Expert panel process to optimise the design of a randomised controlled trial in chronic rhinosinusitis (the MACRO programme).

BACKGROUND: MACRO (Defining best Management for Adults with Chronic RhinOsinusitis) is an NIHR-funded programme of work designed to establish best practice for adults with chronic rhinosinusitis (CRS). The 7-year programme comprises three consecutive workstreams, designed to explore NHS care pathways through analysis of primary and secondary data sources, and to undertake a randomised controlled trial to evaluate a longer-term course of macrolide antibiotics and endoscopic sinus surgery for patients with CRS. A number of outstanding elements still required clarification at the funding stage. This paper reports an expert panel review process designed to agree and finalise the MACRO trial design, ensuring relevance to patients and clinicians whilst maximising trial recruitment and retention. METHODS: An expert panel, consisting of the MACRO Programme Management Group, independent advisors, and patient contributors, was convened to review current evidence and the mixed-method data collected as part of the programme, and reach agreement on MACRO trial design. Specifically, agreement was sought for selection of macrolide antibiotic, use of orally administered steroids, inclusion of CRS phenotypes (with/without nasal polyps), and overall trial design. RESULTS: A 12-week course of clarithromycin was agreed as the main trial comparator due to its increasing use as a first- and second-line treatment for patients with CRS, and the perceived need to establish its role in CRS management. Orally administered steroids will be used as a rescue medication during the trial, rather than routinely either pre or post trial randomisation, to limit any potential effects on surgical outcomes and better reflect current UK prescribing habits. Both CRS phenotypes will be included in a single trial to ensure that the MACRO trial is both pragmatic and generalisable to primary care. A modified, three-arm trial design was agreed after intense discussions and further exploratory work. Inclusion criteria were amended to ensure that the patients recruited would be considered eligible for the treatment offered in the trial due to having already received appropriate medical therapy as deemed suitable by their ENT surgeon. A proposed 6-week run-in period prior to randomisation was removed due to the new criteria prior to randomisation. CONCLUSION: The expert panel review process resulted in agreement on key elements and an optimal design for the MACRO trial, considered most likely to be successful in terms of both recruitment potential and ability to establish best management of patients with CRS

iPad colour vision apps for dyschromatopsia screening

Optic neuritis (ON) is a common and important cause of vision loss or vision disturbances in the community, particularly amongst the young, and it is often associated with a persistent dyschromatopsia. Traditionally screening for dyschromatopsia has been carried out using pseudo-isochromatic Ishihara plates. These colour plates were originally developed for testing of colour blindness, and indeed have only more recently been applied to ON. As the Ishihara plate books used for testing are expensive, unwieldy, and are not commonly available in many clinics or wards, many neurologists and ophthalmologists have taken to using untested and unstudied downloadable software packages on portable electronic devices for testing. This study compared the efficacy of printed and iPad (Apple, Cupertino, CA, USA) versions of the Ishihara plates in screening for dyschromatopsia in patients who were suspected of having ON. The main finding was that dyschromatopsia testing using a commercially available application on an iPad was comparable to using the current pragmatic clinical benchmark, the pseudo-isochromatic plates of Ishihara. These findings provide support for the increasingly common practice of screening for dyschromatopsia using the iPad

A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN)

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect resulting from neurotoxic chemotherapeutic agents. This study aimed to assess the efficacy and safety of an oral B group vitamin compared to placebo, in preventing the incidence of CIPN in cancer patients undergoing neurotoxic chemotherapy. Methods: A pilot, randomised, placebo-controlled trial was conducted. Newly diagnosed cancer patients prescribed with taxanes, oxaliplatin or vincristine were invited to participate. A total of 71 participants (female 68\ua0%, male 32\ua0%) were enrolled into the study and randomised to the B group vitamin (n\ua0=\ua038) arm or placebo (n\ua0=\ua033). The data from 47 participants were eligible for analysis (B group vitamins n\ua0=\ua027, placebo n\ua0=\ua022). The primary outcome measure was the total neuropathy score assessed by an independent neurologist. Secondary outcome measures included serum vitamin B levels, quality of life, pain inventory and the patient neurotoxicity questionnaires. Outcome measures were conducted at baseline, 12, 24 and 36\ua0weeks. Results: The total neuropathy score (TNS) demonstrated that a B group vitamin did not significantly reduce the incidence of CIPN compared to placebo (p\ua0=\ua00.73). Statistical significance was achieved for patient perceived sensory peripheral neuropathy (12\ua0weeks p\ua0=\ua00.03; 24\ua0weeks p\ua0=\ua00.005; 36\ua0weeks p\ua0=\ua00.021). The risk estimate for the Patient Neurotoxicity Questionnaire (PNQ) was also statistically significant (OR\ua0=\ua05.78, 95\ua0% CI\ua0=\ua01.63–20.5). The European Organisation of Research and Treatment of Cancer (EORTC) quality of life, total pain score and pain interference showed no significance (p\ua0=\ua00.46, p\ua0=\ua00.9, p\ua0=\ua00.37 respectively). A trend was observed indicating that vitamin B12 may reduce the onset and severity of CIPN. Conclusion: An oral B group vitamin as an adjunct to neurotoxic chemotherapy regimens was not superior to placebo (p\ua0>\ua00.05) for the prevention of CIPN. Patients taking the B group vitamin perceived a reduction in sensory peripheral neuropathy in the PNQ. Moreover, a robust clinical study is warranted given that vitamin B12 may show potential in reducing the onset and severity of CIPN. Trial number: ACTRN12611000078954 Protocol number: UH201000074

The tibialis anterior response revisited

The idiomuscular response to direct percussion is rarely tested nowadays because of its uncertain mechanism and significance. While performing neurological examination, we observed a brisk ankle dorsiflexion response on direct muscle percussion of m. tibialis anterior in patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP). In contrast, in patients with upper motor neuron lesions, an ankle inversion response was seen. In this article we describe our findings in patients with bilateral lower limb weakness. We assessed 73 consecutive patients with bilateral lower limb weakness. A strong dorsiflexion response to percussion of m. tibialis anterior was seen in 11 out of 14 patients with AIDP (sensitivity 78.6 %). None of the other patients showed a strong dorsiflexion response (specificity 100 %). An inversion response was seen in 11 out of 13 patients with UMN involvement (sensitivity 92.3 %). It was also noted in two of 46 patients without proven UMN involvement (specificity 96.7 %). The idiomuscular response to percussion of m. tibialis anterior can be useful in the assessment of patients with lower limb weakness of unclear cause

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): A systematic review

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made

A case of immune-mediated encephalitis related to daclizumab therapy

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy