Deciphering the Tangible Spatio-Temporal Spread of a 25-Year Tuberculosis Outbreak Boosted by Social Determinants.

Outbreak strains of Mycobacterium tuberculosis are promising candidates as targets in the search for intrinsic determinants of transmissibility, as they are responsible for many cases with sustained transmission; however, the use of low-resolution typing methods and restricted geographical investigations represent flaws in assessing the success of long-lived outbreak strains. We can now address the nature of outbreak strains by combining large genomic data sets and phylodynamic approaches. We retrospectively sequenced the whole genome of representative samples assigned to an outbreak circulating in the Canary Islands (the GC strain) since 1993, which accounts for ~20% of local tuberculosis cases. We selected a panel of specific single nucleotide polymorphism (SNP) markers for an in-silico search for additional outbreak-related sequences within publicly available tuberculosis genomic data. Using this information, we inferred the origin, spread, and epidemiological parameters of the GC strain. Our approach allowed us to accurately trace the historical and more recent dispersion of the GC strain. We provide evidence of a highly successful nature within the Canarian archipelago but limited expansion abroad. Estimation of epidemiological parameters from genomic data disagree with a distinctive biology of the GC strain. With the increasing availability of genomic data allowing for the accurate inference of strain spread and critical epidemiological parameters, we can now revisit the link between Mycobacterium tuberculosis genotypes and transmission, as is routinely carried out for SARS-CoV-2 variants of concern. We demonstrate that social determinants rather than intrinsically higher bacterial transmissibility better explain the success of the GC strain. Importantly, our approach can be used to trace and characterize strains of interest worldwide. IMPORTANCE Infectious disease outbreaks represent a significant problem for public health. Tracing outbreak expansion and understanding the main factors behind emergence and persistence remain critical to effective disease control. Our study allows researchers and public health authorities to use Whole-Genome Sequencing-based methods to trace outbreaks, and shows how available epidemiological information helps to evaluate the factors underpinning outbreak persistence. Taking advantage of all the freely available information placed in public repositories, researchers can accurately establish the expansion of an outbreak beyond original boundaries, and determine the potential risk of a strain to inform health authorities which, in turn, can define target strategies to mitigate expansion and persistence. Finally, we show the need to evaluate strain transmissibility in different geographic contexts to unequivocally associate spread to local or pathogenic factors, an important lesson taken from genomic surveillance of SARS-CoV-2.

A Mycobacterium tuberculosis Beijing strain persists at high rates and extends its geographic boundaries 20 years after importation.

Transmission of Beijing Mycobacterium tuberculosis can be investigated based on genotypic analysis of clinical isolates. A Beijing strain began to spread on Gran Canaria Island, Spain, at the end of the last century. In 1996, only 3 years after its importation to the island, its frequency had increased to 27.1% of all the isolates. The strain was tracked during the following years, and the most recent data obtained corresponded to 2007-8, when its presence continued to be alarming (21%). In the current study, we updated data on the distribution of this strain 20 years (2013-2014) after it was first detected on the island and extended the analysis for the first time to all the mycobacteriology laboratories covering the population of the Canary Island archipelago. Rapid updating was enabled by means of 2 different strain-specific PCRs: one targeting a peculiar feature of the strain, which was identified based on an IS6110 copy mapping in the Rv2180c gene, and a newly defined strain-specific single nucleotide polymorphism, which was identified by whole-genome sequencing. The results showed that the strain has remained highly prevalent (20.90% of all isolates), has spread throughout the neighbouring islands, and has also reached high representativeness in them (11-32%).

Long-acting injectable antipsychotics for the treatment of schizophrenia in Spain. / Antipsicóticos inyectables de liberación prolongada para el tratamiento de la esquizofrenia en España.

Antipsychotics are an essential component in the treatment of schizophrenia. Long-acting injectable formulations (LAI) arose to improve adherence with the associated potential of reducing the risk of relapse. The objective of this article is to analyze the use of LAI antipsychotics in Spain, which is similar to other European countries but with a predominance of the use of second generation LAI, to discuss the possible causes of prescribing differences with respect to other countries (including organizational aspects, attitudes of psychiatrists, patients and family members, and clinical practice guidelines), and to discuss their use in acute psychiatric units, first episode, and in children and adolescents. In our view, while it is necessary to increase existing evidence regarding the advantages of LAI antipsychotics and the differentiation between LAI antipsychotics currently available, their use will likely continue to grow driven by clinical experience.

Hydroxide Ions Stabilize Open Carbon Nanotubes in Degassed Water.

The main hurdle preventing the widespread use of single-walled carbon nanotubes remains the lack of methods with which to produce formulations of pristine, unshortened, unfunctionalized, individualized single-walled carbon nanotubes, thus preserving their extraordinary properties. In particular, sonication leads to shortening, which is detrimental to percolation properties (electrical, thermal, mechanical, etc.). Using reductive dissolution and transfer into degassed water, open-ended, water-filled nanotubes can be dispersed as individualized nanotubes in water-dimethyl sulfoxide mixtures, avoiding the use of sonication and surfactant. Closed nanotubes, however, aggregate immediately upon contact with water. Photoluminescence and absorption spectroscopy both point out a very high degree of individualization while retaining lengths of several microns. The resulting transparent conducting films are 1 order of magnitude more conductive than surfactant-based blanks at equal transmittance.

Adherence predicts symptomatic and psychosocial remission in schizophrenia: Naturalistic study of patient integration in the community. / La adherencia predice la remisión sintomática y psicosocial en esquizofrenia: estudio naturalístico de la integración de los pacientes en la comunidad.

INTRODUCTION: Psychosocial functioning in patients with schizophrenia attended in daily practice is an understudied aspect. The aim of this study was to assess the relationship between symptomatic and psychosocial remission and adherence to treatment in schizophrenia. METHODS: This cross-sectional, non-interventional, and multicenter study assessed symptomatic and psychosocial remission and community integration of 1,787 outpatients with schizophrenia attended in Spanish mental health services. Adherence to antipsychotic medication in the previous year was categorized as≥80% vs.<80%. RESULTS: Symptomatic remission was achieved in 28.5% of patients, and psychosocial remission in 26.1%. A total of 60.5% of patients were classified as adherent to antipsychotic treatment and 41% as adherent to non-pharmacological treatment. During the index visit, treatment was changed in 28.4% of patients, in 31.1% of them because of low adherence (8.8% of the total population). Adherent patients showed higher percentages of symptomatic and psychosocial remission than non-adherent patients (30.5 vs. 25.4%, P<.05; and 32 vs. 17%, P<.001, respectively). Only 3.5% of the patients showed an adequate level of community integration, which was also higher among adherent patients (73.0 vs. 60.1%, P<.05). CONCLUSIONS: Adherence to antipsychotic medication was associated with symptomatic and psychosocial remission as well as with community integration.

Towards a pragmatic and operational definition of relapse in schizophrenia: A Delphi consensus approach.

OBJECTIVE: To develop pragmatic and operational definitions of relapse in schizophrenia. METHODS: A two-round Delphi consensus approach was used. The final questionnaire based on seven pre-established definition relapse models developed by a panel of eight experts was presented to 33 general psychiatrists who attended an "ad hoc" meeting. RESULTS: The most frequent components of the pragmatic definition were the psychopathological severity of the psychotic spectrum (70%), more intense management of the case (68%), a previously stabilized episode (67%), and impairment in functioning and social behavior (67%). In the operational definition, reappearance of symptoms was considered indispensable by 71% of the participants, and reappearance of positive symptoms measured by clinical scales was considered recommendable by 67%. Between 46% and 53% rated worsening of severity status and worsening of functioning as indispensable or recommendable. An increase of ≥ 10 points in the positive subscale of Positive and Negative Symptom Scale was rated by 51% of the participants, a score of 6 points in the Clinical Global Impression scale (much worse) by 89%, and a reduction of ≥ 20 points in the Global Assessment of Functioning scale by 62%. CONCLUSIONS: A better understanding of the definition of relapse in schizophrenia is necessary to improve effective prevention strategies.

Nurses' perceptions of medication adherence in schizophrenia: results of the ADHES cross-sectional questionnaire survey.

OBJECTIVES: Poor adherence to antipsychotic treatment is a widespread problem within schizophrenia therapy with serious consequences including increased risks of relapse and rehospitalization. Mounting evidence supports the key roles that nurses play in monitoring patient progress and facilitating long-term treatment adherence. The Adherencia Terapéutica en la Esquizofrenia (ADHES) nurses' survey was designed to assess the opinions of nurses on the causes and management of partial/nonadherence to antipsychotic medication. METHODS: A questionnaire-based cross-sectional survey of 4120 nurses from Europe, the Middle East and Africa. Interpretation of results was based on a descriptive comparison of responses. RESULTS: Nurses perceived 54% of patients seen in the preceding month to be partially/nonadherent to treatment. Most nurses (90%) reported some level of experience with administration of long-acting injectable (LAI) antipsychotics, with 24% of nurses administering >10 injections per month. The majority (85%) of nurses surveyed believed that improving adherence would improve patient outcomes. Nearly half (49%) reported that most of their patients depend on a family member or other nonprofessional carer to remind them to take their medication as prescribed. A similar proportion of nurses (43%) reported that most of their patients relied on a professional to remind them to take medication. Most nurses (92%) felt that ensuring continuous medication with LAI antipsychotics would yield long-term benefits for patients, but their opinion was that over a third of patients were unaware of LAI antipsychotic treatments. In a series of forced options, the strategy used most often by respondents (89%) to promote medication adherence was to build trusting relationships with patients while listening to and interpreting their needs and concerns. Respondents also rated this as the most effective strategy that they used (48%). CONCLUSION: Nurses are highly aware of adherence issues faced by their patients; further patient education on treatment options is needed.

Resistance to first-line antituberculosis drugs in Spain, 2010-2011. RETUBES Study.

INTRODUCTION: The magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. METHODS: Prospective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. RESULTS: A total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR=2.3; 95%CI: .98-5.67 and OR=2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03). CONCLUSIONS: The rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.

Treatment adherence and quality of sleep in schizophrenia outpatients.

OBJECTIVE: Patients with schizophrenia (SZ) often present sleep complaints, and patients with sleep disturbances are at a greater risk for symptom worsening after antipsychotic discontinuation. Long-term adherence to antipsychotic treatment remains a challenge for clinicians, and the relationship between quality of sleep and treatment adherence in SZ outpatients has been poorly studied. METHODS: In this cross-sectional, non-interventional study, 811 adult outpatients with a diagnosis of SZ were divided into two groups according to the presence (or absence) of sleep disturbances, and assessed using measures of symptom severity, quality and patterns of sleep, adherence/compliance to treatment, and family support degree. RESULTS: Patients with sleep disturbances were significantly more symptomatic (p < 0.0001), and scored significantly higher on the Pittsburgh Sleep Quality Index (PSQI) as compared with patients without sleep disturbances (p < 0.0001). More compliant patients showed less sleep disturbances (p < 0.0001); moreover, patients with worse compliance to pharmacological treatment showed significantly higher scores on the PSQI (p < 0.0001). Regarding family support degree, patients with sleep disorders presented a lower family support (p = 0.0236), and patients with worse treatment adherence had worse family support (p < 0.0001). CONCLUSIONS: Our findings show that SZ outpatients reporting sleep disturbances show greater symptom severity, and worse adherence/compliance to treatment, as well as a lower family support.

Satisfaction with Life of Schizophrenia Outpatients and Their Caregivers: Differences between Patients with and without Self-Reported Sleep Complaints.

Patients with schizophrenia often present sleep complaints, but its relationship with general satisfaction with life (SWL) and burden for caregivers has been understudied. We aimed to assess the differences in SWL between patients with and without self-reported sleep disturbances and that of their caregivers. In a noninterventional study, 811 schizophrenia adult outpatients were screened for their subjective perception of having (or not) sleep disturbances and evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Pittsburgh Sleep Quality Index (PSQI). Patients self-reporting sleep disturbances were significantly more symptomatic (P < 0.001), presented significantly worse family support (P = 0.0236), and self-reported worse SWL in all domains. Caregivers of patients with schizophrenia self-reporting sleep disturbances also reported worse SWL in all domains, as compared to caregivers of patients without subjective sleep disturbances. Patient and caregivers' SWL was significantly correlated to patients' quality of sleep (P < 0.0001 for all domains). Patient' and caregivers' SWL was negatively affected by patients' poor quality of sleep. We found that patients self-reporting sleep disturbances showed greater symptom severity, worse quality of sleep, worse SWL, and less caregiver support. SWL was also worse for caregivers of patients with schizophrenia reporting sleep disturbances.

Psychiatrists' awareness of adherence to antipsychotic medication in patients with schizophrenia: results from a survey conducted across Europe, the Middle East, and Africa.

BACKGROUND: Nonadherence is common among patients with schizophrenia, although the rates vary according to means of assessment and patient population. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes, including increasing the risk of relapse and rehospitalization. Understanding psychiatrists' perception of the causes and consequences of nonadherence is crucial to addressing adherence problems effectively. METHODS: The Europe, the Middle East, and Africa (EMEA) Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was conducted by questionnaire during January-March 2010 among psychiatrists treating patients with schizophrenia in 36 countries. The survey comprised 20 questions. In addition to recording the demographic details of the 4722 respondents (~12% response rate), it canvassed their preferred methods of assessing adherence, their perceptions of adherence rates, reasons for nonadherence, and strategies to improve adherence. RESULTS: Psychiatrists estimated that 53% of their patients with schizophrenia were partially/nonadherent during the previous month. They estimated only one-third of patients who deteriorated after stopping medication were able to attribute this to nonadherence. Psychiatrists assessed adherence most often by patient interview. Lack of insight was viewed as the most important cause of medication discontinuation, followed by patients feeling better and thinking their medication unnecessary, and experiencing undesirable side effects. Considerably fewer psychiatrists viewed insufficient efficacy, cognitive impairment, or drug/alcohol abuse as the most important reasons for their patients stopping medication. CONCLUSION: Psychiatrists throughout EMEA recognize the impact of partial/nonadherence to medication, with patient enquiry being the most commonly used means of assessment. There remains a need for more proactive management of patients with schizophrenia, particularly in increasing patient insight of their illness in order to improve adherence and minimize the consequences of relapse. Strategies focused on raising awareness of the importance of adherence are also warranted, with the aim of improving patient outcomes in schizophrenia.

Improving treatment adherence in your patients with schizophrenia: the STAY initiative.

Partial and non-adherence to medication is a common problem in schizophrenia, leading to an increased risk of relapse, increased likelihood of hospitalization and poorer long-term outcomes. In contrast, continuous medication in the treatment of schizophrenia is associated with positive outcomes, including improved clinical status, improved quality of life and functioning, and reduced risk of relapse and rehospitalization. Strategies aimed at improving medication adherence are therefore key for patients to achieve their treatment goals. In an attempt to address the issues of partial/non-adherence to antipsychotic medication in schizophrenia, a group of psychiatrists convened to discuss and develop a set of principles aimed at helping patients adhere to their medication. These principles were then refined and developed into the STAY (the Six principles to improve Treatment Adherence in Your patients) initiative following presentation to a wider group of psychiatrists from across Europe. This manuscript summarizes these principles and explains the rationale for their selection. These principles are: (1) recognizing that most patients with schizophrenia are at risk of partial/non-adherence at some time during the course of their illness; (2) the benefits of a good therapeutic alliance for identifying potential adherence issues; (3) tailored treatment plans to meet an individual's needs, including the most suitable route of delivery of antipsychotic medication; (4) involving family/key persons in care and psychoeducation of the patient, assuming the patient agrees to this; (5) ensuring optimal effectiveness of care; and (6) ensuring continuity in the care of patients with schizophrenia. The application of these six principles should help to raise awareness of and address poor patient adherence, as well as generally improving care of patients with schizophrenia. In turn, this should lead to improved overall clinical outcomes for patients receiving long-term treatment for schizophrenia.

Rapid test for identification of a highly transmissible Mycobacterium tuberculosis Beijing strain of sub-Saharan origin.

The development of a rapid test to identify Mycobacterium tuberculosis Beijing isolates and specifically strain GC1237, coming from a sub-Saharan country, is needed due to its alarming wide spread on Gran Canaria Island (Spain). A rapid test that detects IS6110 present between dnaA and dnaN in the Beijing strains and in a specific site for GC1237 (Rv2180c) has been developed. This test would be a useful tool in the surveillance of subsequent cases.

Practical guidance for prescribing ziprasidone in acute manic or mixed episodes of bipolar I disorder.

INTRODUCTION: Limited information is available on the clinical issues and strategies for optimal clinical usage of ziprasidone in the treatment of adult patients with acute manic or mixed episodes of bipolar disorder. AREAS COVERED: To address those issues, information from clinical trials addressing the efficacy and tolerability of ziprasidone in acute bipolar mania was reviewed and supplemented with the input from an expert faculty of European psychiatrists with extensive experience in treating patients with bipolar mania, both in clinical trials and in everyday clinical practice. EXPERT OPINION: Effective use of oral ziprasidone in the treatment of acute bipolar mania requires rapid titration to doses in the range 120 - 160 mg/day and administration with meals of ≥ 500 kcal. As in the clinical trials, temporary short-term use of benzodiazepines (in particular lorazepam for agitation or temazepam for insomnia) could be advisable. Available evidence from randomized clinical trials in combination with clinical experience supports the use of ziprasidone as one of the first-line effective and safe treatments for acute manic or mixed episodes associated with bipolar I disorder.

Switching among antipsychotics in everyday clinical practice: focus on ziprasidone.

OBJECTIVES: This article addresses points to consider when switching patients to the second-generation antipsychotic (SGA), ziprasidone, in everyday clinical practice: 1) the pharmacologic properties of the pre-switch antipsychotic and of ziprasidone; 2) switch and dosing strategies to ensure maintenance or attainment of efficacy; 3) recognition and management of possible rebound effects of the pre-switch medication discontinuation; 4) recognition and management of potential side effects of ziprasidone; and 5) education and support for patients/caregivers concerning correct ziprasidone administration. METHODS: A Medline search (up to July 7, 2010) identified studies in which adult patients with schizophrenia were switched to ziprasidone from another antipsychotic. In addition, based on their extensive clinical experience, an expert faculty of European psychiatrists provided advice on identifying patients who may be appropriate candidates for switching to ziprasidone, and on establishing optimal strategies for switching to ziprasidone in everyday clinical practice. RESULTS: Data from 10 studies, in which 1395 patients were switched to ziprasidone, showed that switching from first-generation antipsychotics (FGAs) or SGAs generally resulted in maintenance or improvement of efficacy across all studied symptom domains, improvements in tolerability, and acute and long-term benefits regarding cardiometabolic parameters, including body weight. Maintenance of efficacy is most likely to be achieved using a plateau cross-titration strategy, with a rapid uptitration of ziprasidone to a dose range of 60 to 80 mg administered twice daily with food. Temporary coadministration of benzodiazepines, anticholinergics, or beta-blockers should be considered for the management of potential rebound effects. CONCLUSION: Optimal switching of patients with schizophrenia from FGAs or SGAs to ziprasidone requires careful attention to differences in the pharmacological profiles of the pre-switch medication and of ziprasidone, which may impact efficacy and tolerability. Good communication between the clinician and patient/caregiver about the goals of switching, the importance of adherence to the chosen switch strategy, and the correct administration of ziprasidone are essential.

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review.

IMPORTANCE OF THE FIELD: Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP). AREAS COVERED IN THIS REVIEW: Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency. WHAT THE READER WILL GAIN: RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI. TAKE HOME MESSAGE: Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Strategies for successful clinical management of schizophrenia with ziprasidone.

IMPORTANCE OF THE FIELD: This review addresses practical clinical issues related to the use of ziprasidone in the treatment of schizophrenia using information from clinical trials, unpublished data, manufacturer's information, and input from an expert faculty of European psychiatrists with extensive experience of the use of ziprasidone, both in clinical trials and in everyday clinical practice. AREAS COVERED IN THIS REVIEW: A Medline search of published data (1998 - 2010) was carried out, together with a review of unpublished data and manufacturer's information. In addition, expert opinion was sought from psychiatrists with extensive experience of ziprasidone in the treatment of schizophrenia in clinical settings across Europe. WHAT THE READER WILL GAIN: This review has been undertaken to determine how the information from clinical trials can be optimally translated into 'real-life' practice and to establish how a decade of experience with ziprasidone in clinical practice can inform its optimal use to maximize effectiveness and minimize side effects. TAKE HOME MESSAGE: Effective use of ziprasidone in everyday clinical practice usually requires rapid titration to doses in the range of 120 - 160 mg/day and administration with proper meals, thereby achieving the high levels of schizophrenia symptom control reported in clinical trials. Additional guidance is provided about effective management of side effects, and appropriate coadministration of benzodiazepines and other agents, to achieve desired outcomes.

Adherence to treatment and therapeutic strategies in schizophrenic patients: the ADHERE study.

AIM: To assess the degree of compliance and adherence to treatment during the follow-up of schizophrenic outpatients after a new therapeutic strategy had been initiated. METHODS: A multicenter, retrospective, prospective, observational study of 1,848 outpatients with schizophrenia or schizoaffective disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was conducted. Patients were treated either with oral or injectable conventional or second generation antipsychotics, and were followed up for 3 months at mental health centers. Patient compliance with the pharmacological treatment was assessed by the use of questionnaires, scales, medication accountability, and the Medication Event Monitoring System. Patients were considered compliant if they reported a high compliance rate (> or = 80%). RESULTS: At baseline only 29% of patients on oral medication were compliant compared with 79% of patients on injectable medication (injection counting) (OR= 9.11; 95% CI 6.02-13.77; P<.0001). At the 3 month visit, 84% of patients had changed their treatment and in these, the compliance rate of those on injectable medication was 94% versus 87% of patients taking oral medication (OR= 2.47; 95% CI 1.21-5.05; P=.022). CONCLUSION: The use of long-acting injectable antipsychotics, which improves compliance rates and patient follow-up, should facilitate the management of Spanish patients with schizophrenia in mental health centers.

A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Cost-effectiveness analysis of ziprasidone versus haloperidol in sequential intramuscular/oral treatment of exacerbation of schizophrenia: economic subanalysis of the ZIMO trial.

OBJECTIVE: This study aimed to assess the cost effectiveness of ziprasidone versus haloperidol in sequential intramuscular (IM)/oral treatment of patients with exacerbation of schizophrenia in Spain. METHODS: A cost-effectiveness analysis from the hospital perspective was performed. Length of stay, study medication and use of concomitant drugs were calculated using data from the ZIMO trial. The effectiveness of treatment was determined by the percentage of responders (reduction in baseline Brief Psychiatric Rating Scale [BPRS] negative symptoms subscale >or=30%). Economic assessment included estimation of mean (95% CI) total costs, cost per responder and the incremental cost-effectiveness ratio (ICER) per additional responder. The economic uncertainty level was controlled by resampling and calculation of cost-effectiveness acceptability curves. RESULTS: A total of 325 patients (ziprasidone n = 255, haloperidol n = 70) were included in this economic subanalysis. Ziprasidone showed a significantly higher responder rate compared with haloperidol (71% vs 56%, respectively; p = 0.023). Mean total costs were euro3582 (95% CI 3226, 3937) for ziprasidone and euro2953 (95% CI 2471, 3436) for haloperidol (p = 0.039), mainly due to a higher ziprasidone acquisition cost. However, costs per responder were lower with ziprasidone (euro5045 [95% CI 4211, 6020]) than with haloperidol (euro5302 [95% CI 3666, 7791], with a cost per additional responder (ICER) for ziprasidone of euro4095 (95% CI -130, 22 231). The acceptability curve showed an ICER cut-off value of euro13 891 at the 95% cost-effectiveness probability level for >or=30% reduction in BPRS negative symptoms. CONCLUSIONS: Compared with haloperidol, ziprasidone was significantly better at controlling psychotic negative symptoms in acute psychoses. The extra cost of ziprasidone was offset by a higher effectiveness rate, yielding a lower cost per responder. In light of the social benefit (less family burden and greater restoration of productivity), the incremental cost per additional responder with sequential IM/oral ziprasidone should be considered cost effective in patients with exacerbation of schizophrenia in Spain.