65 yr of age for dementia; mini-cog most reasonable
screen for most physicians; MMSE useful, especially for obtaining more information than mini-cog provides
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| Vitamin D: meta-analysis found decrease in mortality with vitamin D supplementation; rationale—associations
found between latitude, seasons, and mortality from various conditions; vitamin D expressed in many tissues; activation
of vitamin D receptors can induce cell differentiation, and inhibit proliferation, invasiveness, and metastatic
potential; theoretic and in vitro evidence suggests that vitamin D might play protective role in many chronic diseases;
meta-analysis—57,000 patients and 4700 deaths analyzed; average study duration of 5.7 yr; average vitamin
D dose of 300 to 2000 IU; most studies performed in frail elders; all cause mortality reduced by 7%; trends for decreases
in CV and cancer deaths, but not statistically significant; clinical bottom line—vitamin D supplementation
now linked to decreased falls, fractures, and mortality; multiple other vitamin studies published in last 10 yr negative;
for elders, check 25-OH vitamin D levels in all patients >65 yr of age; target levels 30 to 40 ng/mL; for those
with low levels (<15 ng/mL), give loading dose of 50,000 IU weekly for 2 to 8 wk, followed by 800 IU daily; another
approach includes treating everyone with 800 IU daily and checking 25-OH levels in those at high risk
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| Zoledronic acid: trial—RCT of 2000 patients with hip fractures randomized to receive 5 mg IV zoledronic acid or
placebo within 90 days of fracture; all received calcium and vitamin D; if vitamin D levels low, loading dose given;
2-yr follow-up; primary outcome new clinical fractures; mean age 75 yr; 75% women; 41% osteoporotic, 35% osteopenic,
12% receiving other therapy for osteoporosis; results showed 13.9% with any fractures in placebo group,
compared to 8.6% in zoledronic acid group (NNT 19); similar results with nonvertebral fractures; hip fractures
showed statistical significance, with NNT 67; reduced risk for death in zoledronic acid group (13% vs 9.6%; NNT
27); adverse events low in both groups and included pyrexia, myalgia, or bone pain (no osteonecrosis of jaw or
atrial fibrillation); bottom line—IV zoledronic acid given within 90 day of hip fracture reduces fractures and mortality
at 2 yr; zoledronic acid expensive; new evidence that zoledronic acid given too soon after fracture may impair
healing (give between 30 and 90 days)
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| Chronic constipation: example—80-yr-old man with Parkinson’s disease and chronic constipation; colonic transit
study confirmed diagnosis of slow-transit constipation; increased fiber safe and effective first-line treatment for
“run of the mill” person with idiopathic constipation; for this patient with Parkinson’s disease, fiber not best choice
and may increase risk for impaction; osmotic laxatives, eg, polyethylene glycol, lactulose, sorbitol best choice; recent
guidelines—American Gastroenterological Association (available online); study—showed that at 6 mo, polyethylene
glycol (MiraLax) safe in patients with chronic constipation without any observable increase in incidence
of electrolyte abnormalities or other adverse effects
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| Osteoarthritis (OA): study—people with severe symptomatic OA of hip with daily pain despite maximum doses
of drugs randomized to receive intra-articular steroid injection by fluoroscopic guidance of either bupivacaine,
bupivacaine and triamcinolone, or saline placebo; outcomes included improvement in standard OA pain scores and
quality of life scores; corticosteroids improved pain scores, and showed some improvement in global assessment of
health, and physical function (NNT 3)
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| Hypertension: Hypertension in the Very Elderly Trial (HYVET) —patients in Europe, China, and Australia, 80 yr of
age, with systolic blood pressure (BP) of 160 mm Hg; run-in study in European countries found increased mortality
with aggressive control of BP; patients randomized to indapamide 1.5 mg or placebo; if target BP of 150/80
mm Hg (loose target) not reached, perindopril or placebo was added; primary outcome stroke (fatal or nonfatal)
and secondary outcomes mortality, CV mortality, heart failure, or CV events; most outcomes start to diverge at 1
yr; statistical difference in death from any cause (NNT=8); slight difference in death from CV disease; difference
in death from stroke (NNT=7) and congestive heart failure (NNT=3); any cardiovascular event (NNT 6); evidence
of benefit to treating hypertension in this population; study population very healthy, so use caution in frail elders
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Suggested Reading
Brunner RL et al: Calcium, Vitamin D Supplementation, and Physical Function in the Women’s Health Initiative. J Am Diet
Assoc 108:1472, 2008; Cadman L: The future of cervical cancer prevention: human papillomavirus vaccines. J Fam Health
Care 14:131, 2008; Cheah CY, Wilson MD: Treatment of hypertension in the elderly. N Engl J Med 359:973, 2008; Dipalma
JA et al: A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of
chronic constipation. Am J Gastroenterol 102:1436, 2007; Hato N et al: Steroid and antiviral treatment for Bell’s palsy. Lancet
371:1818, 2008; Lyles KW et al: Zoledronic Acid in Reducing Clinical Fracture and Mortality after Hip Fracture. N Engl
J Med 357:nihpa40967, 2007; Mendelow AD et al: Management of patients with head injury. Lancet 372:685, 2008; Robinson
P et al: Clinical effectiveness and dose response of image-guided intra-articular corticosteroid injection for hip osteoarthritis.
Rheumatology 46:285, 2007; Sickels M: Treatment options for patients with Bell’s palsy. Am Fam Physician 78:316,
2008; Somasundaram K: HPV vaccine: End to women’s major health problem? Indian J Med Res 127:511, 2008; Stein et
al: Routine serial computed tomographic scans in mild traumatic brain injury: when are they cost-effective? J Trauma 65:66,
2008; Blood Pressure. Drug The Bull 46:65, 2008; Vitamin D abd Health in the 21st Century: an Update. Proceedings of a conference
held September 2007 in Bethesda, Maryland, USA. Am J Clin Nutr 88:483S, 2008; Merck, FDA expand Gardasil warnings.
AIDS Read 18:442, 2008.
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