Clinical Health Updates

Tadalafil (Cialis) effective for benign prostatic hypertrophy (BPH)

Clinical Question:
Is tadalafil safe and effective in the treatment of benign prostatic hypertrophy?

Bottom Line:
Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction. It is uncertain, however, how clinically relevant a 3-point change from baseline is on a symptom scale from 4 to 34.

Reference:
McVary KT, Roehrborn CG, Kaminetsky JC, et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urology 2007;177:1401-1407.

Study Design:
Randomized controlled trial (single-blinded)

Synopsis:
The authors assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were “erection increased,” dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment.

Alfuzosin (10 mg) does not affect blood pressure in young healthy men

Clinical Question:
Does Alfuzosin 10mg safe in a normotensive BPH, distal ureteral stones and prostatitis patients?

Bottom Line:
Study shows that alfuzosin 10mg is well tolerated by young healthy subjects and may therefore be safely administered to young normotensive patients affected by distal ureteral stones and prostatitis.

Reference:
Alfuzosin (10 mg) does not affect blood pressure in young healthy men. Mondaini N, Giubilei G, Ungar A, Gontero P, Cai T, Gavazzi A, Bartoletti R, Geppetti P, Carini M. Eur Urol. 2006 Dec;50(6):1292-6; discussion 1297-8

Study Design:
Randomized Controlled Trial (Double Blind)

Synopsis:
Alfuzosin 10mg is a uroselective alpha(1)-adrenoceptor antagonist used to treat lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Recent studies have suggested the potential efficacy of alfuzosin in the treatment of distal ureteral stones and prostatitis syndrome, two conditions frequently encountered in young patients. The authors evaluated the effect of 10mg alfuzosin on blood pressure (BP) and heart rate (HR) in young healthy volunteers. They did a randomized, double-blind, placebo-controlled, crossover study, the effect of alfuzosin 10mg on BP and HR was evaluated in 14 male volunteers (mean age: 28 yr; range: 24-30). BP<135/85>10%) was recorded during each treatment.

Holmium Laser Enucleation versus Transurethral Resection in the treatment of BPH

Clinical Question:
Is holmium laser enucleation of the prostate (HoLEP) effective compare to transurethral resection of the prostate (TURP) for treatment of men with bladder outflow obstruction (BOO) secondary to benign prostatic hyperplasia?

Bottom Line:
HoLEP has less perioperative morbidity and produces superior urodynamic outcomes than TURP, when treating prostates >40 g. At 24 months of follow-up, HoLEP is equivalent to TURP.

Reference:
A randomised trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years.Wilson LC, Gilling PJ, Williams A, Kennett KM, Frampton CM, Westenberg AM, Fraundorfer MR. Eur Urol. 2006 Sep;50(3):569-73. Epub 2006 May 2

Study Design:
Randomized Controlled Trial

Synopsis:
The authors compared holmium laser enucleation of the prostate (HoLEP) with transurethral resection of the prostate (TURP) for treatment of men with bladder outflow obstruction (BOO) secondary to benign prostatic hyperplasia with a minimum of 24-month follow-up. Sixty-one patients were randomised to either HoLEP or TURP. All patients had BOO proven on urodynamic studies pre-operatively (prostate size 40-200 g). One patient died before treatment, which left 30 patients in each group. Perioperative data, as well as symptom scores, Quality of Life (QoL) scores, and maximum urinary flow rates (Qmax) were obtained at one, three, six,12, and 24 months. Post-void residual volumes, transrectal ultrasound (TRUS) volumes, and pressure flow studies were obtained six months post-operatively. Continence and potency data were also recorded. There were no significant differences between the two surgical groups pre-operatively. Mean pre-operative TRUS volume was 77.8+/-5.6 g (42-152) in the HoLEP group and 70.0+/-5.0 g (46-156) in the TURP group. Patients in the HoLEP group had shorter catheter times and hospital stays. More prostate tissue was retrieved in the HoLEP group. At six months, HoLEP was urodynamically superior to TURP in relieving BOO. At 24 months, there was no significant difference between the two surgical groups with respect to American Urology Association scores, QoL scores, or Qmax values; however, two patients in the TURP group required re-operation.

Medications help passage of kidney stones

Clinical Question:
Do medications help the passage of kidney stones?

Bottom Line:
The limited amount of available data suggest that alpha blockers and calcium channel blockers appear to speed the passage of kidney stones. Furthermore, it appears that combining these medications with steroids provides additional benefit.

Reference:
Hollingsworth JM, Rogers MA, Kaufman SR, et al. Medical therapy to facilitate urinary stone passage: a meta-analysis. Lancet 2006;368:1171-1179.

Study Design:
Meta-analysis (randomized controlled trials)

Various (meta-analysis)

Synopsis:
Medical therapies to ease urinary-stone passage have been reported, but are not generally used. If effective, such therapies would increase the options for treatment of urinary stones. To assess efficacy, the authors sought to identify and summarise all randomised controlled trials in which calcium-channel blockers or alpha blockers were used to treat urinary stone disease. They searched MEDLINE, Pre-MEDLINE, CINAHL, and EMBASE, as well as scientific meeting abstracts, up to July, 2005. All randomised controlled trials in which calcium-channel blockers or alpha blockers were used to treat ureteral stones were eligible for inclusion in our analysis. Data from nine trials (number of patients=693) were pooled. The main outcome was the proportion of patients who passed stones. We calculated the summary estimate of effect associated with medical therapy use using random-effects and fixed-effects models. Patients given calcium-channel blockers or alpha blockers had a 65% (absolute risk reduction=0.31 95% CI 0.25-0.38) greater likelihood of stone passage than those not given such treatment (pooled risk ratio 1.65; 95% CI 1.45-1.88). The pooled risk ratio for alpha blockers was 1.54 (1.29-1.85) and for calcium-channel blockers with steroids was 1.90 (1.51-2.40). The proportion of heterogeneity not explained by chance alone was 28%. The number needed to treat was 4.

Furosemide (Lasix) doesn’t prevent acute renal failure

Clinical Question:
Is furosemide (frusemide) effective in treating or preventing acute renal failure in adults?

Bottom Line:
Furosemide is not associated with any significant clinical benefits in the prevention and treatment of acute renal failure in adults. High doses may be associated with an increased risk of ototoxicity.

Reference:
Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ 2006;333:406-407.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
The authors investigate the potential beneficial and adverse effects of frusemide to prevent or treat acute renal failure in adults. Meta-analysis of randomised controlled trials. DATA SOURCES: Cochrane controlled trials register (2005 issue 4), Embase, and Medline (1966 to 1 February 2006), without language restrictions. Two reviewers checked the quality of the studies and independently extracted data. Nine randomised controlled trials totalling 849 patients with or at risk of acute renal failure were included. Outcome measures not significantly different after frusemide treatment were in-hospital mortality (relative risk 1.11, 95% confidence interval 0.92 to 1.33), risk for requiring renal replacement therapy or dialysis (0.99, 0.80 to 1.22), number of dialysis sessions required (weight mean difference–0.48 sessions, -1.45 to 0.50), and proportion of patients with persistent oliguria (urine output < 500 ml/day: 0.54, 0.18 to 1.61). Stratifying studies that used frusemide to prevent or treat acute renal failure did not change the results on mortality (relative risk ratio 2.10, 95% confidence interval 0.67 to 6.63) and the risk for requiring dialysis (4.12, 0.46 to 37.2). Evidence suggested an increased risk of temporary deafness and tinnitus in patients treated with high doses of frusemide (relative risk 3.97, 95% confidence interval 1.00 to 15.78).

Morphine + ketorolac better for renal colic

Clinical Question:
In adults presenting with acute renal colic to an emergency department, is the combination of morphine and ketorolac more effective then either drug given alone?

Bottom Line:
A combination of morphine and ketorolac offered pain relief superior to either drug alone and was associated with a decreased requirement for rescue analgesia.

Reference:
Safdar B, Degutis LC, Landry K, Vedere SR, Moscovitz HC, D’Onofrio G. Intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. Ann Emerg Med 2006;48:173-181.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The authors study the efficacy of intravenous ketorolac, morphine, and both drugs in combination in reducing pain in acute renal colic. They conducted a prospective, double-blinded, randomized controlled trial in an urban, teaching emergency department. Patients aged 18 to 55 years and with a clinical diagnosis of acute renal colic and a pain rating greater than 5 on a 10-cm visual analogue scale or at least “moderate pain” on a 4-category verbal pain scale were eligible for inclusion. Exclusion criteria were contraindication to nonsteroidal anti-inflammatory drugs or opiates, a history of drug dependence, presence of peritonitis, or analgesics within 6 hours of presentation. Patients received either morphine 5 mg at time zero and 5 mg at 20 minutes, ketorolac 15 mg at time zero and 15 mg at 20 minutes, or a combination of both. Primary outcomes were pain reduction and the need for rescue analgesia at 40 minutes. Of the 555 consecutive patients screened, 158 patients met inclusion criteria and 130 patients were randomized during 6 months. Mean difference in change in pain score (visual analog scale 40 minutes minus visual analog scale 0 minutes) between combination group and morphine group was 1.8 cm (95% confidence interval [CI] -3.3 to -0.1) and, compared to the ketorolac group, was 2.2 cm (95% CI -3.7 to -0.5); P<.003. Patients with combination therapy were less likely to require rescue morphine compared to the morphine group (odds ratio 0.2; 95% CI 0.1 to 0.7; P=.007).

Immediate- and extended-release ciprofloxacin similar for UTI

Clinical Question:
Does a single dose of extended-release ciprofloxacin improve outcomes for women with uncomplicated urinary tract infection?

Bottom Line:
A single dose of an extended-release version of ciprofloxacin (Cipro XR) is as effective as the immediate-release version taken twice daily for 3 days. The tiny reduction in the likelihood of gastrointestinal adverse effects (number needed to treat (NNT) = 60 – 80) is likely to be heavily promoted, and must be balanced against the higher cost of this formulation. As we are given more such options, it is important to remember the key elements in choosing a drug: its safety, tolerability, efficacy, price, and simplicity. Although extended-release ciprofloxacin is simpler, it is no more effective and will almost certainly cost more.

Reference:
Fourcroy JL, Berner B, Chiang YK, Cramer M, Rowe L, Shore N. Efficacy and safety of a novel once-daily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women. Antimicrob Agents Chemother 2005;49:4137-43.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The efficacy and safety of a novel once-daily extended-release ciprofloxacin (ciprofloxacin ER) 500-mg dose were compared with those of an immediate-release ciprofloxacin (ciprofloxacin IR) 250-mg twice-daily dose, each administered orally for 3 days in the treatment of acute uncomplicated urinary tract infection (uUTI) in women. Adult female outpatients (mean age, 39 years) with clinical signs and symptoms of acute uUTI and a positive pretreatment urine culture (> or =10(5) CFU/ml) were enrolled in a multicenter, randomized, double-blind, noninferiority trial. Patients were assessed at a test-of-cure visit (4 to 11 days posttreatment) and a late-posttreatment visit (4 to 6 weeks posttreatment) for microbiological and clinical outcomes and safety. The primary efficacy endpoint and microbiological eradication rate at the test-of-cure visit in the ciprofloxacin ER group (254/272; 93.4%) were noninferior to those in the ciprofloxacin IR group (225/251; 89.6%) (95% confidence interval [CI] of difference, -0.99%, 8.59%). Clinical-cure rates at the test-of-cure visit were 85.7% (233/272) for ciprofloxacin ER and 86.1% (216/251) for ciprofloxacin IR (95% CI of difference, -6.37%, 5.57%). At the late-posttreatment visit, microbiological and clinical outcomes were similar for the two treatments and consistent with test-of-cure results. Both treatments were well tolerated, but the frequencies of nausea and diarrhea were lower in the ciprofloxacin ER group than in the ciprofloxacin IR group (nausea, ER, 0.6%; IR, 2.2%; P = 0.033; diarrhea, ER, 0.2%; IR, 1.4%; P = 0.037). Once-daily ciprofloxacin ER was safe, effective, and noninferior to twice-daily ciprofloxacin IR in the treatment of acute uUTI. Additionally, ciprofloxacin ER was associated with significantly reduced frequencies of nausea and diarrhea.

Well done meat associated with Prostate Cancer

Clinical Question:
Is eating high-temperature cooked meat increase risk with prostate cancer?

Bottom Line:
Very well done meat was positively associated with prostate cancer risk. In addition, this study lends epidemiologic support to the animal studies, which have implicated PhIP as a prostate carcinogen. (Cancer Res 2005; 65(24): 11779-84).

Study:
Prospective Study

Reference:
A prospective study of meat and meat mutagens and prostate cancer risk.Cross AJ, Peters U, Kirsh VA, Andriole GL, Reding D, Hayes RB, Sinha R. Cancer Res. 2005 Dec 15;65(24):11779-84.

Synopsis:
High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of >/=7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CI, 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61).