Longitudinal Clinical Observation Research Articles

Uncertainty-Aware Variational-Recurrent Imputation Network for Clinical Time Series.

Electronic health records (EHR) consist of longitudinal clinical observations portrayed with sparsity, irregularity, and high dimensionality, which become major obstacles in drawing reliable downstream clinical outcomes. Although there exist great numbers of imputation methods to tackle these issues, most of them ignore correlated features, temporal dynamics, and entirely set aside the uncertainty. Since the missing value estimates involve the risk of being inaccurate, it is appropriate for the method to handle the less certain information differently than the reliable data. In that regard, we can use the uncertainties in estimating the missing values as the fidelity score to be further utilized to alleviate the risk of biased missing value estimates. In this work, we propose a novel variational-recurrent imputation network, which unifies an imputation and a prediction network by taking into account the correlated features, temporal dynamics, as well as uncertainty. Specifically, we leverage the deep generative model in the imputation, which is based on the distribution among variables, and a recurrent imputation network to exploit the temporal relations, in conjunction with utilization of the uncertainty. We validated the effectiveness of our proposed model on two publicly available real-world EHR datasets: 1) PhysioNet Challenge 2012 and 2) MIMIC-III, and compared the results with other competing state-of-the-art methods in the literature.

Machine learning approaches for the mortality risk assessment of patients undergoing hemodialysis.

Introduction:Mortality is a major primary endpoint for long-term hemodialysis (HD) patients. The clinical status of HD patients generally relies on longitudinal clinical observations such as monthly laboratory examinations and physical examinations.Methods:A total of 829 HD patients who met the inclusion criteria were analyzed. All patients were tracked from January 2009 to December 2013. Taken together, this study performed full-adjusted-Cox proportional hazards (CoxPH), stepwise-CoxPH, random survival forest (RSF)-CoxPH, and whale optimization algorithm (WOA)-CoxPH model for the all-cause mortality risk assessment in HD patients. The model performance between proposed selections of CoxPH models were evaluated using concordance index.Results:The WOA-CoxPH model obtained the highest concordance index compared with RSF-CoxPH and typical selection CoxPH model. The eight significant parameters obtained from the WOA-CoxPH model, including age, diabetes mellitus (DM), hemoglobin (Hb), albumin, creatinine (Cr), potassium (K), Kt/V, and cardiothoracic ratio, have also showed significant survival difference between low- and high-risk characteristics in single-factor analysis. By integrating the risk characteristics of each single factor, patients who obtained seven or more risk characteristics of eight selected parameters were dichotomized as high-risk subgroup, and remaining is considered as low-risk subgroup. The integrated low- and high-risk subgroup showed greater discrepancy compared with each single risk factor selected by WOA-CoxPH model.Conclusion:The study findings revealed WOA-CoxPH model could provide better risk assessment performance compared with RSF-CoxPH and typical selection CoxPH model in the HD patients. In summary, patients who had seven or more risk characteristics of eight selected parameters were at potentially increased risk of all-cause mortality in HD population.

Clinical experience of quartz reinforcing mesh usage in production of full removable laminar upper dentures

The study is devoted to one of relevant topics in orthopaedic dentistry: orthopaedic treatment for fully edentulous patients with application of removable laminar dentures the basis of which is produced from acrylic plastic. The main problem of this approach has been formulated: the possibility of frequent crashing of the basis by the patient within earlier and later periods after the beginning of prosthesis exploitation. Options in prevention of this problem have been considered — reinforcing of the denture basis using standard and individually produced metal meshes — as well as their disadvantages. A study based on longitudinal clinical observation within terms of up to five years of exploitation effectiveness in quartz reinforcing mesh application to removable denture bases as an alternative approach to modern technologies has been carried out. Application features and advantages of this technology have been presented.

Teamwork in primary palliative care: general practitioners\u2019 and specialised oncology nurses\u2019 complementary competencies

BackgroundGeneralists such as general practitioners and district nurses have been the main actors in community palliative care in Norway. Specialised oncology nurses with postgraduate palliative training are increasingly becoming involved. There is little research on their contribution. This study explores how general practitioners (GPs) and oncology nurses (ONs) experience their collaboration in primary palliative care.MethodsA qualitative focus group and interview study in rural Northern Norway, involving 52 health professionals. Five uni-professional focus group discussions were followed by five interprofessional discussions and six individual interviews. Transcripts were analysed thematically.ResultsThe ideal cooperation between GPs and ONs was as a “meeting of experts” with complementary competencies. GPs drew on their generalist backgrounds, including their often long-term relationship with and knowledge of the patient. The ONs contributed longitudinal clinical observations and used their specialised knowledge to make treatment suggestions. While ONs were often experienced and many had developed a form of pattern recognition, they needed GPs’ competencies for complex clinical judgements. However, ONs sometimes lacked timely advice from GPs, and could feel left alone with sick patients. To avoid this, some ONs bypassed GPs and contacted palliative specialists directly.While traditional professional hierarchies were not a barrier, we found that organization, funding and remuneration were significant barriers to cooperation. GPs often did not have time to meet with ONs to discuss shared patients. We also found that ONs and GPs had different strategies for learning. While ONs belonged to a networking nursing collective aiming for continuous quality improvement, GPs learned mostly from their individual experience of caring for patients.ConclusionsThe complementary competences and autonomous roles of a specialised nurse and a general practitioner represented a good match for primary palliative care. When planning high-quality teamwork in primary care, organizational barriers to cooperation and different cultures for learning need consideration.

Prescribing and Verifying Hearing Aids Applying the American Academy of Audiology Pediatric Amplification Guideline: Protocols and Outcomes from the Ontario Infant Hearing Program.

Guidelines and protocols for pediatric hearing aid fitting are necessary to meet the goals of Early Hearing Detection and Intervention (EHDI) programs. The American Academy of Audiology published an update to their Pediatric Amplification Guideline in 2013. Ontario's Infant Hearing Program (IHP) offers specific protocols that aim to fulfill recommended guidelines. It has recently been updated to align with the American Academy of Audiology Guideline and other evidence. A summary of the updates to the Ontario IHP's Amplification Protocol is described. In addition, data illustrating hearing-related outcomes of the program are offered. The updated Ontario protocol is based on evidence, wherever possible. Where research is not yet available, clinical decision support has been described in a systematic way. Outcomes of the Ontario IHP were obtained through a longitudinal clinical observation study. One hundred and fifteen children with hearing loss, who wore hearing aids, were included in the outcome analyses (mean = 28.6 mo; range = 1.3-115.3 mo). Hearing losses ranged from mild to profound, unilateral or bilateral sensorineural (pure-tone average = 52.3 dB HL). They were recruited from four IHP clinics within Ontario. Children with complexities in addition to hearing loss were included. The children were fitted with hearing aids following Ontario's Amplification Protocol. During routine clinical appointments, IHP Audiologists administered questionnaires to the parents of their pediatric patients using a systematic outcome measurement protocol (University of Western Ontario Pediatric Audiological Monitoring Protocol). Hearing aid fitting details (e.g., speech intelligibility index) were also gathered to describe the quality of the hearing aid fittings in relation to the functional outcomes. Regression analyses were conducted to characterize scores on the questionnaires and the impact of important variables. Children with complexities were analyzed separately from those who were typically developing. Important updates to Ontario's Amplification Protocol offer new details about candidacy considerations as well as technical updates. Outcomes from the IHP reveal protocol elements can be executed clinically and when they are, typically developing children who wear hearing aids are meeting auditory development and performance milestones. Updates to Ontario's Amplification Protocol are necessary to support the evolution of EHDI programs and the evidence which sustains them. With advances in technology and additional research, pediatric hearing aid fitting will continue to progress and support systematic measurement of outcomes for children who wear hearing aids. The application of state-of-the-art hearing aid fitting practices to the pediatric population within EHDI programs supports good outcomes for infants and children with hearing loss.

“Common Developmental Delay” in Full-term Children: A Common Neurological Profile to Aid in Clinical Diagnosis

Depending on the course, developmental disorders can be divided into three groups. In clinical practice of child neurology, developmental delay of unknown etiology without regression is probably the most common group. To date, no reports have described commonly encountered developmental delay in full-term children. Based on what is known and longitudinal clinical observation, in this review, we propose and describe a common neurological profile in a homogenous population of children with “common developmental delay”. In authors’ view, adherence to the proposed profile will (1) identify common developmental delay, (2) differentiate it from other treatable conditions, (3) optimize the need for laboratory investigation, (4) facilitate clinical interventions in timely manner, (5) avoid a legal implication of delay in management, and (6) allow to define the developmental status of subjects for clinical research. Future studies should analyze prospectively the diagnostic significance of the proposed common neurological profile in full-term children with “common developmental delay”.

Plasma Biomarkers of HIV-associated Cognitive Disease

By controlling human immunodeficiency virus (HIV) replication and allowing recovery of immune system function, combination antiretroviral therapy (cART) has revolutionised the outlook for people-living-with-HIV (PLWH) to that of a chronic but manageable medical condition. Despite this success, other medical problems, such as hypertension and cardiovascular disease, are reported to occur more frequently and at a younger age in PLWH compared to matched control populations (Schouten et al., 2014). Another medical problem with a high prevalence and high morbidity is cognitive impairment (Robertson et al., 2007). For many co-morbidities, surrogate markers aid diagnosis and assist in the clinical staging of a disease state. For cognitive impairment however, disease markers to date have either been unreliable or impractical to measure. For instance, clinical assessments such as formal neuropsychological testing are time consuming to perform and prone to many confounding issues such as illicit drug and alcohol use, the presence of depression and anxiety, and day to day variability in a patient's performance. Novel cerebral imaging techniques show promise in the diagnosis and assessment of HIV-associated cognitive impairment (Descamps et al., 2008). However, many of these novel imaging techniques are not widely available and may only be accessible as part of a research study, rather than in general clinical care. And lastly, although cerebrospinal fluid (CSF) markers, such as neurofilament light protein (NFL) concentration, show promise, collection of CSF is problematic. Lumbar puncture, whilst generally safe, is an invasive and resource expensive procedure which does not lend itself particularly well to repeated measure (Peterson et al., 2014). In this issue of EBioMedicine, Gisslen et al. (2015) report on the measurement of plasma NFL concentrations, using a new ultrasensitive single molecule assay, and its correlations with CSF NFL concentrations in several cohorts of PLWH. Groups assessed included individuals with primary HIV-infection, neuroasymptomatic PLWH not on cART with different ranges of CD4 + lymphocyte counts (above 350 cells/uL, 200–349 cells/uL, 50–199 cells/uL and below 50 cells/uL), individuals with overt HIV-associated dementia and subjects on cART with plasma HIV RNA < 50 copies/mL for greater than one year. Furthermore an HIV-uninfected control group was included in their analysis. As expected, CSF concentration of NFL was dependent on the cohorts studied with the highest concentrations observed in those with HIV-associated dementia and higher concentrations in PLWH with untreated HIV-disease and low CD4 + lymphocyte counts. Of importance, in all groups studied, a strong correlation between plasma NFL and CSF NFL was reported. The values of NFL plasma concentrations were 1–2 log10 lower than in the CSF. However, by developing and utilising this new ultrasensitive plasma NFL assay, concentrations as low as a mean of 9.3 nmol/L were measured in the HIV-uninfected control group and every subject had a detectable and quantifiable concentration. This impressive dynamic range highlights the potential sensitivity of this biomarker to detect subtle axonal injury in a variety of patient groups. The ability to utilise a sensitive plasma biomarker which closely correlates with active CNS axonal injury has several potential implications for future research. Within longitudinal cohorts, clinical observations and non-invasive neuroimaging observations could now be correlated with readily obtainable plasma biomarkers. Within interventional studies, a novel plasma biomarker which correlates with the effects of a drug or other interventions on cerebral function, could dramatically simplify the practical issues which are currently associated with the development of such therapeutics. Furthermore, this assay has the potential in clinical practice, as well as research studies, to discriminate between those with ongoing CNS injury in whom intervention may be more successful and those with quiescent disease in whom it may not. In summary, these initial results described are highly promising with further work needed to assess the utility of this marker in other cohorts of PLWH, such as those with minor cognitive complaints, and other neurodegenerative diseases.

Preictal Symptomatology in Migraines: Diagnostic and Therapeutic Significance

Prodrome and aura constitute preictal symptomatology of migraines. The objective of this clinical review is to examine the diagnostic and therapeutic significance of preictal symptomatology in children with migraines. The systemic review of the literature identified a single study in children with migraines. The majority studies were in adults. Based on our search and longitudinal clinical observation, we describe the clinical characteristics of diagnostic and therapeutic significance of preictal symptoms and various types of auras in migraines. Such significance can be substantially increased by including prodromal physical signs in children with migraines. Future studies’ methodology should include physical signs in addition to symptoms and identify the spectrum of the various auras, and relate to their temporal association with ictal and postictal phases of migraines. In addition these clinical parameters should be statistically analyzed.

Longitudinal clinical observation of 4 patients with preclinical stage of idiopathic normal pressure hydrocephalus

In patients with idiopathic normal pressure hydrocephalus (iNPH) with features of Disproportionately Enlarged Subarachnoid-space Hydrocephalus (DESH), ventriculomegaly and the tight high-convexity and medial subarachnoid spaces appear in magnetic resonance (MR) images before the occurrence of objective symptoms. There are few reports of longitudinal observation of clinical course in DESH-type iNPH patients with no objective symptom.

Is it safe to implant bioresorbable scaffolds in ostial side-branch lesions? Impact of ‘neo-carina’ formation on main-branch flow pattern. Longitudinal clinical observations

Formation of a ‘neo-carina’ has been reported after bioresorbable vascular scaffolds (BVS) implantation over side-branches. However, as this ‘neo-carina’ could protrude into the main-branch, its hemodynamic impact remains unknown. We present two cases of BVS implantation for ostial side-branch lesions, and investigate the flow patterns at follow-up and their potential impact. Computational fluid dynamics analysis was performed, using a 3D mesh created by fusion of 3-dimensional angiogram with optical coherence tomography images. In our first case, mild disturbances were seen when ‘neo-carina’ did not protrude perpendicularly into the main branch. In the second case, extensive flow re-distribution was observed due to a more pronounced protrusion of the ‘neo-carina’. Importantly, these areas of hemodynamic disturbance were observed together with lumen narrowing in a non-stenotic vessel segment. Our case observations highlight the importance of investigating the hemodynamic consequences of BVS implantation in bifurcation lesions and illustrate a novel method to do so in vivo.

The influence of bevacizumab on platelet function

Systemic treatment with bevacizumab is associated with increased rates of arterial and venous thromboembolism and haemorrhage. In order to investigate the pathophysiological mechanism involved, platelet adhesive and aggregatory functions were tested with a platelet function analyser (PFA-100®) in an in vitro study and in a longitudinal clinical observation study. For the in vitro study, blood from ten healthy volunteers was incubated with different concentrations of bevacizumab (0-1000 μg/ml plasma) and vascular endothelial growth factor (0-500 μg/ml). In the clinical observation study, PFA-100® closure times (CTs) and soluble P-selectin (sP-selectin) serum levels as a serological marker of platelet activation were assessed in 20 patients with metastatic cancer who were treated with bevacizumab in addition to cytotoxic chemotherapy. No significant changes of PFA-100® CTs were observed in the in vitro study. In the clinical observation study, mean PFA-100® CTs after treatment with bevacizumab were unchanged. sP-selectin was decreased after bevacizumab infusion by 18% (p = 0.045), which could suggest an inhibitory action on platelets. Our data do not support the view that increased platelet activation or increased platelet adhesiveness and aggregation by bevacizumab are relevant mechanisms for thrombus formation in clinical practice.

The Impact of Early Life Trauma on Health and Disease: The Hidden Epidemic. Edited by R. A. Lanius, E. Vermetten and C. Pain (Pp. 334; £55.00; ISBN 9780521880268 hb.) Cambridge University Press: Cambridge, UK. 2010.

Part I. Early Life Trauma, Impact of Health and Disease Section 1. Childhood Trauma: Epidemiology and Historical Themes: 1. The history of early life trauma and abuse from the 1850s to the current time: how the past influences the present 2. The epidemiology of early life trauma 3. Historical themes in the study of recovered and false memories of trauma 4. Early life trauma, later outcome: results from longitudinal studies and clinical observations Synopsis Section 2. The Effects of Life Trauma: Mental and Physical Health: 5. Attachment dysregulation as hidden trauma in infancy 6. Towards a developmental trauma in infancy, early stress, maternal buffering, and psychiatric morbidity in young adulthood 7. Complex adult sequelae of early life exposure to psychological trauma 8. The relationship of adverse childhood experiences to adult health, well being, social function and health care Synopsis Part II. Biological Approaches to Early Life Trauma Section 3. The Impact of Early Life Trauma: Psychobiological Sequelae in Children: 9. Translational studies of the effects of early life stress 10. Lateral asymmetries in infants' regulatory and communicative gestures 11. Neurobiology of childhood trauma and adversity 12. Neurobiology of neglect 13. Early life trauma as a risk factor for disease in adulthood Synopsis Section 4. The Impact of Childhood Trauma: Psychobiological Sequelae in Adults: 14. Early life stress and psychiatric risk/resilience: the importance of a developmental neurobiological model in understanding gene by environment interactions 15. Neuroendocrine effects of early life trauma 16. Long lasting effects of early life trauma on neurobiological circuits 17. Biological framework for early life related traumatic dissociation 18. The role of resilience in early life trauma Synopsis Part III. Clinical Perspectives, Assessment and Treatment of Trauma Spectrum Disorders Section 5. Assessment on the Impact of Early Life Trauma: Clinical Science and Societal Effects: 19. Assessment of early- and mid-childhood trauma in adults 20. Memory and trauma: examining disruptions in implicit, explicit and autobiographical memory 21. Scientific progress and methodological issues in the study of recovered and false memories of trauma 22. The psychosocial consequences of organized violence in children Synopsis Section 6. Strategies to Reduce Impact: 23. The role of mentalizing in treating attachment trauma 24. Pragmatic approaches to stage oriented treatment for complex post traumatic stress and dissociative disorders 25. Cognitive behavioral treatments 26. Emotions and emotion regulation in the process of trauma recovery: implications for the treatment of post traumatic stress disorder 27. Psychodynamic psychotherapy: adaptations for the treatment of patients with chronic complex PSTD Synopsis Epilogue Index.

Study of the prevalence of Parkinson's disease using dopamine transporter imaging

Introduction: To investigate the prevalence of Parkinson's disease (PD), a three-phase study was conducted.Methods: In phase 1, standardized interviews were performed in a random sample of elderly aged 65 years or older using a questionnaire. In phase 2, neurological examinations were performed to clinically diagnose PD. In phase 3, dopamine transporter (DAT) imaging was performed to support the clinical diagnosis. After the three-phase study, longitudinal clinical observation was performed.Results: A total of 714 subjects participated in the phase-1. Two hundred and twenty-two subjects, scored more than two points, were referred to the movement disorder specialist. Eighteen of these subjects showed overt or equivocal Parkinsonian features. Three subjects were clinically diagnosed with possible PD: five with essential tremor with equivocal extrapyramidal signs, eight with frontal-subcortical gait disorder and two with drug-induced Parkinsonism. The three subjects with possible PD showed a typical PD pattern of reduced DAT density. DAT density was normal in the other 15 subjects. Results of long-term follow-up supported the diagnoses. The crude prevalence of PD was 0·42 per 100 persons.Conclusion: During the clinical evaluation, we encountered a very large proportion of subjects with equivocal Parkinsonian features, who posed a diagnostic challenge and a substantial risk of misestimating the prevalence of PD. The combination of DAT imaging and longitudinal clinical observation of equivocal cases enabled us to differentiate PD from other conditions. We suspect that the variation in estimates of the prevalence of PD may be attributable to a considerable proportion of subjects with equivocal Parkinsonian features and how they are evaluated.

Transition of Distinctive Symptoms of Semantic Dementia during Longitudinal Clinical Observation

Background/Aims: The aim of this study is to examine the clinical symptoms in a number of semantic dementia (SD) patients and to reveal the longitudinal progression and clinical course of these distinctive symptoms of SD. Methods: 19 consecutive SD patients were examined. Symptoms were classified into 23 distinct categories: behavioral symptoms, language and cognitive symptoms and symptoms concerning the impairment of activities of daily living (ADL). We divided patients into two subgroups, left- and right-dominant SD, and compared the onset of each symptom. Results: Language impairments occurred as the initial symptom in 16 cases. At the first examination, all cases showed both anomia and impairment of word comprehension. By around 3 years after onset, almost all language impairments were observed. Approximately 3–5 years after onset, prosopagnosia and behavioral symptoms appeared. Around the period when the loss of the language faculty and apathy became remarkable, impairment of ADL appeared. Patients spent all day in bed at this stage. Moreover, prosopagnosia appeared significantly earlier in right-dominant SD. Conclusion: Our findings clarify the progression of distinctive symptoms of SD patients. It is necessary to create a treatment strategy for SD patients with such a disease-specific course of SD.

Transition of distinctive symptoms of semantic dementia during longitudinal clinical observation

Background/Aims: The aim of this study is to examine the clinical symptoms in a number of semantic dementia (SD) patients and to reveal the longitudinal progression and clinical course of these distinctive symptoms of SD. Methods: 19 consecutive SD patients were examined. Symptoms were classified into 23 distinct categories: behavioral symptoms, language and cognitive symptoms and symptoms concerning the impairment of activities of daily living (ADL). We divided patients into two subgroups, left- and right-dominant SD, and compared the onset of each symptom. Results: Language impairments occurred as the initial symptom in 16 cases. At the first examination, all cases showed both anomia and impairment of word comprehension. By around 3 years after onset, almost all language impairments were observed. Approximately 3–5 years after onset, prosopagnosia and behavioral symptoms appeared. Around the period when the loss of the language faculty and apathy became remarkable, impairment of ADL appeared. Patients spent all day in bed at this stage. Moreover, prosopagnosia appeared significantly earlier in right-dominant SD. Conclusion: Our findings clarify the progression of distinctive symptoms of SD patients. It is necessary to create a treatment strategy for SD patients with such a disease-specific course of SD.

Mandibular Asymmetry and the Fourth Dimension

This paper represents more than 30 years of discussion and collaboration with Drs Joseph Murray and John Mulliken in an attempt to understand growth patterns over time (ie, fourth dimension) in patients with hemifacial microsomia (HFM). This is essential for the development of rational treatment protocols for children and adults with jaw asymmetry. Traditionally, HFM was thought of as a unilateral deformity, but it was recognized that 20% to 30% of patients had bilateral abnormalities. However, early descriptions of skeletal correction addressed almost exclusively lengthening of the short (affected) side of the face. Based on longitudinal clinical observations of unoperated HFM patients, we hypothesized that abnormal mandibular growth is the earliest skeletal manifestation and that restricted growth of the mandible plays a pivotal role in progressive distortion of both the ipsilateral and contralateral facial skeleton. This hypothesis explains the progressive nature of the asymmetry in patients with HFM and provides the rationale for surgical lengthening of the mandible in children to prevent end-stage deformity. During the past 30 years, we have learned that this phenomenon of progressive distortion of the adjacent and contralateral facial skeleton occurs with other asymmetric mandibular undergrowth (tumor resection, radiation therapy, or posttraumatic defects) and overgrowth (mandibular condylar hyperplasia) conditions. In this paper, I describe the progression of deformity with time in patients with mandibular asymmetry as a result of undergrowth and overgrowth. Understanding these concepts is critical for the development of rational treatment protocols for adults with end-stage asymmetry and for children to minimize secondary deformity.

Heparin cofactor II–thrombin complex: A biomarker of MPS disease

The mucopolysaccharidoses are a group of lysosomal storage disorders caused by defects in the degradation of glycosaminoglycans. Each disorder is characterized by progressive multi-system disease with considerable clinical heterogeneity. The clinical heterogeneity of these disorders is thought to be related to the degree of the metabolic block in glycosaminoglycan degradation which in turn is related to the underlying mutation at the respective locus. There are currently no objective means other than longitudinal clinical observation, or the detection of a recurrent genetic mutation to accurately predict the clinical course for an individual patient, particularly when diagnosed early. In addition, there are no specific disease biomarkers that reflect the total body burden of disease. The lack of specific biomarkers has made monitoring treatment responses and predicting disease course difficult in these disorders. The recent introduction of enzyme replacement therapy for MPS I, II, and VI highlights the need for objective measures of disease burden and disease responsiveness. We show that serum levels of heparin cofactor II–thrombin complex is a reliable biomarker of the mucopolysaccharidoses. Untreated patients have serum levels that range from 3- to 112-fold above control values. In a series of patients with varying severity of mucopolysaccharidosis I, the serum complex concentration was reflective of disease severity. In addition, serum heparin cofactor II–thrombin levels showed responsiveness to various treatment regimens. We propose that serum levels of heparin cofactor II–thrombin complex may provide an important assessment and monitoring tool for patients with mucopolysaccharidosis.

Hypericum-induced mood disorder: switch from depression to mixed episodes in two patients

Objective. To point out the danger of worsening mood disorders with the use of hypericum. Methods. Longitudinal clinical observation of two cases treated with hypericum. Results. The two patients underwent mixed episodes following hypericum treatment. One of them needed hospitalization for suicidal risk. Conclusion. Caution is warranted in the use of hypericum in depressed patients with hidden bipolarity. Patients should be informed that hypericum may induce manic symptoms, increase cycling of mood states, or worsen the depressive state.

Forecasting clinical disease in pigs: comparing a naive and a Bayesian approach

In veterinary practice the clinician often evaluates and predicts herd health status over time according to clinical criteria. In this paper, we modeled three different clinical signs among pigs based on longitudinal clinical observations in 15 pig herds. We compared and discussed the outputs from two different approaches for making clinical forecasts in a herd: a naive approach using a simple time series model with previous disease observations as predictors and a Bayesian state space models approach, in which the time lag variable entered into the random component of the model. We used the Markov chain Monte Carlo technique to calculate posterior distributions of the forecasts. For the herd specific forecasts the results showed that there were only minor differences between the forecasts from the simple time series model and the median forecasts from the Bayesian model. However, the credibility intervals from the Bayesian model were wider than the forecasts from the simple model and, therefore the Bayesian model encompassed the variability in the forecasts better. Compared to the statistical model, the simple time series would be easier to implement in a practical setting. However, the latter lacks the inherent “generality” from the statistical model that allows the user to make statements about the distribution of the herds and to predict disease status based on the “average” correlation among the herds. The applicability of the Bayesian approach within a clinical decision-making framework was discussed, with special emphasis on the use of prior information and clinical forecasting.

Is episodic obsessive compulsive disorder bipolar? a report of four cases

Several reports have noted cases of OCD which were unusual in showing an abrupt remission. We report longitudinal clinical observation of four cases of acute onset OCD without major depression through a variety of treatments. These patients had prominent feelings of shamefulness; compared to patients with typical OCD they were ill for months rather than years and were older. Two had previous episodes of psychiatric illness with full recovery. Full and persistent recovery occurred in response to lithium or an acute course of ECT but not to tricyclic or SSRI antidepressants. The generalizability of these observations is limited by its uncontrolled nature and the small numbers. The courses observed were consistent with episodic OCD as a possible expression of bipolar disorder and consideration of corresponding treatments. This perspective offers a new rationale for reported observations of remissions of acute onset OCD in response to lithium without lithium effectiveness for typical OCD.