When to start: as soon as possible

Debate regarding “When to start” antiretroviral (ARV) therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome (002) study, the field has been anchored to “CD4 counts” as the prime metric to indicate ARV treatment initiation for asymptomatic HIV‐positive individuals. The pendulum has swung back and forth, based mostly on the efficacy and toxicity of available regimens. In today's world, several factors have converged that compel us to initiate therapy as soon as possible: (i) The biology of viral replication (1 to 10 billion viruses/day) screams that we should be starting early. (ii) Resultant inflammation from unchecked replication is associated with earlier onset of multiple co‐morbid conditions. (iii) The medications available today are more efficacious and less toxic than in years past. (iv) Clinical trials have demonstrated benefit for all but the highest CD4 strata (>450 to 500 cells/µL). (v) Some cohort studies have demonstrated clear benefit of ARV therapy at any CD4 count, and almost all cohort studies have demonstrated no detrimental effects of early treatment. (vi) In addition to the demonstrated and inferred benefits to the individual patient, we now have a public health benefit of earlier intervention: treatment is prevention. Finally, from a practical/common sense perspective, we are talking about life‐long therapy. Whether we start at a CD4 count of 732 or 493/µL, the patient will be on therapy for over 40 to 50 years! There does not seem to be much benefit in waiting, and there is likely to be significant long‐term harm. Treat early!     

Implementing a fast-track protocol for patients undergoing bowel resection: not so fast

Background

Multimodality fast-track protocols have been shown to enhance recovery after bowel resection. However, it remains unclear which of the components impact outcomes and whether processes actually occur as intended.

Methods

Consecutive patients who underwent elective bowel resection at a university teaching hospital under a standardized fast-track recovery protocol were compared with patients who underwent similar procedures before protocol initiation. Compliance was measured with the 7 major elements of the protocol: administration of nonopioid analgesia, perioperative lidocaine, nasogastric tube removal, early feeding, early ambulation, and fluid restriction.

Results

Eighty pathway patients were compared with 87 conventional patients. Only 3 of the 7 major components were successfully implemented. Fluid restriction was achieved in only 2 patients. Pain scores and ileus-related morbidities were comparable with the exception of nasogastric tube reinsertion, which was required twice as often in pathway patients (17 vs 8, P = .02). Thirteen pathway patients were readmitted compared with 7 control patients (P = .11).

Conclusions

The delivery of expected care cannot be assumed. There was no discernible benefit in patient outcomes.     

Vascular calcification: not so crystal clear

Patients with renal failure are predisposed to calcification of the medial layer of arteries. This calcification is far more complex than simple precipitation of calcium and phosphate and involves multiple forms of calcium phosphate. Like bone, calcification in the vessels also involves biologic events. The two are necessarily linked and unraveling the pathophysiology will require an understanding of both.     

Tamoxifen in breast cancer: not so easy to write off

For the past 30 years, tamoxifen has saved millions of lives throughout the world. The same has been proven in randomized trials and metaanalyses. Recent trials have shown clinical superiority of aromatase inhibitors over tamoxifen in terms of disease free survival and reduction in complications. However, because of the unique mechanism of tamoxifen, intrinsic advantages and low cost, this wonderdrug may still be a reasonable choice for hormonal therapy in breast cancer.     

Posing the research question: not so simple

Purpose

The success of any research process relies, in part, on how well investigators are able to translate a clinical problem into a research question—a task that is not so simple for novice investigators. The PICOT approach requires that the framing of the research question specify the target Population, the Intervention of interest, the Comparator intervention, key Outcomes, and the Time frame over which the outcomes are assessed. This paper describes the use of the PICOT structure in framing research questions and examines PICOT criteria as applied to the anesthesia literature. We also provide a roadmap for applying the PICOT format in identifying and framing clear research questions.

Methods

In addition to searching MEDLINE for the literature on framing research questions, we performed a systematic review of articles published in four key anesthesia journals in 2006, including Anesthesiology, Anesthesia & Analgesia, the British Journal of Anaesthesia, and the Canadian Journal of Anesthesia.

Results

Three hundred thirteen articles (n = 313) were included in this review, with the following distribution by study design: 139 (44%) randomized controlled trials, 129 (41%) cohort studies, and 45 (15%) case-controlled, cross-sectional studies or systematic reviews. Overall, 96% (95% confidence interval: 91,100) of articles did not apply the PICOT approach in reporting the research question.

Conclusions

The PICOT approach may be helpful in defining and clearly stating the research question. It remains to be determined whether or not compliance with the PICOT style, or any other format for framing research questions, is associated with a higher quality of research reporting.     

Vestibular rehabilitation: useful but not universally so.

OBJECTIVE: Although vestibular rehabilitation (VR) is gaining popularity, few data support its utility in improving locomotor stability, and no good predictors exist of whom will benefit most. STUDY DESIGN AND SETTING: A double-blind, placebo-controlled randomized trial of vestibular rehabilitation was conducted at a large tertiary care hospital on 124 patients (59 +/- 18 years old) with unilateral (n = 51) or bilateral (n = 73) vestibular hypofunction, of whom 86 completed a 12-week intervention. Of these 86, 27 returned for long-term (1-year) follow-up testing. The primary outcome measure was locomotor stability. RESULTS: Group A (6 weeks of VR) significantly (P < 0.01) increased their gait velocity and stability compared with group B (6 weeks of strengthening exercise), but there was a smaller difference (P = 0.05) between groups at 12 weeks, when both had had VR; there were no group differences at 1 year. Of the 86 who completed the intervention, 52 (61%) had clear locomotor gains. CONCLUSION AND SIGNIFICANCE: VR is helpful for most patients in providing locomotor stability, but further work is needed to determine the factors that prevent VR from being effective for all patients with vestibulopathy.