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Previous literature supports antipsychotics’ (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning.
Methods
A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables.
Results
Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011–0.0091) and (b = 0.0026, 95% CI 0.0001–0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033–0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden.
Conclusion
CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant.
One factor greatly influencing the prognosis and progression of the Schizophrenia is compliance and it is essential to find new drugs which carry minimal side effects.
Objectives:
To identify the profile of patients who are treated with aAripiprazole and to assess the effectiveness, tolerability and treatment adherence.
Patients and Methods:
This was a multicentre, observational, retrospective study with participation of 200 psychiatrists. Data from the medical records of patients treated with aAripiprazole with at least two months were collected between October and December 2005.
Results:
A total of 997 patients were included. 95% of patients had been treated with another drug prior to receiving aAripiprazole. The pattern for switching from the previous treatment was substitution in 75% of cases and addition in 25%. Reasons for switching were: 56,6% lack of efficacy and 35,6% adverse reactions. The investigator's assessment of aAripiprazole's effectiveness and tolerability showed these was very good or good in 76% and 90% of cases respectively. Around 87.6% showed good treatment compliance. Efficacy of treatment was correlated with duration of the disease: the proportion of patients with good efficacy is greater in patients who had suffered the disease for less than ten years (78.7 vs. 73.8%) (p=0.01).
Conclusions:
aAripiprazole was considered to have a good effectiveness and tolerability in most patients. Effectiveness was greater in the acute phase of the disease, in patients with shorter duration of the disease and in those only taking full dose aAripiprazole
After the commercialization of Aripiprazole in Spain, two observational studies were proposed, one was conducted when the drug was first launched, and the other when the starting dose of Aripiprazole was modified, in order to understand the switching strategies, the effectiveness, tolerability and adherence to treatment in standard use conditions.
Patients and Methods:
Two multicenter, retrospective, observational studies were carried out involving 200 psychiatrists throughout Spain with approximate 1000 patients treated with Aripiprazole during the previous four months in each one of the studies during 2005 and 2006 respectively.
Results:
Both groups of patients had a very similar demographic profile that matches with the general schizophrenic population. In the first study, the main reasons for switching medication were low efficacy (56% of cases) and intolerance (35%), and 44% and 43% respectively in the second study. Despite the poor response to previous treatment, clinical evaluation of effectiveness and tolerability with Aripiprazole was very positive: In the first study, 76% of patients had very good or good effectiveness and tolerability was very good or good in 90%. In the second study, these values were 75% and 93%, respectively. Patterns of change from the previous treatment were switching in 75% of cases in the first study and in 60% in the second study.
Conclusions:
Effectiveness of treatment with Aripiprazole is good in patients who had a poor response to their previous antipsychotic treatments. The most frequent and effective pattern for change patients to Aripiprazole treatments is switching.
The conditions for the use of study medications are different in a clinical trial than when the same drugs are marketed and administered to larger population groups. This study was proposed after the recent change in the range of doses marketing of Aripiprazole in our country and following a change in the range of doses used.
Objectives:
To identify the type of patients treated with aAripiprazole during 4 months (May 06) after the change in the SmPC (10-30 mg dose) and to establish the doses used. To identify the proportion of patients switching to aAripiprazole from previous antipsychotic treatments due to reduced efficacy or low tolerance to the previous drugs.
Patients and Methods:
This is a retrospective, observational, multicenter study. Data will be collected from the medical records of 1000 patients treated with aAripiprazole during the four months prior to the study initiation, with a minimum of 1 month treatment. The information will be gathered by 200 psychiatrists each one providing 5 cases. Data collection was initiated in October 2006 and is expected to last two months. The sample size based on the primary objective obtained will enable a 95% confidence interval with a maximum acceptable error of 3% to estimate the proportion based on the primary objective.
Conclusions:
The collection of data will enable us to know how psychiatrists prescribe aAripiprazole, considering the type of patient, dosage regime, switching strategy of antipsychotic treatment (by identifying the ratios of treatment switches) under standard conditions of use.
Public hospital systems have struggled to identify ways of cutting costs while improving quality of mental health treatment, even more since the economic downturn.
Objective
To compare mental health care expenditures and quality in two large sites, Boston and Madrid, and to analyze the amount of the expenditure corresponding to pharmacy, ER, outpatient and inpatient care.
Methods
Data are mental health electronic records from three hospitals in Madrid (n=31,183 person-years) and in Boston(n=8,805). Adequacy of care was measured as four or more visits within the last year. Unadjusted comparisons of variables were conducted using t-tests. Multivariate generalized linear regression models were computed with log link and residual variance proportional to mean squared, adjusting for covariates. Results were also adjusted for World Bank Purchasing Power Parity and converted to U.S. dollars.
Results
The annual average treatment expenditure is $4,874 in Boston and $2,693 in Madrid . Boston patients had a bigger percentage of use (13,6% vs 5,3%) and greater annual expenditure ($25,175 vs $15,470) for inpatient services (p<0,05). Conversely, Madrid patients used and spent more on outpatient treatments (87% vs 84%;$1,670 vs $1,378;p<0,05). Being in the Boston site, having a bipolar, psychotic or alcohol disorder was a significant positive predictor of total expenditure. Adequacy of care was bigger in Boston (32,8% vs 23,1%)
Conclusions
Emphasis on outpatient care appears to reduce inpatient stays and global expenditures. An earlier recognition due to a more open access to treatments in Spain may help decreasing costs. Bipolar, psychotic and alcohol disorders imply bigger costs.
Diagnosis of schizophrenia spectrum disorders (SSD) may be difficult in clinical practice, particularly during the first episodes of early-onset psychosis (FE-EOP).
Aims:
To develop a Support Vector Machine (SVM) algorithm as a predictive tool for diagnostic outcome in patients with FE-EOP, based on clinical and biomedical data at the emergence of the illness.
Methods:
Two-year, prospective longitudinal study, where 81 patients (9-17 years of age) with a FE-EOP and stable diagnosis at follow-up and 41 age and sex-matched healthy controls (HC) were included. Structured diagnostic interviews, clinical and cognitive scales, a MRI scan and biochemical tests were conducted at baseline. Three SVM classification algorithms were developed (SSD vs HC group, non-SSD vs HC group, and SSD vs non-SSD group). Jackknifing was used to validate the algorithms and to calculate performance estimates. Enhanced-Recursive Feature Elimination was performed in order to gain information about the predictive weight for diagnosis of each variable.
Results:
The SSD-versus-non-SSD classifier achieved an overall accuracy of 83.1%, sensitivity of 86.6% and specificity of 77.8%. The variables during a FE-EOP with higher predictive value for a diagnosis of SSD were clinical variables such as negative symptoms preceding or during the psychotic onset, poor insight and duration of illness until first psychiatric contact. Biochemical, neuroimaging, and cognitive variables at baseline did not provide any additional predictive value.
Conclusions:
SVM may serve as a predictive tool for early diagnosis of SSD during a FE-EOP. The most discriminative variables during a FE-EOP for a future diagnosis of SSD are clinical variables.
Early-onset first-episode psychosis (FEP) and high functioning autism spectrum disorders (ASD) are complex neuro–developmental disorders that share symptomatology but it is not clear if they also share neurobiological abnormalities (Chisholm et al., 2015). We examined thickness, surface area and volume in a direct comparison of children and adolescents with FEP (onset before 18 years), high-functioning ASD, and healthy subjects.
Methods
Magnetic resonance imaging scans of 85 participants (30 ASD, 29 FEP, 26 healthy controls, age range 10–18 years) were obtained from the same MR scanner using the same acquisition protocol. The FreeSurfer analysis suite was used to quantify vertex-wise estimates of the metrics thickness, surface area, and volume.
Results
ASD and FEP had spatially overlapping insular deficits for each metric. The transdiagnostic overlap of deficits was greatest for volume (55% of all insular vertices) and smallest for thickness (18%). Insular thickness and surface area deficits did not overlap in ASD and overlapped only in 8% of all insular vertices in FEP.
Conclusions
Morphological insular deficits are common to FEP and high functioning ASD when compared to healthy participants. The pattern of deficits was similar in both disorders, i.e. a largely non-overlap of insular thickness and surface area. The non-overlap provides further evidence that these metrics represent two independent outcomes of corticogenesis, both of which are affected in FEP and ASD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The use of valid and practical screening scales might ease the burden for greatly needed universal testing for mental health, substance use and dual disorders, but do they work well with all populations? Do they miss correct identification of certain groups?
Objective
To understand discrepancies in diagnostic prediction using the AC-OK screen in conjunction with other standardized assessment scales.
Methods
Two hundred and twenty-six Latino participants were recruited from primary care and community clinics in Madrid, Barcelona and Boston and assessed with standardized mental health and substance abuse measures including the AC-OK screen and with a Computerized adaptive test for mental health (CAT-MH). A measure of frequency of discrepancies and an adjusted and unadjusted comparison of results and demographic characteristics or respondents were made for mental health, substance abuse or for discrepancies in both categories.
Results
35.4% of cases were discrepant in mental health (AC-OK-Mental Health vs. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7 or PTSD Checklist) and 14.2% in substance abuse (AC-OK-substance abuse vs. drug abuse screening test or Alcohol use disorders identification test). When CAT-MH scale was incorporated, discrepant results were found in 24.3% and 14.2%, respectively. No association was found between substance abuse discrepancies and patient demographics. In logit regressions being from Barcelona, of younger age and male were significant predictors of discrepancies.
Conclusions
Discrepancies were observed in the diagnostic prediction, with differences detected for site and sociodemographic characteristics of participants suggesting the importance of testing screeners for site and population differences. Evidence for the misclassification of young males is discussed. Caution is warranted in the implementation of screeners for at risk populations.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Methods for measuring cognitive reserve (CR) are limited and controversial. Dual task cost (DTC) paradigms, assessing links between gait and cognition, are increasingly regarded as robust measures of CR.
Objectives
Here, we aimed to validate a simplified methodology for a DTC paradigm in healthy volunteers for application in clinical settings as a measurement of CR.
Methods
We tested if subtracting by 7's (cognitive task) while walking (motor task) induced a DTC in a sample of 39 healthy young adults. For the cognitive task, we recorded the number of correct and incorrect subtractions, as well as the latency between subtractions. Gait parameters were recorded on a tri-axial accelerometer fixed to the left ankle. Both tasks were performed separately (single task) and simultaneously (double task) to assess the DTC. A battery for neuropsychological assessment and questionnaires to assess quality of life and affective symptoms were also applied, to measure possible correlations with the DTC.
Results
Subtracting 7's while walking caused significant changes in gait parameters and in cognitive task performance. A significant decrease in the autocorrelation of the accelerometer signal during the dual task was also found (DTC = 37.92 ± 7.56%; P < 0.0001). This measure has not been previously used and may be a more sensitive measure of the dual task induced disturbance of the gait periodic signal pattern. Correlations between DTC and quality of life, affective or cognitive measures were not significant.
Conclusion
Our study provides an effective, portable and non-intrusive DTC experimental protocol that can be easily applied in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
Methods:
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
Conclusions:
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Xenarthra is an endemic South American lineage of mammals, probably the sister clade of the other placental mammals. The oldest records of Xenarthra are from the latest Paleocene, although its current diversity is much lower than that recorded in some intervals of the Cenozoic Era. A new Neogene Xenarthra (Pilosa and Cingulata) assemblage from two localities of the Argentine Eastern Puna (Calahoyo and Casira) is described. The newly recorded taxa—Cingulata, Dasypodidae, Eutatini: Stenotatus sp. indet. and Eutatini indet., Euphractini: Macrochorobates scalabrinii (Moreno and Mercerat, 1891), and Tardigrada, Mylodontinae: cf. Simomylodon sp. indet. and Simomylodon cf. S. uccasamamensis Saint-André et al., 2010—and those already published from Calahoyo—Cingulata: Macrochorobates chapadmalensis (Ameghino, 1908), Eosclerocalyptus sp. indet., and Tardigrada, Megatheriidae: Pyramiodontherium bergi (Moreno and Mercerat, 1891)—suggest a middle–late Miocene age for the fossil-bearing levels. In Calahoyo, the presence of Stenotatus sp. indet., in addition to some rodents currently under study in the lower levels, suggest a closer similarity with the palaeofauna of Cerdas (southern Bolivia), probably involving the last part of the Miocene Climatic Optimum. The Xenarthra recorded in the middle and upper levels of Calahoyo and Casira suggest a late Miocene–Pliocene age. A comparative analysis between Calahoyo and Casira highlights the absence of Cingulata in the latter and a high diversity in the former. This situation probably indicates different paleoenvironmental conditions. Finally, we present the first certain record of the genus Simomylodon Saint-André et al., 2010 in Argentina, which includes the oldest record of dermal ossicles for sloths in South America.
We determined the molecular epidemiology of Bordetella pertussis isolates to evaluate its potential impact on pertussis reemergence in a population of Mexico. Symptomatic and asymptomatic cases were included. Pertussis infection was confirmed by culture and real-time polymerase chain reaction (PCR). Selected B. pertussis isolates were further analysed; i.e. clonality was analysed by pulsed-field gel electrophoresis (PFGE) and ptxP-ptxA, prn, fim2 and fim3 typing was performed by PCR and sequencing. Out of 11 864 analysed samples, 687 (5.8%) were positive for pertussis, with 244 (36%) confirmed by both culture and PCR whereas 115 (17%) were positive only by culture and 328 (48%) were positive only by PCR. One predominant clone (clone A, n = 62/113; 55%) and three major subtypes (A1, A2 and A3) were identified by PFGE. All 113 selected isolates had the allelic combination ptxP3-ptxA1. The predominant clone A and the three major subtypes (A1, A2 and A3) corresponded to the emerging genotypes ptxP3-ptxA1-prn2-fim2-1-fim3-2 and ptxP3-ptxA1-prn2-fim2-1-fim3-1. In conclusion, the presence of an endemic clone and three predominant subtypes belonging to the genotypes ptxP3-ptxA1-prn2-fim2-1-fim3-2 and ptxP3-ptxA1-prn2-fim2-1-fim3-1 were detected. This finding supports the global spread/expansion reported for these outbreaks associated genotypes.
To search the international literature (any language) for publications reporting outcomes of tracheostomy performed to treat obstructive sleep apnoea in children.
Method
Data sources included: Google Scholar, Cumulative Index to Nursing and Allied Health Literature, Embase, Scopus, and PubMed/Medline. Four authors searched systematically through to 20 January 2018.
Results
A total of 597 studies were screened; 64 were downloaded and 11 met criteria. A total of 196 patients underwent tracheostomy (mean age, 4.2 years; range, newborn to 18 years); 40 had detailed qualitative data and 6 had detailed quantitative data. Apnoea/hypopnoea index showed a 97 per cent reduction (n = 2) and apnoea index showed a 98 per cent reduction (n = 3). Lowest oxygen saturation showed a 34 oxygen saturation point improvement (n = 3). Several patients demonstrated significant improvement in breathing. All identified patients were syndromic, had significant co-morbidities or had severe obstructive sleep apnoea.
Conclusion
Based on reports of children who have undergone a tracheostomy, for whom there are pre- and post-operative data, tracheostomy appears to be a successful treatment for obstructive sleep apnoea. However, additional research is recommended given the small number of patients in the literature.