Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.

BACKGROUND: Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy. METHOD: This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group. CONCLUSION: Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.

A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.

BACKGROUND: Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine. The purpose of this study was to carry out a placebo-controlled, randomized, double-blind trial of the efficacy, safety, and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine. METHOD: In this 6-week double-blind study, 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were randomly assigned to risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale, the Clinical Global Impressions-Severity of Illness scale, the Global Assessment of Functioning scale, and the Quality of Life Scale. A variety of safety and tolerability measures were also obtained. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was noted in both groups on a variety of measures of psychopathology, but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure, the PANSS positive symptom subscale. There were no significant differences between the treatment groups regarding extrapyramidal symptoms, weight gain, vital signs, serum clozapine levels, and QTc interval. The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation. The patients treated with risperidone developed significant increases in plasma prolactin levels. CONCLUSION: Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period.

[The current problems and cross-cultural perspectives of patient-doctor relation: an overview]. / Hasta-hekim iliskisinin güncel sorunlari ve kültürlerarasi yönleri: bir bakis

The success of the treatment in medicine, especially in psychiatry is based on the form and the strength of the patient-doctor relation. This complex and dynamic relation is changing in accordance with the social and technological development of the society. The context of the patient-doctor relation is determined by the present day culture as well as the traditional background. An overview of current patient-doctor relation and of problems that physicians and in particular psychiatrists meet is presented. Physicians have responsibilities in building patient-doctor relation. The ethical and legal aspects of these responsibilities are presented. The former paternalistic type of patient-doctor relation is evolving into a more equal and democratic relation. New problems are being encountered continuously in the changing process. Beside the of the process itself, the effects of progress in medical technology and communication systems on patient-doctor relation and the pressure, put from the insurance companies and/or authorities on physicians, which impair the trust between the physician and his patient, are making the process more difficult. The issues of compliance, sexual harassment and unique problems of patient-doctor relations in psychiatry are the other subtopics in the article. The cross-cultural aspects of patient-doctor relations and encountered clinical problems are discussed with case examples particularly about Turkish immigrants, who live in Germany. Suggestions for psychiatrists in Germany to work out the challenges facing them are presented in the conclusion.

The Turkish version of the Auditory Consonant Trigram Test as a measure of working memory: a normative study.

The following study was conducted to adapt the Auditory Consonant Trigram Test (ACT) to Turkish, acquire a new and larger set of normative data, and finally investigate the reliability and validity of the adapted version. The data were collected from a sample of 236 healthy individuals. To test the validity of the Turkish version of ACT, the normative results of ACT were first compared with those obtained from the Digit Span Test (DST) backwards section. Secondly, the ACT performance of 53 schizophrenic patients was compared with that of a matched group selected from the normative sample. Age and education variables influenced performance, whereas gender did not in the normal sample. The ACT and DST backwards scores were positively correlated. As expected, the ACT performance was worse in schizophrenic patients compared to controls. The internal consistency of the adapted version of ACT was found to be at a reliable level (alpha=0.8535). The Turkish version of ACT can be considered to be a reliable and valid measure of working memory.