The Medical Short Case: An examination guide

We have come out with a book on clinical examination with the emphasis on local experience and cases. These are common examination cases.

This book is designed to meet the need of those preparing for exam (undergraduate or postgraduate).We try to illustrate each case with reasonable approach and share interesting signs. The cases chosen are relevant to our local practice. Commonly asked questions

were discussed in this book.

Topical Timolol Effective for Infantile Hemangioma

Khunger N and Pahwa M. Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome. Br J Dermatol 2011 Apr; 164:886.

Since 2008, propranolol has been used increasingly for the off-label treatment of infantile hemangiomas. Timolol is a topical beta-blocker commonly used for glaucoma that showed therapeutic promise for hemangiomas in a few case reports and small pilot studies.

Case report from India describe the treatment of an 18-month-old girl with PHACE syndrome and an extensive, disfiguring hemifacial hemangioma complicated by ulceration, palpebral occlusion, and ipsilateral cerebellar hypoplasia.

After systemic corticosteroids failed to produce response, topical timolol ophthalmic solution 0.5% was applied to the hemangioma (10 drops, twice daily). The hemangioma shrank dramatically within a week, and timolol was discontinued at 12 weeks.

Pulse, blood pressure, and serum glucose were monitored closely and remained stable throughout treatment. Local irritation was the only reported adverse effect.

Comments:
Randomized, controlled studies of the safety and efficacy of topical beta-blockers for hemangiomas are under way.

In this case report, systemic absorption of timolol may have been a key factor in the dramatic success. Until we know more, systemic therapy should probably remain first-line therapy for time-sensitive problematic hemangiomas (e.g., those that threaten vision).

Antiretrovirals Protect Partners of HIV-Infected Patients

Treating HIV-infected People with Antiretrovirals Protects Partners from Infection. Findings Result from NIH-funded International Study

Large-scale clinical study (phase 3 clinical trial) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The clinical trial, known as HPTN 052, was slated to end in 2015 but the findings are being released early as the result of a scheduled interim review of the study data by an independent data and safety monitoring board (DSMB).

The DSMB concluded that it was clear that use of antiretrovirals by HIV-infected individuals with relatively healthier immune systems substantially reduced transmission to their partners.

The results are the first from a major randomized clinical trial to indicate that treating an HIV-infected individual can reduce the risk of sexual transmission of HIV to an uninfected partner.

HPTN 052 Study

Study Objective:

Primary goal: To evaluate whether ARV use by the HIV-infected individual reduced HIV transmission to the uninfected partner and potentially benefited the HIV-infected individual as well.

Secondary goal: To evaluate the optimal time for a person infected with HIV to initiate antiretrovirals in order to reduce HIV-related sickness and death.

Study Period: Began in April 2005; run until 2015

Number of subjects: Enrolled 1,763 couples

Study Population:

1. All at least 18 years of age.
2. The vast majority of the couples were heterosexual(97%).
3. Precludes any definitive conclusions about effectiveness in MSM.
4. At the time of enrollment, the HIV-infected partners (890 men, 873 women) had CD4+ T-cell levels—a key measure of immune system health—between 350 and 550 cells per cubic millimeter (mm³) within 60 days of entering the study.
5. The HIV-uninfected partners had tested negative for the virus within 14 days of entering the study.
6. The sex of the infected partner was close to a 50-50 split between men and women.
7. At the onset of the trial, all the infected partners had CD4 cell counts that did not warrant HIV treatment for their health.

Study Sites:

The study was conducted at 13 sites in Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe. The U.S. site collected only limited data because of difficulties enrolling participants into the study.

Study Protocol:

1. The investigators randomly assigned the couples to either one of two study groups.
2. In the first group, the HIV-infected partner immediately began taking a combination of three antiretroviral drugs (combination of 3 oral antiretroviral drugs).
3. In the second group (the deferred group / delayed ART), the HIV-infected partners began antiretroviral therapy when their CD4 counts fell below 250 cells/mm³ or an AIDS-related event, such as Pneumocystis pneumonia, occurred.
4. A trigger point set by the World Health Organization that the organization raised to 350 cells/mm3 in the middle of the study.
5. Throughout the study, both groups received HIV-related care that included counseling on safe sex practices, free condoms, treatment for sexually transmitted infections, regular HIV testing, and frequent evaluation and treatment for any complications related to HIV infection.
6. Each group received the same amount of care and counseling.
7. Individuals who became HIV-infected during the course of the study were referred to local services for appropriate medical care and treatment.
8. HIV-infected participants in the deferred treatment group will be offered antiretroviral therapy.
9. The study investigators will continue following the study participants for at least one year.

Study Sponsor:

The study was conducted by the HIV Prevention Trials Network, which is largely funded by NIAID with additional funding from the National Institute on Drug Abuse and the National Institute of Mental Health, both part of the NIH.

Additional support was provided by the NIAID-funded AIDS Clinical Trials Group.

The antiretroviral drugs used in the study were made available by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/Viiv Healthcare and Merck & Co., Inc.

Background of the study:

Clinicians have long suspected that antiretrovirals that benefit HIV-infected patients also could benefit their partners, but no clinical trial has proven that beyond a reasonable doubt.

Previous data about the potential value of antiretrovirals in making HIV-infected individuals less infectious to their sexual partners came largely from observational and epidemiological studies.

This new finding convincingly demonstrates that treating the infected individual—and doing so sooner rather than later—can have a major impact on reducing HIV transmission.

Starting HIV-infected patients immediately after diagnosis on oral antiretroviral therapy (ART) while their immune systems are still relatively healthy is highly effective in protecting their partners from infection.

HPTN findings provide "a powerful policy argument" to encourage widespread testing of individuals to identify those with HIV and get them started right away on ART, not only for their sake but also for their partners.

Results:

The 11 HIV drugs that were used in various combinations included the following:
•Atazanavir (300 mg once daily)
•Didanosine (400 mg once daily)
•Efavirenz (600 mg once daily)
•Emtricitabine/tenofovir disoproxil fumarate (200 mg emtricitabine/300 mg tenofovir disoproxil fumarate once daily)
•Lamivudine (300 mg once daily)
•Lopinavir/ritonavir 800/200 mg once daily (QD) or lopinavir/ritonavir 400/100 mg twice daily (BID)
•Nevirapine (200 mg taken once daily for 14 days followed by 200 mg taken twice daily)
•Ritonavir (100 mg once daily, used only to boost atazanavir)
•Stavudine (weight-dependent dosage)
•Tenofovir disoproxil fumarate (300 mg once daily)
•Zidovudine/lamivudine (150 mg lamivudine/300 mg zidovudine taken orally twice daily)

In its review, the DSMB found a total of 39 cases of HIV infection among the previously uninfected partners.

Of those, 28 were linked through genetic analysis to the HIV-infected partner as the source of infection. 7 infections were not linked to the HIV-infected partner, and 4 infections are still undergoing analysis.

Of the 28 linked infections, 27 infections occurred among the 877 couples in which the HIV-infected partner did not begin antiretroviral therapy immediately.

Only one case of HIV infection occurred among those couples where the HIV-infected partner began immediate antiretroviral therapy.

This finding was statistically significant and means that earlier initiation of antiretrovirals led to a 96% reduction in HIV transmission to the HIV-uninfected partner. The infections were confirmed by genetic analysis of viruses from both partners.

Additionally, 17 cases of extrapulmonary tuberculosis occurredin the HIV-infected partners in the deferred treatment arm compared with 3 cases in the immediate treatment arm, a statistically significant difference.

There were also 23 deaths during the study. 10 occurred in the immediate treatment group and 13 in the deferred treatment group, a difference that did not reach statistical significance.

Discussions:

The timing of ART gets debated,

With the adverse effects and expense of the therapy prompting some to advocate waiting until a patient's immune system takes a turn toward the worse.

Study results were promising but were not conclusive when it comes to choosing immediate over delayed treatment.Of the 23 deaths among study participants, 13 occurred in the delayed-treatment group compared with 10 in the other group. Some of the deaths were not related to HIV.

When all morbidity and mortality events were tallied, "there was a trend towards benefit" with immediate ART, "but it did not reach the 20% difference between study arms required for statistical significance."

In an ongoing international clinical study called Strategic Timing of Antiretroviral Therapy, NIAID is examining the optimal time for asymptomatic HIV-infected individuals to begin antiretrovirals.

Conclusion:

96% Reduction in HIV Transmission With Immediate ART

The efficacy of ART in preventing HIV transmission should not prompt serodiscordant couples to abandon other safe-sex practices such as condom use.

Anesthesia Reactions May Be More Common Than Thought - at Least in France

J Allergy Clin Immunol 2011
Dr. Paul Michel Mertes of the University Hospital Center of Nancy in France reported that allergic reactions to anesthesia are rare, but they may be more common than some past studies have suggested.

Using two national databases;
1. Estimated that between 1997 and 2004, there were about 100 allergic reactions for every million anesthesia procedures performed in France. That's somewhat higher,if compared with the earlier estimates from a pair of studies in the 1990s -- including a French study that put the rate at 100 reactions for every 1.3 million anesthesia procedures.

2. Women appeared to be at particular risk
The rate of allergic reaction among women was 155 per million anesthesia procedures, versus 55 per million for men. Unclear is why women in this study had a significantly higher rate of allergic reaction than men.

3. 72% of allergic reactions were IgE-mediated. Among adults with IgE-mediated reactions, 60% suffered serious cardiovascular or breathing problems.

4. The common cause of allergic reactions are neuromuscular numbing agents (58%), Latex then followed by antibiotics, which were linked to 13% of allergic reactions.


Different opinion from Dr. Richard P. Dutton, executive director of the Anesthesia Quality Institute -- a U.S. group that was formed in 2008 to create a national registry on anesthesia outcomes.

1. The findings do not mean that the rate of allergic reactions to anesthesia is going up. Traditionally, there has been no systematic reporting of allergic reactions to anesthesia in the U.S., so there is no hard number to compare the French estimate to. The (French study)current findings are based on more-comprehensive reporting of allergic reactions than were the earlier studies.

2. Doubts about how applicable these findings would be in the U.S - "That doesn't match with the American experience," where antibiotics and propofol have been most commonly implicated in allergic reactions during anesthesia.

3. Why female are more prone to develop allergic reactions. But there are two theories, according to Dutton.
a. Strogen plays some role in the reactions to certain anesthesia agents.
b. French women may have been exposed to certain chemicals in cosmetics that primed their immune systems to react to structurally similar chemicals used in anesthesia.

Herpes Shedding Patterns Show Wide Risks for Transmission

Herpes Shedding Patterns Show Wide Risks for Transmission
JAMA 2011;305(14):1441-1449. doi: 10.1001/jama.2011.420

Among patients seropositive for herpes simplex virus type 2, genital shedding is "likely universal," regardless of symptoms, according to a JAMA study.

Researchers followed some 500 seropositive individuals for 2 months, during which the subjects collected daily swabs from the genital area. Rates of viral shedding were twice as high among symptomatic participants, but even asymptomatic subjects showed shedding on 10% of days. In addition, the number of virus copies shed was similar between symptomatic and asymptomatic participants.

The authors say their findings suggest that clinical management of seropositive — but asymptomatic — patients should include anticipatory guidance on recognizing genital symptoms as well as counseling on condom use, valacyclovir therapy, and the need to disclose serostatus to sexual partners.

Finally, Evidence That Sunscreen Delivers

Primary melanomas developed less often with daily, rather than discretionary, sunscreen use.

Published in Journal Watch Dermatology March 11, 2011

Citation:
Green AC et al. Reduced melanoma after regular sunscreen use: Randomized trial follow-up. J Clin Oncol 2011 Jan 20; 29:257.
Gimotty PA and Glanz K. Sunscreen and melanoma: What is the evidence? J Clin Oncol 2011 Jan 20; 29:249.

Comment:

This large, community-based sunscreen trial is likely the last of its scope.

The findings won't change sunscreen recommendations but do provide clear support for its use.

Sunscreen alone is insufficient to eliminate melanoma risk, and the effects of all-form sun protection on melanoma mortality are unknown. Also, these findings leave unaddressed sunscreen use in less-sunny locations and in populations with other skin tones.

Nevertheless, this carefully executed and ambitious study is commendable. The same trial has already shown reduced squamous cell carcinoma risk, so its clinical implications are compelling.

One could question the borderline significance of the risk reductions, or note that the incidence of melanoma versus non-melanoma skin cancers undermined the study's power from the beginning, but the author of an accompanying editorial carefully outlines the statistical rigor of this trial.

Penang Dermatology Symposium 2011 - Final Announcement

Visit web at www.penangdermatologysymposium.blogspot.com or www.dermatologyhpp.blogspots.com