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1.  The Longitudinal Pattern of Response When Morphine Is Used To Treat Chronic Refractory Dyspnea 
Journal of Palliative Medicine  2013;16(8):881-886.
While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern.
This secondary analysis used breathlessness intensity scores (100 mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved <10% improvement over their own baseline at one week (10 mg) were titrated to 20 mg and if no response, another week later to 30 mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling.
Of the 83 participants, 17/52 responders required >10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3 mm/day (p=0.16); the average improvement in the first 24 hours of response was 10.9 mm (7.0 to 14.7; p<0.0001), with continued improvement of 2.2 mm/day (p<0.001) for six more days.
When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered.
PMCID: PMC3718325  PMID: 23746231
2.  Prospectively Collected Characteristics of Adult Patients, Their Consultations and Outcomes as They Report Breathlessness When Presenting to General Practice in Australia 
PLoS ONE  2013;8(9):e74814.
Breathlessness is a subjective sensation, so understanding its impacts requires patients’ reports, including prospective patient-defined breathlessness as a reason for presenting to general practitioners (GP).The aim of this study was to define the prevalence of breathlessness as a reason for GP consultations while defining the clinico-demographic factors of these patients and the characteristics and outcomes of those consultations.
Using nine years of the Family Medicine Research Centre database of 100 consecutive encounters from 1,000 practices annually, the patient-defined reason for encounter ‘breathlessness’ was explored using prospectively collected data in people ≥18 years with clinical data coded using the International Classification for Primary Care V2. Dichotomous variables were analysed using chi square and 95% confidence intervals calculated using Kish’s formula for a single stage clustered design.
Of all the 755,729 consultations collected over a nine year period from 1 April, 2000, 7255 included breathlessness as a reason for encounter (0.96%; 95% CI 0.93 to 0.99) most frequently attributed to chronic obstructive pulmonary disease. Only 48.3% of GPs saw someone reporting breathlessness. The proportion of consultations with breathlessness increased with age. Breathlessness trebled the likelihood that the consultation occurred in the community rather than the consulting room (p<0.0001) and increased 2.5 fold the likelihood of urgent referral to hospital (p<0.0001). Of those with breathlessness, 12% had undiagnosed breathlessness at the end of the consultation (873/7255) with higher likelihood of being younger females.
Breathlessness is a prevalent symptom in general practitioner. Such prevalence enables future research focused on understanding the temporal pattern of breathlessness and the longitudinal care offered to, and outcomes for these patients, including those who leave the consultation without a diagnosis.
PMCID: PMC3775798  PMID: 24069352
3.  Diagnosis and management of people with venous thromboembolism and advanced cancer: how do doctors decide? a qualitative study 
The treatment of cancer associated thrombosis (CAT) is well established, with level 1A evidence to support the recommendation of a low molecular weight heparin (LMWH) by daily injection for 3–6 months. However, registry data suggest compliance to clinical guidelines is poor. Clinicians face particular challenges in treating CAT in advanced cancer patients due to shorter life expectancy, increased bleeding risk and concerns that self injection may be too burdensome. For these reasons decision making around the diagnosis and management of CAT in people with advanced cancer, can be complex, and should focus on its likely net benefit for the patient. We explored factors that influence doctors’ decision making in this situation and sought to gain an understanding of the barriers and facilitators to the application of best practice.
Think aloud exercises using standardised case scenarios, and individual in depth interviews were conducted. All were transcribed. The think aloud exercises were analysed using Protocol Analysis and the interviews using Framework Analysis.
Participants: 46 participants took part in the think aloud exercises and 45 participants were interviewed in depth. Each group included oncologists, palliative physicians and general practitioners and included both senior doctors and those in training.
Setting: Two Strategic Health Authority regions, one in the north of England and one in Wales.
The following key issues arose from the data synthesis: the importance of patient prognosis; the concept of “appropriateness”; “benefits and burdens” of diagnosis and treatment; LMWH or warfarin for treatment and sources of information which changed practice. Although interlinked, they do describe distinct aspects of the factors that influence doctors in their decisions in this area.
The above factors are issues doctors take into account when deciding whether to send a patient to hospital for investigation or to anticoagulate a patient with confirmed or suspected VTE. Many factors interweave and are themselves influenced by and dependent on each other. It is only after all are taken into account that the doctor arrives at the point of referring the patient for investigation. Some factors including logistic and organisational issues appeared to influence whether a patient would be investigated or treated with LMWH for a confirmed VTE. It is important that services are optimised to ensure that these do not hinder the appropriate investigation and management of individual patients.
PMCID: PMC3445826  PMID: 22818215
Venous thromboembolism; Cancer; Palliative; Clinical decision making
4.  Malignant melanoma as a target malignancy for the study of the anti-metastatic properties of the heparins 
Cancer Metastasis Reviews  2010;29(4):777-784.
The outlook for metastatic melanoma to the brain is dismal. New therapeutic avenues are therefore needed. The anti-metastatic mechanisms that may underpin the effects of low molecular weight heparins (LMWHs) in in vitro and preclinical melanoma models warrant translating to a clinical setting. This review outlines a rationale that supports our proposal that metastatic melanoma to the brain is a clinical setting in which to study the anti-metastatic potential of LMWHs. Prevention or delay of brain metastases in melanoma is a clinically relevant and measurable target. Studies to explore the effect of anticoagulants on cancer survival are underway in other malignancies such as lung, pancreas, ovary, breast, and stomach cancer. However, no study to our knowledge has a methodology that could produce clinical evidence in support of a mechanism for whatever benefit may be seen. The setting we propose would allow translation of the molecular knowledge of the metastatic pathways mediated by platelets and the selectins—all potential targets of heparin—in a “time to appearance” of brain metastases endpoint. Since brain metastases are so common and they have a singularly adverse impact on survival, the “biological neuroprotection” model we propose in metastatic melanoma could provide the translational evidence to support the benefit of LMWHs in melanoma. More significantly, this would open the door to a wider “anti-metastatic” approach that could have much greater impact in patients with minimal disease being treated in adjuvant settings for the more common malignancies such as breast and colon cancer.
PMCID: PMC2962791  PMID: 20936327
Low molecular weight heparins; Metastatic melanoma; Selectin; Anti-metastatic
5.  Management of end stage cardiac failure 
Postgraduate Medical Journal  2007;83(980):395-401.
Optimum heart failure medication and an increasing array of interventions have had an enormous effect on morbidity and mortality over the past 10 years. However, patients with end stage disease can still be highly symptomatic. Moreover, such patients are disadvantaged compared with patients with malignant disease. They are less likely to have an understanding of their illness or have access to supportive care. They are also less likely to have the opportunity to plan for care with regard to death and dying. There is increasing demand that the multi‐professional clinical team gain good communication and supportive care skills, and that appropriate access to specialist palliative care services is available.
PMCID: PMC2600041  PMID: 17551071

Results 1-5 (5)