Five Month-Persistent Extrapyramidal Symptoms following a Single Injection of Paliperidone Palmitate: A Case Report.
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ABSTRACT:
SUBMITTER: Jang S
PROVIDER: S-EPMC5565081 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:To date, there have been no detailed reports of patients developing persistent psychotic symptoms following Coronavirus disease 2019 (COVID-19) infection. There have been reports of patients developing transient delirium (with and without hypoxia) after COVID-19 infection as well as other neurological manifestations. We report on a female patient who, post-COVID-19 infection, developed an initial delirium followed by persistent and florid psychotic symptoms consisting of persecutory delusion, complex visual and auditory hallucinations and Capgras phenomenon in the absence of hypoxia but elevated tumour necrosis factor (TNF)-?. The psychotic symptoms persisted for about 40 days. Her magnetic resonance imaging brain scan, electroencephalogram, cerebrospinal fluid examination and extensive autoimmune panel did not show any abnormalities. The cause of the psychotic symptoms in this patient were not ascertained but we propose either an inflammatory state, characterised by the patient's elevated TNF-alpha levels as a possible contributing mechanism for her psychosis in line with the proinflammatory changes observed in some cases of psychosis. Or, an alternative, but unproven, hypothesis is one of an antibody-mediated encephalitic event induced by viral infection.
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Project description:BackgroundThis report describes and objectivizes reported problems among a cohort of previously hospitalized COVID-19 patients by clinical examination and determination of the required level of rehabilitation sevices.MethodsThis report forms part of the Linköping COVID-19 Study (LinCoS) that included 745 individuals from one of 21 Swedish healthcare regions, Region Östergötland (RÖ), admitted to hospital for COVID-19 during March 1st-May 31st, 2020. In this descriptive ambidirectional cohort study, all 185 individuals who had reported concerning persisting symptoms were invited to a multi-professional clinical assessment of somatic, functional, affective, neuropsychological status and rehabilitation needs. Rehabilitation needs were assessed using three sub-scales of the Rehabilitation Complexity Scale-Extended.FindingsAmong the 158 (85·4%) cases consenting and included in the analysis, we found a broad array of symptoms and signs attributable to COVID-19 involving respiratory, visual, auditory, motor, sensory and cognitive functions that could be confirmed clinically at five months post-discharge. This translated into 16% [95% CI 13-20] of survivors (70/433) of the total regional cohort of hospitalised patients requiring further rehabilitative interventions at follow-up. Weakness in extremities was reported in 28·5% [21·6, 36·2] (45/158). On examination, clinically overt muscle weakness could be corroborated in 15 individuals (10·5%) [6·1, 16·4]. 48% [40, 56] (76/158) reported cognitive symptoms, while the physician noted overt cognitive impairments in only 3% [1·1, 7·5]. In neuropsychological testing, 37% [28-46] (45/122) performed 1.5 SD below the norm, indicating neurocognitive deficits. Fifty-five individuals (34·8%) [27·4, 42·8] reported new or aggravated pain. In three fourths of them, it exerted a 'moderate' or worse detrimental effect on their ability to work.InterpretationOur study underscores the importance of providing extensive examination of cases with persisting problems after COVID-19, especially since symptoms such as fatigue and breathlessness are highly nonspecific, but may represent significant underlying functional impairments. Robust neurocognitive testing should be performed, as cognitive problems may easily be overlooked during routine medical consultation. In the Swedish context, most rehabilitative interventions could be provided in a primary care setting. A substantial minority of patients should be triaged to specialized rehabilitation services.
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Project description:ObjectiveThe aim of this study was to evaluate the safety of 3-monthly paliperidone palmitate (PP3M) vs once-monthly paliperidone palmitate (PP1M) treatment with regard to extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) in patients with schizophrenia, previously stabilized on PP1M treatment.Patients and methodsData on overall incidence, time to onset (TTO), and time to resolution (TTR) of EPS-related TEAEs (overall, subclasses such as dyskinesia, dystonia, hyperkinesia, parkinsonism, and tremor) from a randomized double-blind (DB) non-inferiority study were compared between PP3M and PP1M. Subgroup analysis was performed by age (18-25, 26-50, and 50+ years) and final open-label (OL) dose (50/75, 100, and 150 mg eq.).ResultsOverall incidence of spontaneously reported EPS-related TEAEs decreased from 12.6% (PP1M) in OL phase to 8.3% (PP3M) and 7.4% (PP1M) in the DB phase; overall median TTO and TTR values were comparable between both groups. Among patients with reported EPS-related TEAEs, the median TTO for all EPS-related TEAEs was 17 days (PP1M) in OL phase and 115 days (PP3M) and 98.5 days (PP1M) in DB phase; median TTR was 36.5 days (PP1M) in OL phase and 91 days (PP3M) and 85.5 days (PP1M) in DB phase. No clear dose- or age-related differences in TTO and TTR of EPS-related TEAEs were noted.ConclusionDespite differences in apparent half-life and pharmacokinetic profiles (peak plasma exposure of PP3M formulation is 70% higher than that of PP1M formulation), both PP3M and PP1M formulations exhibited comparable incidence of EPS-related TEAEs, TTO, and TTR in patients with schizophrenia.
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Project description:In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality "in silico" of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N?=?131) and replicate it in two independent cohorts (Replication Cohort 1, N?=?113; Replication Cohort 2, N?=?113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original.
| S-EPMC6293322 | biostudies-literature
Project description:Extrapyramidal (EP) symptoms such as tremor, rigidity, and bradykinesia are common side effects of most antipsychotics, and may associate with impaired performance in neurocognitive testing. We studied EP symptoms in first-episode psychosis (FEP; n = 113). Cognitive testing and EP symptoms (three items of the Simpson-Angus Scale) were assessed at baseline and follow-up (mean follow-up time 12 months). Mild EP symptoms were present at treatment onset in 40% of the participants. EP symptoms were related with lower performance in neurocognitive testing at baseline and at follow-up, especially among those with nonaffective psychotic disorder, and especially in tasks requiring speed of processing. No associations between EP symptoms and social cognition were detected. In linear regression models, when positive and negative symptom levels and chlorpromazine equivalents were accounted for, baseline EP symptoms were associated with worse baseline global neurocognition and visuomotor performance. Baseline EP symptoms also longitudinally predicted global, verbal, and visuomotor cognition. However, there were no cross-sectional associations between EP symptoms and cognitive performance at follow-up. In sum, we found both cross-sectional and longitudinal associations between EP symptoms and neurocognitive task performance in the early course of psychosis. Those without EP symptoms at the start of treatment had higher baseline and follow-up neurocognitive performance. Even mild EP symptoms may represent early markers of long-term neurocognitive impairment.
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Project description:Background:Negative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms. Objective:To compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations. Methods:Data from a randomized double-blind (DB), phase-3, non-inferiority study in patients with schizophrenia were analyzed. Following screening, patients entered a 17-week open-label (OL) phase to receive flexibly dosed PP1M followed by a 48-week DB phase where patients were randomized (1:1) to receive either PP1M or PP3M. Positive and Negative Syndrome Scale (PANSS) total scores with emphasis on 7-item negative subscale scores for PP1M vs PP3M were assessed. Results:Of 1429 patients enrolled, 1016 were randomized to receive PP3M (n=504) or PP1M (n=512). At baseline, mean (SD) PANSS negative subscale was 23.2 (4.60) and negative symptom factor score was 22.3 (4.87), indicating moderate-to-severe negative symptoms. Negative subscale and symptoms factor scores showed continuous improvements throughout OL (15.9 [4.99]) and DB (14.9 [4.81]) phases. Mean (SD) changes from DB baseline in the PANSS negative subscale score were comparable between PP1M (-1.4 [3.67]) and PP3M (-1.4 [3.63]) treatment groups. Conclusion:Treatment with PP3M or PP1M demonstrated comparable improvement in negative symptoms in patients with moderate-to-severe negative symptoms and in patients with prominent negative symptoms. Long-term treatment with PP3M demonstrated benefit, suggesting that continuous antipsychotic medication treatment for >1 year is needed to achieve greater benefit for negative symptoms. Trial Registration:ClinicalTrials.gov Identifier: NCT01515423.
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Project description:IntroductionStress cardiomyopathy, also known as takotsubo syndrome, is characterized by transient left ventricular dysfunction not attributable to obstructive epicardial coronary artery disease. Several pathological mechanisms have been proposed, including multivessel coronary artery vasospasm, coronary microcirculatory dysfunction, and excess catecholamine secretion.Case presentationA 68-year-old male presented to our institution for elective surgical removal of a cutaneous basal cell carcinoma on the right side of his face. Within minutes following the administration of local anaesthesia, the patient developed severe hypertension, tachycardia, ST-segment elevation on the electrocardiogram, and non-sustained broad-complex tachycardia. Urgent cardiac catheterization revealed non-obstructive coronary artery disease and left ventriculography demonstrated apical hypokinesia and moderate systolic dysfunction consistent with the takotsubo syndrome. On review of the medications administered, it was noted that an unintentionally large dose of adrenaline (4mg) had been injected subcutaneously with lignocaine. He was monitored in the coronary care and recovered fully with supportive care only. Bisoprolol was initiated on day 1 post procedure. On follow-up one month later, his left ventricular function had normalized.DiscussionOur case report provides direct evidence supporting the pathogenetic role of excess catecholamine secretion in the development of the takotsubo syndrome. A review of the literature reveals that both exogenous catecholamine administration (adrenaline injection in the context of anaphylaxis or infiltrative anaesthesia) and excess endogenous catecholamine (phaechromocytoma) secretion has been associated with the takotsubo syndrome. Local infiltrative anaesthesia with the addition of adrenaline is commonly used as a vasoconstrictor in a wide variety of surgical procedures. To reduce the risk of adverse events, the lowest effective concentration of adrenaline to provide pain control and vasoconstriction is recommended.
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