Clinical implementation of preemptive pharmacogenomics in psychiatry: Τhe "PREPARE" study.

PREemptive Pharmacogenomic testing for Preventing Adverse drug REactions (PREPARE) is the first prospective, pre-emptive pharmacogenomic study conducted in Europe, within the frame of the Horizon 2020 program. It aims to determine whether implementing pre-emptive pharmacogenomics (PGx) testing of clinically relevant biomarkers, so as the dose and drug selection to be guided, will result in an overall reduction of both the occurrence and the severity of drug-genotype-associated adverse drug reactions (ADRs). To achieve that, two groups of patients will be recruited; one that will receive treatment according to standard clinical practice and one other that will receive pharmacogenomic-guided treatment. The Laboratory of Pharmacogenomics and Individualized Treatment of the University of Patras, which coordinates and represents Greece in this study, in collaboration with the Department of Psychiatry of the General University Hospital of Patras, the Department of Psychiatry of the Hospital "Attikon" and the Departments of Psychiatry of the Psychiatric Hospital of Athens "Dafni" is going to recruit 1500 psychiatric patients that are going to receive antidepressant or antipsychotic treatment. Our scientific hypothesis is that patients who receive pharmacogenomic guided drug and dose selection will experience 30% less ADRs than patients following standard care. Eligible drugs for inclusion in the PREPARE study, are those for which the clinical decision regarding drug and dose choice can be guided according to the Dutch Pharmacogenomics Working Group Guidelines (DPWG). Overall, 7 antidepressants (citalopram, escitalopram, sertraline, paroxetine, venlafaxine, clomipramine, amitriptyline) and 3 antipsychotics (haloperidol, zuclopenthixol, aripiprazole) related to 17 genetic variations in 2 genes (CYP2D6, CYP2C19) will be examined. Occurrence, severity and causality of adverse drug events (ADEs) will be assessed during monitoring, at month 1 and 3 after starting the index-drug, and at the end of each arm, by using the Common Toxicity Criteria for Adverse Events Scale (CTCAE) and the Liverpool Causality Assessment Tool (LCAT), respectively. The results of our study are expected to significantly contribute to the improvement of psychiatric patients' quality of life, by helping to provide the right drug, to the right dose in terms of efficacy, safety and cost-effectiveness.

The impact of obstructive sleep apnea syndrome severity on physical performance and mental health. The use of SF-36 questionnaire in sleep apnea.

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is a common disorder defined by repeated episodes of airflow cessation (apneas)leading to arterial hypoxemia and sleep disruption. OSAS has been associated with increased morbidity, mortality and diminished quality of life so far. This cross-sectional study aimed to assess the impact of OSAS on patients' Quality of Life, as measured by the Medical Outcomes Study Short Form-36 (SF-36). PATIENTS AND METHODS: Two hundred and forty five subjects referred to the sleep laboratory and underwent full polysomnography overnight. Prior to sleep study onset, we registered height and weight, medical history, smoking habit, drug consumption. Afterwards, each patient completed the SF-36. Eighty subjects not diagnosed with sleep apnea [apnea hypopnea index (AHI < 5)] were excluded. Therefore, 165 subjects (121 male and 44 female) remained. RESULTS AND CONCLUSIONS: Statistical analysis revealed that in patients with respiratory disturbance index (RDI) ≥ 15, (n = 115), RDI was independently associated with lower performance in role limitations due to physical problems (p = 0.005). Additionally, RDI was the only factor associated with decreased vitality (p = 0.014) and mental health scores (p = 0.047). In the same patient subgroup, body mass index (BMI) and age were associated with poorer scores in physical functioning (p < 0.001 and p = 0.003, respectively). BMI was an independent clinical predictor of worse scores in bodily pain (p = 0.006) general health (p = 0.006), social functioning (p = 0.025) and role limitations due to emotional problems (p = 0.004).

Assessing personality traits by questionnaire: psychometric properties of the Greek version of the Zuckerman-Kuhlman personality questionnaire and correlations with psychopathology and hostility.

BACKGROUND: The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) was developed in an attempt to define the basic factors of personality or temperament. We aimed to assess the factor structure and the psychometric properties of its Greek version and to explore its relation to psychopathological symptoms and hostility features. METHODS: ZKPQ was translated into Greek using back-translation and was administered to 1,462 participants (475 healthy participants, 619 medical patients, 177 psychiatric patients and 191 opiate addicts). Confirmatory and exploratory factor analyses were performed. Symptoms Distress Check-List (SCL-90R) and Hostility and Direction of Hostility Questionnaire (HDHQ) were administered to test criterion validity. RESULTS: Five factors were identified, largely corresponding to the original version's respective factors. Retest reliabilities were acceptable (rli's: 0.79-0.89) and internal consistency was adequate for Neuroticism-Anxiety (0.87), Impulsive Sensation Seeking (0.80), Aggression-Hostility (0.77) and Activity (0.72), and lower for Sociability (0.64). Most components were able to discriminate psychiatric patients and opiate addicts from healthy participants. Opiate addicts exhibited higher rates on Impulsive Sensation Seeking compared to healthy participants. Neuroticism-Anxiety (p<0.001) and Impulsive Sensation Seeking (p<0.001) were significantly associated with psychological distress and Aggression-Hostility was the most powerful correlate of Total Hostility (p<0.001), and Neuroticism-Anxiety was the stronger correlate of introverted hostility (p<0.001), further supporting the instrument's concurrent validity. CONCLUSIONS: Present findings support the applicability of the Greek version of ZKPQ within the Greek population. Future studies could improve its psychometric properties by finding new items, especially for the Sociability scale.

[The Life Style Index: correlations with psychological distress and hostility].

The Life Style Index (LSI) was designed to assess defense mechanisms, assuming that their use is related to specific emotional states and diagnostic concepts. Aiming to further investigate the psychometric properties of the Greek version of the LSI, the aim of the present study was to investigate the relationship of specific defense mechanisms with dimensions of psychological distress and hostility features in three different populations. The sample comprised 1261 adults (410 healthy participants, 723 medical patients and 128 psychiatric patients). Along with defense mechanisms (LSI), Psychological Distress (General Health Questionnaire, GHQ-28) and Hostility features (Hostility and Direction of Hostility Questionnaire, HDHQ) were also assessed. The results showed that increased psychological distress is related with increased use of all defenses except Denial, with which psychological distress is negatively associated. Regression is constantly related with psychological distress and differentiates psychiatric patients from the other groups of participants, while Compensation and Reaction Formation are related to depressive symptomatology. In medical patients, Repression was found to increase the physical dimension of psychological distress and the social dysfunction. On the contrary,Denial was negatively associated with these dimensions of psychological distress. In the psychiatric patient and healthy participant samples, Projection plays the most detrimental role. Regarding hostility and direction of hostility, those who were found to introvert their hostility presented with higher scores in Denial, indicating that they possibly 'deny' their hostility, and the degree of the Denial was found to be negatively associated with the degree of Introverted Hostility. Those who directed their hostility towards the others, presented with higher rates of Projection, while neither Denial nor Reaction Formation seemed sufficient enough to temper the degree of Extroverted Hostility. In conclusion,the present results strengthen further the validity of the Greek version of the LSI and provide additional evidence about the relation of defence mechanisms with dimensions of psychological distress and the direction of hostility in different populations, indicating that the empirical assessment of defense mechanisms can contribute significantly in the study of the factors that mediate or moderate the course or the outcome of medical or psychiatric disorders.

Effect of epoetin alpha therapy on cognitive function in anaemic patients with solid tumours undergoing chemotherapy.

The primary aim of this study was to assess whether epoetin alpha (Ea) would improve cognitive performance in a group of anaemic cancer patients receiving chemotherapy. The secondary aim was to confirm the positive impact of Ea on haematological parameters, and quality of life (QOL). Fifty patients with solid tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for 12 weeks and were administered the Mini-Mental State Examination and the European Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior to Ea therapy and at study completion. No clinically significant alterations were observed on cognitive function during Ea treatment. Changes in cognitive function were unrelated to Hb change and there were no significant differences in cognitive performance between Ea responders and non-responders. The analyses revealed clinically significant improvements in Hb levels, physical and role function, and clinically meaningful reductions in fatigue. Hb changes were significantly associated with the magnitude of improvement in QOL parameters. The lack of a clinical benefit in cognition observed in this study during Ea treatment may redirect the focus of research from enhancing to maintaining cognitive function, since stability in cognitive performance through time may be as well clinically important.

Doxazosin for the management of distal-ureteral stones.

PURPOSE: To evaluate the efficacy of doxazosin in inducing spontaneous passage of stones in the distal ureter and to compare its efficacy according to the size of the stone. PATIENTS AND METHODS: Seventy-three patients with a mean age of 46.38 +/- 10.17 years who presented with a distal-ureteral stone were divided into four groups according to stone size and drug treatment: <5 mm without doxazosin (group A; n=15); 5-10 mm (group B; n=16); <5 mm with doxazosin 4 mg/day for 4 weeks (group C; n=20); and 5-10 mm with doxazosin 4 mg/day for 4 weeks (group D; n=22). Groups A and B served as controls for groups C and D, respectively. RESULTS: Spontaneous stone passage was documented in 9 patients (60%) in group A v 17 (85%) in group C (P=0.047) and 7 (43.75%) in group B v 16 (72.73%) in group D (P=0.036). The average expulsion time was 8.78 +/- 1.09 days in group A v 7.59 +/- 0.80 days in group C (P=0.004) and 12.14 +/- 1.35 days in group B v 7.06 +/- 1.29 days in group D (P<0.0001). The number of pain episodes in group D patients was significantly lower than in group B (P +/- 0.0078). CONCLUSIONS: Doxazosin treatment proved to be safe and effective for distal-ureteral stones, as determined by earlier expulsion, decreased colic frequency, and absence of side effects. The efficacy of doxazosin was significantly higher for 5-to 10-mm stones than for smaller ones.

Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy.

We conducted a randomized, open-label, controlled trial to assess the efficacy of oxcarbazepine for prophylaxis against oxaliplatin-induced peripheral neuropathy (OxIN). Thirty-two patients with colon cancer received 12 courses of the FOLFOX-4 regimen and were randomly assigned to receive oxcarbazepine (600 mg BID) or chemotherapy without oxcarbazepine. The incidence of OxIN was strikingly decreased in patients receiving oxcarbazepine (31.2% vs 75%). Oxcarbazepine may prevent OxIN symptoms. Further larger placebo-controlled trials are warranted to confirm our results.

Impact of providing booklets about chemotherapy to newly presenting patients with cancer: a randomized controlled trial.

BACKGROUND: There has been limited research examining the efficacy of providing written information to cancer patients in southern and eastern European countries. This study investigated the impact of a booklet about chemotherapy on patient satisfaction, quality of life (QoL) and emotional distress, and assessed booklet use. PATIENTS AND METHODS: A total of 145 Greek cancer outpatients prior to commencing chemotherapy completed a questionnaire and were randomized to receive (n = 72) or not receive (n = 73) the booklet. All patients completed the second questionnaire before the following cycle of chemotherapy. RESULTS: Baseline characteristics were well balanced between the two groups. Experimental group patients reported being significantly more satisfied with the information received and care overall than those in the control group, felt significantly more and better informed, and perceived the information received as being clearer and detailed. The intervention produced no benefits in terms of anxiety, depression or QoL. The booklet was read by almost all patients and to a great extent by significant others. The majority considered the booklet useful to read and helpful in recalling chemotherapy-related information. CONCLUSIONS: The current results provide further evidence on the efficacy of information-giving interventions in societies where disclosure of information to cancer patients still remains controversial.

Ureteral injuries during gynecologic surgery: treatment with a minimally invasive approach.

PURPOSE: To report the safety and efficacy of percutaneous nephrostomy and primary antegrade recanalization for treatment of iatrogenic ureteral strictures after gynecologic surgery. PATIENTS AND METHODS: Ten women had symptoms suggestive of ureteral obstruction during the immediate postoperative period (5 days-1 week after surgery). Under analgesia and conscious sedation, standard percutaneous nephrostomy was performed, and a long 7F sheath was placed in the upper ureter. The obstructions were traversed with the aid of a 0.0035-inch Glidewire and a 5F angled Glide catheter (Terumo, Japan). Subsequently, the areas were dilated with angioplasty balloons to a maximum diameter of 7 mm. Finally, an 8F percutaneous internal/external nephroureteral drainage stent was inserted to secure ureteral patency. Follow-up was carried out by serial nephrostomography until removal of the stent and by renal ultrasonography thereafter. RESULTS: Twelve obstructions with a mean length of 1.4 cm (range 0.4-1.9 cm) were managed. The technical success rate was 100%. No major complications occurred, and normal renal function was restored. The mean follow-up was 12 months. In 60% of the patients, a patent ureter was depicted at 1 week, whereas in four patients, repeat dilation of the obstructed segment was required. The stents were removed after a mean period of 4.8 weeks. CONCLUSION: Percutaneous nephrostomy and primary antegrade ureteral balloon dilation is safe and efficacious for treating ureteral injury after pelvic surgery and obviates open surgical manipulations.