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1.
Br J Dermatol ; 174(3): 617-20, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26385848

ABSTRACT

Perivascular epithelioid cell neoplasms (PEComas) are a group of mesenchymal tumours with concurrent melanocytic and myogenic differentiation. Although many cases are sporadic, PEComas can be associated with tuberous sclerosis. A distinct subset of deep-seated PEComas has been shown to carry TFE3 fusions. To our knowledge, this is the first reported case of primary subcutaneous malignant PEComa with molecular confirmation of TFE3 gene rearrangement.


Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Muscle Neoplasms/genetics , Perivascular Epithelioid Cell Neoplasms/genetics , Adult , Buttocks , Female , Gene Rearrangement/genetics , Humans , Muscle Neoplasms/diagnosis , Perivascular Epithelioid Cell Neoplasms/diagnosis , Thigh
2.
BMC Psychiatry ; 14: 365, 2014 Dec 24.
Article in English | MEDLINE | ID: mdl-25539658

ABSTRACT

BACKGROUND: Quality of life (QoL) is considered an important outcome in health research. It can be rated by the patient, or by an external assessor. We wished to identify the predictors of any discrepancies between these two approaches in people with schizophrenia. METHODS: Patients with DSM schizophrenia and related disorders (N = 80) completed both patient-rated (Lancashire Quality of Life Profile; LQOLP) and assessor-rated (Heinrich's Quality of Life Scale; QLS) measures of QoL. RESULTS: Patient-rated (LQOLP) and assessor-rated (QLS) measures showed a modest correlation (r = 0.38). In a regression analysis, independent predictors of subjectively-rated QoL being higher than objectively-assessed QoL in the same patient, were low insight score (BIS), negative symptoms (PANSS), absence of depression (CDSS), and less positive attitude toward prescribed treatment (DAI). CONCLUSIONS: In people with schizophrenia, scores on objectively- and subjectively-rated measures of quality of life can differ markedly. When comparing subjective to objective assessments, patients with depressive symptoms will value their QoL lower, and those with low insight will value their QoL higher. This has important implications for the utility and interpretation of QoL measures in schizophrenia.


Subject(s)
Quality of Life , Schizophrenic Psychology , Adolescent , Adult , Aged , Antipsychotic Agents/therapeutic use , Depressive Disorder/psychology , Drug Substitution , Female , Humans , Male , Middle Aged , Patient Satisfaction , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Schizophrenia, Paranoid/drug therapy , Young Adult
3.
Br J Psychiatry ; 203(3): 215-20, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23888001

ABSTRACT

BACKGROUND: It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations. AIMS: To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence. METHOD: Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study). RESULTS: Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA. CONCLUSIONS: A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.


Subject(s)
Antipsychotic Agents/administration & dosage , Schizophrenia/drug therapy , Administration, Oral , Adult , Drug Substitution , Female , Humans , Injections, Intramuscular , Male , Medication Adherence , Pragmatic Clinical Trials as Topic , Quality of Life , Randomized Controlled Trials as Topic , Retreatment , Treatment Outcome
4.
BMC Psychiatry ; 13: 34, 2013 Jan 23.
Article in English | MEDLINE | ID: mdl-23343329

ABSTRACT

BACKGROUND: Over the past decade policy makers have emphasised the importance of healthcare technology in the management of long-term conditions. Mobile-phone based assessment may be one method of facilitating clinically- and cost-effective intervention, and increasing the autonomy and independence of service users. Recently, text-message and smartphone interfaces have been developed for the real-time assessment of symptoms in individuals with schizophrenia. Little is currently understood about patients' perceptions of these systems, and how they might be implemented into their everyday routine and clinical care. METHOD: 24 community based individuals with non-affective psychosis completed a randomised repeated-measure cross-over design study, where they filled in self-report questions about their symptoms via text-messages on their own phone, or via a purpose designed software application for Android smartphones, for six days. Qualitative interviews were conducted in order to explore participants' perceptions and experiences of the devices, and thematic analysis was used to analyse the data. RESULTS: Three themes emerged from the data: i) the appeal of usability and familiarity, ii) acceptability, validity and integration into domestic routines, and iii) perceived impact on clinical care. Although participants generally found the technology non-stigmatising and well integrated into their everyday activities, the repetitiveness of the questions was identified as a likely barrier to long-term adoption. Potential benefits to the quality of care received were seen in terms of assisting clinicians, faster and more efficient data exchange, and aiding patient-clinician communication. However, patients often failed to see the relevance of the systems to their personal situations, and emphasised the threat to the person centred element of their care. CONCLUSIONS: The feedback presented in this paper suggests that patients are conscious of the benefits that mobile-phone based assessment could bring to clinical care, and that the technology can be successfully integrated into everyday routine. However, it also suggests that it is important to demonstrate to patients the personal, as well as theoretical, benefits of the technology. In the future it will be important to establish whether clinical practitioners are able to use this technology as part of a personalised mental health regime.


Subject(s)
Cell Phone , Schizophrenia/diagnosis , Activities of Daily Living , Adult , Cross-Over Studies , Female , Humans , Male , Patient Satisfaction , Psychotic Disorders/diagnosis , Psychotic Disorders/psychology , Reproducibility of Results , Schizophrenic Psychology , Text Messaging
5.
Br J Psychiatry ; 200(5): 387-92, 2012 May.
Article in English | MEDLINE | ID: mdl-22442101

ABSTRACT

BACKGROUND: Second-generation antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than first-generation antipsychotics, but recent pragmatic trials have indicated equivalence. AIMS: To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs. METHOD: We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial (n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed first- v. second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points. RESULTS: At baseline those randomised to the first-generation antipsychotic group (n = 118) had similar EPS to the second-generation group (n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS. CONCLUSIONS: The expected improvement in EPS profiles for participants randomised to second-generation drugs was not found; the prognosis over 1 year of those in the first-generation arm was no worse in these terms. The place of careful prescription of first-generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-generation antipsychotics used in routine practice. This has educational implications because a generation of psychiatrists now has little or no experience with first-generation antipsychotic prescription.


Subject(s)
Antipsychotic Agents/adverse effects , Basal Ganglia Diseases/chemically induced , Adolescent , Adult , Aged , Akathisia, Drug-Induced/etiology , Cholinergic Antagonists/therapeutic use , Dyskinesia, Drug-Induced/etiology , Humans , Middle Aged , Parkinsonian Disorders/chemically induced , Prognosis , Psychotic Disorders/drug therapy , Schizophrenia, Paranoid/drug therapy , Young Adult
6.
BMC Psychiatry ; 12: 172, 2012 Oct 17.
Article in English | MEDLINE | ID: mdl-23075387

ABSTRACT

BACKGROUND: Semi-structured interview scales for psychosis are the gold standard approach to assessing psychotic and other symptoms. However, such assessments have limitations such as recall bias, averaging, insensitivity to change and variable interrater reliability. Ambulant, real-time self-report assessment devices may hold advantages over interview measures, but it needs to be shown that the data thus collected are valid, and the collection method is acceptable, feasible and safe. We report on a monitoring system for the assessment of psychosis using smartphone technology. The primary aims were to: i) assess validity through correlations of item responses with those on widely accepted interview assessments of psychosis, and ii) examine compliance to the procedure in individuals with psychosis of varying severity. METHODS: A total of 44 participants (acute or remitted DSM-4 schizophrenia and related disorders, and prodromal) completed 14 branching self-report items concerning key psychotic symptoms on a touch-screen mobile phone when prompted by an alarm at six pseudo-random times, each day, for one week. Face to face PANSS and CDS interviews were conducted before and after the assessment period blind to the ambulant data. RESULTS: Compliance as defined by completion of at least 33% of all possible data-points over seven days was 82%. In the 36 compliant participants, 5 items (delusions, hallucinations, suspiciousness, anxiety, hopelessness) showed moderate to strong (rho 0.6-0.8) associations with corresponding items from interview rating scales. Four items showed no significant correlation with rating scales: each was an item based on observable behaviour. Ambulant ratings showed excellent test-retest reliability and sensitivity to change. CONCLUSIONS: Ambulatory monitoring of symptoms several times daily using smartphone software applications represents a feasible and valid way of assessing psychotic phenomena for research and clinical management purposes. Further evaluation required over longer assessment periods, in clinical trials and service settings.


Subject(s)
Diagnostic Self Evaluation , Monitoring, Ambulatory/methods , Psychotic Disorders/diagnosis , Adult , Cell Phone , Feasibility Studies , Female , Humans , Male , Middle Aged , Psychometrics , Reproducibility of Results , Self Report , Software
7.
Int J Psychiatry Clin Pract ; 16(2): 148-52, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22122652

ABSTRACT

OBJECTIVES: The aim of the study was to investigate sexual function in patients with schizophrenia receiving treatment with a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) drug. Sexual function is an important aspect of human experience, which can be affected by antipsychotic drug treatment. Sexual dysfunction in patients with schizophrenia may be less prevalent with SGA than with FGA drug treatment. METHODS: A cross-sectional prevalence study assessed sexual function in a sample of 144 patients with DSM-IV schizophrenia aged between 18 and 65, using the Derogatis Interview for Sexual Functioning (self-report version: DISF-SR). Two equal-sized groups (N = 72) received treatment with an FGA or an SGA drug for at least 12 weeks. RESULTS: No significant differences were seen on DISF-SR total score or subscale score between the two treatment groups. CONCLUSIONS: There are no differences in measured sexual function of non-randomised patients with schizophrenia treated with an FGA compared with SGA-treated patients.


Subject(s)
Antipsychotic Agents/adverse effects , Schizophrenia/drug therapy , Schizophrenic Psychology , Sexual Dysfunction, Physiological/chemically induced , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Self Report , Young Adult
8.
Schizophr Bull Open ; 2(1): sgab041, 2021 Jan.
Article in English | MEDLINE | ID: mdl-34568827

ABSTRACT

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.71, 0.75) and adequate calibration with intercept alpha of 0.12 (0.02, 0.22) and slope beta of 0.98 (0.85, 1.11). Our model improved the net-benefit by 15% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 15 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact.

9.
Lancet Psychiatry ; 7(7): 602-610, 2020 07.
Article in English | MEDLINE | ID: mdl-32563307

ABSTRACT

BACKGROUND: Delayed treatment for first episodes of psychosis predicts worse outcomes. We hypothesised that delaying treatment makes all symptoms more refractory, with harm worsening first quickly, then more slowly. We also hypothesised that although delay impairs treatment response, worse symptoms hasten treatment, which at presentation mitigates the detrimental effect of treatment delay on symptoms. METHODS: In this longitudinal analysis and modelling study, we included two longitudinal cohorts of patients with first-episode psychosis presenting to English early intervention services from defined catchments: NEDEN (recruiting 1003 patients aged 14-35 years from 14 services between Aug 1, 2005, and April 1, 2009) and Outlook (recruiting 399 patients aged 16-35 years from 11 services between April 1, 2006, and Feb 28, 2009). Patients were assessed at baseline, 6 months, and 12 months with the Positive and Negative Symptom Scale (PANSS), Calgary Depression Scale for Schizophrenia, Mania Rating Scale, Insight Scale, and Social and Occupational Functioning Assessment Scale. Regression was used to compare different models of the relationship between duration of untreated psychosis (DUP) and total symptoms at 6 months. Growth curve models of symptom subscales tested predictions arising from our hypotheses. FINDINGS: We included 948 patients from the NEDEN study and 332 patients from the Outlook study who completed baseline assessments and were prescribed dopamine antagonist antipsychotics. For both cohorts, the best-fitting models were logarithmic, describing a curvilinear relationship of DUP to symptom severity: longer DUP predicted reduced treatment response, but response worsened more slowly as DUP lengthened. Increasing DUP by ten times predicted reduced improvement in total symptoms (ie, PANSS total) by 7·339 (95% CI 5·762 to 8·916; p<0·0001) in NEDEN data and 3·846 (1·689 to 6·003; p=0·0005) in Outlook data. This was true of treatment response for all symptom types. Nevertheless, longer DUP was not associated with worse presentation for any symptoms except depression in NEDEN (coefficients 0·099 [95% CI 0·033 to 0·164]; p=0·0028 in NEDEN and 0·007 [-0·081 to 0·095]; p=0·88 in Outlook). INTERPRETATION: Long DUP was associated with reduced treatment response across subscales, consistent with a harmful process upstream of individual symptoms' mechanisms; response appeared to worsen quickly at first, then more slowly. These associations underscore the importance of rapid access to a comprehensive range of treatments, especially in the first weeks after psychosis onset. FUNDING: UK Department of Health, National Institute of Health Research, and Medical Research Council.


Subject(s)
Antipsychotic Agents/therapeutic use , Dopamine Antagonists/therapeutic use , Psychotic Disorders/drug therapy , Psychotic Disorders/psychology , Time-to-Treatment , Adolescent , Adult , Female , Humans , Logistic Models , Longitudinal Studies , Male , Models, Psychological , Psychiatric Status Rating Scales , Psychotic Disorders/diagnosis , Time Factors , Young Adult
11.
J Dent Res ; 98(11): 1239-1244, 2019 10.
Article in English | MEDLINE | ID: mdl-31425664

ABSTRACT

Dentin hypersensitivity commonly occurs due to opened dentinal tubules for many reasons. In our previous study, copine 7 (CPNE7) could induce dentin formation for an indirect pulp-capping model in vivo. This study aims to investigate the formation of tertiary dentin when CPNE7 is applied to intentionally exposed dentin with nothing over it in vivo, whether it affects microleakage of the teeth, and the penetration ability of CPNE7 molecules through dentinal tubules in vitro. Cervical dentin areas of 6 maxillary incisors of 5 beagles were exposed to a class V-like lesion, and 1 side of 3 maxillary incisors was adapted with recombinant CPNE7 protein for 5 min as the experimental group. The other side was the control group, and there was no treatment of ethylenediaminetetraacetic acid (EDTA) and CPNE7 after preparation. The defects were exposed without any restorations, and all beagles were sacrificed after 4 wk. The fluid penetration of exposed dentin areas was investigated by a microleakage-testing device and confocal laser scanning microscope. Tertiary dentin formation was confirmed with histological scanning electronic microscopic analysis. Tertiary dentin formation reduces dentinal fluid flow due to occluded tubules or discontinuity with primary or secondary dentin. The in vivo hypersensitivity model with the anterior teeth of beagle dogs showed newly formed tertiary dentin at the dentin-pulp boundary in recombinant CPNE7-treated teeth when compared with the untreated control group in histologic analysis. Scanning electronic microscopic analysis revealed occluded sites with mineral deposition of intratubular dentin. In the permeability test, the mean microleakage value of the CPNE7-treated group was significantly lower than that of the control group (P < 0.05). The tubular penetration of rhodamine B-combined CPNE7 was confirmed under confocal laser scanning microscope. CPNE7 induces formation of tertiary dentin through shallowly exposed dentinal tubules, which decreases dentin permeability.


Subject(s)
Dentin Sensitivity/therapy , Dentin, Secondary , Membrane Proteins/therapeutic use , Animals , Dental Pulp Capping , Dogs , Microscopy, Electron, Scanning
13.
Lancet Psychiatry ; 5(10): 797-807, 2018 10.
Article in English | MEDLINE | ID: mdl-30115598

ABSTRACT

BACKGROUND: No established treatment algorithm exists for patients with schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown. METHODS: This three-phase study was done in 27 centres, consisting of general hospitals and psychiatric specialty clinics, in 14 European countries and Israel. Patients aged 18-40 years who met criteria of the DSM-IV for schizophrenia, schizophreniform disorder, or schizoaffective disorder were treated for 4 weeks with up to 800 mg/day amisulpride orally in an open-label design (phase 1). Patients who did not meet symptomatic remission criteria at 4 weeks were randomly assigned to continue amisulpride or switch to olanzapine (≤20 mg/day) during a 6-week double-blind phase, with patients and staff masked to treatment allocation (phase 2). Randomisation was done online by a randomisation website; the application implemented stratification by site and sex, and applied the minimisation method for randomisation. Patients who were not in remission at 10 weeks were given clozapine (≤900 mg/day) for an additional 12 weeks in an open-label design (phase 3). The primary outcome was the number of patients who achieved symptomatic remission at the final visits of phases 1, 2, and 3, measured by intention-to-treat analysis. Data were analysed with a generalised linear mixed model, with a logistic link and binomial error distribution. This trial is registered with ClinicalTrials.gov, number NCT01248195, and closed to accrual. FINDINGS: Between May 26, 2011, and May 15, 2016, we recruited 481 participants who signed informed consent. Of the 446 patients in the intention-to-treat sample, 371 (83%) completed open-label amisulpride treatment, and 250 (56%) achieved remission after phase 1. 93 patients who were not in remission continued to the 6-week double-blind switching trial, with 72 (77%) patients completing the trial (39 on olanzapine and 33 on amisulpride); 15 (45%) patients on amisulpride versus 17 (44%) on olanzapine achieved remission (p=0·87). Of the 40 patients who were not in remission after 10 weeks of treatment, 28 (70%) started on clozapine; 18 (64%) patients completed the 12-week treatment, and five (28%) achieved remission. The number of serious adverse events did not differ between the treatment arms in phase 2: one patient on olanzapine was admitted to hospital because of an epileptic seizure, and one patient on amisulpride was admitted to hospital twice because of exacerbations of psychotic symptoms. Over the course of the trial, two serious suicide attempts were reported. INTERPRETATION: For most patients in the early stages of schizophrenia, symptomatic remission can be achieved using a simple treatment algorithm comprising the sequential administration of amisulpride and clozapine. Since switching to olanzapine did not improve outcome, clozapine should be used after patients fail a single antipsychotic trial-not until two antipsychotics have been tried, as is the current recommendation. FUNDING: European Commission Seventh Framework Program.


Subject(s)
Amisulpride/therapeutic use , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Olanzapine/therapeutic use , Schizophrenia/drug therapy , Adolescent , Adult , Antipsychotic Agents/adverse effects , Europe , Female , Humans , Male , Treatment Outcome , Young Adult
14.
Schizophr Bull ; 33(3): 682-7, 2007 May.
Article in English | MEDLINE | ID: mdl-16973786

ABSTRACT

There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis. A randomized controlled trial compared cognitive therapy (CT) over 6 months with monthly monitoring in 58 patients meeting criteria for ultrahigh risk of developing a first episode of psychosis. Participants were followed up over a 3-year period. Logistic regression demonstrated that CT significantly reduced likelihood of being prescribed antipsychotic medication over a 3-year period, but it did not affect transition to psychosis defined using the Positive and Negative Syndrome Scale (PANSS) or probable Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis. However, exploratory analyses revealed that CT significantly reduced the likelihood of making progression to psychosis as defined on the PANSS over 3 years after controlling for baseline cognitive factors. Follow-up rate at 3 years was 47%. There appear to be enduring benefits of CT over the long term, suggesting that it is an efficacious intervention for people at high risk of developing psychosis.


Subject(s)
Cognitive Behavioral Therapy , Psychotic Disorders/prevention & control , Schizophrenia/prevention & control , Schizophrenic Psychology , Schizotypal Personality Disorder/therapy , Adolescent , Adult , Antipsychotic Agents/therapeutic use , Diagnostic and Statistical Manual of Mental Disorders , Early Diagnosis , England , Female , Follow-Up Studies , Humans , Likelihood Functions , Male , Outcome Assessment, Health Care , Psychiatric Status Rating Scales , Psychotic Disorders/diagnosis , Psychotic Disorders/psychology , Regression Analysis , Risk , Schizophrenia/diagnosis , Schizotypal Personality Disorder/diagnosis , Schizotypal Personality Disorder/psychology , Single-Blind Method
15.
Arch Gen Psychiatry ; 63(10): 1079-87, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17015810

ABSTRACT

CONTEXT: Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. OBJECTIVE: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. DESIGN: A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. SETTING: Fourteen community psychiatric services in the English National Health Service. PARTICIPANTS: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. INTERVENTIONS: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. MAIN OUTCOME MEASURES: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. RESULTS: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. CONCLUSIONS: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.


Subject(s)
Antipsychotic Agents/therapeutic use , Quality of Life , Schizophrenia/drug therapy , Adolescent , Adult , Antipsychotic Agents/adverse effects , Antipsychotic Agents/classification , Cost-Benefit Analysis , England , Female , Follow-Up Studies , Health Care Costs , Humans , Male , Middle Aged , Patient Satisfaction , Practice Patterns, Physicians'/statistics & numerical data , Psychiatric Status Rating Scales , Treatment Outcome
16.
Schizophr Bull ; 32(4): 715-23, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16540702

ABSTRACT

There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.


Subject(s)
Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Schizophrenia/drug therapy , Adolescent , Adult , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Depressive Disorder/diagnosis , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Drug Resistance , Female , Follow-Up Studies , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Quality of Life/psychology , Schizophrenia/diagnosis , Schizophrenic Psychology
17.
J Dent Res ; 95(8): 906-12, 2016 07.
Article in English | MEDLINE | ID: mdl-27013639

ABSTRACT

If there is a partial loss of dentin, the exposed dentinal surface should be protected by an indirect pulp capping (IPC) procedure to preserve pulp vitality and prevent symptoms of dentin hypersensitivity. In our previous study, copine7 (CPNE7) induced odontoblast differentiation in vitro and promoted dentin formation in vivo. The aim of this study was to investigate the possibility of IPC therapy using the CPNE7 protein at the exposed dentinal surface and the resulting effects on tertiary dentin formation in a beagle model. CPNE7 promoted mineralization of odontoblasts and had high calcium ion-binding capacity. The in vivo IPC model with canine teeth showed that regeneration of physiologic reactionary dentin with dentinal tubule structures was clearly observed beneath the remaining dentin in the CPNE7 group, whereas irregular features of reparative dentin were generated in the mineral trioxide aggregate (MTA) group. The CPNE7+MTA group also showed typical reactionary dentin without reparative dentin, showing synergistic effects of CPNE7 with MTA. A scanning electron microscopy analysis showed that dentinal tubules beneath the original dentin were occluded by the deposition of peritubular dentin in the CPNE7 and CPNE7+MTA groups, whereas those in the control group were opened. Therefore, CPNE7 may be able to serve as a novel IPC material and improve symptoms of dentin hypersensitivity.


Subject(s)
Dental Pulp Capping/methods , Dentin/growth & development , Membrane Proteins/therapeutic use , Animals , Blotting, Western , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Dentin/drug effects , Dogs , Humans , Odontoblasts/drug effects , Odontoblasts/physiology , Real-Time Polymerase Chain Reaction
18.
PLoS One ; 11(6): e0157199, 2016.
Article in English | MEDLINE | ID: mdl-27249413

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pone.0144623.].

19.
PLoS One ; 11(5): e0156120, 2016.
Article in English | MEDLINE | ID: mdl-27191956

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pone.0144623.].

20.
J Clin Psychiatry ; 77(3): e283-9, 2016 03.
Article in English | MEDLINE | ID: mdl-26890690

ABSTRACT

OBJECTIVE: Male gender and young age at onset of schizophrenia are traditionally associated with poor treatment outcome and often used to determine prognosis. However, many studies use nonincident samples and fail to adjust for symptom severity at onset. We hypothesized that age and gender would influence severity of presentation but would not predict outcome after adjustment for symptoms at presentation. METHOD: 628 people with first-episode ICD-9 and DSM-IV nonaffective psychosis from 2 historical cohorts recruited from sequential presentations in Canada and the United Kingdom (1996-1998) were assessed prospectively at presentation and over 12-18 months using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Models of the age-at-onset distributions with 2 underlying modes at similar ages in women (ages 23 years and 47 years) and men (ages 22 years and 46 years) had relatively good fits compared to single-mode models (χ(2)1 better by 9.2 for females, 8.0 for males, both P < .05). At presentation, scores for negative symptoms were 1.84 points worse for males (95% CI, 1.05 to 2.58; P < .001) in a mixed effects model. Younger age also predicted higher negative scores at presentation (partial correlation r = -0.18, P < .01; P < .001 in the mixed effects model). Findings were similar for cognitive-disorganized symptoms. However, after controlling for baseline symptoms, age at onset and gender did not significantly predict subsequent symptom course in the mixed effects models. CONCLUSIONS: Gender and age at onset are independently associated with symptoms at presentation but not with medium-term course of schizophrenia. This finding reinforces the importance of early identification and prevention of severe negative symptoms at first episode, whatever an individual's age and gender.


Subject(s)
Schizophrenia/diagnosis , Adolescent , Adult , Age Factors , Age of Onset , Aged , Aging/psychology , Canada/epidemiology , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Models, Psychological , Prognosis , Schizophrenia/epidemiology , Sex Characteristics , Sex Factors , United Kingdom/epidemiology , Young Adult
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