Prostate cancer risk assessment by the primary care physician and urologist: transabdominal- versus transrectal ultrasound prostate volume-based use of the Rotterdam Prostate Cancer Risk Calculator.

Background: Our objective was to assess the accuracy of transabdominal ultrasound (TAUS) measured prostate volume in the primary care setting with transrectal ultrasound (TRUS) measured prostate volume by the urologist as the reference test. Furthermore, our objective was to assess whether risk-stratification using TAUS prostate volume by the primary care physician could reduce unnecessary referrals to the urologist. Methods: Men in two Dutch primary care offices with a prostate cancer (PCa) screening request received a digital rectal examination (DRE), prostate specific-antigen (PSA), and TAUS prostate volume measurement by the general practitioner, followed by Rotterdam Prostate Cancer Risk Calculator (RPCRC) risk assessment. The examination was repeated by a urologist using TRUS. A prostate biopsy was performed in case of a RPCRC positive biopsy advice. A non-inferiority analysis was performed comparing TAUS and TRUS prostate volume differences. A risk-based referral strategy using TAUS and the RPCRC in the primary care setting was compared with the standard referral strategy based on PSA (≥3 ng/mL) and DRE. Results: A total of 105 men were included with a median PSA of 1.9 ng/mL. The mean prostate volumes measured by TAUS and TRUS were 55 and 45 mL, respectively. The mean overestimation of the prostate volume by TAUS as compared to the reference test was 9.9 mL (95% CI: 5.9-13.8). According to Dutch standard practice, 41 out of 105 (39%) men would have been referred to the urologist. Stratification in primary care based on the RPCRC using TAUS prostate volume would have avoided 29 out of the 41 (71%) referrals, at the expense of non-referral of 5 out of 11 (45%) men with a biopsy indication, according to the urologist. Conclusions: RPCRC-based risk stratification in primary care using TAUS prostate volume measurement is feasible and may prevent unnecessary referrals to the urologist and reduce costs. The accuracy of the risk assessment with TAUS might be improved by sufficient training and centralization to achieve a higher volume of consultations in primary care facilities.

A randomized, double-blind study comparing the efficacy and safety of trazodone once-a-day and venlafaxine extended-release for the treatment of patients with major depressive disorder.

This double-blind, randomized study evaluated the efficacy and safety of trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients (166 trazodone and 158 venlafaxine) with major depressive disorder (MDD). The primary efficacy endpoint was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) at week 8. Both treatments were effective in reducing the HAM-D-17 total score at week 8 vs. baseline (intent-to-treat: trazodone -12.9, venlafaxine -14.7; per protocol: trazodone -15.4, venlafaxine -16.4). Patients in the venlafaxine group achieved better results after 8 weeks, whereas the trazodone group achieved a statistically significant reduction in HAM-D-17 following only 7 days of treatment. The most frequent adverse events (AEs) were dizziness and somnolence in the trazodone group, and nausea and headache in the venlafaxine group. Most AEs were mild-to-moderate in severity. This study confirmed that both venlafaxine XR and trazodone OAD may represent a valid treatment option for patients with MDD.

Psychogenic non-epileptic seizures: our video-EEG experience.

OBJECTIVE: The aim of our study was to assess the number of psychogenic non-epileptic seizures (PNES) in our patients with a refractory seizure disorder, to determine the 'typical' PNES semiology using video-EEG monitoring and describe other PNES parameters. METHODS: We evaluated prospectively 596 patients with pharmacoresistant seizures. All these patients underwent continuous video-EEG monitoring. In consenting patients, we used suggestive seizure provocation. We assessed seizure semiology, interictal EEG, brain MRI, psychiatric co-morbidities, personality profiles, and seizure outcome. RESULTS: In the sample of 596 monitored patients, we detected 111 (19.3%) patients with PNES. Of the 111 patients with PNES, 86.5% had spontaneous and 76.5% had provoked seizures. The five most typical symptoms were: initially closed eyelids (67.6%), rapid tremor (47.7%), asynchronous limb movement (37.8%), preictal pseudosleep (33.3%), and side-to-side head movement (32.4%). Interictal EEG was rated as abnormal in 46.2% and with epileptiform abnormality in 9%. Brain MRI was abnormal in 32 (28.8%) patients. Personality disorders (46.8%), anxiety (39.6%), and depression (12.6%) were the most frequent additional psychiatric co-morbidities. PNES outcome after at least 2 years is reported; 22.5% patients was seizure-free; one-third had markedly reduced seizure frequency. We have not seen any negative impact of the provocative testing on the seizure outcome. DISCUSSION: Video-EEG monitoring with suggestive seizure provocation supported by clinical psychiatric and psychological evaluation significantly contributes to the correct PNES diagnosis, while interictal EEG and brain MRI are frequently abnormal. Symptoms typical for PNES, as opposed to epileptic seizures, could be distinguished.

Is pseudo-intractability in population of patients with epilepsy still alive in the 21st century? Audit of 100 seizure-free patients, referred with the diagnosis of pharmacoresistant epilepsy.

OBJECTIVE: There is no universally accepted definition of pseudo-intractable epilepsy. Pseudo-intractability means that the resistance to treatment is, in fact, caused by clinical errors. The purpose of our study was to identify the reasons for intractability and subsequent effective therapeutic management approaches in a group of patients with established pseudo-intractable epilepsy. METHODS: The study was designed as a retrospective audit of 100 adult patients who, in their past medical history, were diagnosed as having intractable epilepsy but, following adjustments to their medical management, were seizure free for at least 2 years. Patients underwent standard clinical evaluation, including EEG and/or video-EEG monitoring. We re-evaluated past medical, family, seizure and pharmacological history and morphological findings. Epilepsy was re-classified according to the ILAE classification. RESULTS: We identified possible errors including incorrect diagnosis and/or inappropriate previous epilepsy management in all 100 patients. Incorrect diagnosis (seizure type and/or syndrome) was observed in 47 patients (47%). Thirty two patients (32%) with idiopathic generalized epilepsy were treated for complex focal seizures with inappropriate choice of medication. Therapeutic errors were identified in 48 patients (48%). Issues with medication compliance were found in 20 patients (20%). Potential seizure precipitating factors were detected in 23 patients (23%). CONCLUSIONS: Our study of 100 patients confirmed that the problem of pseudo-intractability still exists. Every case of pharmacoresistance in epilepsy could potentially be caused by one or more clinical errors.

A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study.

BACKGROUND: Naturalistic effectiveness trials of atypical antipsychotics are needed to provide broader information on efficacy, safety, and tolerability in patients with schizophrenia treated in a community practice setting. METHOD: In this 26-week, open-label, multicentre study, patients with schizophrenia requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled were randomized to receive aripiprazole or an atypical antipsychotic standard of care (SOC) treatment (i.e., olanzapine, quetiapine, or risperidone based on the investigator's judgment of the optimal treatment for the individual patient and the patient's prior response to antipsychotic medication). The primary objective was to compare the effectiveness of a 26-week treatment of aripiprazole versus SOC, as measured by the Investigator Assessment Questionnaire (IAQ) total score at Week 26 last observation carried forward (LOCF) (primary endpoint), a validated measure that monitors relief or worsening of 10 key symptoms associated with the psychopathology of schizophrenia and side effects of antipsychotic treatment. Secondary objectives were to further assess effectiveness using the Clinical Global Impression - Global Improvement (CGI-I) and Clinical Global Impression - Severity of Illness scale, to assess time to treatment discontinuation, patient preference of medication, quality of life, and the tolerability of aripiprazole compared with SOC. RESULTS: Aripiprazole treatment (n=268) resulted in significantly better effectiveness than SOC treatment (n=254; P<0.001; Week 26 LOCF) as evidenced by the IAQ total score beginning at Week 4 (the first assessment point) and sustained through Week 26. A similar relationship was demonstrated among patients who completed the study (observed cases analysis); aripiprazole was associated with significantly better effectiveness at all time points with a greater differential effect from SOC over time. Patients treated with aripiprazole also demonstrated significantly greater improvements on the CGI-I scale (responder rate, P=0.009 at Week 26 LOCF), as well as on quality of life (Quality of Life scale total score; P<0.001 at Week 26). Furthermore, a significantly higher proportion of patients receiving aripiprazole rated their study medication as "much better" on the Preference of Medication Questionnaire (POM) scale than their pre-study medication compared with SOC patients (P<0.001; Week 26). Time to treatment discontinuation and rates of discontinuation due to adverse events were similar in both treatment groups. The incidence of patients with one or more extrapyramidal symptom (e.g., akathisia, dystonia, parkinsonian events, and residual events) was higher in patients receiving aripiprazole compared with patients treated with SOC (13.5% vs. 5.6%); however, a higher proportion of patients in the SOC-treated group had clinically significant weight gain (21.2% vs. 7.3% for aripiprazole) and potentially clinically relevant elevated fasting levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and serum prolactin compared with patients receiving aripiprazole. CONCLUSIONS: Aripiprazole is an effective atypical antipsychotic for the treatment of schizophrenia, demonstrating better effectiveness than SOC agents used in this study in patients for whom a switch in antipsychotic medication was warranted.

Psychogenic non-epileptic seizures, prospective clinical experience: diagnosis, clinical features, risk factors, psychiatric comorbidity, treatment outcome.

In our study, we evaluated 249 patients with refractory seizures using video-EEG monitoring. In this sample, we identified 56 (22.5%) patients with psychogenic non-epileptic seizures - PNES only. Spontaneous seizures were recorded in 49 (87%) patients with PNES. Suggestive seizure induction using intravenous saline placebo was successful in 77.1% of induced PNES cases. Disease duration prior to PNES diagnosis was quite long. Prolonged past and current intake of high number of different antiepileptic drugs was also typical for these patients. We evaluated ictal PNES semiology. Whereas ictal EEG was normal in all PNES patients, interictal EEG was abnormal in 46.4%. Brain MRI was abnormal in 30.4%. Personality disorders were the most frequent psychiatric co-morbidity (in 44.6% of PNES patients), emotionally unstable (borderline) personality disorder was predominant (in 32.1% of PNES patients). Risk factors for epilepsy misdiagnosis and PNES manifestation are discussed. Therapeutic outcome after two years of combined treatment (psychopharmacotherapy and/or psychotherapy) is presented; approximately one third of patients were seizure-free following two years of treatment, one third of patients were responders (>or= 50% reduction in seizure frequency) and one third did not respond to treatment.

Lamotrigine: a depression mood stabiliser.

Depression mood stabilisers, which stabilise mood from below the mood baseline (euthymia) without inducing switch into mania or episode acceleration, are urgently needed for the effective treatment of bipolar depression. The anticonvulsant lamotrigine, recently approved as maintenance therapy for bipolar depression, has undergone evaluation as acute and maintenance therapy for bipolar disorder in several controlled clinical trials. Data from these trials suggest that lamotrigine is effective in the treatment and prevention of bipolar depression without destabilising mood. Although the majority of evidence comes from studies in patients with bipolar I disorder, a recent naturalistic study suggests that these observations may also extend to patients with bipolar II disorder. Lamotrigine may therefore fulfil the unmet need for an effective depression mood stabiliser.

Treatment of Interictal Depression with Citalopram in Patients with Epilepsy.

The purpose of this study is to assess the efficacy and safety of the selective serotonin-reuptake inhibitor (SSRI) citalopram in depressed epileptic patients. We evaluated 43 epileptic patients who suffered from depression and whose total score on the 21 items of the Hamilton Scale for Depression (HAMD 21) exceeded 15 points. These patients were examined by the psychiatrist and scaled before treatment and after 4 and 8 weeks of treatment with citalopram. The dose of citalopram was flexible, related to the actual condition of the patient. In each patient and in the whole group of patients we compared the monthly seizure frequency (total, partial seizures, generalized tonic-clonic seizures) recorded during treatment with citalopram with that recorded during the 2 months preceding the start of citalopram. During treatment we observed a decrease in the total score on the HAMD 21 from a mean initial value of 21.5 +/- 2.9 (range, 17-26) prior to therapy 14.5 +/- 2.9 (range, 10-19) (P < 0.001) after 4 weeks of treatment and to 9.9 +/- 3.1 (range, 4-19) (P < 0.001) after 8 weeks of treatment. There were 9 (20.9%) responders after 4 weeks of treatment and 28 responders (65.1%) after 8 weeks, all of them with decrease on the HAMD 21 greater than 50%. Nausea was the most common adverse event in 7 patients (16.3%) during the first month of treatment and in 3 patients (6.9%) during the second month of treatment. Sexual dysfunction (decrease of libido) was reported in 2 (4.7%) male patients during the entire course of treatment. No seizure worsening was observed in our patients. Monthly seizure frequency did not change significantly: 2.24 (+/-0.76) seizures before treatment with citalopram, 2.29 (+/-0.81) seizures in the first month of treatment, 2.21 (+/-1.00) seizures in the second month of treatment. No occurrence of de novo generalized tonic-clonic seizures was recorded in individual patients. Citalopram is a safe and effective antidepressant in the treatment of depressed epileptic patients.