Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients.

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

An European Organisation for Research and Treatment of Cancer phase I study of lapatinib and docetaxel as neoadjuvant treatment for Human Epidermal Growth Factor Receptor 2 (HER2) positive locally-advanced/inflammatory or large operable breast cancer.

BACKGROUND: Lapatinib is an effective anti-HER2 therapy in advanced breast cancer and docetaxel is one of the most active agents in breast cancer. Combining these agents in pre-treated patients with metastatic disease had previously proved challenging, so the primary objective of this study aimed to determine the maximum tolerated dose (MTD) in treatment-naive patients, by identifying acute dose-limiting toxicities (DLT) during cycle 1 in the first part of a phases 1-2 neoadjuvant European Organisation for Research and Treatment of Cancer (EORTC) trial. PATIENTS AND METHODS: Patients with large operable or locally-advanced HER2 positive breast cancer were treated with continuous lapatinib, and docetaxel every 21days for 4 cycles. Dose levels (DLs) were: 1000/75, 1250/75, 1000/85, 1250/85, 1000/100 and 1250/100 (mg/day)/(mg/m(2)). RESULTS: Twenty-one patients were included. Two DLTs occurred at dose level 5 (1000/100); one grade 4 neutropenia ⩾7days and one febrile neutropenia. A further 3 patients were therefore treated at the same dose with prophylactic granulocyte-colony stimulating factor (G-CSF), and 3 patients at dose level 6. No further DLTs were observed. CONCLUSIONS: Our recommended dose for phase II is lapatinib 1000mg/day and docetaxel 100mg/m(2) with G-CSF in HER2 positive non-metastatic breast cancer. The dose of lapatinib should have been 1250mg/day but we were mindful of the high rate of treatment discontinuation in GeparQuinto with lapatinib 1250mg/day combined with docetaxel. No grade 3-4 diarrhoea was observed. Pharmacodynamics analysis suggests that concomitant medications altering P-glycoprotein activity (in addition to lapatinib) can modify toxicity, including non-haematological toxicities. This needs verification in larger trials, where it may contribute to understanding the sources of variability in clinical toxicity and treatment discontinuation.

KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours.

A recent randomized EORTC phase III trial, comparing two doses of imatinib in patients with advanced gastrointestinal stromal tumours (GISTs), reported dose dependency for progression-free survival. The current analysis of that study aimed to assess if tumour mutational status correlates with clinical response to imatinib. Pre-treatment samples of GISTs from 377 patients enrolled in phase III study were analyzed for mutations of KIT or PDGFRA by combination of D-HPLC and direct sequencing of tumour genomic DNA. Mutation types were correlated with patients' survival data. The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for response to imatinib, increasing the relative risk of progression by 171% (P<0.0001) and the relative risk of death by 190% (P<0.0001) when compared with KIT exon 11 mutants. Similarly, the relative risk of progression was increased by 108% (P<0.0001) and the relative risk of death by 76% (P=0.028) in patients without detectable KIT or PDGFRA mutations. In patients whose tumours expressed an exon 9 KIT oncoprotein, treatment with the high-dose regimen resulted in a significantly superior progression-free survival (P=0.0013), with a reduction of the relative risk of 61%. We conclude that tumour genotype is of major prognostic significance for progression-free survival and overall survival in patients treated with imatinib for advanced GISTs. Our findings suggest the need for differential treatment of patients with GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug.

Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP).

BACKGROUND: Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. METHODS: Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. RESULTS: Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 microm, and decreased significantly to a mean of 224 microm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 microm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. CONCLUSIONS: Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.

A multicenter phase II study (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and is in most cases an incurable disease. It is characterized by the translocation t(11;14) leading to Cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) threonine kinase and can be effectively blocked by mTOR inhibitors. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus in a prospective, multicentre trial in patients with relapsed or refractory MCL (NCT00516412).Methods: Eligible patients with confirmed relapsed or refractory MCL received everolimus 10 mg for 28 days (one cycle) for a total of 6 cycles or until disease progression. The primary endpoint was the best objective response (OR) with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints.Results: A total of 36 patients with 35 evaluable patients at a median age of 69 years (range 40 to 85 years) from 19 centers were enrolled between August 2007 and January 2010. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade 3 or higher. The OR rate was 20% (95% CI: 8-37%) with 2 complete remissions (CR) and 5 partial response (PR), stable disease (SD) 48% and progression disease (PD) 28%. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Three patients achieved a lasting complete molecular response when assessed in the peripheral blood.Conclusion: This study demonstrates that single agent everolimus is well tolerated and has anti-lymphoma activity including lasting molecular responses. Further studies of everolimus either in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.

Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne): implementation of an early intervention programme for psychosis in Switzerland.

AIM: In a survey conducted in the Lausanne catchment area in 2000, we could estimate on the basis of file assessment that first-episode psychosis (FEP) patients had psychotic symptoms for more than 2 years before treatment and that 50% did not attend any outpatient appointment after discharge from hospital. In this paper, we describe the implementation of a specialized programme aimed at improving engagement and quality of treatment for early psychosis patients in the Lausanne catchment area in Switzerland. METHOD: The Treatment and Early Intervention in Psychosis Program-Lausanne is a comprehensive 3-year programme composed of (i) an outpatient clinic based on assertive case management; (ii) a specialized inpatient unit; and (iii) an intensive mobile team, connected for research to the Center for Psychiatric Neuroscience. RESULTS: Eight years after implementation, the programme has included 350 patients with a disengagement rate of 9% over 3 years of treatment. All patients have been assessed prospectively and 90 participated in neurobiological research. Based on this experience, the Health Department funded the implementation of similar programmes in other parts of the state, covering a total population of 540 000 people. CONCLUSION: Programmes for early intervention in psychosis have a major impact on patients' engagement into treatment. While development of mobile teams and assertive case management with specific training are crucial, they do not necessitate massive financial support to be started. Inclusion of a research component is important as well, in terms of service planning and improvement of both quality of care and impact of early intervention strategies.

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

BACKGROUND: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. METHODS: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. FINDINGS: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). INTERPRETATION: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial.

OBJECTIVE: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind) normalizes blood pressure (BP) in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials. METHODS: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3-6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032); in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423); in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483). BP was considered normalized when < or = 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed. RESULTS: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage). Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. CONCLUSIONS: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.

Contribution of PaTrin-2 in Radiotherapy with Temozolomide for the Treatment of Glioblastoma Expressing MGMT

Purpose/Objective(s): Current standard treatment of glioblastoma is radiotherapy (RT) concomitant with temozolomide (TMZ), an alkylating agent. O6-methylguanine-DNA methyltransferase (MGMT) expression is a major mechanism of resistance to Proceedings of the alkylating agent chemotherapy, and MGMT gene promoter methylation (present in 30-45 % of tumors) has been shown to be predictive for tumor response to TMZ therapy. MGMT, an exhaustible repair protein can be depleted by specific inhibitors such as O6- benzylguanine or the non-toxic O6-(4-bromothenyl)guanine (PaTrin-2). Here we have studied the efficacy of the combination of TMZ, RT, and PaTrin-2 to improve the treatment outcome in glioblastoma expressing MGMT. Materials/Methods: 3 glioblastoma lines were chosen: LN18 and T98G expressing MGMT and U251 lacking MGMT expression. A shRNA approach was used to selectively and permanently knockdown level of MGMT in LN18 line. Cells were treated with 10 mM PaTrin-2. After 2 h, various concentrations of TMZ were added, cells were incubated for 24 h, and clonogenic assays were performed. After the same PaTrin-2 pretreatment and 100 mM TMZ exposure, cells were plated 4 h before irradiation with increasing RT doses of up to 6 Gy. Clonogenic survival was assessed after 14 days. Results: Western blot analysis confirmed that reduction of MGMT expression was achieved in LN18A1 expressing MGMT-targeting shRNA. The shRNA non-targeting control sequence did not influenceMGMTprotein level (LN18NT). PaTrin-2 showed no toxicity at 10 mMon the 5 cell lines. TMZ induced up to 70 and 97%of cell death on LN18A1 and U251, respectively, but was not toxic up to 50 mMfor T98G, LN18, and LN18NT. Up to 53%increased TMZ toxicity was observed on the 5 cell lines when treated with the 2 drugs. Irradiation of the 5 lines treated or not with PaTrin-2 showed no survival difference at any irradiation dose. When LN18A1 and U251 cells were irradiated post TMZ treatment, an up to 2.5 and 139.4 fold increase in toxicity, respectively, was observed compared to un-pretreated controls. By contrast, TMZ pretreatment did not increase irradiation toxicity on T98G, LN18, and LN18NT. When cells were incubated with PaTrin-2 and TMZ before the irradiation, up to 3.7, 3.9, 5.8, 6.6 and 348.5 fold increase in toxicity was observed compared to controls on LN18, LN18NT, LN18A1, T98G and U251, respectively. Conclusions: We present here results of TMZ and PaTrin-2 combination ± RT on glioblastoma lines. U251 and LN18A1 cells were much more sensitive to TMZ than LN18, LN18NT, and T98G. PaTrin-2 enhanced the toxicity of TMZ on the MGMT expressing glioblastoma lines. RT further increased TMZ and PaTrin-2 efficacy. These results are encouraging for the treatment of patients with glioblastoma expressing MGMT who have the worst prognosis and respond poorly to RT combined with TMZ.

A low-dose stimulation protocol using highly purified follicle-stimulating hormone can lead to high pregnancy rates in in vitro fertilization patients with polycystic ovaries who are at risk of a high ovarian response to gonadotropins.

OBJECTIVE: To study the benefits of a low-dose stimulation (LDS) protocol with purified urinary follicle-stimulating hormone in patients with polycystic ovaries who have presented previously with a very high ovarian response to a standard hMG stimulation. DESIGN: Cohort study. SETTING: Fertility center in a university hospital. PATIENT(S): Sixty-one patients involved in an IVF/ICSI program from January 1995 to December 1996. INTERVENTION(S): The patients were first stimulated with a standard protocol using hMG and presented with a very high ovarian response. These patients were then stimulated a second time using a low-dose protocol. Cryopreserved embryos were transferred in later artificial or natural cycles until to December 1999. MAIN OUTCOME MEASURE(S): Number of gonadotropin ampules; estradiol level on the day of ovulation induction; follicles, oocytes, and cryopreserved zygotes; fertilization, implantation, and pregnancy rates; and number of ovarian hyperstimulation syndromes (OHSS). RESULT(S): The number of ampules used, the estradiol level reached, and the number of oocytes obtained were significantly lower under the LDS than the standard protocol. High implantation (21.8%) and clinical pregnancy (38.4%) rates were obtained after LDS. The cumulated deliveries per cycle started and per patient were, respectively, 41.6% and 52.5%. Five patients suffered OHSS with the standard protocol, and none with the LDS. CONCLUSION(S): The LDS protocol offers a safe and efficient treatment for patients who present with echographic polycystic ovaries and are at risk of an excessive ovarian response to standard IVF stimulation protocols.

Impact of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry on the Clinical Management of Patients With Gram-negative Bacteremia: A Prospective Observational Study.

Background. Early identification of pathogens from blood cultures using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry may optimize the choice of empirical antibiotic therapy in the setting of bloodstream infections. We aimed to assess the impact of this new technology on the use of antibiotic treatment in patients with gram-negative bacteremia. Methods. We conducted a prospective observational study from January to December 2010 to evaluate the sequential and separate impacts of Gram stain reporting and MALDI-TOF bacterial identification performed on blood culture pellets in patients with gram-negative bacteremia. The primary outcome was the impact of MALDI-TOF on empirical antibiotic choice. Results. Among 202 episodes of gram-negative bacteremia, Gram stain reporting had an impact in 42 cases (20.8%). MALDI-TOF identification led to a modification of empirical therapy in 71 of all 202 cases (35.1%), and in 16 of 27 cases (59.3%) of monomicrobial bacteremia caused by AmpC-producing Enterobacteriaceae. The most frequently observed impact was an early appropriate broadening of the antibiotic spectrum in 31 of 71 cases (43.7%). In total, 143 of 165 episodes (86.7%) of monomicrobial bacteremia were correctly identified at genus level by MALDI-TOF. Conclusions. In a low prevalence area for extended spectrum betalactamases (ESBL) and multiresistant gram-negative bacteria, MALDI-TOF performed on blood culture pellets had an impact on the clinical management of 35.1% of all gram-negative bacteremia cases, demonstrating a greater impact than Gram stain reporting. Thus, MALDI-TOF could become a vital second step beside Gram stain in guiding the empirical treatment of patients with bloodstream infection.

Risk of cardiovascular events and blood pressure control in hypertensive HIV-infected patients: Swiss HIV Cohort Study (SHCS).

BACKGROUND: Prevalence of hypertension in HIV infection is high, and information on blood pressure control in HIV-infected individuals is insufficient. We modeled blood pressure over time and the risk of cardiovascular events in hypertensive HIV-infected individuals. METHODS: All patients from the Swiss HIV Cohort Study with confirmed hypertension (systolic or diastolic blood pressure above 139 or 89 mm Hg on 2 consecutive visits and presence of at least 1 additional cardiovascular risk factor) between April 1, 2000 and March 31, 2011 were included. Patients with previous cardiovascular events, already on antihypertensive drugs, and pregnant women were excluded. Change in blood pressure over time was modeled using linear mixed models with repeated measurement. RESULTS: Hypertension was diagnosed in 2595 of 10,361 eligible patients. Of those, 869 initiated antihypertensive treatment. For patients treated for hypertension, we found a mean (95% confidence interval) decrease in systolic and diastolic blood pressure of -0.82 (-1.06 to -0.58) mm Hg and -0.89 (-1.05 to -0.73) mm Hg/yr, respectively. Factors associated with a decline in systolic blood pressure were baseline blood pressure, presence of chronic kidney disease, cardiovascular events, and the typical risk factors for cardiovascular disease. In patients with hypertension, increase in systolic blood pressure [(hazard ratio 1.18 (1.06 to 1.32) per 10 mm Hg increase], total cholesterol, smoking, age, and cumulative exposure to protease inhibitor-based and triple nucleoside regimens were associated with cardiovascular events. CONCLUSIONS: Insufficient control of hypertension was associated with increased risk of cardiovascular events indicating the need for improved management of hypertension in HIV-infected individuals.

Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 360 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using chi2, t, and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients (p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 (p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group (p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.

Religious beliefs in schizophrenia: Their relevance for adherence to treatment

The study examined how religious beliefs and practices impact upon medication and illness representations in chronic schizophrenia. One hundred three stabilized patients were included in Geneva's outpatient public psychiatric facility in Switzerland. Interviews were conducted to investigate spiritual and religious beliefs and religious practices and religious coping. Medication adherence was assessed through questions to patients and to their psychiatrists and by a systematic blood drug monitoring. Thirty-two percent of patients were partially or totally nonadherent to oral medication. Fifty-eight percent of patients were Christians, 2% Jewish, 3% Muslim, 4% Buddhist, 14% belonged to various minority or syncretic religious movements, and 19% had no religious affiliation. Two thirds of the total sample considered spirituality as very important or even essential in everyday life. Fifty-seven percent of patients had a representation of their illness directly influenced by their spiritual beliefs (positively in 31% and negatively in 26%). Religious representations of illness were prominent in nonadherent patients. Thirty-one percent of nonadherent patients and 27% of partially adherent patients underlined an incompatibility or contradiction between their religion and taking medication, versus 8% of adherent patients. Religion and spirituality contribute to shaping representations of disease and attitudes toward medical treatment in patients with schizophrenia. This dimension should be on the agenda of psychiatrists working with patients with schizophrenia.

A randomized trial of spiritual assessment of outpatients with schizophrenia: Patients' and clinicians' experience

Objective: Recovery-oriented care for patients with schizophrenia involves consideration of cultural issues, such as religion and spirituality. However, there is evidence that psychiatrists rarely address such topics. This study examined acceptance of a spiritual assessment by patients and clinicians, suggestions for treatment that arose from the assessment, and patient outcomes-in terms of treatment compliance and satisfaction with care (as measured by treatment alliance). Methods: Outpatients with psychosis were randomly assigned to two groups: an intervention group that received traditional treatment and a religious and spiritual assessment (N=40) and a control group that received only traditional treatment (N=38). Eight psychiatrists were trained to administer the assessment to their established and stable patients. After each administration, the psychiatrist attended a supervision session with a psychiatrist and a psychologist of religion. Baseline and three-month data were collected. Results: The spiritual assessment was well accepted by patients. During supervision, psychiatrists reported potential clinical uses for the assessment information for 67% of patients. No between-group differences in medication adherence and satisfaction with care were found at three months, although patients in the in- tervention group had significantly better appointment attendance dur- ing the follow-up period. Their interest in discussing religion and spirituality with their psychiatrists remained high. The process was not as well accepted by psychiatrists. Conclusions: Spiritual assessment can raise important clinical issues in the treatment of patients with chronic schizophrenia. Cultural factors, such as religion and spirituality, should be considered early in clinical training, because many clinicians are not at ease addressing such topics with patients.