‘Berlin Patient’ Raises Hopes For HIV Treatment Gains

The patient—dubbed "the Berlin patient" after his home city—was started on antiretroviral therapy soon after being infected with HIV but prior to seroconversion on the Western blot test. He was treated with the "new HAART" (highly active anti-retroviral therapy) regimen, consisting of hydroxyurea (HU), didanosine (ddI), and indinavir. The regimen was designed to provide a simple, long-lasting, and affordable means of leveraging the immune system’s ability to fight HIV, with less potential for treatment resistance than is the case with other HIV pharmacotherapy approaches.

The patient’s HIV viral load quickly declined with treatment and became undetectable in plasma. Viral load rebounded, however, during a temporary treatment suspension while the patient had an accompanying infection. After 176 days of intermittent treatment with the HAART regimen, and during the two years after stopping treatment completely, the patient has not had a rebound, and immune markers seem to have normalized. Phenotypic markers such as CD4 count and the ratio of CD4 to CD8 T lymphocytes increased to normal levels.

While no HIV-neutralizing antibodies were found, a "vigorous HIV-specific helper T [cell] response progressively increased during two years of follow-up in the absence of treatment," Julianna Lisziewicz, PhD, and colleagues at Georgetown University, Washington, D.C., reported in a letter detailing the case of the Berlin patient (N Engl J Med 1999;340:1683). "There are three factors that separated the ‘Berlin patient’ from other HIV-infected persons: HU/ddI-based combination therapy, early treatment, and stop- and-go therapy," they noted.

The case has led some HIV researchers to explore the idea of bolstering the immune system without completely eradicating HIV. The Georgetown University researchers reported that eight patients to date have undergone robust suppression of HIV and rapid immune system normalization on the new HAART regimen. While these patients were not treated intermittently, their experience furthers supports the hypothesis that a HU-ddI combination can reduce viral load and reconstitute the immune system.

Are New Antidepressants Really Better than Old Stand-bys?

The study was a multivariate analysis of 206 randomized studies involving a total of 16,290 patients. Comparison of outcomes data revealed that improvement in depressive symptoms of at least 50% occurred in about 54% of patients regardless of whether they were taking older or newer medications.

The older agents studied included first- and second-generation tricyclic antidepressants, one tetracyclic agent, and triazolopyridine. The newer agents studied included: the selective serotonin uptake inhibitors (SSRIs) fluoxetine, fluvoxamine, paroxetine, and sertraline; the selective norepinephrine reuptake inhibitors mirtazapine and venlafaxine; the reversible monoamine oxidase A inhibitors moclobemide, medifoxamine, brofaromine, and toloxatone; the 5-HT2 receptor antagonist nefazodone; the 5-HT1A receptor agonist gepirone; the ganamimetic agent fengabine; and the dopamine reuptake inhibitor bupropion.

Overall, fewer patients stopped taking the newer agents than stopped taking the older agents. Drop-out rates due to adverse events among those using newer agents, tricyclic agents, and placebo were 8%, 13%, and 2%, respectively. Adverse effects associated with the newer drugs were different—but not necessarily more benign—than those associated with the older drugs, the AHCPR study found. For example, while patients receiving the first-generation tricyclics had significantly higher rates of dry mouth, constipation, dizziness, blurred vision, and tremors than those receiving SSRIs, use of SSRIs was associated with significantly higher rates of diarrhea, nausea, insomnia, and headache.

In light of their apparently comparable effectiveness, both older and newer agents should be considered when making treatment decisions for depression, the study authors concluded. "When selecting antidepressants, clinicians should consider costs, the small but statistically significant differences in dropouts due to adverse effects, the lack of information about relative benefits compared to alternative therapies, and an individual patient’s tolerance for particular adverse effects."

Results of another recent AHCPR-funded study focusing on treatment of sinus disorders suggest that amoxicillin and folate inhibitors are in many cases as effective as newer, more expensive antibiotics. "The current evidence does not justify the use of new antibiotics" for treating community-acquired acute bacterial rhinosinusitis, the investigators concluded.

Less Drugs, More Exercise Hold Key to Fall Prevention

In their 25-year study, the investigators noted an alarming increase in the number and rate of falls after age 50. The study also found that the number of falls among older Finns quadrupled from 5,622 in 1970 to 21,574 in 1995, while the rate of falls nearly tripled over that period, from 494 to 1,398 per 100,000.

The steep rise in falls and fall rates in recent decades is partly explained by growth in the numbers of elderly people. Yet even after accounting for demographic factors, the researchers found that the incidence of falls more than doubled among both men and women during the study period (JAMA 1999;281:1895–9).

While their study was not designed to elucidate potential reasons for the increased number of falls, the investigators noted that previous research has shown that increased use of medications, coupled with naturally deteriorating mobility, sharply boosts the risk of falls in the elderly. Thinning bones and reduced muscular strength further increase the risk.

Commenting on the findings in an editorial in the same issue of JAMA, Mary Tinetti, MD, chief of geriatrics at Yale University School of Medicine, pointed out that a number of studies have documented the effectiveness of two fall-prevention measures: reduced medication use, and exercise to improve strength and balance. Dance or tai chi are good exercise options for healthy older persons, while frailer individuals might need physical therapy to guard against falls, she noted.

Readmission Rates Among Medicare HMO Enrollees

Analyzing Medicare hospital admission data, a team of researchers found that hospital readmission rates among 190 Medicare beneficiaries varied widely by service delivery model. In the FFS group, 13.7% were readmitted during the study period. Readmission rates were far higher in the Medicare HMO group (29.7%) and among elderly managed care enrollees receiving both Medicare and Medicaid benefits ("dual-eligibles").

Likewise, rates of "preventable" hospital readmissions were lower in the FFS group—7.8%, compared to 21.6% among the dual-eligibles and 26.2% among the HMO enrollees. HMO enrollees were about 3.55 times as likely to be readmitted as FFS beneficiaries, a statistically significant difference (Am J Prev Med 1999;16:163–72).

Speculating as to reasons for the observed wide variation in readmission rates, the study authors noted that while all groups studied had similar discharge protocols, HMO beneficiaries were initially authorized for only two home health care visits, while the FFS and dual-eligibles had no restrictions on these visits. Another contributing factor, the authors suggested, may be the generally shorter duration of initial hospital stays among HMO enrollees.

Origin of ‘Rx’ Symbol May Lie in the Eye of an Egyptian

According to a recent article by clinical pharmacologist Jeff Aronson in the British Medical Journal, the symbol does not represent the letters "R" and "x," an abbreviation of the Latin word for "recipe." Instead, he contends, the symbol derives from the symbol used by ancient Egyptians to signify the utchat, the eye of the ancient god Horus the Elder.

Egyptian legend holds that Horus had two eyes, the sun and the moon. Set, the god of darkness and evil, stole the sun eye. The deity Thoth attempted to end the conflict, but Set kept battling and cut off pieces of Horus’ remaining moon eye, which Thoth renewed each month—tidily explaining the lunar phases. Because of the theme of miraculous restoration, "the eye of Horus became a potent symbol of good fortune and healing, later adopted by the Greeks, Arabs, and others," according to Aronson (BMJ 1999;318:1543).

The eye symbol is easily recognized as the letter "R." In recent times, the use of "R," followed by "x" to indicate an abbreviation, has led to many new abbreviations, such as "Hx" for history and "Dx" for diagnosis.

Four amateur historians have already written to the journal to refute Aronson’s hypothesis and offer alternative theories about the origins of the "Rx" symbol.

To find out more, visit BMJ’s Web site (www.bmj.com).

David K. Buerger
Managing Editor