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1.  The Impact on the Family Carer of Motor Neurone Disease and Intervention with Noninvasive Ventilation 
Journal of Palliative Medicine  2013;16(12):1602-1609.
Background: The diagnosis of motor neurone disease (MND) has a profound effect on the functioning and well-being of both the patient and their family, with studies describing an increase in carer burden and depression as the disease progresses.
Aim: This study aimed to assess whether patient use of noninvasive ventilation (NIV) impacted on their family carer, and to explore other sources of carer burden.
Design: The study used qualitative interviews and scaled measures of carer health and well-being completed at three monthly intervals until patient end of life.
Participants: Sixteen family carers were followed up over a period ranging from one month to two years.
Results: NIV was perceived as having little impact on carer burden. The data however highlighted a range of sources of other burdens relating to the physical strain of caring. The Medical Outcomes Study Short Form (SF-36 Health Survey) Physical Component Summary (PCS) scores were considerably below that of the Mental Component Summary (MCS) score at baseline and at all following time points. Carers described the physical effort associated with patient care and role change; the challenge inherent in having time away; and problems relating to the timing of equipment and service delivery.
Conclusions: NIV can be recommended to patients without concerns regarding increasing carer burden. The predominant source of burden described related to the physical impact of caring for a patient with MND. Services face challenges if this physical burden is to be reduced by providing equipment at an optimal time and successfully coordinating their input.
PMCID: PMC3868397  PMID: 24236958
2.  Effects of a Pragmatic Lifestyle Intervention for Reducing Body Mass in Obese Adults with Obstructive Sleep Apnoea: A Randomised Controlled Trial 
BioMed Research International  2014;2014:102164.
This study investigated the effects of a pragmatic lifestyle intervention in obese adults with continuous positive airway pressure-treated obstructive sleep apnoea hypopnoea syndrome (OSAHS). Sixty patients were randomised 1 : 1 to either a 12-week lifestyle intervention or an advice-only control group. The intervention involved supervised exercise sessions, dietary advice, and the promotion of lifestyle behaviour change using cognitive-behavioural techniques. Outcomes were assessed at baseline (week 0), intervention end-point (week 13), and follow-up (week 26). The primary outcome was 13-week change in body mass. Secondary outcomes included anthropometry, blood-borne biomarkers, exercise capacity, and health-related quality of life. At end-point, the intervention group exhibited small reductions in body mass (−1.8 [−3.0, −0.5] kg; P = 0.007) and body fat percentage (−1 [−2, 0]%; P = 0.044) and moderate improvements in C-reactive protein (−1.3 [−2.4, −0.2] mg·L−1; P = 0.028) and exercise capacity (95 [50, 139] m; P < 0.001). At follow-up, changes in body mass (−2.0 [−3.5, −0.5] kg; P = 0.010), body fat percentage (−1 [−2, 0]%; P = 0.033), and C-reactive protein (−1.3 [−2.5, −0.1] mg·L−1; P = 0.037) were maintained and exercise capacity was further improved (132 [90, 175] m; P < 0.001). This trial is registered with NCT01546792.
PMCID: PMC4127266  PMID: 25136550
3.  Protocol for diaphragm pacing in patients with respiratory muscle weakness due to motor neurone disease (DiPALS): a randomised controlled trial 
BMC Neurology  2012;12:74.
Motor neurone disease (MND) is a devastating illness which leads to muscle weakness and death, usually within 2-3 years of symptom onset. Respiratory insufficiency is a common cause of morbidity, particularly in later stages of MND and respiratory complications are the leading cause of mortality in MND patients. Non Invasive Ventilation (NIV) is the current standard therapy to manage respiratory insufficiency. Some MND patients however do not tolerate NIV due to a number of issues including mask interface problems and claustrophobia. In those that do tolerate NIV, eventually respiratory muscle weakness will progress to a point at which intermittent/overnight NIV is ineffective. The NeuRx RA/4 Diaphragm Pacing System was originally developed for patients with respiratory insufficiency and diaphragm paralysis secondary to stable high spinal cord injuries. The DiPALS study will assess the effect of diaphragm pacing (DP) when used to treat patients with MND and respiratory insufficiency.
108 patients will be recruited to the study at 5 sites in the UK. Patients will be randomised to either receive NIV (current standard care) or receive DP in addition to NIV. Study participants will be required to complete outcome measures at 5 follow up time points (2, 3, 6, 9 and 12 months) plus an additional surgery and 1 week post operative visit for those in the DP group. 12 patients (and their carers) from the DP group will also be asked to complete 2 qualitative interviews.
The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND with respiratory muscle weakness. The project is funded by the National Institute for Health Research, Health Technology Assessment (HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association and the Henry Smith Charity. Trial Registration: Current controlled trials ISRCTN53817913. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.
PMCID: PMC3462709  PMID: 22897892
4.  Subversion of a Lysosomal Pathway Regulating Neutrophil Apoptosis by a Major Bacterial Toxin, Pyocyanin1 
Neutrophils undergo rapid constitutive apoptosis that is accelerated following bacterial ingestion as part of effective immunity, but is also accelerated by bacterial exotoxins as a mechanism of immune evasion. The paradigm of pathogen-driven neutrophil apoptosis is exemplified by the Pseudomonas aeruginosa toxic metabolite, pyocyanin. We previously showed pyocyanin dramatically accelerates neutrophil apoptosis both in vitro and in vivo, impairs host defenses, and favors bacterial persistence. Here, we investigated the mechanisms of pyocyanin-induced neutrophil apoptosis. Pyocyanin induced early lysosomal dysfunction, shown by altered lysosomal pH, within 15 mins of exposure. Lysosomal disruption was followed by mitochondrial membrane permeabilization, caspase activation and destabilization of Mcl-1. Pharmacological inhibitors of a lysosomal protease, cathepsin D (CTSD), abrogated pyocyanin-induced apoptosis and translocation of CTSD to the cytosol followed pyocyanin treatment and lysosomal disruption. A stable analogue of cyclic AMP (dbcAMP) impeded the translocation of CTSD and prevented the destabilization of Mcl-1 by pyocyanin. Thus pyocyanin activated a co-ordinated series of events dependent upon lysosomal dysfunction and protease release, the first description of a bacterial toxin utilising a lysosomal cell death pathway. This may be a pathological pathway of cell death to which neutrophils are particularly susceptible, and could be therapeutically targeted to limit neutrophil death and preserve host responses.
PMCID: PMC2262923  PMID: 18292577
Neutrophils; apoptosis; inflammation

Results 1-4 (4)