Post-void residual urine volume is not a good predictor of the need for invasive therapy among patients with benign prostatic hyperplasia.

PURPOSE: We assessed the value of baseline PVR as predictor of the need for invasive therapy during long-term followup of patients with clinical BPH treated initially with alpha1-blockers or WW. MATERIALS AND METHODS: The records of a cohort of 942 patients with BPH treated with alpha(1)-blockers or WW were reviewed. Baseline I-PSS scores, PSA, prostate volume, uroflowmetry, pressure flow parameters and followup data were collected prospectively. Correlations between PVR and other baseline parameters were calculated. The 5-year cumulative risks of invasive therapy were calculated with the Kaplan-Meier method. After stratification of PVR by various cutoff levels (50, 100 and 300 ml), rate ratios between large and small PVRs were calculated using proportional hazards analyses. RESULTS: PVR has weak (-0.2

Treatment of benign prostatic hyperplasia and occurrence of prostatic surgery and acute urinary retention: a population-based cohort study in the Netherlands.

OBJECTIVES: To assess and compare the risk of prostatic surgery in (subsets of) patients with a diagnosis of BPH. We sought to expand on data of an earlier pharmacy-based study by obtaining more information on BPH disease parameters by using a Dutch GP-based research database. METHODS: A retrospective cohort study (1994-mid-year 2002) was conducted among 1430 men aged > or =45 years with > or =6 months of registration with the GP. BPH case identification was based on review of medical records. RESULTS: Overall, we found that there was no difference in the risk of prostatic surgery between patients on medical treatment and watchful waiting. Patients using 5alpha-reductase inhibitors (5-ARIs) at any stage had a statistically significant reduced risk of surgery compared to patients using alpha-blockers only: adjusted hazard ratio 0.35 (95%CI: 0.13-0.96). The routine collection of BPH parameters were insufficient to be useful in the analysis. CONCLUSION: Patients using 5-ARIs seemed to have a reduced risk of prostatic surgery compared to patients using alpha-blockers. However, it was unknown whether the disease profile of 5-ARI users is different compare to non-5-ARI-treated and untreated patients with BPH, as detailed medical information necessary to characterise patients according to the BPH disease severity and development of disease parameters is not routinely recorded by GPs.

Prognostic role of prostate-specific antigen and prostate volume for the risk of invasive therapy in patients with benign prostatic hyperplasia initially managed with alpha1-blockers and watchful waiting.

OBJECTIVES: To investigate the prognostic role of prostate-specific antigen (PSA) level and prostate volume (PV) for the need for benign prostatic hyperplasia (BPH)-related invasive therapy among patients initially treated with an alpha1-blocker or watchful waiting (WW) in real-life clinical practice. METHODS: Data were collected from 2264 consecutive patients with clinical BPH. Patients initially treated with an alpha1-blocker or WW were included in this study. They were stratified by baseline PSA level (less than 1.5, 1.5 to less than 3.0, 3.0 to 10.0 ng/mL) and PV (less than 30 and 30 to 200 cm3), and analyzed for the time to BPH-related invasive therapy. RESULTS: Of the 2264 patients, 389 treated with alpha1-blockers and 553 who chose WW were included. Across the PSA and PV strata, the alpha1-blocker group had worse symptoms, peak flow, postvoid residual urine volumes, and obstruction than did the WW group. Increasing PSA levels produced an increase in the 5-year cumulative risk of invasive treatment: 20%, 34%, and 44% in the alpha1-blocker and 8%, 9%, and 15% in the WW group for a PSA level of less than 1.5, 1.5 to less than 3.0, and 3.0 to 10.0 ng/mL, respectively. The hazard ratio for the highest compared with the lowest PSA strata was 2.8 for alpha1-blocker and 2.7 for WW patients. An increasing PV increased the 5-year cumulative risk from 21% to 35% in the alpha1-blocker group and 8% to 11% in the WW group. The hazard ratio for the large versus small prostates in the alpha1-blocker group was 1.8 and in the WW group was 1.0. CONCLUSIONS: A higher PSA level and larger PV resulted in a greater risk of BPH-related invasive therapy that was more pronounced in the alpha1-blocker than in the WW patients. However, symptom severity, flow parameters, and obstruction grade may have contributed to the difference in risk between the two treatment groups.

Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine.

AIMS: We performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas. METHODS: We enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine prophylaxis during the period between 1 May 1999 and 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after starting weekly intake of 250 mg mefloquine. We compared the intraindividual change in scores between baseline and follow-up visit on the Dutch shortened Profile of Mood States, and on the Continuous Performance Test (CPT) which measures sustained attention. RESULTS: The final cohort consisted of 151 subjects with a mean age of 38 years. In this population, a significant impairment of mood state was observed in those with a body mass index (BMI) < or = 20 kg m(-2). Stratification for gender showed that the total mood disturbance in females in the lowest BMI category significantly increased by 8.42 points [95% confidence interval (CI) 3.33, 13.50], whereas BMI did not affect the risk in males. Stratification for history of use of mefloquine showed that the risks were highest in first-time users. Analyses of the CPT showed that reaction time in women with a BMI < or = 20 kg m(-2) increased significantly by 22.5 ms (95% CI 7.80, 37.20), whereas reaction time in men showed a slight and nonsignificant decrease. CONCLUSION: Risk factors for mefloquine-associated neuropsychiatric adverse events and concentration impairment are female gender, low BMI, and first-time use. The frequency of neuropsychiatric effects is highest in women with a BMI < or = 20 kg m(-2).

Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia.

OBJECTIVES: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). METHODS: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values. RESULTS: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml. CONCLUSIONS: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management.

Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: a focus on neuropsychiatric adverse events.

OBJECTIVES: We performed a prospective, double-blind, randomized study to compare the occurrence of neuropsychiatric adverse events and concentration impairment during prophylactic use of either mefloquine or atovaquone plus chloroguanide (INN, proguanil). METHODS: Our potential study population consisted of all persons who were included in the MAL30010 trial at the Travel Clinic, Rotterdam, The Netherlands. All subjects were randomized to receive either active atovaquone (250 mg) plus chloroguanide (100 mg) daily plus a placebo for mefloquine weekly or active mefloquine (250 mg) weekly plus a placebo for atovaquone plus chloroguanide daily. Each subject was followed up from a baseline screening visit up to the index date, 7 days after he or she left the malaria-endemic area. We measured the interindividual and intraindividual changes in mood disturbance by means of the Dutch shortened Profile of Mood States and 3 domains of the Neurobehavioral Evaluation System, which included sustained attention, coding speed, and visuomotor accuracy between baseline and follow-up visit. RESULTS: The cohort consisted of 119 subjects with a mean age of 35 years. A significant deterioration in depression, anger, fatigue, vigor, and total mood disturbance domains occurred during use of mefloquine but not during use of atovaquone plus chloroguanide. Stratification for sex showed between-treatment differences in female patients but not in male patients. In both treatment groups, sustained attention deteriorated after travel, especially with increased duration of stay. CONCLUSIONS: Prophylactic use of mefloquine was associated with significantly higher scores on scales for depression, anger, and fatigue and lower scores for vigor than prophylactic use of atovaquone plus chloroguanide.

Neuropsychiatric events during prophylactic use of mefloquine before travelling.

INTRODUCTION: It has been suggested that neuropsychiatric events during use of mefloquine are more common in females than in males and are partly explained by the psychological stress of travelling. Therefore, we investigated neuropsychiatric events in females and males on mefloquine in the 3-week prophylactic period that precedes travelling. Furthermore, we investigated whether first-time users had a higher risk of neuropsychiatric adverse events than subjects with a history of mefloquine use. METHODS: We enrolled all patients who visited a Travel Clinic for mefloquine prophylaxis during the period 1 May 1999 to 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after the start of mefloquine but before travelling. We asked patients to register any adverse event in a diary and measured the intra-individual change in scores on the Dutch Shortened Profile Of Mood States (POMS) at baseline and at the end of follow-up. RESULTS: The final cohort consisted of 179 subjects with a mean age of 3 years. Females reported adverse events more frequently than males ( P=0.005). Overall, we observed a small but significant increase in the score on the domain fatigue [0.74 points, 95% confidence interval (CI) 0.18, 1.30]. The effect was exclusively present in females and not in males. First-time users of mefloquine increased 2.81 points (95% CI 0.70, 4.92) on the total score of the POMS, and among those, women showed the largest increase of 4.58 points (95% CI 0.74, 8.43). CONCLUSION: The use of mefloquine was associated with neuropsychiatric adverse effects. Females encountered neuropsychiatric effects more frequently than males, which could be confirmed by validated psychological tests. Neuropsychiatric effects were more common in first-time users than in individuals who had used mefloquine before.

Neuro-psychiatric effects of antimalarials.

OBJECTIVE: To study the neuro-psychiatric adverse effects of antimalarial drugs. SETTING: Persons who visited a Travel Clinic in Rotterdam over a period of 3 months. DESIGN: Prospective cohort study on 394 persons taking mefloquine, 493 persons taking proguanil and 340 persons not taking antimalarial drugs who visited Africa, South America, Asia, or the Middle East. METHODS: All persons received a structured questionnaire within 14 days of their return to the Netherlands. The questionnaire consisted of questions regarding use of alcohol, smoking, general health, medical history, tropical diseases during the trip, and other medicines, and contained an extensive list of general complaints regarding all body systems at four levels of severity. A modified and validated version of the Profile of Mood States was included. RESULTS: In the study period, 2541 persons visited the Travel Clinic, of whom 1791 (70%) were both eligible and willing to co-operate. Of these 1791, data were obtained from 1501 (84%). Insomnia was most frequently encountered in users of mefloquine and mouth ulcers in proguanil users. After adjustment for gender, age, destination, and alcohol use, the relative risk for insomnia to mefloquine versus non-users of antimalarials was 1.6, and the excess risk was 6 per 100 users over an average period of 2 months. There were no significant differences between groups in depression, anxiety, agitation, and confusion. Stratification by gender demonstrated that insomnia was more common in women on mefloquine, but not in men. Also, women more frequently mentioned palpitations as an adverse event. After adjustment for age, destination, and alcohol use in women, the relative risks for insomnia and palpitations to mefloquine versus non-use of antimalarials were 2.4, and 22.5, respectively. When travellers were specifically asked for the adverse reactions they had experienced, anxiety, vertigo, agitation, and nightmares were significantly more frequently mentioned by mefloquine users. CONCLUSION: Insomnia was more commonly encountered during use of mefloquine than proguanil or during non-use of antimalarials.

Taste loss to terbinafine: a case-control study of potential risk factors.

1. To identify risk factors associated with taste loss to terbinafine, we performed a case-control study of 87 reports of probably terbinafine-induced taste loss and 362 controls on terbinafine without taste loss, who had filled prescriptions from the same pharmacy and GP. Data on general health, diet, alcohol, smoking, drug use and medical history were collected by means of a self-administered questionnaire. 2. The mean latent period between first intake of terbinafine and taste loss was 35 days. Most patients recovered within 4 months after discontinuation. Cases were significantly older than controls. The odds ratio of taste loss in patients of 65 years and older was 4.4 in comparison with persons younger than 35 years of age (95% CI: 1.4-16.1). The risk in persons with a body mass index (BMI) below 21 kg m-2 was 4.4 times higher than in those with a BMI of more than 27 kg m-2 (95% CI: 1.6-14.2). The risk of taste loss in patients of 55 years and older with a BMI below 21 kg m-2 was 12.8 times higher than that in patients below 35 years of age (95% CI: 1.9-88.6). 3. A low BMI, a history of taste loss, and ageing are risk factors for developing taste loss to terbinafine. Prescription of this drug to elderly patients with low BMI and low daily intake of nutrients requires careful follow-up.

[Reasons to report or not report side effects of drugs to the national monitoring system in the Netherlands]. / Redenen om wel of niet bijwerkingen van geneesmiddelen te melden bij het landelijke meldingssysteem in Nederland.

OBJECTIVE: To assess the awareness of medical practitioners in the Netherlands regarding the national voluntary reporting scheme for adverse reactions to drugs, and the reasons for non-reporting. DESIGN: Questionnaire. SETTING: Netherlands Centre for Monitoring of Adverse Reactions to Drugs. METHOD: A questionnaire was sent to a random sample of 500 practitioners aged under 65 in the database of the Dutch Inspectorate for Health Care. RESULTS: Of the 500 questionnaires 265 (53%) were returned and completely filled in. Sixty-seven (25%) practitioners had reported a suspected adverse reaction on one or several occasions during their practising career; 229 (86%) would report a serious adverse reaction, 190 (72%) an unknown one, 185 (70%) an adverse reaction to a new product, and 83 (31%) a proven adverse reaction. Almost 20% said they had had difficulties reporting because they could not find the telephone number or reporting forms. Forty practitioners (15%) claimed that they were too busy to report adverse reactions. Almost all practitioners (94%) were aware of the fact that the reporting scheme serves the early detection of unknown adverse reactions.

[Skin reactions attributed to the use of bromhexine]. / Huidreacties toegeschreven aan het gebruik van broomhexine.

Since 1972, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs has received 22 reports of skin reactions attributed to use of bromhexine. The reports concerned II men and II women. The ages ranged between 5 months and 88 years. The skin reactions occurred within one to 30 days after starting the use of bromhexine. Most skin reactions consisted of generalised urticaria. Other reports concerned once an angioedema and once an anaphylactic reaction. Most patients recovered completely after cessation of bromhexine without further treatment.