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Serotonin Syndrome (SS) is an adverse drug reaction that drives mental-status changes, autonomic hyperactivity and neuromuscular abnormalities.
Neuroleptic Malignant Syndrome (NMS) is an idiopathic reaction to dopamine-antagonist that consists of extra-pyramidal symptoms, autonomic dysfunction, hyperthermia, diaphoresis and fluctuating consciousness.
Differential diagnosis is sometimes difficult for their overlapping clinical features. Potentially lethal, both require heightened clinical awareness for prevention, recognition and prompt treatment.
Caucasian 59 years-old woman with Catatonic profile (Scored: severity-17points/ 5 screening in Bush-Francis Catatonia-Rating-Scale).
Past Medical History
- Bipolar Disorder type-2 (25 years of evolution)
15 days before hospitalization, anafranil and fluoxetine treatment was replaced by Trazodone 200 mg/day and venlafaxine 150mg/day. She was also on valpromida and lorazepam 15 mg/day.
Mutism, negativism. No reaction to painful stimuli, stuporous. Diaphoresis, pallor, tremor, axial rigidity without pyramidalism (>lower limbs), high fever (40°C), tachycardia (>100lpm), rhabdomyolysis (CPK reached 17.000, 48 hours after the admission), leukocytosis, upper transaminasas, hiponatremia with hiperpotasemia.
-NMS: Intensity, duration and high CPK are suggestive (Sternbach). This syndrome has been described due to Venlafaxine.
-SS: Combination of Venlafaxine and Trazodone favors but she doesn't have acatisia, hiperreflexia, diarrhea and it wasn't resolved after 96 hours.
Drugs were removed and Lorazepam on high doses (5mg/day) was prescribed. One month later the patient was totally recovered of the episode.
If unsure diagnoses it's priority to remove the causing drugs and supportive care. Afterwards, it can be used benzodiacepines, also dantroleno in SNM.
To explore different longitudinal patterns of social functioning before onset of psychotic illness and how they relate to clinical presentation, substance use and acute treatment response.
Inclusion criteria: Drug-naïve first-episode psychosis, 18-50 yo, criteria for Schizophrenia or Other Psychotic Disorders (DSM-IV), excluding Psychotic Disorder due to a General Medical Condition and Substance-Induced Psychotic Disorder.
Mental Retardation, neurological disease, brain injury or drug dependence.
Premorbid Adjustment Scale (PAS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS).
Ward cluster analyses were carried out to differentiate three longitudinal patterns of social premorbid adjustment from childhood to late adolescence: stable good (N=75), stable bad (N=44) and deteriorating (N=35). Chi-square and ANOVA tests were used.
154 subjects (64.5% male, mean age 26.81, SD=6.98) participated in the study.
At baseline the socially stable good group had more positive symptoms, SAPS 13.85 (3.99), than the stable bad group, SAPS 11.82 (3.93) (p=0.023).
At six weeks post-treatment the socially deteriorating group had more negative symptoms, SANS 8 (4.89), than the stable good, SANS 3.85 (4.11), and the stable bad, SANS 5.23 (5.45) (p=0.000).
The stable good group had the highest rates of substance use, followed by the deteriorating group.
A good premorbid social life was related to higher substance use and more positive symptoms at presentation. A social deteriorating pattern was associated with more negative symptoms at baseline and six weeks post-treatment. These differences would argue for different pathogeneses of psychosis.
Pregabalin is indicated for the treatment of GAD in adults in Europe. The efficacy and safety of pregabalin for the treatment of adults and elderly patients with GAD has been demonstrated in 6 of 7 short-term clinical trials of 4 to 8 weeks.
To characterise the long-term efficacy and safety of pregabalin in subjects with GAD.
Subjects were randomised to double-blind treatment with either high-dose pregabalin (450-600 mg/d), low-dose pregabalin (150-300 mg/d), or lorazepam (3-4 mg/d) for 3 months. Treatment was extended with drug or blinded placebo for a further 3 months.
At 3 months, mean change from baseline Hamilton Anxiety Rating Scale (HAM-A) for pregabalin high- and low-dose, and for lorazepam ranged from -16.0 to -17.4. Mean change from baseline Clinical Global Impression-Severity (CGI-S) scores ranged from -2.1 to -2.3 and mean CGI-Improvement (CGI-I) scores were 1.9 for each active treatment group. At 6 months, improvement was retained for all 3 active drug groups, even when switched to placebo. HAM-A and CGI-S change from baseline scores ranged from -14.9 to -19.0 and -2.0 to -2.5, respectively. Mean CGI-I scores ranged from 1.5 to 2.3. The most frequently reported adverse events were insomnia, fatigue, dizziness, headache, and somnolence.
Efficacy was observed at 3 months, with maintained improvement in anxiety symptoms over 6 months of treatment. These results are consistent with previously reported efficacy and safety trials of shorter duration with pregabalin and lorazepam in subjects with GAD.
Pregabalin is indicated for the treatment of generalised anxiety disorder (GAD) in adults in Europe. When pregabalin is discontinued, a 1-week (minimum) taper is recommended to prevent potential discontinuation symptoms.
To evaluate whether a 1-week pregabalin taper, after 3 or 6 months of treatment, is associated with the development of discontinuation symptoms (including rebound anxiety) in subjects with GAD.
Subjects were randomised to double-blind treatment with low- (150-300 mg/d) or high-dose pregabalin (450-600 mg/d) or lorazepam (3-4 mg/d) for 3 months. After 3 months ~25% of subjects in each group (per the original randomisation) underwent a double-blind, 1-week taper, with substitution of placebo. The remaining subjects continued on active treatment for another 3 months and underwent the 1-week taper at 6 months.
Discontinuation after 3 months was associated with low mean changes in Physician Withdrawal Checklist (PWC) scores (range: +1.4 to +2.3) and Hamilton Anxiety Rating Scale (HAM A) scores (range: +0.9 to +2.3) for each pregabalin dose and lorazepam. Discontinuation after 6 months was associated with low mean changes in PWC scores (range: -1.0 to +3.0) and HAM A scores (range: -0.8 to +3.0) for all active drugs and placebo. Incidence of rebound anxiety during pregabalin taper was low and did not appear related to treatment dose or duration.
A 1-week taper following 3 or 6 months of pregabalin treatment was not associated with clinically meaningful discontinuation symptoms as evaluated by changes in the PWC and HAM A rating scales.
The use of second-generation antipsychotic (SGA) treatments in psychosis has been associated with metabolic changes. However, there are differences in metabolic profile between SGAs. In a previous study conducted in our sample of first episode psychosis patients, we observed that the ziprasidone had a more benign metabolic profile compare to aripiprazole and quetiapine, at short-term (12 weeks). However, to detect clinically-relevant impairment in metabolic parameters a long-term follow-up is preferred.
The aim of this study was to investigate if the differentiated metabolic profile of aripiprazole, ziprasidone and quetiapine observed at short-term is maintained after 1 year of treatment in a sample of drug-naïve patients with a first episode of psychosis.
One hundred and sixty-eight, drug-naïve patients, suffering from a non-affective first episode of psychosis, were included in the present study. Patients were randomly assigned to receive quetiapine, ziprasidone or aripiprazole. Weight and glucemic/lipid parameters were recorded at baseline and after 1 year of treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.
No significant differences between antipsychotic groups (all F < 2.61; P > 0.05) were found in any of the metabolic parameters studied after one year of treatment.
Despite the metabolic profile differences observed at short-term in our previous studies, we did not find significant differences in the metabolic and weight parameters studied between treatment groups after one year of treatment, concluding that they present similar metabolic profiles at long-term. Other clinical individual interventions (e.g.: diet, exercise), not here controlled, may have influenced possible differences in long-term metabolic outcomes.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
There is growing evidence indicating that the use of second-generation antipsychotic (SGA) treatments in psychosis is related to potential metabolic side effects. Previous studies have shown clear metabolic side effects at short-term (12 weeks). However, to detect clinically-relevant impairment in metabolic parameters a long-term follow-up is preferred.
The aim of this study was to investigate the effect of aripiprazole, ziprasidone and quetiapine on metabolic measures in medication-naïve first episode psychosis patients after 1 year of treatment.
One hundred and sixty-eight, drug-naïve patients, suffering from a non-affective first episode of psychosis, were included in the present study. Patients were randomly assigned to quetiapine, ziprasidone or aripiprazole treatment lines. Weight and glucemic/lipid parameters were recorded at baseline and after 1 year of treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.
Weight (t = −10.85; P < 0.001), BMI (t = −11.38; P < 0.001), total cholesterol (t = −5.37; P < 0.001), LDL-cholesterol (t = −5.21; P < 0.001), triglycerides (t = −5.18; P < 0.001) and the triglyceride/HDL insulin resistance index (t = −4.09; P < 0.001), showed statistically significant increments after 1 year of treatment.
Moreover, on comparing the percentage of patients with pathological levels before and 1 year after the antipsychotic treatment, we detected higher percentages of patients with obesity (5.1% vs. 15.3%; P < 0.001), hypercholesterolemia (23.2% vs. 39.6%; P < 0.001) and hypertriglyceridemia (5.8% vs. 14.2%; P = 0.021) after 1 year of treatment.
The primary exposure to SGAs during the first year of psychosis was associated with significant increments in weight and metabolic parameters leading to a significant increment in the proportion of obesity, hypertriglyceridemia and hypercholesterolemia in our sample.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Although mild to moderate major depressive disorder (MDD) is one of the main reasons for consulting a general practitioner (GP), there is still no international consensus on the most appropriate therapeutic approach.
The aim of this study is to evaluate the clinical effectiveness of watchful waiting (WW) compared with the use of antidepressants (ADs) for the treatment of mild to moderate depressive symptoms in 263 primary care (PC) usual-practice patients in a 12-month pragmatic non-randomised controlled trial. Both longitudinal and per-protocol analyses were performed, through a multilevel longitudinal analysis and a sensitivity analysis.
We observed a statistically significant time x treatment interaction in the severity of depression (Patient Health Questionnaire, PHQ-9) and disability (World Health Organization Disability Assessment Schedule, WHODAS) in favour of the AD group at 6 months but not at 12 months. The effect size of this difference was small. No statistically significant differences were observed between groups in severity of anxiety (Beck Anxiety Inventory, BAI) or health-related quality-of-life (EuroQol-5D, EQ-5D). Sensitivity analysis and per-protocol analysis showed no differences between the two groups in any of the evaluated scales.
Superiority of either treatment (WW and AD) was not demonstrated in patients treated for depression in PC after one year of follow-up.
Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures
eV and electron densities
. The iron will be probed using continuum X-rays emitted in a
diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design,
of the NIF beams deliver 500 kJ to the
mm diameter hohlraum, and the remaining
directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.
The objective of this study was to assess the effectiveness of a catheter-related bloodstream infection (CR BSI) reduction programme and healthcare workers' compliance with recommendations. A 3-year surveillance programme of CR BSIs in all hospital settings was implemented. As part of the programme, there was a direct observation of insertion and maintenance of central venous catheters (CVCs) to determine performance. A total of 38 education courses were held over the study period and feedback reports with the results of surveillance and recommendations were delivered to healthcare workers every 6 months. A total of 6722 short-term CVCs were inserted in 4982 patients for 58 763 catheter-days. Improvements of compliance with hand hygiene was verified at the insertion (87·1–100%, P < 0·001) and maintenance (51·1–72·1%, P = 0·029) of CVCs; and the use of chlorhexidine for skin disinfection was implemented at insertion (35·7–65·4%, P < 0·001) and maintenance (33·3–45·9%, P < 0·197) of CVCs. There were 266 CR BSI incidents recorded with an annual incidence density of 5·75/1000 catheter-days in the first year, 4·38 in the second year [rate ratio (RR) 0·76, 95% confidence interval (CI) 0·57–1·01] and 3·46 in the third year (RR 0·60, 95% CI 0·44–0·81). The education programme clearly improved compliance with recommendations for CVC handling, and was effective in reducing the burden of CR BSIs.
Schizophrenia is a chronic brain disorder associated with structural brain abnormalities already present at the onset of the illness. Whether these brain abnormalities might progress over time is still under debate.
The aim of this study was to investigate likely progressive brain volume changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The study included 109 patients with a schizophrenia spectrum disorder and a control group of 76 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. The effects of brain changes on cognitive and clinical variables were examined along with the impact of potential confounding factors.
Overall, patients and healthy controls exhibited a similar pattern of brain volume changes. However, patients showed a significant lower progressive decrease in the volume of the caudate nucleus than control subjects (F1,307.2 = 2.12, p = 0.035), with healthy subjects showing a greater reduction than patients during the follow-up period. Clinical and cognitive outcomes were not associated with progressive brain volume changes during the early years of the illness.
Brain volume abnormalities that have been consistently observed at the onset of non-affective psychosis may not inevitably progress, at least over the first years of the illness. Taking together with clinical and cognitive longitudinal data, our findings, showing a lack of brain deterioration in a substantial number of individuals, suggest a less pessimistic and more reassuring perception of the illness.
Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.
This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.
Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.
Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.
Heliciculture is an excellent alternative to obtain edible snails but its viability is seriously threatened by pathogens. A parasitological survey was conducted in 3 mixed system-based heliciculture farms in Galicia (NW Spain), with the species Tetrahymena rostrata, Tetrahymena limacis, Tetratrichomonas limacis, Cryptobia helicogenae, Brachylaima aspersae (metacercariae and sporocysts), Alloionema appendiculatum, Nemhelix bakeri, and Riccardoella limacum being commonly found infecting Helix aspersa aspersa (petit-gris) snails. With the exception of C. helicogenae, N. bakeri, and B. aspersae sporocysts, all species were also detected in Helix aspersa maxima (gros-gris) snails, although generally with lower parameters. Most monoxenous infections, and consequently multiple parasitism, exhibited a rising trend during the first 2 months of intensive mating, with tendencies being slowed down or even reversed during the third month as a result of accumulated mortality and a sampling-derived reduction in host density. No parasites were vertically transmitted and infections were initially acquired from invading gastropod and micromammal reservoirs during fattening. Finally, artificial hibernation reduced significantly the prevalence of most species. These results confirm the importance of parasites in heliciculture and emphasize the need to prevent the entry of wild reservoirs into the farms and to rapidly remove the carcasses of dead snails from the reproduction units and fattening pens.
This study examines part of the thick palaeoweathering mantle that formed on the northern area of the Spanish Central System. The study of a compound profile indicates that despite weathering processes, the primary structure of the metamorphic rocks is preserved, and is only partially lost in some intervals of the upper part of the compound profile. Macro/micromorphology, mineralogy and geochemical changes within the profiles revealed two weathering paths. In the first path, Fe-chlorite weathered to chlorite-smectite mixed-layer/smectite/kaolinite+ iron oxides. In the second path, biotite and/or muscovite weathered to kaolinite + iron oxides. The profiles show a progressive decrease, from base to top, in mica and mixed-layers and an increase in smectite and kaolinite. Thus, the profiles only comprise the lower or intermediate zones of the weathering mantle. The weathering occurred under humid climates; the lower zones of the profiles were poorly drained, whereas the topmost zones were better drained and more oxidizing. The results obtained indicate that detailed mineralogical studies are very useful to reconstruct the characteristics of the weathering mantles, and as palaeogeographic and palaeoclimatic indicators.
Suitable in situ techniques capable of sensing for the presence of a biofilm on metallic surfaces are becoming increasingly necessary, especially in order to maintain seawater pipe system performance. This study has investigated the detection of aerobic marine bacterial biofilms using electrochemical impedance spectroscopy by monitoring the interfacial response of Pseudoalteromonas sp. NCIMB 2021 attachment and growth in order to identify characteristic events on a 0.2 mm diameter gold electrode surface. Uniquely, the applicability of surface charge density has been proven to be valuable in determining biofilm attachment and cell enumeration over 72 h duration on a gold surface within a modified continuous culture flow cel(lsa controlled low laminar flow regime with a Reynolds number ≈ 1).In addition, the potential for biofilm disruption has been evaluated using 500 nM of the nitric oxide (NO) donor sodium nitroprusside (NO is important for the regulation of a number of diverse biological processes). Ex situ confocal microscopy studies were performed to confirm biofilm coverage and morphology, plus the determination and quantification of the NO biofilm dispersal effects. Overall, the capability of the sensor to electrochemically detect the presence of initial bacterial biofilm formation and extent has been established and shown to have potential for real-time biofilm monitoring.
The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features.
We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated.
Patients showed a significant total cortical thinning (F=17.55, d=−0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=−0.24, p=0.021) and parietal cortical thickness (r=−0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls.
Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.
We introduce a general framework for modelling the dynamics of the propensity to offend in a population of (possibly interacting) agents. We consider that each agent has an ‘honesty index’ which parameterizes his probability of abiding by the law. This probability also depends on a composite parameter associated to the attractiveness of the crime outcome and of the crime setting (the context which makes a crime more or less likely to occur, such as the presence or not of a guardian). Within this framework we explore some consequences of the working hypothesis that punishment has a deterrent effect, assuming that, after a criminal act, an agent's honesty index may increase if he is caught and decrease otherwise. We provide both analytical and numerical results. We show that in the space of parameters characterizing the probability of punishment, there are two ‘phases’: one corresponding to a population with a low crime rate and the other to a population with a large crime rate. We speculate on the possible existence of a self-organized state in which, due to the society reaction against crime activities, the population dynamics would be stabilized on the critical line, leading to a wide distribution of propensities to offend in the population. In view of empirical works on the causes of the recent evolution of crime rates in developed countries, we discuss how changes of socio-economic conditions may affect the model parameters, and hence the crime rate in the population. We suggest possible extensions of the model that will allow us to take into account more realistic features.
In recent years, there have been strategy changes in international and European policies and procedures about the environment and sustainable development. The focus has been on the agents and activities that exhaust natural resources and harm the environment. The International Maritime Organization (IMO) and shipping companies' international organisations are trying to reduce the polluting emissions and greenhouse gases generated by vessels. This article looks at various alternative energy sources that can be used to power vessels and their auxiliary equipment, as well as at their economic and environmental repercussions on the transport of goods by sea.
Domestic ruminant selectivity induces floristic changes in pasturelands, risking sustainability and limiting the subsequent availability of susceptible plant species. Development of preferences for species of lower nutritional quality may help to overcome those problems. In this study, we tested the hypothesis that early experience of sheep with a low-quality food (LQF) in a nutritional enriched context increases preference for LQF in adulthood. We predicted a higher proportional consumption of LQF in experienced lambs (EL) than in inexperienced lambs (IL) in choice situations involving LQF and alternative foods. Additionally, we determined intake of LQF by EL and IL at different levels of high-quality food (HQF) availability. From 60 to 210 days of age, EL were fed in separated feed bunks mature oat hay (LQF) simultaneously with sunflower meal (SM) and corn grain (CG), whereas IL were fed alfalfa hay (HQF) simultaneously with SM and CG. After exposure, EL and IL were offered LQF in free choice situations involving alternative foods, and also at five levels of HQF availability (100%, 75%, 50%, 25% and 0% of ad libitum intake). Proportional consumption of LQF was lower or similar in EL than IL. Intake of LQF was also lower or similar in EL than IL at all levels of HQF availability, except when the LQF was the only food available. Our results did not support the hypothesis that early experience with a LQF in a nutritional enriched context increases preference for LQF in adulthood. On the contrary, experience with LQF diminished subsequent preference for LQF in adulthood. It is proposed that, in the conditions of our study, continuous comparison between the LQF and the high-quality supplements (CG and SM) during the early exposure period lead to devaluation of LQF by EL through a simultaneous negative contrast effect.