Eliciting patients’ preferences for adjuvant chemotherapy in breast cancer: development and validation of a bedside decision‐making instrument in a French Regional Cancer Centre

Introduction

In developed countries, the physician‐patient relationship is moving from a paternalistic model to new decision‐making models that take patient preferences into account.

Objectives

Our aim was to develop a Decision Board (DB) and to test its acceptability in a French Regional Cancer Centre regarding the decision on whether or not to use chemotherapy after surgery in postmenopausal women with breast cancer. This paper presents the development process for this instrument and reports the pretesting phase, as well as the corresponding results.

Methods

A working group was created with oncologists, psychologists and economists. Following the first phase, i.e. the development process, a first version of the instrument was presented to health professionals. Their feedback led to important modifications of the instrument. The DB was then presented to experienced patients, which resulted in slight changes. The second phase consisted of pretesting the comprehension, internal and across‐time consistency of the DB on healthy volunteers.

Results

The DB was pretested in a group of 40 healthy volunteers. Eighteen respondents chose chemotherapy and 22 chose not to have chemotherapy. Comprehension rates were very high (≥87.5%). Internal consistency was assessed considering option attitudes based on outcomes and option attitudes based on process. Women shifted their choices in a predictable way. Across‐time consistency was appraised using the test‐retest method with Visual Analog Scales. The Intraclass Correlation Coefficient was 0.97.

Discussion‐conclusion

Due to cultural differences, the DB developed in our French Cancer Centre is quite different from the DBs previously developed elsewhere. Our instrument showed good comprehension and consistency properties, which are corroborated by the DB literature. Whether our DB is acceptable for patients with breast cancer must still be tested. Patients’ reactions will tell us which type of decision‐making model is at work. Further research is needed in order to explore the shared decision‐making process and clarify the concept.

     

A double-blind,randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months

OBJECTIVE: To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia. DESIGN AND SETTING: A multinational, double-blind randomised clinical trial. PATIENTS AND TREATMENT: Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d). MAIN OUTCOME MEASURES: Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated. RESULTS: Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7 +/- 3.9 kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9 +/- 3.2 kg, p < 0.0001). CONCLUSIONS: Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.     

Toxic cardiac effects of catecholamines: role of beta-adrenoceptor downregulation

This study investigates the effect of microinjections of capsaicin in the periaqueductal grey matter of rats on nociceptive behaviour and the possible interactions with NMDA and mGlu receptors. Intra-periaqueductal grey microinjection of capsaicin (1-3-6 nmol/rat) increased the latency of the nociceptive reaction in the plantar test. This effect was prevented by pretreatment with capsazepine (6 nmol/rat), which had no effect per se on the latency of the nociceptive reaction. 7-(Hydroxyimino)cyclopropa[b]chromen-1alpha-carboxylate ethyl ester (CPCCOEt, 50 nmol/rat) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP, 50 nmol/rat), antagonists of mGlu(1) and mGlu(5) receptors, respectively, completely blocked the effect of capsaicin. Similarly, pretreatment with DL-2-Amino-5-phosphonovaleric acid (DL-AP5, 5 nmol/rat) and riluzole (4 nmol/rat), an NMDA receptor antagonist and a voltage-dependent Na(+) channels blocker which inhibits glutamate release, respectively, completely antagonized the effect of capsaicin. However, pretreatment with (2S)-alpha-Ethylglutamic acid (30 nmol/rat) and (RS)-alpha-Methylserine-O-phosphate (MSOP, 30 nmol/rat), antagonists of group II and group III mGlu receptors, respectively, had no effects on capsaicin-induced analgesia. Similarly, pretreatment with N-(piperidin-1-yl)-5-(4-chlophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR 141716A, 5 pmol/rat), a selective cannabinoid CB(1) receptor antagonist, did not affect the capsaicin-induced antinociception. In conclusion, this study shows that capsaicin might produce antinociception at the periaqueductal grey level by increasing glutamate release, which activates postsynaptic group I mGlu and NMDA receptors.     

Long-term complete haematological and molecular remission after allogeneic bone marrow transplantation in a patient with a stem cell myeloproliferative disorder associated with t(8;13)(p12;q12)

A rare atypical myeloproliferative disorder (aMPD) associated with chromosomal translocations involving the short arm of chromosome 8, region p11-p12 has been described. In most patients, the cytogenetic abnormality is a t(8;13)(p12;q12) that fuses fibroblast growth factor receptor 1, the 8p12 key gene, to FIM/ZNF198 gene. Prognosis is poor with frequent evolution to acute myeloid leukaemia within 1 year of diagnosis. We report a new patient with aMPD with a t(8;13) translocation. Complete haematological, cytogenetic and molecular remission was demonstrated 39 months after allogeneic bone marrow transplantation. This is the first report to demonstrate a molecular remission in this disorder.     

Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene

BACKGROUND: The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. OBJECTIVE: To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. METHODS: Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. RESULTS: Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. CONCLUSION: Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.     

Postoperative spondylodiskitis due to Stomatococcus mucilaginosus in an immunocompetent patient

A case is reported of postoperative spondylodiskitis due to Stomatococcus mucilaginosus in an immunocompetent woman. The route of infection remains unknown. Intravenous treatment with cefotaxime and fosfomycin was given, followed by oral administration of rifampin and pristinamycin until resolution of infection. This report shows that this bacterium can cause severe infections in immunocompetent patients.     

Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice

Interleukin-10 markedly reduces production of proinflammatory cytokines by activated microglia or macrophages and downregulates the expression of activating molecules on these cells. In studies performed in adults or in cell cultures, interleukin-10 protected against hypoxic-ischemic neuronal death and against lipopolysaccharide-mediated oligodendrocyte cell death. Furthermore, it was recently shown that interleukin-10 counteracts metabolic and microcirculatory effects of hypoxia-ischemia in the perinatal pig brain. Intracerebral injection of the glutamatergic analogue ibotenate to newborn mice induces cortical plate and white matter lesions mimicking the brain damage associated with cerebral palsy, and pretreatment with proinflammatory cytokines such as interleukin-1-beta or with interleukin-9 significantly exacerbates these lesions. The present study evaluated the influence of interleukin-10 on ibotenate-induced brain lesions in newborn mice under basal conditions or after exposure to cytokines. Intraperitoneal injection of interleukin-10 for 3 days following ibotenate significantly reduced the size of excitotoxic brain lesions. Intraperitoneal injection of neutralizing anti-interleukin-10 antibody for 3 days following ibotenate had no detectable effect and no difference in ibotenate-induced brain lesion size was found between wild type pups and pups deleted for the interleukin-10 gene, suggesting that endogenous interleukin-10 in newborn mice may have limited effects. Co-administration of intracerebral ibotenate and interleukin-10 had no detectable effect, arguing against a direct neuroprotective effect of interleukin-10 on neurons. While pretreatment with intraperitoneal interleukin-10 alone had no detectable effect on excitotoxic brain lesions, interleukin-10 given with interleukin-1-beta pretreatment blunted the toxic effects of interleukin-1-beta. On the other hand, combined pretreatment with IL-9 and anti-IL-10 antibody largely reversed the exacerbating effect of IL-9 on excitotoxic brain lesions. Altogether, these data suggest that, in newborn mice, exogenous interleukin-10 can be neuroprotective when acting in an inflammatory context.     

Blackberry anthocyanins are slightly bioavailable in rats

Anthocyanins are phenolic compounds widely distributed in fruits and vegetables. Several positive effects of anthocyanin feeding have been described. We evaluated the absorption and metabolism of anthocyanins (cyanidin 3-glucoside and malvidin 3-glucoside) in rats adapted for 8 d to a diet enriched with a lyophilized blackberry powder. Rats had free access to an anthocyanin-containing diet for 8 h/d. Food was consumed throughout this period, and no anthocyanin accumulated in plasma at any of the times of sampling. Anthocyanins were recovered in urine as the intact glycosidic forms, whereas neither aglycone nor conjugates were detected. Moreover, peonidin 3-glucoside was present in urine and could have resulted from hepatic methylation at the 3' hydroxyl moiety position of cyanidin 3-glucoside. Urinary recovery of cyanidin 3-glucoside in either intact or methylated forms was approximately 0.26% of the ingested amount, whereas that of malvidin 3-glucoside was 0.67%. This result suggested that structure of the aglycone moiety of anthocyanins could play an important role in their metabolism. Low amounts of glucosides as well as of cyanidin were recovered in cecal contents. This could result from adaptation of microflora to anthocyanin degradation. Overall, these data indicate that blackberry anthocyanins are excreted in urine as intact and methylated glucoside forms and that their bioavailability is very low compared with other flavonoids.