Cost of antipsychotic polypharmacy in the treatment of schizophrenia

<p>Abstract</p> <p>Background</p> <p>This study compared the costs of antipsychotic polypharmacy for patients who initiated on 1 of the 3 most commonly prescribed atypical antipsychotics – olanzapine, quetiapine, or risperidone.</p> <p>Methods</p> <p>Data were drawn from a large, prospective, naturalistic, multi-site, nonrandomized study of treatment for schizophrenia in the United States conducted between July 1997 and September 2003. Participants who were initiated on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276) were followed for 1 year post initiation and compared on: (a) average daily cost of the index antipsychotic while on the index antipsychotic, (b) average daily cost of the coprescribed antipsychotics while on the index antipsychotic, (c) average daily cost of the index antipsychotic and the coprescribed antipsychotics while on the index antipsychotic, (d) total annual cost of antipsychotic medications prescribed in the year following initiation on the index antipsychotic, using propensity score-adjusted bootstrap resampling method. Average daily antipsychotic costs and total annual antipsychotic costs were also estimated using more recent (2004) antipsychotic drug prices.</p> <p>Results</p> <p>During the 1 year following initiation on the index antipsychotic, the total average daily cost of the index antipsychotic was higher for quetiapine ($15.33) than olanzapine ($13.90, p < .05) and risperidone ($11.04, p < .01), although the average daily cost of the index antipsychotic was higher for olanzapine ($10.08) than risperidone ($6.74, p < .01) or quetiapine ($6.63, p < .01). Lower total average daily costs were observed in risperidone than olanzapine or quetiapine. Significantly lower average daily cost of concomitant antipsychotic medications for olanzapine ($3.82) compared to quetiapine ($8.70, p < .01) or risperidone-initiated patients ($4.30, p < .01) contributed to the lower average daily cost of all antipsychotic medication for olanzapine-initiated patients. Each dollar spent on the index antipsychotic was accompanied by spending an additional$1.31 on concomitant antipsychotics for quetiapine compared to $0.64 for risperidone and$0.38 for olanzapine-initiated patients. A separate intent-to-treat analysis of the total annual antipsychotic cost found a significantly higher total annual antipsychotic cost for quetiapine-initiated patients ($5320) compared to olanzapine ($4536, p < .01) or risperidone ($3813, p < .01).</p> <p>Conclusion</p> <p>Prevalent antipsychotic polypharmacy adds substantial cost to the treatment of schizophrenia. Comparison of medication costs need to address the costs of all antipsychotics. A better understanding of concomitant antipsychotic costs provides a more accurate portrayal of antipsychotic medication costs in the treatment of schizophrenia.</p

Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

BACKGROUND: Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy) is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. METHODS: Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796) who were initiated during the study on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276). The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. RESULTS: During the 1-year period, only a third (35.7%) of the patients were treated predominately with monotherapy (>300 days). Most patients (57.7%) had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days). Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043) or quetiapine (p = .002). The number of monotherapy days was significantly greater for olanzapine than quetiapine (p < .001), but not for olanzapine versus risperidone, or for risperidone versus quetiapine-initiated patients. CONCLUSION: Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic polypharmacy for prolonged periods is very common during the treatment of schizophrenia patients in usual care settings. In addition, in this non-randomized naturalistic observational study, the most commonly used atypical antipsychotics significantly differed on the rate and duration of antipsychotic monotherapy. Reasons for and the impact of the predominant use of polypharmacy will require further study

Computer-aided detection in breast MRI: a systematic review and meta-analysis

To evaluate the additional value of computer-aided detection (CAD) in breast MRI by assessing radiologists' accuracy in discriminating benign from malignant breast lesions. A literature search was performed with inclusion of relevant studies using a commercially available CAD system with automatic colour mapping. Two independent researchers assessed the quality of the studies. The accuracy of the radiologists' performance with and without CAD was presented as pooled sensitivity and specificity. Of 587 articles, 10 met the inclusion criteria, all of good methodological quality. Experienced radiologists reached comparable pooled sensitivity and specificity before and after using CAD (sensitivity: without CAD: 89%; 95% CI: 78-94%, with CAD: 89%; 95%CI: 81-94%) (specificity: without CAD: 86%; 95% CI: 79-91%, with CAD: 82%; 95% CI: 76-87%). For residents the pooled sensitivity increased from 72% (95% CI: 62-81%) without CAD to 89% (95% CI: 80-94%) with CAD, however, not significantly. Concerning specificity, the results were similar (without CAD: 79%; 95% CI: 69-86%, with CAD: 78%; 95% CI: 69-84%). CAD in breast MRI has little influence on the sensitivity and specificity of experienced radiologists and therefore their interpretation remains essential. However, residents or inexperienced radiologists seem to benefit from CAD concerning breast MRI evaluation

Cataract research using electronic health records

<p>Abstract</p> <p>Background</p> <p>The eMERGE (electronic MEdical Records and Genomics) network, funded by the National Human Genome Research Institute, is a national consortium formed to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic health record (EHR) systems for large-scale, high-throughput genetic research. Marshfield Clinic is one of five sites in the eMERGE network and primarily studied: 1) age-related cataract and 2) HDL-cholesterol levels. The purpose of this paper is to describe the approach to electronic evaluation of the epidemiology of cataract using the EHR for a large biobank and to assess previously identified epidemiologic risk factors in cases identified by electronic algorithms.</p> <p>Methods</p> <p>Electronic algorithms were used to select individuals with cataracts in the Personalized Medicine Research Project database. These were analyzed for cataract prevalence, age at cataract, and previously identified risk factors.</p> <p>Results</p> <p>Cataract diagnoses and surgeries, though not type of cataract, were successfully identified using electronic algorithms. Age specific prevalence of both cataract (22% compared to 17.2%) and cataract surgery (11% compared to 5.1%) were higher when compared to the Eye Diseases Prevalence Research Group. The risk factors of age, gender, diabetes, and steroid use were confirmed.</p> <p>Conclusions</p> <p>Using electronic health records can be a viable and efficient tool to identify cataracts for research. However, using retrospective data from this source can be confounded by historical limits on data availability, differences in the utilization of healthcare, and changes in exposures over time.</p

Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD) are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD) patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ) using a highly sensitive ELISA kit.</p> <p>Results</p> <p>We found a small but statistically significant increase in saliva Aβ₄₂levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ₄₂between patients with PD and healthy controls. Saliva Aβ₄₀expression was unchanged within all the studied sample. The association between saliva Aβ₄₂levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity.</p> <p>Conclusions</p> <p>We suggest that saliva Aβ₄₂levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.</p

Basin-Scale Control on the Phytoplankton Biomass in Lake Victoria, Africa

The relative bio-optical variability within Lake Victoria was analyzed through the spatio-temporal decomposition of a 1997–2004 dataset of remotely-sensed reflectance ratios in the visible spectral range. Results show a regular seasonal pattern with a phase shift (around 2 months) between the south and north parts of the lake. Interannual trends suggested a teleconnection between the lake dynamics and El-Niño phenomena. Both seasonal and interannual patterns were associated to conditions of light limitation for phytoplankton growth and basin-scale hydrodynamics on phytoplankton access to light. Phytoplankton blooms developed during the periods of lake surface warming and water column stability. The temporal shift apparent in the bio-optical seasonal cycles was related to the differential cooling of the lake surface by southeastern monsoon winds. North-south differences in the exposure to trade winds are supported by the orography of the Eastern Great Rift Valley. The result is that surface layer warming begins in the northern part of the lake while the formation of cool and dense water continues in the southern part. The resulting buoyancy field is sufficient to induce a lake-wide convective circulation and the tilting of the isotherms along the north-south axis. Once surface warming spreads over the whole lake, the phytoplankton bloom dynamics are subjected to the internal seiche derived from the relaxation of thermocline tilting. In 1997–98, El-Niño phenomenon weakened the monsoon wind flow which led to an increase in water column stability and a higher phytoplankton optical signal throughout the lake. This suggests that phytoplankton response to expected climate scenarios will be opposite to that proposed for nutrient-limited great lakes. The present analysis of remotely-sensed bio-optical properties in combination with environmental data provides a novel basin-scale framework for research and management strategies in Lake Victoria

The neurobiology of mouse models syntenic to human chromosome 15q

Autism is a neurodevelopmental disorder that manifests in childhood as social behavioral abnormalities, such as abnormal social interaction, impaired communication, and restricted interest or behavior. Of the known causes of autism, duplication of human chromosome 15q11–q13 is the most frequently associated cytogenetic abnormality. Chromosome 15q11–q13 is also known to include imprinting genes. In terms of neuroscience, it contains interesting genes such as Necdin, Ube3a, and a cluster of GABAA subunits as well as huge clusters of non-coding RNAs (small nucleolar RNAs, snoRNAs). Phenotypic analyses of mice genetically or chromosomally engineered for each gene or their clusters on a region of mouse chromosome seven syntenic to human 15q11–q13 indicate that this region may be involved in social behavior, serotonin metabolism, and weight control. Further studies using these models will provide important clues to the pathophysiology of autism. This review overviews phenotypes of mouse models of genes in 15q11–q13 and their relationships to autism

Impact of early psychosocial factors (childhood socioeconomic factors and adversities) on future risk of type 2 diabetes, metabolic disturbances and obesity: a systematic review

<p>Abstract</p> <p>Background</p> <p>Psychological factors and socioeconomic status (SES) have a notable impact on health disparities, including type 2 diabetes risk. However, the link between childhood psychosocial factors, such as childhood adversities or parental SES, and metabolic disturbances is less well established. In addition, the lifetime perspective including adult socioeconomic factors remains of further interest.</p> <p>We carried out a systematic review with the main question if there is evidence in population- or community-based studies that childhood adversities (like neglect, traumata and deprivation) have considerable impact on type 2 diabetes incidence and other metabolic disturbances. Also, parental SES was included in the search as risk factor for both, diabetes and adverse childhood experiences. Finally, we assumed that obesity might be a mediator for the association of childhood adversities with diabetes incidence. Therefore, we carried out a second review on obesity, applying a similar search strategy.</p> <p>Methods</p> <p>Two systematic reviews were carried out. Longitudinal, population- or community-based studies were included if they contained data on psychosocial factors in childhood and either diabetes incidence or obesity risk.</p> <p>Results</p> <p>We included ten studies comprising a total of 200,381 individuals. Eight out of ten studies indicated that low parental status was associated with type 2 diabetes incidence or the development of metabolic abnormalities. Adjustment for adult SES and obesity tended to attenuate the childhood SES-attributable risk but the association remained. For obesity, eleven studies were included with a total sample size of 70,420 participants. Four out of eleven studies observed an independent association of low childhood SES on the risk for overweight and obesity later in life.</p> <p>Conclusions</p> <p>Taken together, there is evidence that childhood SES is associated with type 2 diabetes and obesity in later life. The database on the role of psychological factors such as traumata and childhood adversities for the future risk of type 2 diabetes or obesity is too small to draw conclusions. Thus, more population-based longitudinal studies and international standards to assess psychosocial factors are needed to clarify the mechanisms leading to the observed health disparities.</p

Review of methods used by chiropractors to determine the site for applying manipulation

Background: With the development of increasing evidence for the use of manipulation in the management of musculoskeletal conditions, there is growing interest in identifying the appropriate indications for care. Recently, attempts have been made to develop clinical prediction rules, however the validity of these clinical prediction rules remains unclear and their impact on care delivery has yet to be established. The current study was designed to evaluate the literature on the validity and reliability of the more common methods used by doctors of chiropractic to inform the choice of the site at which to apply spinal manipulation. Methods: Structured searches were conducted in Medline, PubMed, CINAHL and ICL, supported by hand searches of archives, to identify studies of the diagnostic reliability and validity of common methods used to identify the site of treatment application. To be included, studies were to present original data from studies of human subjects and be designed to address the region or location of care delivery. Only English language manuscripts from peer-reviewed journals were included. The quality of evidence was ranked using QUADAS for validity and QAREL for reliability, as appropriate. Data were extracted and synthesized, and were evaluated in terms of strength of evidence and the degree to which the evidence was favourable for clinical use of the method under investigation. Results: A total of 2594 titles were screened from which 201 articles met all inclusion criteria. The spectrum of manuscript quality was quite broad, as was the degree to which the evidence favoured clinical application of the diagnostic methods reviewed. The most convincing favourable evidence was for methods which confirmed or provoked pain at a specific spinal segmental level or region. There was also high quality evidence supporting the use, with limitations, of static and motion palpation, and measures of leg length inequality. Evidence of mixed quality supported the use, with limitations, of postural evaluation. The evidence was unclear on the applicability of measures of stiffness and the use of spinal x-rays. The evidence was of mixed quality, but unfavourable for the use of manual muscle testing, skin conductance, surface electromyography and skin temperature measurement. Conclusions: A considerable range of methods is in use for determining where in the spine to administer spinal manipulation. The currently published evidence falls across a spectrum ranging from strongly favourable to strongly unfavourable in regard to using these methods. In general, the stronger and more favourable evidence is for those procedures which take a direct measure of the presumptive site of care– methods involving pain provocation upon palpation or localized tissue examination. Procedures which involve some indirect assessment for identifying the manipulable lesion of the spine–such as skin conductance or thermography–tend not to be supported by the available evidence.https://doi.org/10.1186/2045-709X-21-3