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1.
Neurología (Barc., Ed. impr.) ; 38(4): 246-255, May. 2023. tab, graf
Article in Spanish | IBECS | ID: ibc-219233

ABSTRACT

Introducción: El envejecimiento poblacional implica un desafío para los países respecto a prevenir y detectar trastornos neurodegenerativos. El Montreal Cognitive Assessment (MoCA), test de cribado breve, de simple aplicación, válido y confiable, evalúa el estado cognitivo general, siendo útil en contextos de salud pública. El estudio busca normalizar y estandarizar el test MoCA para población chilena. Método: Se presenta estudio de validación para prueba diagnóstica de tipo descriptivo y correlacional, se evaluó a 526 sujetos, hombres y mujeres, de entre 18 y 90 años, sanos, del norte, centro y sur de Chile, analizando: el efecto de la edad, nivel educativo y sexo, para rendimiento de MoCA. Resultados: Se demuestra un efecto significativo de la edad y el nivel educativo sobre el rendimiento cognitivo general según MoCA. La edad, educación y sexo explican 1-7% de la varianza. El rendimiento cognitivo medio del total de la muestra fue de 24,04 ± 3,22, para un rango definido originalmente por el instrumento de 26 puntos sobre 30. Los adultos mayores con menor educación formal presentaron bajos resultados y menor rendimiento cognitivo. Se propone protocolo de evaluación de resultados en percentiles y puntuaciones por rango de edad y puntuación escalar normalizada individual. Discusión: Se presentan datos normativos de MoCA según las características sociodemográficas chilenas y puntos de corte propuestos para discriminar el rendimiento cognitivo normal de trastornos neurocognitivos según rangos de edad, ajustando los resultados al nivel educacional, la propuesta permitiría facilitar el uso del instrumento y disminuir la aparición de falsos positivos.(AU)


Introduction: Population ageing poses a challenge for countries in preventing and detecting neurodegenerative disorders. The Montreal Cognitive Assessment (MoCA), a short, simple, valid, and reliable screening test, assesses general cognitive status, and is useful in public health contexts. This study aims to normalise and standardise the MoCA test for the Chilean population. Method: We performed a descriptive, correlational validation study of the MoCA test, using a sample including 526 healthy individuals of both sexes, aged between 18 and 90 years, from the north, centre, and south of Chile. We analysed the effects of age, education level, and sex on MoCA performance. Results: Age and education level had a significant impact on general cognitive performance, as determined by MoCA score. Age, education, and sex account for 1-7% of variance. The mean (standard deviation) score for the total sample was 24.04 (3.22), whereas the normal range originally defined for the instrument is 26-30 points. Older adults with less formal education presented poorer results and lower cognitive performance. We propose a protocol for evaluating results by percentiles and scores for different age ranges, and an individual normalised scalar score. Discussion: We present normative data for the MoCA test in the Chilean population, and propose cut-off points for different age ranges to discriminate normal cognitive performance from neurocognitive disorders; results are adjusted for education level. This proposal would assist in the use of the test and reduce the rate of false positives.(AU)


Subject(s)
Humans , Female , Pregnancy , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Mass Screening , Diagnostic Tests, Routine , Educational Status , Neurodegenerative Diseases , Chile , Neuropsychological Tests
2.
Neurologia (Engl Ed) ; 38(4): 246-255, 2023 May.
Article in English | MEDLINE | ID: mdl-35668009

ABSTRACT

INTRODUCTION: Population ageing poses a challenge for countries in preventing and detecting neurodegenerative disorders. The Montreal Cognitive Assessment (MoCA), a short, simple, valid, and reliable screening test, assesses general cognitive status, and is useful in public health contexts. This study aims to normalise and standardise the MoCA test for the Chilean population. METHOD: We performed a descriptive, correlational validation study of the MoCA test, using a sample including 526 healthy individuals of both sexes, aged between 18 and 90 years, from the north, centre, and south of Chile. We analysed the effects of age, education level, and sex on MoCA performance. RESULTS: Age and education level had a significant impact on general cognitive performance, as determined by MoCA score. Age, education, and sex account for 1%-7% of variance. The mean (standard deviation) score for the total sample was 24.04 (3.22), whereas the normal range originally defined for the instrument is 26-30 points. Older adults with less formal education presented poorer results and lower cognitive performance. We propose a protocol for evaluating results by percentiles and scores for different age ranges, and an individual normalised scalar score. DISCUSSION: We present normative data for the MoCA test in the Chilean population, and propose cut-off points for different age ranges to discriminate normal cognitive performance from neurocognitive disorders; results are adjusted for education level. This proposal would assist in the use of the test and reduce the rate of false positives.


Subject(s)
Cognitive Dysfunction , Male , Female , Humans , Aged , Adolescent , Young Adult , Adult , Middle Aged , Aged, 80 and over , Chile , Mental Status and Dementia Tests , Cognitive Dysfunction/diagnosis , Cognition , Aging
3.
Neurologia (Engl Ed) ; 2020 Nov 05.
Article in English, Spanish | MEDLINE | ID: mdl-33160725

ABSTRACT

INTRODUCTION: Population ageing poses a challenge for countries in preventing and detecting neurodegenerative disorders. The Montreal Cognitive Assessment (MoCA), a short, simple, valid, and reliable screening test, assesses general cognitive status, and is useful in public health contexts. This study aims to normalise and standardise the MoCA test for the Chilean population. METHOD: We performed a descriptive, correlational validation study of the MoCA test, using a sample including 526 healthy individuals of both sexes, aged between 18 and 90 years, from the north, centre, and south of Chile. We analysed the effects of age, education level, and sex on MoCA performance. RESULTS: Age and education level had a significant impact on general cognitive performance, as determined by MoCA score. Age, education, and sex account for 1-7% of variance. The mean (standard deviation) score for the total sample was 24.04 (3.22), whereas the normal range originally defined for the instrument is 26-30 points. Older adults with less formal education presented poorer results and lower cognitive performance. We propose a protocol for evaluating results by percentiles and scores for different age ranges, and an individual normalised scalar score. DISCUSSION: We present normative data for the MoCA test in the Chilean population, and propose cut-off points for different age ranges to discriminate normal cognitive performance from neurocognitive disorders; results are adjusted for education level. This proposal would assist in the use of the test and reduce the rate of false positives.

4.
Radiologia (Engl Ed) ; 61(4): 315-323, 2019.
Article in English, Spanish | MEDLINE | ID: mdl-30905489

ABSTRACT

BACKGROUND AND OBJECTIVES: The standard treatment for endometrial cancer is simple hysterectomy with bilateral salpingo-oophorectomy. Patients with high risk also benefit from lumbo-aortic lymphadenectomy. High risk patients include those with grades and histologic subtypes associated with poor prognosis and depth of myometrial invasion greater than 50% (M2). To determine which patients would benefit from lumbo-aortic lymphadenectomy, the depth of myometrial invasion can be assessed by intraoperative frozen section or by magnetic resonance imaging (MRI). We aimed to determine the diagnostic yield of intraoperative frozen section and MRI for detecting the presence of M2 in patients with endometrial cancer. MATERIALS AND METHODS: This cross-sectional study included women with a histologically confirmed diagnosis of endometrial cancer who underwent baseline MRI and surgical intervention in our institution between 1 January 2010 and 31 December 2017. We reviewed the MRI studies and the intraoperative frozen section reports and compared them with the information in the histopathology report. We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the two tests. We also calculated the diagnostic accuracy of each method and the percentages of underestimation and overestimation. Finally, we calculated the predictive value of MRI for the presence of M2, adjusting it for the histologic variables known to be associated with poor prognosis. RESULTS: To detect M2, MRI had 63% sensitivity, 87% specificity, 73% PPV, and 81% NPV; the diagnostic accuracy was 78.8%, with 13.12% underestimation and 8.13% overestimation of M2. Intraoperative frozen section had 69% sensitivity, 86.7% specificity, 69% PPV, and 86% NPV; the diagnostic accuracy was 81.5%, with 9.24% underestimation and 9.24% overestimation of M2. The degree of concordance between the two methods was moderate (k=0.54, p < 0.00001). CONCLUSIONS: In our experience, MRI and intraoperative frozen section have adequate diagnostic yields for determining M2, though intraoperative frozen section is slightly better. The contribution of MRI in determining the presence and the site of deep myometrial invasion, as well as the factors that can confound the diagnosis, when added to the contribution of intraoperative frozen section, means that both methods help reduce the number of unnecessary lymph node dissections and the morbidity, mortality, and health costs associated with this practice.


Subject(s)
Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/pathology , Frozen Sections , Magnetic Resonance Imaging , Myometrium/diagnostic imaging , Myometrium/pathology , Aged , Cross-Sectional Studies , Endometrial Neoplasms/surgery , Female , Humans , Intraoperative Period , Middle Aged , Neoplasm Invasiveness
5.
Drug Deliv Transl Res ; 8(1): 123-131, 2018 02.
Article in English | MEDLINE | ID: mdl-29159694

ABSTRACT

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.


Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Polyelectrolytes , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/urine , Ciprofloxacin/administration & dosage , Ciprofloxacin/chemistry , Ciprofloxacin/pharmacokinetics , Ciprofloxacin/urine , Cross-Over Studies , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Double-Blind Method , Drug Liberation , Female , Healthy Volunteers , Humans , Male , Polyelectrolytes/administration & dosage , Polyelectrolytes/chemistry , Polyelectrolytes/pharmacokinetics , Tablets , Young Adult
6.
Med. intensiva ; 30(4): [1-10], 2013. fig, tab
Article in Spanish | LILACS | ID: biblio-905898

ABSTRACT

Introducción: La circulación de membrana extracorpórea consiste en el uso de una bomba de circulación extracorpórea con intercambio gaseoso, de forma prolongada, para proveer soporte vital temporario. Brinda soporte circulatorio, oxigena y remueve dióxido de carbono sin las complicaciones que puede generar la ventilación mecánica convencional. Diseño: Descriptivo, retrospectivo, observacional. Población: Se revisaron los registros clínicos de pacientes pediátricos y neonatos con diagnóstico de patología respiratoria y cardiovascular (0-192 meses) ingresados en ECMO entre el 1 de octubre de 2008 y el 30 de septiembre de 2013. Criterios de inclusión: edad gestacional >34 semanas y >2 kg), sin coagulopatía grave ni hemorragia cerebral grados III o IV, con enfermedad cardíaca reversible, enfermedad respiratoria con hipoxemia o hipercapnia , resistentes al mayor soporte mecánico ventilatorio disponible. Resultados: Ingresaron en ECMO 16 pacientes (mediana de la edad 24 meses, 0-192), 10 niñas y 6 niños. Cuatro ingresados por causas respiratorias y 12, por causas cardiovasculares. La mortalidad por ECMO respiratorio fue del 25% (1/4), cardiovascular 75% (10/12). El PIM de ingreso en la UCIP tuvo una mediana de 3 (1-10). La mediana de estadía en ECMO fue de 7 días (rango 3-16), la de estadía en UCIP-UCIN fue de 22 días (3-120) y en el hospital, de 40 (3-300).Cuatro pacientes recibieron canulación venovenosa y los restantes 12, arteriovenosa. El índice de oxigenación medio de ingreso fue de 26 (DE ± 4); mediana de presión media de la vía aérea, 22 (rango 19-35); media de PartO2 43 (DE ± 8) y la media de PCO2 53 (DE ± 5). El índice Pa/Fi al ingreso tuvo una mediana de 42 (rango 32-74). Conclusión: El ECMO es una herramienta útil para el rescate de pacientes con falla cardíaca e insuficiencia respiratoria, pues permite sostener al paciente, evitando los efectos nocivos de la ventilación mecánica convencional (cuando no se puede mantener la estrategia de protección pulmonar) y de altas dosis de drogas vasoactivas. No obstante, el desarrollo de programas costo- efectivos de ECMO en nuestro país plantea un escenario difícil.(AU)


Introduction: Extracorporeal membrane circulation (ECMO) is the use of cardiopulmonary bypass with prolonged gas exchange to provide temporary life support. The ECMO offers circulatory support, oxygenates and removes carbon dioxide without the complications that can generate conventional mechanical ventilation. Design: Descriptive, retrospective, observational. Population: Clinical records of pediatric and neonatal patients diagnosed with respiratory and cardiovascular disease (0-192 months) admitted to ECMO from October 10, 2008 to September 30, 2013 were reviewed. Inclusion criteria: gestational age >34 weeks and >2 kg, absence of severe coagulopathy and cerebral hemorrhage grade III or IV, with reversible heart disease, respiratory disease with hypoxemia and/or hypercapnia refractory to the most ventilatory mechanical support available. Results: Sixteen children with a median age of 24 months (0-192) (10 girls and 6 boys) were admitted to ECMO. Four children were admitted due to respiratory illness and 12 for cardiovascular disease. Mortality from respiratory ECMO was 25% (1/4), cardiovascular 75% (10/12). PIM at the PICU admissions had a median of 3 (1-10). Median ECMO stay was 7 days (range 3-16), median PICU-NICU stay 22 days (3-120) and hospital stay 40 (3-300). The kind of cannulation was veno-venous (4), and arteriovenous (12). Mean oxygenation index at admission, 26 (SD ± SD 4); median average pressure of air, 22 (range 19-35); average PartO2, 43 (SD ± 8) and mean PCO2 53 (SD ± 5). Median Pa/Fi index at admission, 42 (range 32-74 ). Conclusions: The ECMO is a useful tool for the rescue of patients with heart failure and respiratory failure, avoiding the deleterious effects of conventional mechanical ventilation (when it is not possible to maintain lung protective strategy) and high doses vasoactive drug. However the development of cost-effective ECMO programs in our country poses a difficult scenario.(AU)


Subject(s)
Humans , Respiratory Insufficiency , Extracorporeal Membrane Oxygenation , Pediatrics
7.
Nanotechnology ; 20(24): 245604, 2009 Jun 17.
Article in English | MEDLINE | ID: mdl-19471076

ABSTRACT

Polymorphous silicon thin films (pm-Si) have been deposited from mixtures of dichlorosilane and hydrogen, using argon as the diluting gas by plasma-enhanced chemical vapor deposition. The deposition conditions were chosen to simultaneously obtain both Si nanocrystallites and an amorphous silicon matrix in the as-grown samples. High resolution transmission electron microscopy studies show the crystallinity of Si domains whose dimensions are in the interval of 2-14 nm. The surface passivation state of the silicon nanocrystals was inferred from Fourier transform infrared spectroscopy analysis. Two optical absorption edges, corresponding to the amorphous matrix and the Si nanocrystals, were observed for all the pm-Si thin films. Intense visible photoluminescence was observed for the as-grown samples. The possibility of using these thin films for the down-conversion effect in silicon solar cells is discussed.


Subject(s)
Crystallization/methods , Membranes, Artificial , Nanostructures/chemistry , Nanostructures/ultrastructure , Nanotechnology/methods , Silanes/chemistry , Silicon/chemistry , Gases , Hot Temperature , Macromolecular Substances/chemistry , Materials Testing , Molecular Conformation , Particle Size , Surface Properties
8.
Encephale ; 25(5): 485-7, 1999.
Article in French | MEDLINE | ID: mdl-10598313

ABSTRACT

Although almost fifteen cases have been reported since 1970, renal failure during a long term lithium therapy remains in the epidemiologic studies a rare pathology. Lithium treatment side effects can be considered in term of morphologic damages or in terms of kidney physiology impairments in filtration or concentration. For example it has long been known that lithium generates polyuria which results from an induced nephrotic diabetes insipidus (NDI). Fortunately most of these common impairments are reversible without any alarming or starting consequences. Moreover histological injures may also occur such as interstitial fibrosis, sclerotic glomeruli, tubular atrophy or dilatation ... whose evidence still raises some controversy concerning their incidence and specificity. We report here the case of a Bipolar I patient stabilized for at least fifteen years with lithium at a high level of social and professional life, in whom renal failure was found with tubular damage. This injury correlated to the lithium therapy even if always controlled at a normal rate during fifteen years, forced us to withdraw this treatment and switch to valproate. Is our goal to protect the renal function against the patient wishes totally justified since he relapsed in hypomania 63 days after the drop out? We had to choose between renal preservation and mental health.


Subject(s)
Antimanic Agents/adverse effects , Bipolar Disorder/drug therapy , Iatrogenic Disease , Lithium Carbonate/adverse effects , Renal Insufficiency/chemically induced , Renal Insufficiency/diagnosis , Adult , Bipolar Disorder/psychology , Dose-Response Relationship, Drug , Humans , Male , Treatment Outcome
9.
Acta Med Port ; 11(11): 1019-40, 1998 Nov.
Article in Portuguese | MEDLINE | ID: mdl-10021804

ABSTRACT

The guidelines for secondary stroke prevention, graded following available scientific evidence, are presented. Stroke and TIA are defined and the indications for referral established. Basic assessment of stroke patients should include laboratory evaluation, ECG, brain CT, ultrasound examination of the extracranial vessels for events in the carotid distribution, and transthoracic or transesophageal echocardiogram if cardioembolism is suspected. The pharmacological and non-pharmacological reduction of blood pressure and serum cholesterol, stopping smoking and reducing alcohol intake are general measures recommended for secondary stroke prevention, together with healthier life-style changes (eating a Mediterranean type diet and performing regular moderate physical exercise). Concerning antithrombotic therapy, oral anticoagulants are recommended for patients with atrial fibrillation and other high to medium emboligenic cardiac risk conditions. Antiplatelet drugs are recommended for all other survivors of an ischemic cerebral event. Aspirin (75-325 mg/day) is the drug of choice. Alternative antiplatelet agents are clopidrogrel, ticlopidine, dipiridamol or triflusal. They can be used in patients with intolerance or contraindication to aspirin or in high-risk subjects. Endarterectomy of the symptomatic carotid is an additional procedure recommended for patients with ischemic stroke or TIA and carotid stenosis > 80% on the side of the symptomatic cerebral hemisphere.


Subject(s)
Cerebrovascular Disorders/prevention & control , Anticoagulants/therapeutic use , Blood Pressure , Cholesterol/blood , Humans , Ischemic Attack, Transient/prevention & control , Life Style , Platelet Aggregation Inhibitors/therapeutic use
10.
Ginecol Obstet Mex ; 65: 300-4, 1997 Jul.
Article in Spanish | MEDLINE | ID: mdl-9312519

ABSTRACT

The preeclampsia-eclampsia syndrome is a vasospastic disorder and probably has a placental origin. Once the hypertensive syndrome is established the uteroplacental blood flow is reduced as well as the intervillous blood flow. Since 18-24 weeks of gestation and before the symptoms of preeclampsia become overt, changes in placental flow velocity can be detected with Doppler technics. The placental theories for the etiology of preeclampsia are focused on the hypoxic effect in the trophoblastic tissue of second trimester. The placental ischemic changes are evident and seen in the uteroplacental bed. They are interrelated with the stages of trophoblastic invasion of the spiral arteries during the 14 and 20 weeks. When the trophoblastic invasion is over, the spiral arteries become a high resistance system. The defect observed in preeclampsia is the lack of invasion of the trophoblast to the maternal arteries. The diminished placental perfusion probably creates endothelial damage. This damage has several effects: decreased prostaglandin production, activated coagulation cascade, stimulated fibrin aggregation, and increased vascular permeability. The ideal laboratory test for preeclampsia shall predict the onset of this entity. Recent findings seem promising. The fibronectin concentration increases 2-3 wks. prior to the clinical manifestation of preeclampsia. Severe hypertension shows an abnormal decrease in fibronectin levels. Hypocalciuria has been described as an early predictor in the development of preeclampsia. Other agents undergoing extensive evaluation as predictors are: uric acid, b-thromboglobin, prolactin and atrial natriuretic peptide. Recently high levels of b-HCG (human corionic gonadotrophin) have been linked to a lack of trophoblastic invasion during the second trimester, therefore this is a potential marker for those patients that will eventually develop preeclampsia.


Subject(s)
Eclampsia/etiology , Pre-Eclampsia/etiology , Adult , Calcium/urine , Capillary Permeability , Chorionic Gonadotropin/analysis , Eclampsia/diagnosis , Female , Humans , Hypertension/complications , Pre-Eclampsia/diagnosis , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, Second , Prognosis , Syndrome , Trophoblasts/metabolism , Uric Acid/analysis
12.
Ginecol Obstet Mex ; 65: 258-61, 1997 Jun.
Article in Spanish | MEDLINE | ID: mdl-9273338

ABSTRACT

Uterine arteriovenous malformation (AVMs) are fairly rare. Seventy four cases have been reported in the medical literature. The clinical presentation of this entity is quite diverse. The approach to uterine AVM requires clinical alertness and to make the diagnosis a high index of suspicion is required. Prompt treatment is often essential. This article reviews the entire literature on uterine AVM emphasizing the various clinica presentations and treatment modalities available for the gynecologist.


Subject(s)
Arteriovenous Malformations/etiology , Embolization, Therapeutic , Uterine Diseases/etiology , Adolescent , Adult , Aged , Arteriovenous Malformations/diagnosis , Arteriovenous Malformations/therapy , Female , Humans , Middle Aged , Uterus/blood supply
13.
Encephale ; 21 Spec No 3: 41-7, 1995 Jun.
Article in French | MEDLINE | ID: mdl-7628341

ABSTRACT

Clozapine has been shown to be effective in treating schizophrenic patients. In this study we compare the efficacy of clozapine in two groups of treatment resistant psychotics (among the most severe inpatients). 5 chronic schizophrenics (CS). Age 49.6 +/- 12 (paranoid, disorganized residuals). 14 "mixed" patients (MP). Age 34.6 +/- 13, between: major affective disorders (MAD) with mood incongruent psychotic features; schizo affective disorders (SAD). 19 patients (11 females -8 males) have been involved in our trial. They receive 400 up to 800 mg/day of clozapine for a minimum of 12 months and a maximum of 38 months. Treatment responders were defined on the evaluation of the following criteria: scores PANSS-CGI-MADRS (not for the first patients); number of relapses; response to socialisation (exit); quality of life. The results even if based on small sample sizes were classified as: Improvement -->reduction of all major symptoms: patient exit. CS:2/5 (40%); MP:5/14 (35%). Improvement++-->decrease of most major symptoms. CS:1/5 (20%); MP:5/14 (35%). Improvement+-->decrease of one or few major symptoms. CS:2/5 (40%); MP: 1/14 (8%). Failure-->3 from the MP subgroup (16%), 1 leucopenia, 1 worsening, 1 non responder). These finding show that affective disorders and schizoaffective patients are as likely to respond to clozapine as the schizophrenic patients: 60% of the CS and 70% of the MP were very much ( ) and much improved (++). The data also suggest that in the subtype of MP high scores of response occur with the youngest and most recently ill patients (< 30 years, < 18 months).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Clozapine/therapeutic use , Depression/drug therapy , Schizophrenia/drug therapy , Schizophrenic Psychology , Adolescent , Adult , Chronic Disease , Clozapine/adverse effects , Cohort Studies , Depression/psychology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Middle Aged , Psychiatric Status Rating Scales
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