Chief Resident, Internal Medicine, Huntington Memorial Hospital

Judah was a friend and colleague who passed away on September 3rd 2005 after a long battle with illness. Those of us lucky enough to have known Judah have been blessed and will always remember his humor and charm, his dedication to his patients and his friends. Judah would keep photos of all the patients he followed in his clinic and place them in the inside cover of their medical charts. He felt more connected to his patients this way. They were never just a name or number in a chart, they were his patients. We should remember him always and strive to maintain his ideals as we go on to care for others.

Judah will be missed by us all,
R. Toutounjian, MD

Dr. Shriner has asked us to look at two articles for the next Journal Club which will be on Wednesday March 09, 2005. The articles have already been placed in your mailboxes. If you can't find one, click on the link above to get to the articles.

Cost-Effectiveness of Screening for HIV
in the Era of Highly Active Antiretroviral Therapy

Gillian D. Sanders, Ph.D., Ahmed M. Bayoumi, M.D., Vandana Sundaram, M.P.H.,
S. Pinar Bilir, A.B., Christopher P. Neukermans, A.B., Chara E. Rydzak, B.A.,
Lena R. Douglass, B.S., Laura C. Lazzeroni, Ph.D., Mark Holodniy, M.D.,
and Douglas K. Owens, M.D.
n engl j med 352;6 February 10, 2005
__________________________________________________________

Methicillin-Resistant Staphylococcus aureus:
An Evolutionary, Epidemiologic, and Therapeutic Odyssey
Stan Deresinski, Division of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University, Stanford, and Santa Clara Valley
Medical Center, San Jose, California
Clinical Infectious Diseases 2005; 40:562–73

Methicillin-resistant Staphylococcus aureus, first identified just over 4 decades ago, has undergone rapid evolutionary changes and epidemiologic expansion. It has spread beyond the confines of health care facilities, emerging anew in the community, where it is rapidly becoming a dominant pathogen. This has led to an important change in the choice of antibiotics in the management of community-acquired infections and has also led to the development of novel antimicrobials.

Memorandum from David J. Graham, MD, MPH, Associate Director for Science, Office of Drug Safety to Paul Seligman, MD, MPH, Acting Director, Office of Drug Safety entitled, "Risk of Acute Myocardial Infarction and Sudden Cardiac Death in Patients Treated with COX-2 Selective and Non-Selective NSAIDs,"
September 30, 2004

The attached report was prepared for internal FDA use by an FDA staff person who was the principal FDA investigator on a study performed to investigate the cardiovascular risk of the COX-2 selective NSAIDs, rofecoxib and celecoxib, and a variety of non-selective, traditional NSAIDs. This report may differ from any subsequent manuscript publication of the study results. As of the date of posting (November 2), the report has not been fully evaluated by the FDA and may not reflect the official views of the agency. However, in light of the recent market withdrawal of Vioxx, FDA has decided to publicly release the document at this time. An error has been identified on page 6 of the report. The National Disease and Therapeutic Index collects detailed information from a representative panel of 3,500 physicians, not 2,000 physicians.

A 42-year-old woman presents with a palpable mass on the right side of her neck. She
has no neck pain and no symptoms of thyroid dysfunction. Physical examination reveals
a solitary, mobile thyroid nodule, 2 cm by 3 cm, without lymphadenopathy. The
patient has no family history of thyroid disease and no history of external irradiation.
Which investigations should be performed? Assuming that the nodule is benign,
which, if any, treatment should be recommended?

This sounds like an interesting conference. It's only half a day, you should be out by 12:30PM. Registration is free for residents. The breakfast is supposed to be "great!" and the location at the Athenaum, at the corner of Hill and California, is nice. There is free parking.


Objectives: "Identify current imaging techniques, including MRI, that enhance the detection, diagnosis, and treatment of breast disease. Discuss the role of estrogen therapy to include current research trends, safety concerns, and best practices. Discuss use of radiation therapy, brachytherapy, and cosmetic outcomes of the reconstructed radiated breast. Establish criteria for identifying high risk patients who may benefit from genetic testing and prophylactic therapy."

In preparation, please click on the link for the handout I'm preparing. This is a first draft and on the day of the review, I may have expanded it.

Thank You,
R. Toutounjian, M.D.

The issue of abnormal uterine bleeding is a common problem in internal medicine. The following article from AAFP provides a great overview of this topic. Please click on the link in the title above to get the full article.

Thank You,
R. Toutounjian, M.D.

Abnormal Uterine Bleeding
Abnormal uterine bleeding is a common presenting symptom in the family practice setting. In women of childbearing age, a methodical history, physical examination, and laboratory evaluation may enable the physician to rule out causes such as pregnancy and pregnancy-related disorders, medications, iatrogenic causes, systemic conditions, and obvious genital tract pathology. Dysfunctional uterine bleeding (anovulatory or ovulatory) is diagnosed by exclusion of these causes. In women of childbearing age who are at high risk for endometrial cancer, the initial evaluation includes endometrial biopsy; saline-infusion sonohysterography or diagnostic hysteroscopy is performed if initial studies are inconclusive or the bleeding continues. Women of childbearing age who are at low risk for endometrial cancer may be assessed initially by transvaginal ultrasonography. Postmenopausal women with abnormal uterine bleeding should be offered dilatation and curettage; if they are poor candidates for general anesthesia or decline dilatation and curettage, they may be offered transvaginal ultrasonography or saline-infusion sonohysterography with directed endometrial biopsy. Medical management of anovulatory dysfunctional uterine bleeding may include oral contraceptive pills or cyclic progestins. Menorrhagia is managed most effectively with nonsteroidal anti-inflammatory drugs or the levonorgestrel intrauterine contraceptive device. Surgical management may include hysterectomy or less invasive, uterus-sparing procedures. (Am Fam Physician 2004;69:1915-26;1931-2. Copyright© 2004 American Academy of Family Physicians.)

On this day we'll review the various oral agents for the treatment of Type II DM. There is an excellent article in the NEJM called Initial Management of Glycemia in Type II Diabetes Mellitus. Click on the link for the article and an accompanying Letters to the Author section.

Thank You,
R. Toutounjian, M.D.

I thought we could shake things up a little for morning report next Wednesday. Instead of following our usual case presentation and discussion format, we will review an article published in American Academy of Family Physicians. Our Goal is to review insulin therapy for type 2 diabetics. We will cover the various forms of insulin therapy commonly used, from ultra short to very long acting insulins, the various schemes of insulin administration and their proper use. The article is:

Insulin Therapy for Type 2 Diabetes:
Rescue, Augmentation, and Replacement
of Beta-Cell Function
JENNIFER A. MAYFIELD, M.D., M.P.H., Seattle, Washington
RUSSELL D. WHITE, M.D., University of South Florida College of Medicine, Tampa, Florida

Type 2 diabetes is characterized by progressive beta-cell failure. Indications for
exogenous insulin therapy in patients with this condition include acute illness or
surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals
with oral antidiabetic medications, and a need for flexible therapy. Augmentation
therapy with basal insulin is useful if some beta-cell function remains. Replacement
therapy with basal-bolus insulin is required for beta-cell exhaustion. Rescue
therapy using replacement regimens for several weeks may reverse glucose toxicity.
Replacement insulin therapy should mimic normal release patterns. Basal insulin,
using long-acting insulins (i.e., neutral protamine Hagedorn [NPH], ultralente,
glargine) is injected once or twice a day and continued on sick days. Bolus (or
mealtime) insulin, using short-acting or rapid-acting insulins (i.e., regular, aspart,
lispro) covers mealtime carbohydrates and corrects the current glucose level. The
starting dose of 0.15 mg per kg per day for augmentation or 0.5 mg per kg per day
for replacement can be increased several times as needed. About 50 to 60 percent
of the total daily insulin requirement should be a basal type, and 40 to 50 percent
should be a bolus type. The mealtime dose is the sum of the corrective dose plus
the anticipated requirements for the meal and exercise. Adjustments should be
made systematically, starting with the fasting, then the preprandial and, finally, the
postprandial glucose levels. Basal therapy with glargine insulin provides similar
to lower A1C levels with less hypoglycemia than NPH insulin. Insulin aspart and
insulin lispro provide similar A1C levels and quality of life, but lower postprandial
glucose levels than regular insulin. (Am Fam Physician 2004;70:489-500,511-2.
Copyright© 2004 American Academy of Family Physicians.)

For our next Journal Club we thought that using an article grounded more in the outpatient setting might be interesting. Dr. Koerner found this article in Annals that I also liked.

The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial

Linda Stern, MD; Nayyar Iqbal, MD; Prakash Seshadri, MD; Kathryn L. Chicano, CRNP; Denise A. Daily, RD; Joyce McGrory, CRNP; Monica Williams, BS; Edward J. Gracely, PhD; and Frederick F. Samaha, MD

18 May 2004 | Volume 140 Issue 10 | Pages 778-785

Background: A previous paper reported the 6-month comparison of weight loss and metabolic changes in obese adults randomly assigned to either a low-carbohydrate diet or a conventional weight loss diet.

Objective: To review the 1-year outcomes between these diets.

Design: Randomized trial.

Setting: Philadelphia Veterans Affairs Medical Center.

Participants: 132 obese adults with a body mass index of 35 kg/m² or greater; 83% had diabetes or the metabolic syndrome.

Intervention: Participants received counseling to either restrict carbohydrate intake to <30> or to restrict caloric intake by 500 calories per day with <30% of calories from fat (conventional diet).

Measurements: Changes in weight, lipid levels, glycemic control, and insulin sensitivity.

Results: By 1 year, mean (±SD) weight change for persons on the low-carbohydrate diet was –5.1 ± 8.7 kg compared with –3.1 ± 8.4 kg for persons on the conventional diet. Differences between groups were not significant (–1.9 kg [95% CI, –4.9 to 1.0 kg]; P = 0.20). For persons on the low-carbohydrate diet, triglyceride levels decreased more (P = 0.044) and high-density lipoprotein cholesterol levels decreased less (P = 0.025). As seen in the small group of persons with diabetes (n = 54) and after adjustment for covariates, hemoglobin A_1c levels improved more for persons on the low-carbohydrate diet. These more favorable metabolic responses to a low-carbohydrate diet remained significant after adjustment for weight loss differences. Changes in other lipids or insulin sensitivity did not differ between groups.

Limitations: These findings are limited by a high dropout rate (34%) and by suboptimal dietary adherence of the enrolled persons.

Conclusion: Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glycemic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss.

I wanted to make sure everyone was aware that Thursday Sept 2nd we have a mandatory lecture on airway management from 11AM to 1PM in the Braun Auditorium. This is for all residents, including away residents at outpatient and community clinic rotations. Only residents at USC will be excused, but I would still encourage them to attend. Make sure your attendings know that you need to attend this session. We've been trying to coordinate this for 2 months now with surgery and medicine. We'll also have an intubation mannequin to practice techniques on. It will be an in-dept and I think very useful session. Afterwards, at 1PM, interested residents will be allowed into the OR to see a new intubation instrument used on real patients.

Thank You,

R. Toutounjian, M.D.

This month we'll begin our Pulmonary Board Review. Our first session will be Monday September 12. For now we'll have 2 sessions a month. If there is interest, I'm happy to increase these sessions. Please review the MK-SAP 13 Pulmonary section Questions and Answers. The MedStudy Pulmonary section is very good if you wish to review that as well. For this month, I'll expect all 3rd year residents to have reviewed the MK-SAP 13 Pulmonary Questions and Answers section and be prepared. For 1st year and 2nd year residents, I think you'll get much more out of the session if you're prepared. We will try not to read each question which will save time, therefore if you're prepared, you'll get much more out of these sessions.

Thank You,

R. Toutounjian, M.D.

Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis
NEJM March 8, 2001

ABSTRACT
Background Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis.
Methods We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 µg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C.
Results A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06).
Conclusions Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.

See Editorial in NEJM for this article

This link it to an excellent article on the Initial Management of Hyperglycemia in Diabetes and has the accomponieng Letters from the NEJM.

Raphael Toutounjian, M.D.

This years first Journal Club will be on the classic PIOPED study, JAMA May 23, 1990.
The full text of the article is available by clicking the link.

This article was one of the first really good evidence based articles that really ushered in the current era of Evidence Based Medicine. As residents in Internal Medicine, you will be expected to be familiar with this study and it's findings. This is tested on the IM board exam and is discussed in the ICU and on the Wards. We will be focusing on the statistics of the article although the content is very good also.

Thank you,
Raffi

Link to Internal Medicine calendar

Also check out this article on Guidewire Complication with Central Line Placement from Hospital Physician June 2004

Excellent medical articles. Click on the link!
I will strive to make available articles that are highly relevent to our lecture series. I will also include articles that I feel are important to us as Internal Medicine Doctors. My goal is not to have numerous articles, but rather articles that are focused to our teaching goals.

Thank You,

R. Toutounjian, M.D.