Do pilocarpine drops help dry mouth in palliative care patients: A protocol for an aggregated series of n-of-1 trials

Background: It is estimated that 39,000 Australians die from malignant disease yearly. Of these, 60% to 88% of advanced cancer patients suffer xerostomia, the subjective feeling of mouth dryness. Xerostomia has significant physical, social and psychological consequences which compromise function and quality of life. Pilocarpine is one treatment for xerostomia. Most studies have shown some variation in individual response to pilocarpine, in terms of dose used, and timing and extent of response.We will determine a population estimate of the efficacy of pilocarpine drops (6 mg) three times daily compared to placebo in relieving dry mouth in palliative care (PC) patients. A secondary aim is to assess individual patients' response to pilocarpine and provide reports detailing individual response to patients and their treating clinician. Methods/Design. Aggregated n-of-1 trials (3 cycle, double blind, placebo-controlled crossover trials using standardized measures of effect). Individual trials will identify which patients respond to the medication. To produce a population estimate of a treatment effect, the results of all cycles will be aggregated. Discussion. Managing dry mouth with treatment supported by the best possible evidence will improve functional status of patients, and improve quality of life for patients and carers. Using n-of-1 trials will accelerate the rate of accumulation of high-grade evidence to support clinical therapies used in PC. Trial registration. Australia and New Zealand Clinical Trial Registry Number: 12610000840088. © 2013 Nikles et al.; licensee BioMed Central Ltd

A modular micromachined high-density connector system for biomedical applications

This paper presents a high-density, modular, low-profile, small, and removable connector system developed using micromachining technologies for biomedical applications. This system consists of a silicon or polyimide electrode with one end in contact with the biological tissue and its back-end supported in a titanium base (12.5 mm in diameter and 2.5 mm in height) that is fixed on the test subject. An external glass substrate (6 x 6 x 0.75 mm(3)), which supports a flexible polyimide diaphragm and CMOS buffers, is attached to the titanium base whenever electrical contact is required. The polyimide flexible diaphragm contains high-density gold electroplated pads (32 pads, each having an area of 100 x 100 mu m(2) and separated by 150 mu m) which match similar pads on the electrode back-end. When vacuum is applied between the two, the polyimide diaphragm deflects and the corresponding gold pads touch, therefore, establishing electrical connection. In vitro electrical tests in saline solution have been performed on a 32-site connector system demonstrating <5 Omega contact resistance, which remained stable after 70 connections, and -55 dB crosstalk at 1 kHz between adjacent channels. In vivo experiments have also confirmed the establishment of multiple contacts and have produced simultaneous biopotential recordings from the guinea pig occipital cortex

Single-patient multiple crossover studies to determine the effectiveness of paracetamol in relieving pain suffered by patients with advanced cancer taking regular opioids: A pilot study

Paracetamol is a useful adjunct when used in combination with “weak opioids” for chronic pain in palliative care patients with advanced cancer, however it is not certain that there is continuing benefit when used in conjunction with “strong” opioids. N-of-1 trials allowed individual treatment decisions to be made for each participant: there was no added benefit for any of the participants, although no conclusion about the added benefit of paracetamol above regular opioids was possible for the group, due to insufficient numbers recruited. Paracetamol may not provide added benefit above regular opioids; this should assessed on a case by case basis to justify the extra tablet load

Insights into prion strains and neurotoxicity.

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that are caused by prions and affect humans and many animal species. It is now widely accepted that the infectious agent that causes TSEs is PrPSc, an aggregated moiety of the host-derived membrane glycolipoprotein PrPC. Although PrPC is encoded by the host genome, prions themselves encipher many phenotypic TSE variants, known as prion strains. Prion strains are TSE isolates that, after inoculation into distinct hosts, cause disease with consistent characteristics, such as incubation period, distinct patterns of PrPSc distribution and spongiosis and relative severity of the spongiform changes in the brain. The existence of such strains poses a fascinating challenge to prion research