Clinical Briefs in Primary Care
Should Empiric Treatment be Given to Women with UTI
Source: Richards D, et al. BMJ. 331:143.
Women with a history of urinary tract infection (UTI) quickly learn to identify recurrences. Not uncommonly, women present with typical UTI Sx, but normal dipstick urinalysis results may discourage antibiotic treatment. Whether on-treatment is appropriate in this clinical scenario is called into question by this study.
Adult women (59) with acute onset dysuria and frequency plus negative dipstick (normal leukocytes and negative nitrite) were randomly assigned in a placebo-controlled double-blind fashion to trimethoprim (TRI) or placebo for 7 days.
Median time to dysuria resolution was significantly shorter for TRI than placebo (3 days vs 5 days). Constitutional symptomatology was also significantly reduced by 4 days with active treatment.
Only 5 women with UTI symptoms had positive bacterial culture results, and these women were equally distributed between treatment and placebo groups (3 and 2, respectively).
United States clinicians may be somewhat unfamiliar with prescription of trimethoprim as monotherapy. Oral TMP-SMX (eg, Bactrim, Septra) has been removed from the market in England except for inpatient parenteral therapy based upon the UK experience that the commonplace utilization of sulfonamides for UTI is responsible for an unacceptable burden of Steven’s-Johnson syndrome and agranulocytosis.
The authors conclude that symptom-driven empiric treatment of UTI is with trimethoprim is appropriate even in the face of a normal dipstick result.
Is Routine Fundoscopy Worth the Bother in Hypertension?
Source: van den Born BJ, et al. BMJ. 2005;331:73.
Common wisdom suggests that fundoscopy (FND) should be a routine examination among patients with hypertension. Although findings at FND may shape management choices in situations of hypertensive urgency or emergency, whether meaningful impact is achieved by FND in other settings is poorly defined. To that end, van den Born et al addressed data from 5 different trials (n ≥ 23,000) that provided information on retinal changes and blood pressure.
Because of the low prevalence of hypertensive retinopathy (HTN-R) in hypertension, the sensitivity of HTN-R was found to be only 3-21%. On the other hand, specificity (the percent of normal patients without HTN-R) was very high: 88-98%.
The predictive value of hemorrhages/exudates, AV nicking, and focal arteriolar narrowing as well as the association between HTN-R and LVH were each examined. Overall, the authors derive that there is limited value of fundoscopy in routine HTN management. Indeed, more than half of the time when hypertensive patients have retinal changes, it is not the HTN that is responsible for those changes.
Autoantibody Signatures in Prostate Cancer
Source: Wang X, et al N Engl J Med. 2005;353:1224-1235.
The value of routine psa screening continues to be debated. Despite convincing evidence that PSA-screened patients enjoy a reduced prostate cancer related mortality, no major trial has demonstrated that overall mortality is favorably effected by PSA screening. Hence, at this point, it is unknown whether the benefits outweigh the risks of PSA screening. Additionally, a not-insubstantial group of men with confirmed prostate cancer—perhaps as many 15-20%—do not have an elevated PSA at the time of diagnosis.
Cancer patients may produce plasma autoantibodies against tumor antigens. For instance, of persons proven to have prostate cancer, as many as 62% have plasma autoantibodies against alpha-methylacyl-coenzyme A racemase (AMCAR).
Use of a 22-phage-peptide panel in persons with confirmed prostate CA demonstrated 80-90% sensitivity to discriminate between patients with prostate cancer and controls. Interestingly, when prostate cancer subjects were analyzed for autoantibodies post-prostatectomy, many fewer positive tests were seen, suggesting that when the immunologic stimulus for autoantibody development is removed (ie, prostate cancer mass is excised), autoantibodies regress or disappear. Whether such a methodology will prove useful in large-scale screening remains to be determined.
Beta-Blockers and Treatment of Primary Hypertension
Source: Lindholm LH, et al. Lancet. 2005;366:1545-1553.
With all the cardiovascular science that has flowed through our journals in the past decade, one would think that all of the basic questions about hypertension (HTN) would have been answered by now. Were you to ask most clinicians whether beta-blockers (BETA) are appropriate first-line hypertensive agents, most would surely reply affirmatively. Remember that the ALLHAT trial, our largest-ever antihypertensive trial, did not contain a BETA treatment arm, hence the only available comparisons from that trial are between diuretic, ACE inhibitor, calcium channel blocker, and alpha blocker.
Although the merit of BETA in either the post-MI setting or heart failure is not disputed, recent analysis of BETA treatment for HTN—atenolol, specifically—has suggested much less sanguine efficacy than clinician utilization would imply. Lindholm et al performed a meta-analysis to evaluate the efficacy of a various BETA treatment for HTN.
The data analysis by Cochrane review included subjects (n = 105,951) from randomized, controlled trials (RCT). Studies involved either BETA versus placebo, or BETA compared with other classes of treatment.
Stroke reduction is one of the hallmarks of HTN treatment success. Disappointingly, this meta-analysis indicates that stroke reductions afforded by BETA treatment of HTN were only about 19%, or about half the degree of stroke reduction seen in RCT of other antihypertensive drug classes. Based upon these findings, the authors suggest that BETA no longer be considered as first-line treatment and that BETA are not appropriate as comparator treatment in controlled trials, since other treatments (eg, diuretic, calcium blocker, ACE) are superior.
Obstructive Sleep Apnea as a Risk Factor for Stroke and Death
Source: Yaggi H, et al. N Engl J Med. 2005;353:2034-2041.
The reductions in stroke achieved through treatment of hypertension and atrial fibrillation notwithstanding, stroke remains the #2 cause of death worldwide. Obstructive sleep apnea (OSA) has been associated with increased risk of cardiovascular morbidity and mortality. OSA has a 4% prevalence amongst the general population, compared with 60% in the stroke population. OSA has also been associated with hypertension (HTN), but whether OSA is independently associated with stroke (ie, separate from the fact that OSA leads to increased BP which leads to stroke) has not yet been ascertained.
An observational cohort study population (n = 1022) of persons referred to the Yale Center for Sleep Medicine underwent polysomnography. A diagnosis of OSA was based upon an apnea-hypopnea index (AHI) of 5 or greater (ie, at least 5 events/hour of sleep); the mean AHI of the study group was 35, compared with the control group AHI of 2 . Study subjects were followed for 4 years.
There was a statistically significant association between OSA and stroke or death. This relationship remained significant even after adjustment for sex, race, smoking, alcohol, BMI, diabetes, lipids, atrial fibrillation, and hypertension. The worse the degree of OSA was, the greater the risk. Overall, OSA was associated with approximately a doubling of risk for stroke or death. Whether treatment of OSA will reduce this heightened CV risk remains to be clarified.
Cholinesterase Inhibitors for Patients with ALZ
Source: Kaduszkiewicz H, et al. BMJ. 2005;331:321-327.
Clinicians and caregivers alike hope for useful pharmacotherapeutic tools to forestall decline in cognitive function in persons with Alzheimer’s disease (ALZ). Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) are often prescribed for ALZ, predicated on the belief that raising CNS acetylcholine levels will compensate for the recognized deficit in CNS acetylcholine, and provide either improved cognitive function, or at least a slowing of cognitive function decline. The authors inform us that they were prompted to do a systematic review of these medications based upon the observation that only 10% of dementia pharmacotherapy in Germany is comprised of cholinesterase inhibitors, calling into question the perceived efficacy of this choice.
A review of 22 published, double- blind, randomized, controlled trials of a cholinesterase inhibitor vs placebo was performed. Unfortunately, based upon their review the authors conclude that the combination of flaws in study design plus small increments in clinical benefit places the scientific foundation for recommendation of cholinesterase inhibitors into the category of "questionable."
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