Possible Loss of the Chloroplast Genome in the Parasitic Flowering Plant Rafflesia lagascae (Rafflesiaceae)

Rafflesia is a genus of holoparasitic plants endemic to Southeast Asia that has lost the ability to undertake photosynthesis. With short-read sequencing technology, we assembled a draft sequence of the mitochondrial genome of Rafflesia lagascae Blanco, a species endemic to the Philippine island of Luzon, with ∼350× sequencing depth coverage. Using multiple approaches, however, we were only able to identify small fragments of plastid sequences at low coverage depth

Development and content validity of a patient reported outcomes measure to assess symptoms of major depressive disorder

<p>Abstract</p> <p>Background</p> <p>Although many symptoms of Major Depressive Disorder (MDD) are assessed through patient-report, there are currently no patient-reported outcome (PRO) instruments that incorporate documented evidence of patient input in PRO instrument development. A review of existing PROs used in MDD suggested the need to conduct qualitative research with patients with MDD to better understand their experience of MDD and develop an evaluative instrument with content validity. The aim of this study was to develop a disease-specific questionnaire to assess symptoms important and relevant to adult MDD patients.</p> <p>Methods</p> <p>The questionnaire development involved qualitative interviews for concept elicitation, instrument development, and cognitive interviews to support content validity. For concept elicitation, ten MDD severity-specific focus group interviews with thirty-eight patients having clinician-confirmed diagnoses of MDD were conducted in January 2009. A semi-structured discussion guide was used to elicit patients' spontaneous descriptions of MDD symptoms. Verbatim transcripts of focus groups were coded and analyzed to develop a conceptual framework to describe MDD. A PRO instrument was developed by operationalizing concepts elicited in the conceptual framework. Cognitive interviews were carried out in patients (n = 20) to refine and test the content validity of the instrument in terms of item relevance and comprehension, instructions, recall period, and response categories.</p> <p>Results</p> <p>Concept elicitation focus groups identified thirty-five unique concepts falling into several domains: i) emotional, ii) cognitive, iii) motivation, iv) work, v) sleep, vi) appetite, vii) social, viii) activities of daily living, ix) tired/fatigue, x) body pain, and xi) suicidality. Concept saturation, the point at which no new relevant information emerges in later interviews, was achieved for each of the concepts. Based on the qualitative findings, the PRO instrument developed had 15 daily and 20 weekly items. The cognitive interviews confirmed that the instructions, item content, and response scales were understood by the patients.</p> <p>Conclusions</p> <p>Rigorous qualitative research resulted in the development of a PRO measure for MDD with supported content validity. The MDD PRO can assist in understanding and assessing MDD symptoms from patients' perspectives as well as evaluating treatment benefit of new targeted therapies.</p

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder:a meta-analysis of randomized controlled trials

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ≥6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5,364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents

Quality of life and drug costs associated with switching antipsychotic medication to once-daily extended release quetiapine fumarate in patients with schizophrenia.

OBJECTIVE: The objective of this study was to assess the quality of life and drug costs associated with switching from any ongoing antipsychotic treatment to once-daily extended release quetiapine fumarate (quetiapine XR) in patients with schizophrenia. METHODS: This assessment was based on data collected during a 12-week study in patients with schizophrenia (n = 477) who switched from their current antipsychotic due to insufficient efficacy or poor tolerability to a flexible dose of quetiapine XR. Patients were assigned utilities based on their Positive and Negative Syndrome Scale (PANSS) scores and the presence of adverse events by applying the methods of Lenert et al.1. Quality adjusted life year (QALY) gains were calculated assuming a linear change of utility between two consecutive visits. Incremental costs were calculated by comparing the hypothetical mean drug cost (assuming patients stay on previous treatment) with the actual mean cost of quetiapine XR based on European prices. RESULTS: Patients who completed the study (n = 279) increased their average utility by 0.116, corresponding to a QALY gain of 0.0207. For the total sample, the mean utility increased by 0.09, reflecting a QALY gain of 0.0170. The additional costs for quetiapine XR per QALY gained varied from approximately 16,000 euro to 24,000 euro. Notably, this is a non-comparative study; therefore, no conclusions can be reached regarding the relative impact of switching to quetiapine XR compared with other antipsychotics. Further limitations included the short trial duration on which the utility estimates are based, and the restriction of cost data to drug costs alone. Furthermore, in a 'real world' scenario, it is to be expected that other drug regimens might be introduced during periods of treatment failure. CONCLUSION: This analysis demonstrates that patients with schizophrenia who switch their antipsychotic medication to quetiapine XR because of insufficient efficacy or poor tolerability benefit from significant QALY gains at a reasonable increase in drug cost