Impact of patient selection in various study designs: identifying potential bias in clinical results.

Many different study designs are used to address different types of clinical questions. The two broad categories are the experimental study, which is the randomized controlled trial, and observational studies, which includes all of the other basic study designs (cohort [prospective and retrospective] studies, case-control [etiologic] studies, cross-sectional [prevalence] studies, case series, and case reports). These study designs address basic categories of clinical questions: treatment, diagnosis, prognosis, and harm. This article focuses on some of these study designs, highlighting the impact of patient selection, inclusion, and exclusion criteria on results and outcomes through the use of specific examples.

Tricyclic antidepressants and headaches: systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches. DESIGN: Meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks. DATA EXTRACTION: Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index. RESULTS: 37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (ß=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97). CONCLUSIONS: Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.

Parathyroidectomy versus cinacalcet hydrochloride-based medical therapy in the management of hyperparathyroidism in ESRD: a cost utility analysis.

BACKGROUND: Previously, patients with end-stage renal disease (ESRD) with uncontrolled hyperparathyroidism had few options other than parathyroidectomy, which was reserved for patients refractory to medical therapy. Newer calcimimetic agents, such as cinacalcet, may be an alternative, but raise the possibility of indefinite medical treatment that also would increase costs. STUDY DESIGN: Cost utility analysis. SETTING & POPULATION: Base case consisted of prevalent adult US patients with ESRD refractory to management with standard medical therapy. Characteristics were obtained from patients who underwent parathyroidectomy in 2001, and, for purposes of comparison, patients in whom cinacalcet was used were assigned similar characteristics. All data came from preexisting literature and trials or from US Renal Data System analysis files. INTERVENTION: Use of cinacalcet hydrochloride versus parathyroidectomy. PERSPECTIVE & TIME FRAME: Medicare and societal costs and quality-adjusted life-years from the date of parathyroidectomy or use of cinacalcet followed up for 2 years, respectively. MODEL & OUTCOMES: Primary outcomes were cost (measured in US dollars) and cost utility measured using cost per quality-adjusted life-years. RESULTS: At base-case surgical and drug costs, surgical and drug success rates, complication rates/costs, and benefit from correction of hyperparathyroidism, parathyroidectomy was found to be both less expensive and more cost-effective at 7.25 +/- 0.25 months. Parathyroidectomy became more cost-effective at 15.28 to 16.32 months at the upper limit of sensitivity analysis, when drug/surgical costs and success/complication rates/costs were maximally weighted to favor cinacalcet-based medical therapy. LIMITATIONS: We assumed current costs of both cinacalcet and parathyroidectomy and assumed cinacalcet use would be indefinite. CONCLUSIONS: For patients with ESRD with uncontrolled hyperparathyroidism who are good candidates for either drug therapy or surgery, cinacalcet hydrochloride is the most cost-effective modality if the patient is to remain on dialysis therapy for 7.25 +/- 0.25 months. Cinacalcet may be more optimal if used in patients who have high risk of mortality or who would expect to receive a kidney transplant quickly. For other subgroups, parathyroidectomy dominated.

Humanitarian assistance medicine: perceptions of preparedness: a survey-based needs assessment of recent U.S. Army internal medicine residency graduates.

The U.S. military provides humanitarian assistance in many areas around the globe. With recent changes in the force structure of the U.S. Army, internal medicine physicians are now at the forefront of providing this care, but the extent of their involvement is not known. This study measured the frequency with which recently trained Army internists provided humanitarian assistance, and it assessed their perceived preparedness for such missions. All graduates from Army internal medicine programs for 4 consecutive years were invited by e-mail to participate in an Internet-based survey. Eighty-nine personnel (49% of those contacted) completed the survey. Of those in a deployable position for >6 months, 72% provided medical humanitarian assistance. Most thought that additional training was needed, especially in tropical disease management, sanitation, and the practices of civilian humanitarian workers. This study demonstrates that military-trained internists are frequently involved in humanitarian assistance medicine, and it suggests that they might benefit from additional training.

The impact of the Stanford Faculty Development Program on ambulatory teaching behavior.

CONTEXT: Faculty development has received considerable investment of resources from medical institutions, though the impact of these efforts has been infrequently studied. OBJECTIVE: To measure the impact of the Stanford Faculty Development Program in Clinical Teaching on ambulatory teaching behavior. DESIGN: Pre-post. SETTING AND PARTICIPANTS: Eight internal medicine faculty participating in local faculty development. INTERVENTION: Participants received 7 2-hour sessions of faculty development. Each session included didactic, role-play, and videotaped performance evaluation. MAIN OUTCOME MEASURE: Before and after the intervention, faculty were video-taped during a case presentation from a standardized learner, who had been trained to portray 3 levels of learners: a third-year medical student, an intern, and a senior medical resident. Teacher and learner utterances (i.e, phrases) were blindly and randomly coded, using the Teacher Learner Interaction Analysis System, into categories that capture both the nature and intent of the utterances. We measured change in teaching behavior as detected through analysis of the coded utterances. RESULTS: Among the 48 videotaped encounters, there were a total of 7,119 utterances, with 3,203 (45%) by the teacher. Examining only the teacher, the total number of questions asked declined (714 vs 426, P=.02) with an increase in the proportion of higher-level, analytic questions (44% vs 55%, P<.0001). The quality of feedback also improved, with less "minimal" feedback (87% vs 76%, P<.0005) and more specific feedback (13% vs 22%) provided. CONCLUSIONS: Teaching behaviors improved after participation in this faculty development program, specifically in the quality of questions asked and feedback provided.

Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis.

Oral pseudoephedrine is commonly used to treat symptoms of rhinitis and rhinorrhea, but its effect on blood pressure (BP) and heart rate (HR) remains uncertain. We assessed whether pseudoephedrine causes clinically meaningful elevations in HR or BP. We searched MEDLINE, EMBASE, and the Cochrane Library for English-language, randomized placebo-controlled trials of oral pseudoephedrine treatment in adults. The primary data extracted were systolic BP (SBP), diastolic BP (DBP), and HR. Study quality was assessed using the methods of Jadad, and data were synthesized using a random-effects model and weighted mean differences. Twenty-four trials had extractable vital sign information (45 treatment arms; 1285 patients). Pseudoephedrine caused a small but significant increase in SBP (0.99, mm Hg; 95% CI, 0.08 to 1.90) and HR (2.83 beats/min; 95% CI, 2.0 to 3.6), with no effect on DBP (0.63 mm Hg, 95% CI, -0.10 to 1.35). The effect in patients with controlled hypertension demonstrated an SBP increase of similar magnitude (1.20 mm Hg; 95% CI, 0.56 to 1.84 mm Hg). Higher doses and immediate-release preparations were associated with greater BP increases. Studies with more women had less effect on BP or HR. Shorter duration of use was associated with greater increases in SBP and DBP.