George Garibaldi - Academia.edu (original) (raw)
Papers by George Garibaldi
PubMed, Mar 1, 1986
After a brief review of the recent literature and the description of the clinical and echocardiog... more After a brief review of the recent literature and the description of the clinical and echocardiographic follow-up of 9 cases observed from 1976 to 1985, the authors stress the relative importance to recognize patients who do not fulfill the classic criteria for the diagnosis of Kawasaki disease, in order to treat with antiaggregants those affected by coronary aneurysms. Moreover they discuss the beneficial effects of steroids, in association with salicylates, given only in the first two weeks of disease when the production and deposit of immunocomplexes and the release of lysosomal enzymes from macrophage cells occur. Finally the authors point out that the treatment with low doses of salicylates selectively acting on thromboxane A2 and not on Pgl2, as shown in experimental studies, remains to be confirmed by clinical trials.
Journal of Geriatric Psychiatry and Neurology, Mar 24, 2015
Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical... more Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical trial setting due to practical and conceptual barriers. Principal challenges include a paucity of data regarding apathy in these disorders, an absence of established diagnostic criteria, the presence of confounding factors (eg, coexisting depression), use of concomitant medications, and an absence of a gold-standard apathy assessment scale. Based on a literature search and ongoing collaboration among the authors, we present recommendations for the design of future clinical trials of apathy, suggesting Alzheimer disease and Parkinson disease as models with relevance across a wider array of neuropsychiatric disorders. Recommendations address clarification of the targeted study population (apathy diagnosis and severity at baseline), confounding factors (mood/cognition, behavior, and treatment), outcome measures, study duration, use of comparators and considerations around environment, and the role of the caregiver and patient assent. This review contributes to the search for an optimal approach to study treatment of apathy in neuropsychiatric disorders.
Value in Health, Nov 1, 2011
La Pediatria medica e chirurgica : Medical and surgical pediatrics
The number of cases of Kawasaki disease increases in Japan. The aetiology is still unknown but ep... more The number of cases of Kawasaki disease increases in Japan. The aetiology is still unknown but epidemiological studies suggest an infectious aetiology in spite that no specific microorganism has been implicated; it must be, probably present a hereditary predisposition connected with HLA subtypes. Many investigators reported an increase in the antibody level against several agents, among which bacteria and virus. Recently they found that aberrant regulation of T- and B-cells functions was associated with initiation of such antibody production, that in the majority of cases is self-limiting. The effectiveness of high- and low-doses of salicylates, given always associated with steroids, only up to fifteen days of illness, and Intravenous Gamma Globulin (IVGG), is also discussed.
European Neuropsychopharmacology, 2012
European Neuropsychopharmacology, Oct 1, 2012
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, Jan 5, 2015
Varying definitions of apathy in the published literature and a lack of a consensus regarding dia... more Varying definitions of apathy in the published literature and a lack of a consensus regarding diagnostic criteria make the identification and quantification of apathy difficult in both clinical trials and clinical practice. The Apathy Evaluation Scale was developed specifically to assess apathy, but variations in the threshold values defined for clinically significant apathy diminish its use as a screening tool in clinical trials, although it has demonstrated sensitivity to changes in treatment in a number of studies. The Neuropsychiatric Inventory contains an Apathy subscale, which has been used to identify clinical trial populations (with a consistent threshold value) and measure changes following treatment. Few of the other assessment tools currently used in patients with neuropsychiatric disorders are specific for apathy or explore it in any depth, most have not been validated in the general population, do not have cut-off points representing clinically significant apathy, and i...
Value in Health, 2013
outcomes. METHODS: Nine clinicians and 43 patients with linear surgical scars participated in a p... more outcomes. METHODS: Nine clinicians and 43 patients with linear surgical scars participated in a photograph sorting exercise. Patients sorted approximately 50 scar photographs consistent with their own skin type (light, medium or dark skin), while clinicians sorted all three sets of photographs (n=151 photographs). All participants arranged the photographs into 5 categories of perceived scar severity (least to most severe) and 5 photographs were considered for inclusion in the photonumeric guide based on analysis of inter-rater reliability, response consistency, redundancy, and variability. When photographs yielded similar results, clinical judgment was used to select the best photo. Instruction and response anchors were developed for the 5 scar photographs and the final guide was cognitively debriefed for relevance, comprehensibility, and acceptability in 24 additional scar patients. RESULTS: Based on the pre-specified criteria for inclusion and exclusion, 5 light skin and 5 dark skin photographs were included in the final photonumeric guide. A "medium" guide was not developed because of significant overlap between it and the light skin guide rendering it superfluous. Inter-rater reliability of the 52 subject cohort was strong (0.95-0.96) across all skin types. The 5 photographs included in the photonumeric guide demonstrated goodness-of-fit (infit mean-square < 1.4 and > 0.6), low variance in severity ratings (SD < one category change), and strong agreement between patients and clinicians. CONCLUSIONS: The Patient and Clinician Reported Scar Severity Scales were systematically developed to easily assess scar severity outcomes in clinical trials. Continued psychometric evaluation of the guide is planned to ensure the scales meet regulatory standards for labeling purposes.
Current Medical Research and Opinion, 2009
Introduction: The primary objective of the study was to evaluate the measurement properties of th... more Introduction: The primary objective of the study was to evaluate the measurement properties of the patient-reported four-item Psoriasis Symptom Scale (PSS). Methods: Analysis of phase III data on the efficacy of risankizumab to assess psychometric characteristics of the PSS in patients with moderate-to-severe psoriasis. Results: PSS items had good range of symptom severity coverage. The PSS had good test-retest reliability (ICCs > 0.90). Convergent and discriminant validity was indicated by moderate-tostrong correlations between the PSS and Dermatology Life Quality Index (DLQI), PSS pain item and EQ-5D pain/discomfort item at week 12 (0.63), and moderate negative correlation with EQ-Visual Analog Scale score at week 12 (-0.37). Known groups validity demonstrated as mean PSS total scores varied by Psoriasis Area and Severity Index (PASI) and Static Physician's Global Assessment (sPGA) defined groups (p < 0.0001). PSS total scores were responsive to changes in PASI score (p < 0.0001) and sPGA (p < 0.0001). PSS minimal, clinical, and meaningful change is estimated to be 1 to 2 points; a preliminary responder definition is a total change score of 3 to 4 points. Conclusions: The PSS is a short, valid unidimensional measure of psoriasis symptom severity, well suited for use in clinical trials.
Biological psychiatry, Jul 15, 2016
There is currently no standard of care for treatment of negative symptoms of schizophrenia, altho... more There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 m...
The Lancet Psychiatry, 2016
Background Many patients with schizophrenia require high doses of medication for their ongoing ps... more Background Many patients with schizophrenia require high doses of medication for their ongoing psychotic symptoms. Glutamate theories and fi ndings from studies showing effi cacy of sarcosine, an endogenous, non-selective glycine-reuptake inhibitor mediated by GlyT1, off er an alternative approach. We undertook the SearchLyte trial programme to examine the effi cacy of bitopertin, a selective GlyT1-mediated glycine-reuptake inhibitor, as an adjunctive treatment to ongoing antipsychotic treatment. Methods SearchLyte consisted of three phase 3, randomised, double-blind, parallel-group, placebo-controlled, multicentre studies done in outpatient clinics in Asia, Europe, and North and South America (TwiLyte done at 109 sites, NightLyte at 84, and MoonLyte at 87). Participants were male and female outpatients, aged at least 18 years, meeting DSM-IV criteria for schizophrenia with suboptimally controlled positive symptoms despite treatment with antipsychotics. Inclusion criteria included a Positive and Negative Syndrome Scale (PANSS) total score of at least 70 and antipsychotic treatment stability for the past 12 weeks before randomisation. Key exclusion criteria included meeting criteria for symptomatic remission or previous treatment with a GlyT1 inhibitor or any other investigational drug. After a screening or 4-week prospective stabilisation period, we randomly assigned participants (1:1:1) to a 12-week, double-blind treatment of either placebo or one of two fi xed doses of oral, once-daily bitopertin (10 or 20 mg in TwiLyte and NightLyte; 5 or 10 mg in MoonLyte) added to their current antipsychotic medicine. After completion of 12 weeks' treatment, the study design allowed for additional double-blind treatment for 40 weeks to assess maintenance of the eff ect, followed by a randomised 4-week washout period to assess withdrawal eff ects. Subsequently, all patients were off ered the opportunity to receive bitopertin treatment in a 3-year follow-up. The primary effi cacy endpoint was the mean change from baseline in the PANSS Positive Symptom Factor Score (PSFS) at week 12, analysed in the modifi ed intention-to-treat population. The trials were registered at ClinicalTrials.gov (numbers NCT01235520 [TwiLyte], NCT01235585 [MoonLyte], and NCT01235559 [NightLyte]).
Neurobiology of Aging, 2016
Alzheimer's & Dementia, 2015
Alzheimer's & Dementia, 2015
Alzheimer's & Dementia, 2015
Schizophrenia Research, 2014
Schizophrenia Research, 2008
Schizophrenia Research, 2014
PubMed, Mar 1, 1986
After a brief review of the recent literature and the description of the clinical and echocardiog... more After a brief review of the recent literature and the description of the clinical and echocardiographic follow-up of 9 cases observed from 1976 to 1985, the authors stress the relative importance to recognize patients who do not fulfill the classic criteria for the diagnosis of Kawasaki disease, in order to treat with antiaggregants those affected by coronary aneurysms. Moreover they discuss the beneficial effects of steroids, in association with salicylates, given only in the first two weeks of disease when the production and deposit of immunocomplexes and the release of lysosomal enzymes from macrophage cells occur. Finally the authors point out that the treatment with low doses of salicylates selectively acting on thromboxane A2 and not on Pgl2, as shown in experimental studies, remains to be confirmed by clinical trials.
Journal of Geriatric Psychiatry and Neurology, Mar 24, 2015
Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical... more Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical trial setting due to practical and conceptual barriers. Principal challenges include a paucity of data regarding apathy in these disorders, an absence of established diagnostic criteria, the presence of confounding factors (eg, coexisting depression), use of concomitant medications, and an absence of a gold-standard apathy assessment scale. Based on a literature search and ongoing collaboration among the authors, we present recommendations for the design of future clinical trials of apathy, suggesting Alzheimer disease and Parkinson disease as models with relevance across a wider array of neuropsychiatric disorders. Recommendations address clarification of the targeted study population (apathy diagnosis and severity at baseline), confounding factors (mood/cognition, behavior, and treatment), outcome measures, study duration, use of comparators and considerations around environment, and the role of the caregiver and patient assent. This review contributes to the search for an optimal approach to study treatment of apathy in neuropsychiatric disorders.
Value in Health, Nov 1, 2011
La Pediatria medica e chirurgica : Medical and surgical pediatrics
The number of cases of Kawasaki disease increases in Japan. The aetiology is still unknown but ep... more The number of cases of Kawasaki disease increases in Japan. The aetiology is still unknown but epidemiological studies suggest an infectious aetiology in spite that no specific microorganism has been implicated; it must be, probably present a hereditary predisposition connected with HLA subtypes. Many investigators reported an increase in the antibody level against several agents, among which bacteria and virus. Recently they found that aberrant regulation of T- and B-cells functions was associated with initiation of such antibody production, that in the majority of cases is self-limiting. The effectiveness of high- and low-doses of salicylates, given always associated with steroids, only up to fifteen days of illness, and Intravenous Gamma Globulin (IVGG), is also discussed.
European Neuropsychopharmacology, 2012
European Neuropsychopharmacology, Oct 1, 2012
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, Jan 5, 2015
Varying definitions of apathy in the published literature and a lack of a consensus regarding dia... more Varying definitions of apathy in the published literature and a lack of a consensus regarding diagnostic criteria make the identification and quantification of apathy difficult in both clinical trials and clinical practice. The Apathy Evaluation Scale was developed specifically to assess apathy, but variations in the threshold values defined for clinically significant apathy diminish its use as a screening tool in clinical trials, although it has demonstrated sensitivity to changes in treatment in a number of studies. The Neuropsychiatric Inventory contains an Apathy subscale, which has been used to identify clinical trial populations (with a consistent threshold value) and measure changes following treatment. Few of the other assessment tools currently used in patients with neuropsychiatric disorders are specific for apathy or explore it in any depth, most have not been validated in the general population, do not have cut-off points representing clinically significant apathy, and i...
Value in Health, 2013
outcomes. METHODS: Nine clinicians and 43 patients with linear surgical scars participated in a p... more outcomes. METHODS: Nine clinicians and 43 patients with linear surgical scars participated in a photograph sorting exercise. Patients sorted approximately 50 scar photographs consistent with their own skin type (light, medium or dark skin), while clinicians sorted all three sets of photographs (n=151 photographs). All participants arranged the photographs into 5 categories of perceived scar severity (least to most severe) and 5 photographs were considered for inclusion in the photonumeric guide based on analysis of inter-rater reliability, response consistency, redundancy, and variability. When photographs yielded similar results, clinical judgment was used to select the best photo. Instruction and response anchors were developed for the 5 scar photographs and the final guide was cognitively debriefed for relevance, comprehensibility, and acceptability in 24 additional scar patients. RESULTS: Based on the pre-specified criteria for inclusion and exclusion, 5 light skin and 5 dark skin photographs were included in the final photonumeric guide. A "medium" guide was not developed because of significant overlap between it and the light skin guide rendering it superfluous. Inter-rater reliability of the 52 subject cohort was strong (0.95-0.96) across all skin types. The 5 photographs included in the photonumeric guide demonstrated goodness-of-fit (infit mean-square < 1.4 and > 0.6), low variance in severity ratings (SD < one category change), and strong agreement between patients and clinicians. CONCLUSIONS: The Patient and Clinician Reported Scar Severity Scales were systematically developed to easily assess scar severity outcomes in clinical trials. Continued psychometric evaluation of the guide is planned to ensure the scales meet regulatory standards for labeling purposes.
Current Medical Research and Opinion, 2009
Introduction: The primary objective of the study was to evaluate the measurement properties of th... more Introduction: The primary objective of the study was to evaluate the measurement properties of the patient-reported four-item Psoriasis Symptom Scale (PSS). Methods: Analysis of phase III data on the efficacy of risankizumab to assess psychometric characteristics of the PSS in patients with moderate-to-severe psoriasis. Results: PSS items had good range of symptom severity coverage. The PSS had good test-retest reliability (ICCs > 0.90). Convergent and discriminant validity was indicated by moderate-tostrong correlations between the PSS and Dermatology Life Quality Index (DLQI), PSS pain item and EQ-5D pain/discomfort item at week 12 (0.63), and moderate negative correlation with EQ-Visual Analog Scale score at week 12 (-0.37). Known groups validity demonstrated as mean PSS total scores varied by Psoriasis Area and Severity Index (PASI) and Static Physician's Global Assessment (sPGA) defined groups (p < 0.0001). PSS total scores were responsive to changes in PASI score (p < 0.0001) and sPGA (p < 0.0001). PSS minimal, clinical, and meaningful change is estimated to be 1 to 2 points; a preliminary responder definition is a total change score of 3 to 4 points. Conclusions: The PSS is a short, valid unidimensional measure of psoriasis symptom severity, well suited for use in clinical trials.
Biological psychiatry, Jul 15, 2016
There is currently no standard of care for treatment of negative symptoms of schizophrenia, altho... more There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 m...
The Lancet Psychiatry, 2016
Background Many patients with schizophrenia require high doses of medication for their ongoing ps... more Background Many patients with schizophrenia require high doses of medication for their ongoing psychotic symptoms. Glutamate theories and fi ndings from studies showing effi cacy of sarcosine, an endogenous, non-selective glycine-reuptake inhibitor mediated by GlyT1, off er an alternative approach. We undertook the SearchLyte trial programme to examine the effi cacy of bitopertin, a selective GlyT1-mediated glycine-reuptake inhibitor, as an adjunctive treatment to ongoing antipsychotic treatment. Methods SearchLyte consisted of three phase 3, randomised, double-blind, parallel-group, placebo-controlled, multicentre studies done in outpatient clinics in Asia, Europe, and North and South America (TwiLyte done at 109 sites, NightLyte at 84, and MoonLyte at 87). Participants were male and female outpatients, aged at least 18 years, meeting DSM-IV criteria for schizophrenia with suboptimally controlled positive symptoms despite treatment with antipsychotics. Inclusion criteria included a Positive and Negative Syndrome Scale (PANSS) total score of at least 70 and antipsychotic treatment stability for the past 12 weeks before randomisation. Key exclusion criteria included meeting criteria for symptomatic remission or previous treatment with a GlyT1 inhibitor or any other investigational drug. After a screening or 4-week prospective stabilisation period, we randomly assigned participants (1:1:1) to a 12-week, double-blind treatment of either placebo or one of two fi xed doses of oral, once-daily bitopertin (10 or 20 mg in TwiLyte and NightLyte; 5 or 10 mg in MoonLyte) added to their current antipsychotic medicine. After completion of 12 weeks' treatment, the study design allowed for additional double-blind treatment for 40 weeks to assess maintenance of the eff ect, followed by a randomised 4-week washout period to assess withdrawal eff ects. Subsequently, all patients were off ered the opportunity to receive bitopertin treatment in a 3-year follow-up. The primary effi cacy endpoint was the mean change from baseline in the PANSS Positive Symptom Factor Score (PSFS) at week 12, analysed in the modifi ed intention-to-treat population. The trials were registered at ClinicalTrials.gov (numbers NCT01235520 [TwiLyte], NCT01235585 [MoonLyte], and NCT01235559 [NightLyte]).
Neurobiology of Aging, 2016
Alzheimer's & Dementia, 2015
Alzheimer's & Dementia, 2015
Alzheimer's & Dementia, 2015
Schizophrenia Research, 2014
Schizophrenia Research, 2008
Schizophrenia Research, 2014