Reynolds G.P.,Sheffield Hallam University |
McGowan O.O.,NHS Lanarkshire |
Dalton C.F.,Sheffield Hallam University
British Journal of Clinical Pharmacology | Year: 2014
The treatment of severe mental illness, and of psychiatric disorders in general, is limited in its efficacy and tolerability. There appear to be substantial interindividual differences in response to psychiatric drug treatments that are generally far greater than the differences between individual drugs; likewise, the occurrence of adverse effects also varies profoundly between individuals. These differences are thought to reflect, at least in part, genetic variability. The action of psychiatric drugs primarily involves effects on synaptic neurotransmission; the genes for neurotransmitter receptors and transporters have provided strong candidates in pharmacogenetic research in psychiatry. This paper reviews some aspects of the pharmacogenetics of neurotransmitter receptors and transporters in the treatment of psychiatric disorders. A focus on serotonin, catecholamines and amino acid transmitter systems reflects the direction of research efforts, while relevant results from some genome-wide association studies are also presented. There are many inconsistencies, particularly between candidate gene and genome-wide association studies. However, some consistency is seen in candidate gene studies supporting established pharmacological mechanisms of antipsychotic and antidepressant response with associations of functional genetic polymorphisms in, respectively, the dopamine D2 receptor and serotonin transporter and receptors. More recently identified effects of genes related to amino acid neurotransmission on the outcome of treatment of schizophrenia, bipolar illness or depression reflect the growing understanding of the roles of glutamate and γ-aminobutyric acid dysfunction in severe mental illness. A complete understanding of psychiatric pharmacogenomics will also need to take into account epigenetic factors, such as DNA methylation, that influence individual responses to drugs. © 2013 The British Pharmacological Society.
Langan J.,NHS Lanarkshire |
Shajahan P.,University of Glasgow
Psychiatrist | Year: 2010
Antipsychotic polypharmacy is an increasingly encountered clinical scenario. This review considers the reasons behind antipsychotic polypharmacy and the patterns of its use. We also consider the evidence of effectiveness of combined therapy v. monotherapy and the rationale behind the potentially beneficial combinations that are used. The potential dangers of antipsychotic polypharmacy are also discussed and the limited research regarding switching from polypharmacy to monotherapy is reviewed. Some provisional recommendations regarding antipsychotic polypharmacy are proposed.
Maguire R.,University of Surrey |
Kotronoulas G.,University of Surrey |
Simpson M.,NHS Lanarkshire |
Paterson C.,Ninewells Hospital
Gynecologic Oncology | Year: 2015
Background: Women with cervical cancer constitute a patient population in need for ongoing, person-centred supportive care. Our aim was to synthesise current available evidence with regard to the supportive care needs of women living with and beyond cervical cancer. Methods: A systematic review was conducted according to the PRISMA Statement guidelines. Seven electronic databases (DARE, Cochrane, MEDLINE, CINAHL, BNI, PsychINFO and EMBASE) were searched to identify studies employing qualitative and/or quantitative methods. Pre-specified selection criteria were applied to all records published between 1990 and 2013. Methodological quality evaluation was conducted using the standardised QualSyst evaluation tool. Findings: were integrated in a narrative synthesis. Findings Of 4936 references initially retrieved, 15 articles (13 unique studies) met eligibility criteria. One study fell below a pre-specified 55% threshold of methodological quality and was excluded. Individual needs were classified into ten domains of need. Interpersonal/intimacy (10; 83.3%), health system/information (8; 66.7%), psychological/emotional (7; 58.3%) and physical needs (6; 50%) were those most frequently explored. Spiritual/existential (1; 8.3%), family-related (2; 16.7%), practical (2; 16.7%), and daily living needs (2; 16.7%) were only rarely explored. Patient-clinician communication needs and social needs were addressed in 4 studies (33.3%). Dealing with fear of cancer recurrence, concerns about appearance/body image, lack of sexual desire, requiring more sexuality-related information, dealing with pain, and dealing with difficulties in relationship with partner were the most frequently cited individual needs (≥ 4 studies). Conclusions: Despite a host of additional needs experienced by women with cervical cancer, a predominant focus on sexuality/intimacy and information seeking issues is noted. Study limitations preclude drawing conclusions as to how these needs evolve over time from diagnosis to treatment and subsequently to survivorship. Whether demographic or clinical variables such as age, race/ethnicity, disease stage or treatment modality play a moderating role, only remains to be answered in future studies. © 2014 Elsevier Inc. All rights reserved.
Fleming E.,NHS Lanarkshire
Nursing in critical care | Year: 2011
This article is a report of a study of the experiences of expert critical care nurses in their transition to the role of advanced nurse practitioner within an intensive care unit (ICU) setting. The advanced nurse practitioner role was developed to support the ICU team and to undertake many of the roles traditionally associated with junior medical staff in this specialized area. The impetus for this study therefore was generated from the need to explore the role development experiences of trainee advanced nurse practitioners to inform future developments and practice. This study used grounded theory methodology to conduct and analyse data from 25 participants. The data were collected between March 2010 and August 2010, using interview format. Data collection and analysis was conducted simultaneously using methods associated with grounded theory, theoretical sampling and the constant comparative method. 'Staying the course to advanced nursing practice' emerged as the core category, with four related major categories and substantive codes. In conjunction, the substantive theory explaining the essential processes involved comprised of three inextricably linked processes: situational, development and conceptual meaning. The developed conceptual model captures the unique experiences of expert critical care nurses during their transition to confident and competent advanced nurse practitioners. This study provides an account of the role transition from expert critical care nurse to advanced nurse practitioner, specifically the synthesis of expert nursing practice with traditional medical values. The conceptual model has the potential to be utilized as a framework for others embarking upon similar projects, informing advanced nurse practitioner roles within and out with critical care settings. © 2011 The Authors. Nursing in Critical Care © 2011 British Association of Critical Care Nurses.
Darrien J.H.,NHS Lanarkshire
Annals of the Royal College of Surgeons of England | Year: 2013
Boerhaave's syndrome represents the most lethal of all gastrointestinal perforations. In 2009 a treatment algorithm was published based on current level 4 evidence indicating that all septic patients should be treated surgically, early presentations without sepsis endoscopically and delayed presentations without sepsis conservatively. No provision was made for septic patients unfit for surgical intervention. Using a case series, we demonstrate how minimally invasive endoscopic therapies can be used successfully to manage such a cohort. Between September 2008 and January 2010, five patients presented to Wishaw General Hospital with Boerhaave's syndrome, all with an associated septic profile and none fit for surgery. They were managed using minimally invasive endoscopic therapies including endoscopic placement of oesophageal stents, elimination of mediastinal/pleural contamination using video assisted thorascopic lavage, management of subsequent collections using sinus tract endoscopy and mini-laparotomy with transhiatal endoscopic drainage, and closure of oesophagocutaneous fistulas using the Surgisis® (Cook Surgical, Bloomington, IN, US) anal fistula plug sited endoscopically with a rendezvous technique. Oesophageal re-epithelialisation and resolution of sepsis was achieved in all five cases on days 50, 50, 51, 59 and 103. Four patients are alive today. The fifth died on day 109 in hospital as a consequence of co-morbidity. Two patients required oesophageal dilatation for benign oesophageal strictures. Minimally invasive endoscopic therapy can be used successfully to achieve oesophageal re-epithelialisation and resolution of sepsis in patients unfit for surgical intervention. It offers a feasible treatment for patients not accounted for in today's literature and expands on currently described endoscopic therapies.