Hayward Zwerling, M.D., FACP  

What I learned at the American College of Physicians – American Society of Internal Medicine Annual Session 2000

Maintaining relative humidity consistently below 50% is associated with …decreased mite population…decreased symptoms in sensitive asthmatic and rhinitic patients…J All Clin Immunol 1999;104(4) Part I, 852

Long term high dose inhaled corticosteroids can result in adrenal suppression, reduction in bone density and posterior subcapsular cataracts, ocular hypertension and glaucoma…
Arch Intern Med 1999;159;941

Rhinitis may be an independent risk factor for asthma……J All Clin Immunol 1999;104;301

Pharameceutical-company sponsored studies were less likely than non-profit studies to report unfavorable qualitative conclusions…JAMA 1999:282;1453

Treating all type 2 diabetics (>50 yo) from the time of diagnosis with ACE-I may be the best option rather than selectively screening and treating for diabetic nephropathy/microalbuminuria. (Based on mathematical model.) Patients who do not tolerate ACE-I (cough) are unlikely to benefit….The ADA, National Kidney Foundation will soon recommend this as standard of care in addition to recommending achieving BP <130/85, annual ophthalmologic assessment, HBA1c<7% (when appropriate)….AIM 1999:131;660 and NEJM 2000:343

The diagnosis of DM-2 implies and increase risk of CV mortality. The ADA dx of DM-2 is based on fasting BS>126 whereas the WHO recommends a 2h oGTT if the Fast BS>100. As a result of these differences, the ADA criteria misses patients who have a normal fasting glucose but a high 2 hour glucose. The ADA criteria thus underestimates the risk of mortality and CV evident. The 2h oGTT may a better assessment if the patient is considered high risk for DM-2. Lancet 1999:354:617

Use of statins in 2nd prevention for CAD (patients 40-70 yo) is cost effective but the cost effectiveness of statins in primary prevention is very controversial (despite demonstrated substantial clinical efficacy in high risk patients)…Arch Int Med 1999:159:593

Aspirin reduces the risk of recurrent cerebrovascular events by 15% independent of dose (50-1500 mg) The lowest effect dose has not yet been established… Arch Int Med 1999:159:1248

Spironolactone improved both morbidity and mortality (30%) and reduced hospitalization (35%) when added to standard drug therapy for sever heart failure (EF≤35%) Side effects included gynecomastia/breast pain (10%) but not hyperkalemia…NEJM 1999:341;709

Gemfibrozil (Lopid 600 mg BID) reduced the risk of CV events (22-24%) in male patients with ASCVD, low HDL (<40) and low LDL (<140) without effecting the LDL cholesterol levels. The risk reduction was apparent after 2 years Rx. 23 patients would have to be treated for 5 years to prevent a single cardiac event (consistent with the use of statins in 2nd prevention)…NEJM 1999:341;410 (Gemfibrozil will reduced triglyercide levels 31%)

The use of a beta blocker given for 7 days pre-operatively and 30 days postoperatively in patients undergoing vascular surgery reduced the risk of death and MI…”Pre-op” clearance of high risk individuals should include non-invasive stress test and short term use of beta-blockers…NEJM 1999:341:1789

In postmenopausal women (31-80 yo, T>-2.5)with osteoporosis raloxifene (Evista 60 or 120 mg qd, a selective estrogen receptor modulator [SERM]) + calcium 500 mg qd + Vitamin D 400-6000 IU qd reduces the risk of vertebral fractures 7% vs 10 % at 3 y (Comparable to Fosamax and HRT). There was no beneficial effect on the hip fracture rate. There is an increased risk of venous thromboembolism (same as ERT) but not of vaginal bleeding. This drug may become an important option in women who can not take estrogen or tolerate bisphosphonate (eg Fosamax). It should not be primary Rx b/o lack of hip efficacy and long term safety data…JAMA 1999:282;637 Fracture reduction with any pharmacologic therapy has only been demonstrated in women with prior fractures or osteoporosis as defined by BMD.

Raloxifene (Evista) reduced the RR of breast cancer over 36 months to 0.35 (vs placebo) This was attributable to a 90% reduction in the incidence of ER positive breast cancer. JAMA 1999:281:2189 There is currently a 7 year study in progress (STAR trial) to compare the efficacy of raloxifene and tamoxifen to reduce the risk of breast cancer.

Women treated with HRT for osteoporosis may benefit from serial BMD. Those who do not respond as desired to HRT may benefit from the addition of alendronate (Fosamax 10 mg qd) which can lead to further increase in BMD (study did not assess fracture rate or long term safety profile)…J Clin Endo Metab 1999;84;3076

After 3y Rx with either Fosamax, the BMD plateaus. When stopping Fosamax, BMD declines. Thus, continuing Fosamax indefinitely is indicated. AIM 1999:1310,935 The same thing happens when HRT is discontinued.

Women with BMD<0.9 gm/cm2, treated with continuous low dose estrogen (Premarin 0.3 mg qd and Provera 2.5 mg qd with 1000 mg calcium and Vitamin D supplementation to maintain 25 OH Vitamin D ≥75 nm/ml) over 3.5 years resulted in an improvement in BMD of 5.2% in women who were compliant. Study did not assess whether low dose estrogen had fewer side effects than usual dose of 0.625 mg. Good option for elderly women. Similar efficacy to higher dose HRT in elderly women…AIM 1999;130;897

Risedronate (Actonel) 5 mg qd (a new bisphosphonate, in the same class as Fosamax and Didronel ) + calcium 1000 mg qd + supplemental Vitamin D (as needed) reduced the risk of vertebral (from 16.3 to 11.3%) and hip fractures (from 8.4 to 5.2%) in postmenopausal women (<85 yo) over 3 years. JAMA 1999:282:1344 The efficacy is similar to Fosamax with less GI side effects. Long term safety is unknown and the study should be repeated before the agent is widely used.

Parathyroidectomy (PTX) for primary hyperparathyroidism (HPTH) results in an 8% increase in bone mineral density (BMD) at 1 year and 12% at 10 y. Over 10 year f/u, 27%of the patients who were followed without PTX had progression of disease(hypercalcemia, hypercalcuria or osteoporosis) to warrant PTX. All pt who do not have surgery should have serial measurements of calcium (q6m,) BMD (q12m) and urinary calcium (q12m). This is a very important study. Trabecular bone increase with PTX but cortical bone lose is not reversed. Thus, patients with symptomatic HPTH should have surgery. Some argue that most pt with HPTH should be operated upon, especially if <50 yo…NEJM 1999:341:1249

The addition of metformin to insulin (DM-2) will further decrease the HBA1c with less weight gain and at a 29% lower dose of insulin. AIM 1999;131;182 Insulin Rx has the best long term track record. Any therapy to bring down HBA1c should be tried. Metformin should not be used in patients with CHF.

Humalog (Lispro insulin) is more effect in controlling post-prandial glucose and associated with fewer hypoglycemic episodes without overall lower HBA1c than with regular insulin. It may be advantageous in DM-1 patients who are already tightly controlled to reduce hypoglycemic episodes, especially severe nocturnal episodes. Diabetes care 22:1607:1999

Glucowatch (a watch which measures the interstitial glucose level every 20 minutes) may be useful in selected patients, but should not replace fingersticks at this time. JAMA 282:1839:1999

The partial substitution of LT3 12.5 mcg for LT4 50 mcg may improve mood and psychological function. The results…need to be verified before becoming standard rx…NEJM 1999:340:424 No cardiac end points, but low dose are unlikely to cause arrhythmias. The ideal LT4 100/LT3 10 mcg (slow release) is not available.

Children born to women with high TSH performed less will on IQ testing. Screening at first prenatal visit may be indicated, as the mother is the total source of LT4 during the first trimester. LT4 requirements increased 25-50% thru pregnancy. …NEJM 1999:341:549

In peri-menopausal women, DHEA Rx had no effect on symptoms or well being while having an adverse impact on lipid profile and raised total testosterone levels. J Clin Endo Metab 1999:84;3896 In men, there is an incr E2, increase T but no effect on well being.

DHEA supplementation in women with adrenal insufficiency may increase overall sense of well being and sexuality. NEJM 341:1013:1999

Most solitary benign nodules do not change with time. LT4 Rx resulted in at 25% decrease in volume vs 8% placebo and a reduced incidence of increase in size of nodule. Given the small effect and the potential risk (arrhythmia, osteoporosis) Can selectively Rx younger patients for 1 year to assess efficacy, if clinically necessary JCEM 83:3881:1998. Previous studies have shown that larger nodules (>2.5 cm diameter) do not shrink in response to LT4. I believe there is little justification to Rx benign thyroid nodules with LT4.

Pt on Actos or Avandia (replacement for Rezulin) should have LFTs q2m x 1 year

There is a strong an probably causal relationship between GERD and adenocarcinoma of the esophagus (esp in white males)…NEJM 1999:340;825

Treating H. Pylori positive, nonulcer dyspepsia with a 14 day BID course of amox 1000 mg/clarithromycin 500 mg/omeprazole 20 mg will alleviate symptoms in only 25-40%…NEJM 1999:341;1106

Marked rebound acid hypersecretion occurs after withdrawal of Prilosec and GERD can worsen when switching a patient from PPI to H2 blockers, especially if PPI duration>3 months. Consider gradual transition over 1-3 months…Gastroenterology 1999:116;239

Celebrex at 100 mg BID, 200 mg BID and 400 mg BID and naprosyn 500 mg BID were all equally effective in treating RA but Celebrex had a lower rate of ulcers by EGD (5% vs 26%)…JAMA 1999:282;1921 and the 12 month incidence of symptomatic PU, GI perf and UGI bleed for patients Rx with Vioxx for OA was 1.3% vs 1.8% for conventional NSAIDs….JAMA 1999:282;1929

Alosetron (serotonin 3 receptor blocker) 1 or 2 mg BID is effective in treatment of abdominal pain and bowel symptoms in female patients with irritable bowel syndrome with predominantly diarrhea/constipation symptoms Side effects: 27% constipation vs 5% placebo…Aliment Pharm Ther 1999:13;1149

Calcium supplementation is associated with a moderate decrease risk (28% vs 31%) in the risk of developing colorectal cancer…NEJM 1999:340:101 (Aspirin and NSAID also has efficacy)

Coffee consumption may reduce the risk of symptomatic gallstones…JAMA 1999:281:2106

Stool assay for H Pylori antigen is a reliable tool for dx of h pylori and to document eradication…Lancet 1999; 354:30

In the setting of elevated transaminases with negative viral and immunologic makers, the most likely histologic dx is steatosis, regardless of obesity, hyperlipidemia or DM. AIM 1999:130:202

The use of ACE-I, in addition to conventional anti-hypertensive Rx, in patients with non-diabetic nephropathy will reduce the progression to ESRF. Lancet 1999;354:359

A comparison of convention anti-HTN Rx (beta blocker ±HCTX±amiloride) vs ACE-I vs Calcium channel blocker in elderly (70-84 yo) with SBP>≥180, and/or DBP≥105. BP was equally lowered and overall end points (CV mortality, MI, CVA, total mortality, major CV event) were the same in all groups. Thus, the choice of Rx should be individualized based on cost, side effects and coexisting dz. Thiazide should be the first line therapy in most elderly unless relevant co-morbidities exist.. Lancet 1999:354:1751

In patients with EF≤40%, metoprolol Cr/XL 12.5-25 mg titrated to 200 mg qd over 2 months, was added to conventional rx for CHF. Mortality was reduced from 11%/year to 7.2%/year Lancet 1999:353:2001

Modest walking is associated with significant reduction in CV mortality in women. More vigorous exercise results in a larger reduction in CV mortality. NEJM 1999:341:650

Patients with idiopathic venous thromboembolic event should be anticoagulated for at least 3 months. The optimum duration for anticoagulation is unknown but the results suggest that 2 years or more Rx may further decrease the risk of recurrent DVT. There was no increased risk of hemorrhage in the prolonged treatment group. NEJM 1999;340:901

Terbinafine (Lamisil) 250 mg qd for 12-16 weeks for patient with onychomycosis had a higher cure rate than itraconazole (Sporanox) pulse Rx. Cost was $400-600/course of therapy. BMJ 1999:318:1031

Helical CT is better (100% sensitivity and specificity) at identifying nephrolithiasis than IVP. AJR 1999 172:1491

In adults with asthma who require at least 1 puff of a bronchodilator a day, adding either beclomethasone 200 mcg puffs BID or montelukast (Singular)10 mg po BID improved respiratory status but beclomethasone was marginally better. AIM 1999;103 487

In patients with an asthmatic exacerbation, who are already on chronic oral steroids, the addition of an inhaled steroid will reduce the asthma relapse rate. JAMA 1999;281;2119

The use of 3 day of Solumedrol 125 mg IV q6h followed by oral Prednisone taper reduces the relapse rate and length of hospitalization in COPD patient admitted with acute exacerbation. The patients should receive only a 2 week course of out patient steroids on discharge. NEJM 1999:340:1941. Oral steroids also will reduce the length of hospitalization. Lancet 1999:354;456. In both studies, hyperglycemia was more common in the treatment group.

Ipratropium bromide should be the first line Rx for COPD, followed by the addition of an inhaled albuterol. Combination rx is better than either agent alone. Chest 1999:354;456

t-PA, (no ASA within 24 h) given within 3 hours of onset of an ischemic stroke reduced disability at 12 months (favorable outcome was 50% vs 38%, NNT=8.3) with a slight increased incidence of ICH (8% vs 1.6%, NNT=15.6). There was no benefit if the initial deficit was large and mortality was the same. NEJM 1999:340:1781. In a second study, t-PA given 3-5 hours after onset of symptoms did not have a favorable effect on neurologic outcome and resulted in an increased incidence of ICH. JAMA 1999;282:2019

The etiology of syncope in geriatric patients can be predicted based on history. A cardiovascular (28%) etiology (including orthostatic hypotension, carotid sinus hypersensitivity and vasovagal) was predicted by the presence of syncope, lightheadedness, pallor, need to sit or lie down and symptoms precipitated by prolonged standing. A peripheral vestibular disorder (18%) if pt described vertigo. 14% had a central neurologic disorder and 18% had more than 1 dx while 22% were idiopathic. JAGS 1999:47:12

Chronic insomnia in the elderly treated with drug therapy alone more often than not leads to dependency. A short course of cognitive therapy (stimuli control, sleep hygiene, sleep restriction,) leads to sustained improvement for at least 2 years. JAMA 1999:281;991

A restricted transfusion policy (maintain hemoglobin of 7-9 g/dl vs 10-12g/dl) in critically ill patients results in at least equal if not superior outcomes in critically ill patients. Thus, do not transfuse patients unless the hct<21%-27%, except possibly in patients with unstable angina. In this study, transfusions increase the rate of cardiac events. NEJM 1999:340:409

One in 200 patient of northern European ancestry are homozygous of hereditary hemochromatosis. Their dx is often delayed as they present with nonspecific complains including arthralgias (44%), fatigue (45%), impotence or loss of libido (28%) 27% were Rx’ed with iron supplements before they were finally diagnosed with HH. The initial screening should be a fasting transferrin saturation followed by HFE genotype (if saturation≥45%). NEJM 1999:341: 718, AIM 1999:130:953, AJM 1999:106:619

IV doxycycline alone is efficacious for mild to moderately severe community acquired pneumonia. It was associated with a lower mean clinical response time, shorter length of hospitalization and lower hospital cost. Arch Int Med 1999:159:266

Antibiotic Rx (erythro, doxycycline or Bactrim) for acute bronchitis decrease d cough by 0.5 days and days loss from work by only 0.3 days and thus the small benefit did not outweigh the societal risks associated with resistance. AJM 1999:107:62

Some of the inefficiencies of clinical care derive from the lack of awareness of tests already done. AJM 1999:106:144 (When tests are ordered using ComChart EMR, the user is inform when the proposed test was last performed.)

When computer algorithms are used, the mean number of days it takes to achieve therapeutic INR is reduced from 4.7 to 2.8 days. J Arthoplasty 1999:14:988

The simultaneous transplant of the pancreas and kidney has beneficial effect on survival when compared to renal transplant alone. Lancet 1999:353:1915

Bed rest is not helpful in treating sciatica and should only be used in the hyperacute phase NEJM 1999:340:418 Exercise program for low back pain reduce days lost from work by 50%. BMJ 1999:319:279

Right frontal lobe damage correlates with loss of ability to appreciate humor Brain 1999:122:657 (I too would be bummed if I infracted my right frontal lobe.)

When possible, the serum sodium should be raised no faster than 9 mEq/l/d to prevent central and extrapontine myelinolysis J Neurology 1999:246;700

Neurontin (gabapentin) is less toxic and as effective as amitriptyline for diabetic neuropathy. Arch Int Med 1999;159;1031

Hyperhomocysteinemia is associated with CVA and death. AIM 1999:131;352

Prophylactic bilateral mastectomy reduced the incidence of breast cancer (in women at moderate to high risk) and death from breast cancer by 90%-100% Approximately 30-35 women would have to have prophylactic bilateral masectomies to save one life. NEJM 1999:340:77 The use of the breast cancer gene (BRCA1 and BRCA2) to better assess risk and treatment with either tamoxifen (49% reduction in women at high risk) or raloxifene to reduce the incidence of breast cancer may provide the patient with a better assessment of their risk and an alternative to mastectomy.

A high intake of dietary fiber does not reduce the risk of colon cancer. NEJM 1999;340;169

Immediate anti-androgen Rx after a radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer. NEJM 1999:341:1781 (The treatment group was only 47 patients)

Men who drink one or more drink per week had a relative risk of stroke of 0.79 compared to those who drink less than one drink per week. NEJM 1999:341:1557 (2-4 drinks per week may be the optimal number.)

In patients who are at high risk of heart disease (h/o ASCVD, h/o CVA, h/o PVD or h/o DM with one other cardiac risk factor), the treatment with ramipril (Altace) 10 mg qd resulted in a relative risk of 0.78 for CV events, death vs the placebo group. NEJM 2000:342,145

Risedronate 5 mg qd, begun at the time of chronic steroid rx help prevent the loss of bone which occurs with chronic steroid Rx. Arth & Rheum 1999:42:2309. Prior studies have shown the Fosamax and cyclic Didronel can help prevent steroid induced bone loss as can thiazides, Vitamin D + calcium rx, Rocaltrol and exercise.

The use of HRT was not associated with a statistically significant increased incidence (RR=1.11) of breast cancer (of all types) when compared to women who never used HRT. However there was an increased incidence of invasive breast cancer of favorable histology (which makes of 5% of all breast cancers) while there was no increased incidence in the remaining 95% of breast cancers (DCIS or invasive ductal or lobular cancers) JAMA 1999:281:2091

There is no significant difference in ovarian cancer mortality between the screened (CA-125 measured) and the control group. Screening is not currently recommended for average risk women.

Optimal cost effective workup for TIA
1.Confirm TIA by history (r/o sz, hypoglycemia, migraine, head trauma, vasculopathy, f/h aneurysm)
2.Thorough medical and neurologic exam to r/o subtle neuro deficit, bilateral BP, heart, carotids,
3.Hospitalize high risk patients
4.Head CT without contrast, ECG, CBC, PT, PTT, glucose, BUN/Cr, ESR, RPR, lipids
5.If known cardiac dz or abnormal ECG, add echo or TEE
6.In general, MRI is not indicated. Consider MRI if suspected vascular malformation, cerebral aneurysm or cerebral thrombosis
7.MRA obtained with contrast bolus method is sensitive for assessing hemodynamically significant extracranial carotid stenosis (better than carotid u/s, institution dependent)
8.Cerebral angiography in selected cases

The new drug Aggrenox (ASA 25 mg + dipyridamole 200 mg) BID may not be any more effective than ASA 325 mg qd or Plavix 75 mg qd in preventing strokes.

Colon cancer screening: All screening methods (stool OB q1y, sig q5y, stool OB q1y + sig q5y, DCBE q10y, colonoscopy q10) are equally effective in year of life gained/persons screened, cost/year of life saved.

Prostate Cancer screening: ACP-ASIM recommends a patient/physician discussion mentioning:
1.prostate cancer is a serious disease
2.The benefits of screening and treatment have not been demonstrated
3.DRE and PSA can have false positive and false negative results
4.Follow-up invasive testing is often triggered by screening
5.Aggressive treatment is usually required if cancer is found
6.Treatment carries a fairly high risk of complications (ED, incontinent)
7.Early detection may save lives
8.Early detection may prevent cancer related illness
“If men are not sure, my default is to not screen, until we have further evidence…” Andrew Wolf, M.D., FACP

Microalbuminuria (30-300 µg/mg Cr) is the earliest manifestation of diabetic nephropathy and is a marker for a greatly increased CV risk in DM-1 and DM-2 patients. If present, screening for other vascular disease may be indicated and other risk factors should be treated aggressively. The measurement of a spot urine albumin/creatinine ratio is the easiest method to screen for nephropathy. Some advocate at least 2-3 samples to make a diagnosis. Others argue that treatment with an ACE-I may be advantageous for all diabetics and stringent diagnosis is thus not necessary if an ACE-I is to be used. Diabetes Care 1999L22(sup I)

There is little added benefit to Rx hypertension with the combination of a high dose ACE-I and an ARB. (Usually the ACE-I is not titrated to a high enough dose.) There is data showing that combination Rx may be useful in CHF, IgA nephropathy and DM nephropathy. Before combination Rx is widely used, further studies are needed…… .Caution must be exercised when using Celebrex and Vioxx in patients with renal insufficiency, CHF, cirrhosis, elderly, volume depleted and poorly controlled hypertension. These agents may be more “renal friendly” but larger studies are needed…. Todd Gehr, M.D.

The TSH is the best screening test for hypothyroidism (with the exception of the rare patient with hypothalamic/pituitary disease). There is no consensus on the issue of whether all patients should routinely be screen for thyroid dysfunction. ACP-ASIM, Amer Assoc of Clin Endo and Amer Thyroid Assoc recommends screening women >50-60 yo whereas the Royal College of Physicians, the Canadian Task Force on The Periodic Health Examination and the US Preventative Services Task Force believes routine screening is unjustified/not indicated. High risk subgroups, in whom screening can be justified include women>60, patients with hyperlipidemia, + thyroid antibodies, other autoimmune diseases, Down’s syndrome, Turner’s syndrome, Klinefelter’s syndrome, depression, DM-1, Addison’s disease, sleep apnea, h/o thyroid dysfunction, Rx with lithium, amiodarone or interferon, women planning pregnancy or immediately post-conception, patient with h/o head/neck XRT, post partum women with DM-1 or h/o post partum thyroiditis…….A high percentage of patients with subclinical hypothyroidism (TSH>6 and normal FTI,T3) will slowly progress to hypothyroidism. Progress is more likely if the initial TSH>10, thyroid Ab are present, older age, h/o thyroid surgery or 131-I rx. There is no consensus on whether to Rx subclinical hypothyroidism. It may be reasonable if TSH>10, + thyroid Ab, mild hyperlipidemia, vague symptoms, h/o 131-I rx, depression and pregnant women. David Gardner, M.D., FACP (I would also Rx subclinical hypothyroid patient with LT4 25 mcq qd if the patient was likely to bounce from MD to MD, as this will assure serial measurement of the patient’s TSH. HZ)

What I learned at the American College of Physicians – American Society of Internal Medicine Annual Session 2000