Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 1 historical and established therapies

Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS.

Costs of bronchoalveolar lavage-directed therapy in the first 5 years of life for children with cystic fibrosis.

To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions.

Acute delirium in the setting of primary hypothyroidism: the role of thyroid hormone replacement therapy.

Psychiatric illness, mostly mania and psychosis, are reported to occur after rapid normalization of thyroid function in patients with primary hypothyroidism. It is generally believed that the gradual restoration of thyroid function may reduce the risk of psychiatric complications. This case report describes the occurrence of acute delirium in a 67-year-old man with primary hypothyroidism shortly after the initiation of thyroid hormone replacement. The use of low-dose thyroxine initially and persistent severe biochemical hypothyroidism on presentation with psychiatric symptoms illustrate that psychiatric illness can still occur despite unaggressive thyroid hormone replacement. A temporal relationship with the initiation of thyroxine and rapid recovery of mental state over 1 to 2 weeks differentiate this condition from hypothyroidism-related psychopathology, which tends to have a more prolonged course.

Changes in the platelet intracellular calcium response to serotonin in patients with major depression treated with electroconvulsive therapy: state or trait marker status.

Platelet serotonin type 2A receptor (5-HT2A) sensitivity changes have previously been documented in depression, although it is unclear if this represents a stable trait marker of the illness, or whether it represents an acute state marker of depression that would change with treatment. Electroconvulsive therapy (ECT) may be a useful intervention to separate out trait and state marker status avoiding the potential confounding effects of pharmacotherapy on receptor function. Using spectrofluorometry, the platelet 5HT2A, receptor sensitivity as reflected by the intracellular calcium response to serotonin stimulation, was measured every week in patients suffering from major depression and undergoing ECT. There was a significant drop in the platelet response to serotonin stimulation over a course of ECT, with an associated progressive decrease in Hamilton Rating Scale of Depression (HAM-D) scores. This may suggest either decreased sensitivity of platelet 5HT2A receptors as a mechanism of action of ECT, or changes in second messengers such as the inositide phospholipid system. This suggests that the enhanced sensitivity of platelet 5HT2A receptors may be a state marker of major depression.

Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study.

The negative symptoms of schizophrenia remain a major clinical challenge. Mirtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these pharmacological actions have clinical or preclinical evidence of efficacy in schizophrenia. This study was a 6-week randomized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The primary finding of the trial was a 42% reduction in Positive and Negative Syndrome Scale (PANSS) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD 1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total scores, Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo. There was no difference between the groups on the Hamilton depression scale at endpoint, suggesting that the improvement in negative symptoms was not an artifact of mood improvement. These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia.

Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study.

The negative symptoms of schizophrenia remain a major clinical challenge. Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor. This study was a 6-week randomized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The trial failed to demonstrate any significant difference between the placebo and reboxetine groups on any of the outcome measures. This trial does not suggest that increased noradreneregic drive mediated by reuptake inhibition in patients taking dopamine antagonists is of therapeutic value in schizophrenia.

Analysis of 177Lu-octreotate therapy-induced DNA damage in peripheral blood lymphocytes of patients with neuroendocrine tumors

Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) can lead to cell death, genome instability and carcinogenesis. Immunofluorescence detection of phosphorylated histone variant H2AX (γ-H2AX) is a reliable and sensitive technique to monitor external beam IR-induced DSBs in peripheral blood lymphocytes (PBL). Here, we investigated whether γ-H2AX could be used as an in vivo marker to assess normal tissue toxicity after extended internal irradiation with (177)Lu-DOTA-octreotate peptide receptor radionuclide therapy (LuTate PRRT) of neuroendocrine tumors.

Can music therapy in medical contexts ever be evidence-based?

This essay seeks to consider some of the issues around evidencethat provide an ongoing challenge to the profession of music therapyto be vigilant and critical with regards the undertaking, butalso the appropriation or application, of research in our alliedhealth discipline. It is written in response to the statement that“medical music therapists need to continue to discuss and debateour views as to what constitutes knowledge, expertise and ‘evidence’in our profession.” (Edwards, 2002, p. 33). A critical perspectiveto current demands for evidence is provided, and the useof quantitative method as the basis for trustworthy research inmusic therapy is discussed. The paediatric medical context is themain site of professional research of the author, however, some ofthe points made will have relevance for other fields of clinicalservice.