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1.  The assessment and impact of sarcopenia in lung cancer: a systematic literature review 
BMJ Open  2014;4(1):e003697.
Objectives
There is growing awareness of the relationship between sarcopenia (loss of muscle mass and function), and outcomes in cancer, making it a potential target for future therapies. In order to inform future research and practice, we undertook a systematic review of factors associated with loss of muscle mass, and the relationship between muscle function and muscle mass in lung cancer, a common condition associated with poor outcomes.
Design
We conducted a computerised systematic literature search on five databases. Studies were included if they explored muscle mass as an outcome measure in patients with lung cancer, and were published in English.
Setting
Secondary care.
Participants
Patients with lung cancer.
Primary outcome
Factors associated with loss of muscle mass and muscle function, or sarcopenia, and the clinical impact thereof in patients with lung cancer.
Results
We reviewed 5726 citations, and 35 articles were selected for analysis. Sarcopenia, as defined by reduced muscle mass alone, was found to be very prevalent in patients with lung cancer, regardless of body mass index, and where present was associated with poorer functional status and overall survival. There were diverse studies exploring molecular and metabolic factors in the development of loss of muscle mass; however, the precise mechanisms that contribute to sarcopenia and cachexia remain uncertain. The effect of nutritional supplements and ATP infusions on muscle mass showed conflicting results. There are very limited data on the correlation between degree of sarcopenia and muscle function, which has a non-linear relationship in older non-cancer populations.
Conclusions
Loss of muscle mass is a significant contributor to morbidity in patients with lung cancer. Loss of muscle mass and function may predate clinically overt cachexia, underlining the importance of evaluating sarcopenia, rather than weight loss alone. Understanding this relationship and its associated factors will provide opportunities for focused intervention to improve clinical outcomes.
doi:10.1136/bmjopen-2013-003697
PMCID: PMC3902311  PMID: 24384894
2.  Spiritual Concerns in Hindu Cancer Patients Undergoing Palliative Care: A Qualitative Study 
Aims:
Spiritual concerns are being identified as important components of palliative care. The aim of this study was to explore the nature of spiritual concerns in cancer patients undergoing palliative care in a hospice in India.
Materials and Methods:
The methodology used was a qualitative method: Interpretive phenomenological analysis. A semi-structured interview guide was used to collect data, based on Indian and western literature reports. Certain aspects like karma and pooja, relevant to Hindus, were included. Theme saturation was achieved on interviewing 10 participants.
Results:
The seven most common spiritual concerns reported were benefit of pooja, faith in God, concern about the future, concept of rebirth, acceptance of one's situation, belief in karma, and the question Why me? No participant expressed four of the concerns studied: Loneliness, need of seeking forgiveness from others, not being remembered later, and religious struggle.
Conclusions:
This study confirms that there are spiritual concerns reported by patients receiving palliative care. The qualitative descriptions give a good idea about these experiences, and how patients deal with them. The study indicates the need for adequate attention to spiritual aspects during palliative care.
doi:10.4103/0973-1075.116716
PMCID: PMC3775032  PMID: 24049350
Cancer patients; Hindu; Karma; Palliative care; Qualitative study; Spirituality; Spiritual concerns
3.  The ethical decisions UK doctors make regarding advanced cancer patients at the end of life - the perceived (in) appropriateness of anticoagulation for venous thromboembolism: A qualitative study 
BMC Medical Ethics  2012;13:22.
Background
Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism (VTE) - which often takes the form of a pulmonary embolism or deep vein thrombosis. The risk increases with advanced disease. Evidence based treatment is low molecular weight heparin (LMWH) by daily subcutaneous injection. The aim of this research is to explore the barriers for doctors in the UK when diagnosing and treating advanced cancer patients with VTE.
Method
Qualitative, in-depth interview study with 45 doctors (30 across Yorkshire, England and 15 across South Wales). Doctors were from three specialties: oncology, palliative medicine and general practice, with a mixture of senior and junior staff. Framework analysis was used.
Results
Doctors opinions as to whether LMWH treatment was ethically appropriate for patients who were symptomatic from VTE but at end of life existed on a shifting continuum, largely influenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of a daily injection had influenced some doctors not to prescribe LMWH. The point at which LMWH injections should be stopped in patients at the end of life was ambiguous. Some perceived ‘overcaution’ in their own and other clinicians’ treatment of patients. Viewpoints were divergent on whether dying of a PE was considered a “good way to go”. The interventionalism and ethos of palliative medicine was discussed.
Conclusions
Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancer patients with VTE. Treatment for this patient group is bounded to the doctors own moral and ethical frameworks.
doi:10.1186/1472-6939-13-22
PMCID: PMC3459796  PMID: 22947200
Venous thromboembolism; Heparin; Low-molecular-weight; Palliative care; Qualitative research; Ethics; Medical
4.  Diagnosis and management of people with venous thromboembolism and advanced cancer: how do doctors decide? a qualitative study 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1472-6947-12-75
PMCID: PMC3445826  PMID: 22818215
Venous thromboembolism; Cancer; Palliative; Clinical decision making
5.  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.
doi:10.1007/s10555-010-9263-y
PMCID: PMC2962791  PMID: 20936327
Low molecular weight heparins; Metastatic melanoma; Selectin; Anti-metastatic
6.  Foreign travel for advanced cancer patients: a guide for healthcare professionals 
Postgraduate Medical Journal  2007;83(981):437-444.
The opportunity for a patient with advanced cancer to travel abroad may, for some, be a life affirming event during a dark period in their life. For others, what they hoped to be a time of joy may become an unmitigated disaster if they become unwell while away from the safety net of local cancer services. The rise of low budget airlines and cheaper foreign travel has led to an increase in the number of people travelling by air. Health professionals are more likely to face requests by patients to advise them on travel plans. Although foreign travel is an unrealistic goal for some patients, appropriate forward planning and proactive management can allow some patients to make an important journey abroad. This paper looks at the practical issues facing cancer patients who intend to travel overseas and offers practical advice on considerations that need to be made.
doi:10.1136/pgmj.2006.054593
PMCID: PMC2600098  PMID: 17621611
7.  FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer 
BMC Cancer  2009;9:355.
Background
Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer.
Methods/Design
The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility.
Trial registration
Current Controlled Trials ISRCTN80812769
doi:10.1186/1471-2407-9-355
PMCID: PMC2761945  PMID: 19807917
8.  Shark cartilage in the water 
BMJ : British Medical Journal  2006;333(7580):1221-1222.
doi:10.1136/bmj.39051.728738.3A
PMCID: PMC1693590  PMID: 17158397
11.  The Hydrophilic Amino-Terminal Arm of Reovirus Core Shell Protein λ1 Is Dispensable for Particle Assembly 
Journal of Virology  2002;76(23):12211-12222.
The reovirus core particle is a molecular machine that mediates synthesis, capping, and export of the viral plus strand RNA transcripts. Its assembly and structure-function relationships remain to be well understood. Following the lead of previous studies with other Reoviridae family members, most notably orbiviruses and rotaviruses, we used recombinant baculoviruses to coexpress reovirus core proteins λ1, λ2, and σ2 in insect cells. The resulting core-like particles (CLPs) were purified and characterized. They were found to be similar to cores with regard to their sizes, morphologies, and protein compositions. Like cores, they could also be coated in vitro with the two major outer-capsid proteins, μ1 and σ3, to produce virion-like particles. Coexpression of core shell protein λ1 and core nodule protein σ2 was sufficient to yield CLPs that could withstand purification, whereas expression of λ1 alone was not, indicating a required role for σ2 as a previous study also suggested. In addition, CLPs that lacked λ2 (formed from λ1 and σ2 only) could not be coated with μ1 and σ3, indicating a required role for λ2 in the assembly of these outer-capsid proteins into particles. To extend the use of this system for understanding the core and its assembly, we addressed the hypothesis that the hydrophilic amino-terminal region of λ1, which adopts an extended arm-like conformation around each threefold axis in the reovirus core crystal structure, plays an important role in assembling the core shell. Using a series of λ1 deletion mutants, we showed that the amino-terminal 230 residues of λ1, including its zinc finger, are dispensable for CLP assembly. Residues in the 231-to-259 region of λ1, however, were required. The core crystal structure suggests that residues in the 231-to-259 region are necessary because they affect the interaction of λ1 with the threefold and/or fivefold copies of σ2. An effective system for studies of reovirus core structure, assembly, and functions is hereby established.
doi:10.1128/JVI.76.23.12211-12222.2002
PMCID: PMC136864  PMID: 12414960

Results 1-11 (11)