Poor Clinical Course Research Articles

Poor clinical course in a child with myelodysplastic syndrome and del(13)(q14q22)

Myelodysplastic syndromes (MDS) are rare in children, representing 3% or less of all hematopoietic malignancies. Cytogenetic abnormalities, such as −7/7q-, +8, and +21 have been reported in 55–80% of children with MDS. Cytogenetic studies have an important impact on diagnosis, treatment selection, and monitoring therapeutic protocols when combined with morphologic data. We report on a pediatric case of MDS with the presence of the rare clonal abnormality del(13)(q14q22) which underwent a malignant transformation to leukemia and ran a very poor clinical course.

Clinical outcomes in patients with chronic congestive heart failure who undergo left ventricular assist device implantation

The use of left ventricular assist devices as a bridge to transplantation for patients with chronic congestive heart failure is well accepted. However, few studies have examined outcomes solely for these patients. This study details one center's left ventricular assist device experience with this population. Two hundred one patients received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif) from January 1, 1996, to April 30, 2004. Of these, 119 (59.2%) had chronic congestive heart failure (diagnosis >6 months) as the primary indication. Outcome parameters included early mortality after left ventricular assist device placement (<30 days), bridge-to-transplantation rate, and posttransplantation survival. Variables examined included patient demographic data; preoperative pacemaker, internal defibrillator, and balloon pump use; and preoperative laboratory values. Advanced age, female sex, and diabetes were independent predictors of early death (P = .048, odds ratio 1.879 per 10 years of age, 95% confidence interval 1.005-3.515; P = .002, odds ratio 10.029, 95% confidence interval 2.256-44.583; P = .040, odds ratio 3.974, 95% confidence interval 1.063-14.861). Advanced age, female sex, and low preoperative albumin were independent predictors of poor bridge-to-transplantation rate (P = .029, odds ratio 0.135 per 10 years of age, 95% confidence interval 0.022-0.819; P = .002, odds ratio 0.013, 95% confidence interval 0.001-0.197; P = .023, odds ratio 19.178 per 1 g/dL albumin, 95% confidence interval 1.504-244.598). There were no independent predictors of poor posttransplantation survival and prolonged intensive care unit stay. Overall bridge-to-transplantation rate was 81.5%. The 1-, 3-, 5-, and 7-year posttransplantation survivals were 88.4%, 84.5%, 78.4%, and 76.0%. Among patients with chronic congestive heart failure, advanced age, female sex, diabetes, and low preoperative albumin predict poor clinical course. Careful risk stratification and comprehensive evaluation by care providers should be performed for candidates who are female, are elderly, and have diabetes, and preoperative nutritional optimization should be encouraged to enhance patient outcomes.

Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis.

With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 (<10%) and p27 (< or =50%) and reduced membranous expression of Ecadherin were significantly associated with a poorer clinical course by univariate analysis. beta-catenin immunostaining had no prognostic impact. Mitotic and apoptotic indices as well as Ki-67 labeling below the median were indicators of poor prognosis. Complete absence of p53 nuclear staining was a significant adverse prognostic factor. By Cox regression, p53 = 0%, p53 = 0%, in combination with p27 < or = 50%, the mitotic index and the combined mitotic and apoptotic index added prognostic information to UICC stage. The authors found that growth pattern, lymphohistiocytic response, lymphatic permeation, and venous spread, too, each was a strong prognosticator in addition to UICC stage. The results support that tissue microarrays are a useful tool for screening immunohistochemical markers for prognostic use. An immunopanel of p21, p27, and p53 could be useful for prognostication in colorectal carcinoma in addition to UICC stage.

Síndrome de Ogilvie poscesárea

We present a case of postcesarean Ogilvie’s syndrome after a twin pregnancy. The patient’s poor postsurgical clinical course, together with progressive abdominal distension, prompted us to perform abdominal x-ray, revealing massive dilation of the colon. Colonoscopy confirmed the dilation and ruled out mechanical obstruction.Conservative treatment was initiated with nasogastric tube and parenteral nutrition until intestinal function returned to normal. Outcome was favorable.

Adaptive and maladaptive self-focus in depression

Background: Studies of rumination suggest that self-focused attention is maladaptive and perpetuates depression. Conversely, self-focused attention can be adaptive, facilitating self-knowledge and the development of the alternative functional interpretations of negative thoughts and feelings on which cognitive therapy of depression depends. Increasing evidence suggests there are distinct varieties of self-focus, each with distinct functional properties. This study tested the prediction that in depressed patients brief inductions of analytical versus experiential self-focus would differentially affect overgeneral autobiographical memory, a phenomenon associated with poor clinical course. It was predicted that, relative to analytical self-focus, experiential self-focus would reduce overgeneral memory. Methods: 28 depressed patients either thought analytically about, or focused on their momentary experience of, identical symptom-focused induction items from [Cogn. Emotion 7 (1993) 561] rumination task. Participants completed the Autobiographical Memory Test [J. Abnorm. Psychol. 95 (1986) 144] before and after self-focus manipulations. Results: Experiential self-focus reduced overgeneral memory compared to analytical self-focus. Analytical and experiential self-focus did not differ in their effects on mood. Limitations: In the absence of a reference condition, only conclusions concerning the relative effects of analytical and experiential self-focus can be made. Conclusions: Results (1) support the differentiation of self-focus into distinct modes of self-attention with distinct functional effects in depression; (2) provide further evidence for the modifiability of overgeneral memory; and (3) provide further evidence for the dissociation of overgeneral memory and depressed mood. Clinically, results support the usefulness of training recovered depressed patients in adaptive experiential forms of self-awareness, as in mindfulness-based cognitive therapy.

Should radiotherapy be standard therapy for brain tumors in the elderly? cons

Elderly patients with malignant gliomas present unique treatment challenges. Data are limited on the efficacy of various treatment modalities for high-grade gliomas in the elderly patient population, particularly for patients over 70 years of age, and the most appropriate treatment strategies remain a matter of debate. These patients generally have a poor clinical course and lower tolerance to therapy compared with younger patients. Standard radiotherapy (RT) may provide a survival benefit for patients with a good Karnofsky performance status (≥70); however, RT is associated with significant neurologic toxicity in elderly patients. Some argue that the apparent modest clinical benefits of RT do not outweigh the risks and inconvenience of the standard schedule. Clearly, more effective and better-tolerated treatments are needed. Chemotherapy agents with good safety profiles, such as oral temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), are being considered as alternatives to RT. When used as single-agent therapy, temozolomide induced objective responses and improved neurologic status in elderly patients with newly diagnosed, unresected glioblastoma. For patients with good performance status, treatment options should be discussed and the risks and potential benefits of RT carefully considered. Furthermore, prospective randomized studies should be performed to define the best therapeutic option for efficacy, toxicity, convenience, and quality of life.

Estimation of Serum Tumour Necrosis Factor-α and Correlation to Tumour Markers in Patients with Oral Squamous Cell Carcinoma

Objectives: Estimation of serum tumour necrosis factor-α levels and correlation with tumour markers for the prognosis of oral squamous cell carcinoma before treatment.Patients and Methods: Serum levels of tumour necrosis factor-α and 3 other tumour markers — carcinoembryonic antigen, squamous cell carcinoma antigen, and immunosuppressive acidic protein — were simultaneously measured in 38 patients with oral squamous cell carcinoma and in 36 healthy controls.Results: The mean serum concentration oftumour necrosis factor-α for patients with oral squamous cell carcinoma (14.1 ± 13.2 pg/mL) was significantly higher than that of healthy controls (5.2 ± 3.1 pg1mL) [p < 0.05]. The mean serum concentration of tumour necrosis factor-α was lower for patients who were pathological node-positive than for pathological node-negative patients. A significant correlation was observed between the serum tumour necrosis factor-α levels and pathological parameters. The mean serum concentration of tumour necrosis factor-α was also significantly higher for patients who had a good clinical course (16.7 ± 18. 6 pg1mL) than for those with a poor clinical course (9.6 ± 5.9 pg1mL) [p < 0.05]. The survival curve revealed a better prognosis for serum tumour necrosis factor-α-positive patients than for serum tumour necrosis factor-α-negative patients. A significant correlation was observed between the serum tumour necrosis factor-α levels and the tumour markers, squamous cell carcinoma antigen and immunosuppressive acidic protein (p < 0.05).Conclusion: An evaluation of serum tumour necrosis factor-α level in patients with oral squamous cell carcinoma appears to be a valuable screening tool for the prognosis and treatment of patients with this cancer.

Prognostic implications derived from ultrasonic tissue characterization with myocardial integrated backscatter in patients with dilated cardiomyopathy

Background: Various clinical parameters have been reported to predict survival in patients with dilated cardiomyopathy (DCM). Myocardial ultrasonic integrated backscatter (IB) imaging has a potential to perform in vivo tissue characterization. The present study was performed to examine whether myocardial IB analysis can predict the prognosis of DCM patients. Methods and results: We prospectively carried out echocardiographic examinations with IB analysis in 43 patients with DCM (31 males, 12 females) under the standard treatment. IB analysis was performed in the left ventricular wall and the calibrated (subtracting pericardial data) myocardial IB intensity (IBI) was obtained from the interventricular septum and the left ventricular posterior wall. After the follow-up (8–39 months), 31 followed a good clinical course, but eight had cardiac death, one had partial left ventriculectomy for uncontrolled heart failure and three were hospitalized for worsening heart failure. β-Blocker responded in 27 (87%) of the 31 with good clinical course, but it did not respond in 11 among the 12 with poor course. In these 12 DCM, left ventricular fractional shortening (LVFS) was lower (good: 18±5%, poor: 14±4, P<0.03) and calibrated IBI was higher in both the septum (good: −16.4±5.6 dB, poor: −11.1±4.2 dB, P<0.006) and the posterior wall (good: −19.5±3.6 dB, poor: −13.8±5.6 dB, P<0.004). On the Cox proportional hazard model analysis, only calibrated IBI in the septum >−17 dB, the cut-off score of calibrated IBI discriminating non-responders to β-blocker therapy in our previous report, was related to the poor outcome ( χ 2=4.43, P=0.035). The stepwise multivariate analysis revealed that both calibrated IBI in the septum>−17 dB ( χ 2=4.43, P=0.035) and LVFS<15% ( χ 2=3.89, P=0.049) were useful to predict the poor clinical outcome. The event free rate assessed by the Kaplan–Meier method was also significantly reduced in patients with calibrated IBI in the septum >−17 dB ( χ 2=6.594, P=0.01) and calibrated IBI in the posterior wall>−17 dB ( χ 2=4.215, P=0.04). However, LVFS<15% ( χ 2=3.576, not significant) did not contribute to discriminating the event free rate in the clinical course. Conclusions: The present study demonstrated that myocardial IB intensity was higher in DCM patients who followed a poor clinical course rather than in those with a good outcome. Therefore, it is clarified that myocardial ultrasonic tissue characterization in DCM patients is useful for assessing their clinical outcome after receiving not only the standard treatment but also β-blocker therapy.

Infection with Burkholderia cepacia complex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replace Burkholderia multivorans.

Infection with Burkholderia cepacia complex in patients with cystic fibrosis (CF) results in highly variable clinical outcomes. The purpose of this study was to determine if there are genomovar-specific disparities in transmission and disease severity. B. cepacia complex was recovered from 62 patients with CF on > or =1 occasions (genomovar III, 46 patients; genomovar II [B. multivorans], 19 patients; genomovar IV [B. stabilis], 1 patient; genomovar V [B. vietnamiensis], 1 patient; and an unclassified B. cepacia complex strain, 1 patient). Patient-to-patient spread was observed with B. cepacia genomovar III, but not with B. multivorans. Genomovar III strains replaced B. multivorans in 6 patients. Genomovar III strains were also associated with a poor clinical course and high mortality. Infection control practices should be designed with knowledge about B. cepacia complex genomovar status; patients infected with transmissible genomovar III strains should not be cohorted with patients infected with B. multivorans and other B. cepacia genomovars.

혈액식작용 증후군을 동반한 구인두의 T/NK세포 림프종

T/NK-cell lymphoma (TNKL) is a subtype of angiocentric T-cell lymphoma showing the characteristics of biphenotype of T-cell and NK-cell, frequent association with Epstein-Barr virus (EBV), and poor clinical course. It usually develops in nasal cavity, paranasal sinus, and nasopharynx. Hemophagocytotic syndrome is a histiocytic proliferation associated with phagocytosis of the hemopoietic elements resulting in fever, profound pancytopenia, hepatosplenomegaly, lymphadenopathy, and coagulopathy. It is considered as a negative prognostic factor for hematologic neoplasms. Epstein-Barr virus infection is considered as pathogenic factor for hemophagocytotic syndrome. We experienced a case of EBV-infected oropharyngeal lymphoma of T/NK-cell lymphoma associated with hemophagocytotic syndrome, which was confirmed by immunohistochemical study, in situ hybridization, and bone marrow biopsy. We report this case with brief review of literatures. (J Clinical Otolaryngol 2001;12:83-88)

Orthotopic liver transplantation for idiopathic portal hypertension: indications and outcome.

Idiopathic portal hypertension is a rare clinical syndrome which may be associated with a spectrum of histological lesions, including nodular regenerative hyperplasia and incomplete septal cirrhosis. Here, we report eight adult patients with idiopathic portal hypertension who experienced an unusually severe clinical evolution characterized by the development of progressive hepatic failure requiring orthotopic liver transplantation. Our aims are: (a) to stress the distinctive clinical presentation of these patients, (b) to describe their biological and histopathological features, and (c) to evaluate the results of orthotopic liver transplantation in this rare indication. Complete clinical charts and histological data were available in all patients. All patients were male. Their age at diagnosis ranged from 17 to 59 years. Complications of portal hypertension revealed the disease in all cases. Medical treatment was performed in all patients and portosystemic shunt in three. The development of progressive hepatic failure led to the indication of liver transplantation after a delay ranging from 3 to 10 years. Explanted livers showed pure nodular regenerative hyperplasia in three patients and incomplete septal cirrhosis in five. Recovery was uneventful. All patients are alive, without recurrence of the disease. This report points to the existence of severe cases of idiopathic portal hypertension occurring without underlying or associated systemic disease and characterized by a poor clinical course and requiring liver transplantation.

Lack of Correlation Between Clinical Characteristics and Serum Soluble Fas Ligand Levels in Patients with Multiple Myeloma

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow and rarely cured by chemotherapy. Villunger et al. showed that the neoplastic plasma cells express Fas ligand (FasL), which transmits a signal of apoptosis upon ligation to Fas, and suggested that the FasL suppresses the T-cells activated against malignant cells, resulting in escape from tumour immunity. We examined serum soluble FasL (sFasL) levels in 35 multiple myeloma patients to evaluate the correlation between sFasL levels and clinical characteristics. The serum sFasL levels were not affected by the disease status, serum monoclonal protein levels, or other prognostic factors. We could not determine whether the expression of FasL is involved in the poor clinical course of the disease.

Orthotopic Liver Transplantation for Idiopathic Portal Hypertension: Indications and Outcome

Background: Idiopathic portal hypertension is a rare clinical syndrome which may be associated with a spectrum of histological lesions, including nodular regenerative hyperplasia and incomplete septal cirrhosis. Here, we report eight adult patients with idiopathic portal hypertension who experienced an unusually severe clinical evolution characterized by the development of progressive hepatic failure requiring orthotopic liver transplantation. Our aims are: (a) to stress the distinctive clinical presentation of these patients, (b) to describe their biological and histopathological features, and (c) to evaluate the results of orthotopic liver transplantation in this rare indication. Methods: Complete clinical charts and histological data were available in all patients. All patients were male. Their age at diagnosis ranged from 17 to 59 years. Complications of portal hypertension revealed the disease in all cases. Medical treatment was performed in all patients and portosystemic shunt in three. Results: The development of progressive hepatic failure led to the indication of liver transplantation after a delay ranging from 3 to 10 years. Explanted livers showed pure nodular regenerative hyperplasia in three patients and incomplete septal cirrhosis in five. Recovery was uneventful. All patients are alive, without recurrence of the disease. Conclusions: This report points to the existence of severe cases of idiopathic portal hypertension occurring without underlying or associated systemic disease and characterized by a poor clinical course and requiring liver transplantation.

The prognostic significance of abnormalities seen on magnetic resonance imaging in late life depression: clinical outcome, mortality and progression to dementia at three years.

To study the course of depressive symptoms over 3 years, rate of dementia and mortality in relation to baseline neuroradiological abnormalities. Retrospective casenote analysis of 38 patients (of 44) who had a Magnetic Resonance Imaging (MRI) scan 3 years earlier. Twenty-two patients also received a detailed interview. Overall outcome was good for around two-thirds of the sample. Poorer clinical course was associated with lesions in pons and more than five Virchow Robins spaces in the corona radiata. Pontine raphe lesions and confluent periventricular lesions were associated with later dementia and with reduced survival from cardiovascular death. Males had more recurrences and a reduced survival. MRI lesions influence outcome, mortality and the onset of dementia. However, because they are quite common in elderly depressed patients they have limited utility on their own as predictors of outcome. The association of periventricular lesions with dementia is a new finding, and suggests that the site and type of lesions may be as important than the quality of them.

Energy Supplements Rich in Linoleic Acid Improve Body Weight and Essential Fatty Acid Status of Cystic Fibrosis Patients

ABSTRACTBackgroundPatients with cystic fibrosis who have steatorrhea frequently are underweight and have essential fatty acid (EFA) depletion, which is associated with a poor clinical course. It has been stated that poor EFA status is difficult to correct in patients with cystic fibrosis, and an impaired EFA metabolism with reduced synthesis of long‐chain polyunsaturated fatty acids has been proposed. In this study, the effects of an oral energy supplement rich in linoleic acid were investigated in patients with cystic fibrosis who had a body weight below 95% of normal for height.MethodsThirty‐six patients (16 girls) more than 4 years of age were randomized either to a control group (n = 20, age 13.3 ± 3.8 years, mean ± SD) receiving intensive dietary counseling only, or an intervention group (n = 16, age, 10.4 ± 4.3 years) treated for 3 months with dietary counseling plus 628 ± 254 mL (=kcal) per day of an energy supplement rich in fat (31% of energy) and linoleic acid (16% of energy).ResultsIn contrast to the control group, the patients with supplemented diets achieved significant increases of energy intake (2189 ± 731 kcal/day vs. 2733 ± 762 kcal/day), weight for height (82.8% ± 8.6% vs. 84.8% ± 9.6% of normal), and body fat (5.1 ± 1.7 kg vs. 5.8 ± 2.2 kg) as well as the initially low values of plasma phospholipid linoleic acid (11.8% ± 1.1% vs. 17.6% ± 1.6% of total phospholipid fatty acids) and its main metabolite arachidonic acid (4.4% ± 0.4% vs. 5.9% ± 0.3%).ConclusionsPatients with cystic fibrosis with low body weight and poor EFA status benefit from EFA‐rich energy supplements and can synthesize arachidonic acid from the precursor linoleic acid.

Clinical and neuropsychological profiles of obsessive-compulsive schizophrenia: a pilot study.

This pilot study compared characteristics of obsessive-compulsive (OC) schizophrenic patients and a matched non-OC schizophrenic control group. The OC-schizophrenic group required more intensive clinical interventions and had a poorer clinical course, lower levels of functioning, and longer periods of hospitalization. They showed greater negative symptoms and more impaired executive functioning. These findings suggest OC-schizophrenic patients may have an atypical set of clinical and neuropsychiatric characteristics, perhaps constituting a subgroup within the schizophrenia spectrum. Pathophysiology and possible treatment implications require further study.

Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma.

Conventional chondrosarcoma (CSA) of the skull base is an uncommon neoplasm that can resemble chordoma, and indeed it is misdiagnosed frequently as such. This has important clinical implications, because when treated with similar aggressive treatment strategies, CSA has a much better prognosis than chordoma. In an effort to identify those morphologic and immunohistochemical features that help to identify conventional skull base CSA correctly and to understand its prognosis better, particularly compared with chordoma, when treated with surgery and proton beam irradiation, the authors performed a clinicopathologic analysis of 200 CSAs. The patients ranged in age from 10 to 79 years (mean, 39 years), 87 patients were male and 113 patients were female, and most presented with symptoms related to the central nervous system. Approximately 6% of the tumors arose in the sphenoethmoid complex, 28% originated in the clivus, and 66% developed in the temperooccipital junction. Histologically, 15 tumors (7.5%) were classified as hyaline CSA, 59 (29.5%) as myxoid CSA, and 126 (63%) as mixed hyaline and myxoid CSA. A total of 101 (50.5%) tumors were grade 1, 57 (28.5%) had areas of grades 1 and 2, and 42 (21%) were pure grade 2 neoplasms. The vast majority of patients originated from referring hospitals, and the diagnosis was changed prospectively at our institution to CSA from chordoma in 74 patients (37%). Of the tumors studied immunohistochemically, 96 of 97 (98.9%) stained for S-100 protein, 0 of 97 (0%) stained for keratin, and faint staining for epithelial membrane antigen was seen in 7 of 88 tumors (7.95%). All patients underwent high-dose postoperative fractionated precision conformal radiation therapy with a dose that ranged from 64.2 to 79.6 Cobalt-Gray-equivalents (median, 72.1 Cobalt-Gray-equivalents, given in 38 fractions. The 200 patients had a median follow-up of 63 months (range, 2.1 mos - 18.5 yrs). Tumor control was defined as lack of progression by clinical and radiographic assessment. Based on this definition, there were three local recurrences, and two of these patients died of tumor-related complications. The 5- and 10-year local control rates were 99% and 98% respectively, and the 5- and 10-year disease-specific survival rates were both 99%. In contrast to CSA, the 5- and 10-year survival rates of chordoma have been reported to be approximately 51 % and 35% respectively, and in our institution intensive treatment has resulted in 5- and 10-year progression-free survival rates of 70% and 45% respectively. CSA of the skull base can be distinguished reliably from chordoma, and this distinction is important because skull base CSA has an excellent prognosis when treated with surgery and proton beam irradiation, whereas chordomas have a substantially poorer clinical course despite similar aggressive management.

Ingreso en el hospital por asma. Análisis descriptivo y factores pronósticos tras el alta

Few authors have looked at admissions in Spain of patients with acute asthma attacks. The aim of this study was to determine the clinical profile of such patients and analyze factors influencing disease course after release. Asthmatics admitted to our hospital were enrolled prospectively over 12 consecutive months. The patients were telephoned one and four months after release. Demographic and clinical data were collected in addition to data on exacerbations, readmissions, treatment and medical follow-up. Sixty-five patients (44 women and 21 men, mean age 45, SD 19). Most (54%) were admitted in autumn and the most common cause of exacerbation was respiratory tract infection (68%). Before admission, 54% had severe asthma, 32% had moderate asthma and 14% had mild asthma. At least one exacerbation occurred for 54% of patients, while 38% required emergency assistance and 19% were readmitted. Two patients (3%) died of asthma. Multiple factor logistic regression analysis showed a relation between the appearance of exacerbation after release and greater severity of asthma and the absence of long-lasting (beta-adrenergic drugs. Readmission was related to shorter duration of treatment with oral glucocorticoids after release and a higher number of prior hospital admissions. 1) Admission due to asthma occurs mainly in autumn and is probably related to respiratory infections, rather than exclusively to severe asthma. 2) After release, short-term morbidity and mortality due to the disease are high. 3) Disease severity itself and inadequate treatment are both related to poor clinical course after release.

Familial occurrence of nodular regenerative hyperplasia of the liver: a report on three families

BACKGROUND/AIMSNodular regenerative hyperplasia of the liver is a histological lesion usually associated with systemic diseases, haematological malignancies, or drugs. Its prognosis depends on portal hypertension, which usually is well tolerated...

Including Children and Adolescents With Schizophrenia in Medication-Free Research

There has been an increasing focus on the ethical issues raised by studies requiring the withdrawal of effective medication in schizophrenic adults. This article examines the risks and benefits of a medication-free period for pediatric patients with treatment-refractory schizophrenia who are participating in an ongoing study. Between April 1993 and March 1998, 31 children and adolescents were admitted with a diagnosis of treatment-resistant, childhood-onset schizophrenia. Parental consent was obtained so that patients could participate in a medication-free research period. Patients were evaluated at screening, at the end of a 4-week washout, at the completion of a 6- to 8-week atypical neuroleptic trial, and at a 2- to 4-year follow-up. At the completion of a 4-week drug-free period, seven patients (23%) were diagnosed with another disorder on the basis of data gained from the drug-free period and their lack of schizophrenic symptoms. Their revised diagnoses were posttraumatic stress disorder (N = 1), an atypical psychosis labeled "multidimensionally impaired" (N = 4), and personality disorder (N = 2). At follow-up, three of these patients remained free of neuroleptic therapy. For eight patients (26%), the washout was curtailed because of rapid and severe deterioration of their schizophrenic symptoms. For children and adolescents with treatment-refractory schizophrenia, a medication-free period can be conducted safely for at least 4 weeks for inpatients. Such trials are useful on clinical grounds and for providing homogeneous patient groups for research. This study also highlights the necessity of having access to hospitalization to observe children and adolescents with psychotic symptoms while medication free.