Showing papers by "Leicester Royal Infirmary published in 2011"

Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies

Abstract: Summary Background Substantial uncertainty exists about prevalence of mood disorders in patients with cancer, including those in oncological, haematological, and palliative-care settings. We aimed to quantitatively summarise the prevalence of depression, anxiety, and adjustments disorders in these settings. Methods We searched Medline, PsycINFO, Embase, and Web of Knowledge for studies that examined well-defined depression, anxiety, and adjustment disorder in adults with cancer in oncological, haematological, and palliative-care settings. We restricted studies to those using psychiatric interviews. Studies were reviewed in accordance with PRISMA guidelines and a proportion meta-analysis was done. Findings We identified 24 studies with 4007 individuals across seven countries in palliative-care settings. Meta-analytical pooled prevalence of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria was 16·5% (95% CI 13·1–20·3), 14·3% (11·1–17·9) for DSM-defined major depression, and 9·6% (3·6–18·1) for DSM-defined minor depression. Prevalence of adjustment disorder alone was 15·4% (10·1–21·6) and of anxiety disorders 9·8% (6·8–13·2). Prevalence of all types of depression combined was of 24·6% (17·5–32·4), depression or adjustment disorder 24·7% (20·8–28·8), and all types of mood disorder 29·0% (10·1–52·9). We identified 70 studies with 10 071 individuals across 14 countries in oncological and haematological settings. Prevalence of depression by DSM or ICD criteria was 16·3% (13·4–19·5); for DSM-defined major depression it was 14·9% (12·2–17·7) and for DSM-defined minor depression 19·2% (9·1–31·9). Prevalence of adjustment disorder was 19·4% (14·5–24·8), anxiety 10·3% (5·1–17·0), and dysthymia 2·7% (1·7–4·0). Combination diagnoses were common; all types of depression occurred in 20·7% (12·9–29·8) of patients, depression or adjustment disorder in 31·6% (25·0–38·7), and any mood disorder in 38·2% (28·4–48·6). There were few consistent correlates of depression: there was no effect of age, sex, or clinical setting and inadequate data to examine cancer type and illness duration. Interpretation Interview-defined depression and anxiety is less common in patients with cancer than previously thought, although some combination of mood disorders occurs in 30–40% of patients in hospital settings without a significant difference between palliative-care and non-palliative-care settings. Clinicians should remain vigilant for mood complications, not just depression. Funding None.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Abstract: Background The eff ects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical S urgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confi rmed mesothelioma and were deemed fi t enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. Af ter further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratifi ed by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (fi ve patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in fi ve patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively af ter receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92–3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21–6·26; p=0·016). Median survival was 14·4 months (5·3–18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no signifi cant diff erences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy off ers no benefi t and possibly harms patients.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.

Abstract: Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Abstract: Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.

Conservative prevention and management of pelvic organ prolapse in women.

Abstract: Background Pelvic organ prolapse is common, and some degree of prolapse is seen in 50% of parous women. Women with prolapse can experience a variety of pelvic floor symptoms. Treatments include surgery, mechanical devices and conservative management. Conservative management approaches, such as giving lifestyle advice and delivering pelvic floor muscle training (PFMT), are often used in cases of mild to moderate prolapse. This is an update of a Cochrane review first published in 2004, and previously updated in 2006. Objectives To determine the effects of conservative management (physical and lifestyle interventions) for the prevention or treatment of pelvic organ prolapse in comparison with no treatment or other treatment options (such as mechanical devices or surgery). Search methods We searched the Cochrane Incontinence Group Specialised Trials Register (searched 6 May 2010), EMBASE (1 January 1996 to 6 May 2010), CINAHL (1 January 1982 to 10 May 2010), PEDro (January 2009), the UK National Research Register (January 2009), ClinicalTrials.gov (April 2009), Current Controlled Trials register (April 2009), CENTRAL (Issue 1, 2009) and ZETOC (January 2009) and the reference lists of relevant articles. Selection criteria Randomised and quasi-randomised trials in women with pelvic organ prolapse that included a physical or lifestyle intervention in at least one arm of the trial. Data collection and analysis Two reviewers assessed all trials for inclusion/exclusion and methodological quality. Data were extracted by the lead reviewer onto a standard form and cross checked by another. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions. Main results Six trials were included; three of these trials are new to this update. Four trials were small (less than 25 women per arm) and two had moderate to high risk of bias. Four trials compared PFMT as a treatment for prolapse against a control group (n = 857 women); two trials included women having surgery for prolapse and compared PFMT as an adjunct to surgery versus surgery alone (n = 118 women). PFMT versus control There was a significant risk of bias in two out four trials in this comparison. Prolapse symptoms and women's reports of treatment outcomes (primary outcomes) were measured differently in the three trials where this was reported: all three indicated greater improvement in symptoms in the PFMT group compared to the control group. Pooling data on severity of prolapse from two trials indicated that PFMT increases the chance of an improvement in prolapse stage by 17% compared to no PFMT. The two trials which measured pelvic floor muscle function found better function (or improvement in function) in the PFMT group compared to the control group; measurements were not known to be blinded. Two out of three trials which measured urinary outcomes (urodynamics, frequency and bother of symptoms, or symptom score) reported differences between groups in favour of the PFMT group. One trial reported bowel outcomes, showing less frequency and bother with symptoms in the PFMT group compared to the control group. PFMT supplementing surgery versus surgery alone Both trials were small and neither measured prolapse-specific outcomes. Pelvic floor muscle function findings differed between the trials: one found no difference between trial groups in muscle strength, whilst the other found a benefit for the PFMT group in terms of stronger muscles. Similarly findings relating to urinary outcomes were contradictory: one trial found no difference in symptom score change between groups, whilst the other found more improvement in urinary symptoms and a reduction in diurnal frequency in the PFMT group compared to the control group. Authors' conclusions There is now some evidence available indicating a positive effect of PFMT for prolapse symptoms and severity. The largest most rigorous trial to date suggests that six months of supervised PFMT has benefits in terms of anatomical and symptom improvement (if symptomatic) immediately post-intervention. Further evidence relating to effectiveness and cost-effectiveness of PFMT, of different intensities, for symptomatic prolapse in the medium and long term is needed. A large trial of PFMT supplementing surgery is needed to give clear evidence about the usefulness of combining these treatments. Other comparisons which have not been addressed in trials to date and warrant consideration include those involving lifestyle change interventions, and trials aimed at prolapse prevention.

A systematic review of comprehensive geriatric assessment to improve outcomes for frail older people being rapidly discharged from acute hospital: ‘interface geriatrics’

Abstract: Background many frail older people who attend acute hospital settings and who are discharged home within short periods (up to 72 h) have poor outcomes. This review assessed the role of comprehensive geriatric assessment (CGA) for such people. Methods standard bibliographic databases were searched for high-quality randomised controlled trials (RCTs) of CGA in this setting. When appropriate, intervention effects were presented as rate ratios with 95% confidence intervals. Results five trials of sufficient quality were included. There was no clear evidence of benefit for CGA interventions in this population in terms of mortality [RR 0.92 (95% CI 0.55-1.52)] or readmissions [RR 0.95 (95% CI 0.83-1.08)] or for subsequent institutionalisation, functional ability, quality-of-life or cognition. Conclusions there is no clear evidence of benefit for CGA interventions in frail older people being discharged from emergency departments or acute medical units. However, few such trials have been carried out and their overall quality was poor. Further well designed trials are justified.

Opioid receptor subtypes: fact or artifact?

Abstract: There is a vast amount of pharmacological evidence favouring the existence of multiple subtypes of opioid receptors. In addition to the primary classification of µ (mu: MOP), δ (delta: DOP), κ (kappa: KOP) receptors, and the nociceptin/orphanin FQ peptide receptor (NOP), various groups have further classified the pharmacological µ into µ1–3, the δ into δ1–2/δcomplexed/non-complexed, and the κ into κ1–3. From an anaesthetic perspective, the suggestions that µ1 produced analgesia and µ2 produced respiratory depression are particularly important. However, subsequent to the formal identification of the primary opioid receptors (MOP/DOP/KOP/NOP) by cloning and the use of this information to produce knockout animals, evidence for these additional subtypes is lacking. Indeed, knockout of a single gene (and hence receptor) results in a loss of all function associated with that receptor. In the case of MOP knockout, analgesia and respiratory depression is lost. This suggests that further sub-classification of the primary types is unwise. So how can the wealth of pharmacological data be reconciled with new molecular information? In addition to some simple misclassification (κ3 is probably NOP), there are several possibilities which include: (i) alternate splicing of a common gene product, (ii) receptor dimerization, (iii) interaction of a common gene product with other receptors/signalling molecules, or (iv) a combination of (i)–(iii). Assigning variations in ligand activity (pharmacological subtypes) to one or more of these molecular suggestions represents an interesting challenge for future opioid research.

Ketamine: new uses for an old drug?

Abstract: In 1996, we published an editorial ‘Ketamine, mechanism(s) of action and unusual clinical uses’ in the British Journal of Anaesthesia. In that editorial, we described the pharmacology of ketamine including bronchodilator, anti-shock, and neuroprotective actions along with some unusual clinical applications. The editorial has been cited more than 130 times in total with around 10 citations every year, which implies that ketamine is still of interest to a wide audience. However, as ketamine anaesthesia is associated with cardiovascular hyperdynamics and disturbing emergence reactions, this agent is often avoided, despite the ease with which these adverse reactions can be prevented by pre-administration, co-administration of sedatives, or both such as benzodiazepines, propofol, dexmedetomidine, or droperidol. In the past 15 yr, ketamine has been reported to possess several new clinically beneficial properties such as potentiation of opioid analgesia, prevention of opioid-induced acute tolerance and spinal ischaemia, anti-inflammatory actions, preventive effects on recall and awareness during general anaesthesia, and anti-tumour actions. In this ‘update’ editorial, we have focused on these potential clinical advantages of ketamine.

Clinical recognition of dementia and cognitive impairment in primary care: a meta-analysis of physician accuracy.

Abstract: Mitchell AJ, Meader N, Pentzek M. Clinical recognition of dementia and cognitive impairment in primary care: a meta-analysis of physician accuracy. Objective: We aimed to examine the ability of the general practitioners (GPs) to recognize a spectrum of cognitive impairment from mild cognitive impairment (MCI) to severe dementia in routine practice using their own clinical judgment. Method: Using PRISMA criteria, a meta-analysis of studies testing clinical judgment and clinical documentation was conducted against semi-structured interviews (for dementia) and cognitive tests (for cognitive impairment). We located 15 studies reporting on dementia, seven studies that examined recognition of broadly defined cognitive impairment, and eight regarding MCI. Results: By clinical judgment, clinicians were able to identify 73.4% of people with dementia and 75.5% of those without dementia but they made correct annotations in medical records in only 37.9% of cases (and 90.5% of non-cases). For cognitive impairment, detection sensitivity was 62.8% by clinician judgment but 33.1% according to medical records. Specificity was 92.6% for those without cognitive impairment by clinical judgment. Regarding MCI, GPs recognized 44.7% of people with MCI, although this was recorded in medical notes only 10.9% of the time. Their ability to identify healthy individuals without MCI was between 87.3% and 95.5% (detection specificity). Conclusion: GPs have considerable difficulty identifying those with MCI and those with mild dementia and are generally poor at recording such diagnoses in medical records.

The Fornix in Health and Disease: An Imaging Review

Abstract: Anatomy and function of the fornix are reviewed and examples of pathologic processes that affect it are discussed, with emphasis on the contribution of forniceal pathologic conditions to cognition in disease states.

Desire for psychological support in cancer patients with depression or distress: validation of a simple help question.

Abstract: Objectives: Despite documented high rates of psychological distress, it is not clear how to identify those who are willing to accept help. The aim of this study was to investigate whether asking patients receiving chemotherapy if they want help with emotional problems is valuable and to investigate the type of help they want. Methods: Patients attending a chemotherapy suite were asked to complete the Hospital Anxiety and Depression Scale, the Brief Patient Health Questionnaire (PHQ) and the Emotion Thermometers tools. Results were compared with a single question on desire for help. Results: In this study, 128 patients completed questionnaires for distress, depression, anxiety and desire for help at initial interview. Only one in five unselected patients had a perceived need for help, and in distressed patients only 36% expressed a desire for help. The addition of the help question to the two questions (PHQ-2) about mood and interest improved the ability to rule-in depression by increasing the specificity. However, by addition of this question, sensitivity was significantly reduced. Desire for help was modestly associated with severity of distress, anxiety and depression. Conclusions: The addition of a help question appears to have limited value in screening for psychological symptoms, but it may highlight those who are willing to accept addition support. Clinicians should attempt to offer a range of psychosocial interventions that will be acceptable to patients with distress. Copyright © 2010 John Wiley & Sons, Ltd.

Detection of HER2 amplification in circulating free DNA in patients with breast cancer.

Abstract: Human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in 20–25% of breast cancers. This study investigated circulating free DNA (cfDNA) for detection of HER2 gene amplification in patients with breast cancer. Circulating free DNA was extracted from plasma of unselected patients with primary breast cancer (22 before surgery and 68 following treatment), 30 metastatic patients and 98 female controls using the QIAamp Blood DNA Mini Kit (Qiagen). The ratio of HER2 to an unamplified reference gene (contactin-associated protein 1 (CNTNAP1)) was measured in cfDNA samples by quantitative PCR (qPCR) using SK-BR-3 cell line DNA as a positive control. We validated the qPCR assay with DNA extracted from 23 HER2 3+ and 40 HER2-negative tumour tissue samples; the results agreed for 60 of 63 (95.2%) tumours. Amplification was detected in cfDNA for 8 of 68 patients following primary breast cancer treatment and 5 of 30 metastatic patients, but was undetected in 22 patients with primary breast cancer and 98 healthy female controls. Of the patients with amplification in cfDNA, 10 had HER2 3+ tumour status by immunohistochemistry. The results demonstrate for the first time the existence of amplified HER2 in cfDNA in the follow-up of breast cancer patients who are otherwise disease free. This approach could potentially provide a marker in patients with HER2-positive breast cancer.

Revascularisation and mortality rates following acute coronary syndromes in people with severe mental illness: comparative meta-analysis.

Abstract: Background High levels of comorbid physical illness and excess mortality rates have been previously documented in people with severe mental illness, but outcomes following myocardial infarction and other acute coronary syndromes are less clear. Aims To examine inequalities in the provision of invasive coronary procedures (revascularisation, angiography, angioplasty and bypass grafting) and subsequent mortality in people with mental illness and in those with schizophrenia, compared with those without mental ill health. Method Systematic search and random effects meta-analysis were used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies of mental health and cardiovascular procedures following cardiac events were eligible but we required a minimum of three independent studies to warrant pooling by procedure type. We searched Medline/PubMed and EMBASE abstract databases and ScienceDirect, Ingenta Select, SpringerLink and Online Wiley Library full text databases. Results We identified 22 analyses of possible inequalities in coronary procedures in those with defined mental disorder, of which 10 also reported results in schizophrenia or related psychosis. All studies following acute coronary syndrome originated in the USA. The total sample size was 825 754 individuals. Those with mental disorders received 0.86 (relative risk, RR: 95% CI 0.80–0.92, P<0.0001) of comparable procedures with significantly lower receipt of coronary artery bypass graft (CABG; RR = 0.85, 95% CI 0.72–1.00), cardiac catheterisation (RR = 0.85, 95% CI 0.76–0.95) and percutaneous transluminal coronary angioplasty or percutaneous coronary intervention (PTCA/PCI; RR = 0.87, 95% CI 0.72–1.05). People with a diagnosis of schizophrenia received only 0.53 (95% CI 0.44–0.64, P<0.0001) of the usual procedure rate with significantly lower receipt of CABG (RR = 0.69, 95% CI 0.55–0.85) and PTCA/PCI (RR = 0.50, 95% CI 0.34–0.75). We identified 6 related studies examining mortality following cardiac events: for those with mental illness there was a 1.11 relative risk of mortality up to 1 year (95% CI 1.00–1.24, P = 0.05) but there was insufficient evidence to examine mortality rates in schizophrenia alone. Conclusions Following cardiac events, individuals with mental illness experience a 14% lower rate of invasive coronary interventions (47% in the case of schizophrenia) and they have an 11% increased mortality rate. Further work is required to explore whether these factors are causally linked and whether improvements in medical care might improve survival in those with mental ill health.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease.

Abstract: Aliment Pharmacol Ther 2011; 33: 946–953 Summary Background Adalimumab is efficacious therapy for adults with Crohn’s disease (CD). Aim To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. Methods British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow-up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn’s Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). Results Seventy-two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric-centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1–17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ28.8, P = 0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). Conclusions Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.

Avotermin for Scar Improvement following Scar Revision Surgery: A Randomized, Double-Blind, Within-Patient, Placebo-Controlled, Phase II Clinical Trial

Abstract: BACKGROUND: Skin scarring is associated with psychosocial distress and has a negative effect on quality of life. The transforming growth factor (TGF)-? family of cytokines plays a key role in scarring. TGF-?3 improves scar appearance in a range of mammalian species. This study was performed to assess the efficacy of intradermal avotermin (TGF-?3) for the improvement of scar appearance following scar revision surgery. METHODS: Sixty patients (35 men and 25 women; age, 19 to 78 years; 53 Caucasians; scar length, 5 to 21 cm) received intradermal avotermin (200 ng/100 ?l/linear cm wound margin) and placebo to outer wound segments immediately after, and again 24 hours after, complete (group 1) or staged (group 2) scar revision surgery. A within-patient design was chosen to control for interindividual factors that affect scarring. The primary efficacy variable was a total scar score derived from a visual analogue scale, scored by a lay panel from standardized photographs from months 1 through 7 following treatment. RESULTS: : Primary endpoint data from the combined surgical groups showed that avotermin significantly improved scar appearance compared with placebo (total scar score difference, 21.93 mm; p = 0.04). Profilometry showed a greater reduction in scar surface area from baseline with avotermin treatment compared with placebo, significant in group 2 at months 7 and 12 (difference, 41.99 mm and 25.85 mm, respectively; p = 0.03 for both comparisons). Histologic analysis from group 2 showed that, compared with placebo treatment, collagen organization in avotermin-treated scars more closely resembled normal skin in 14 of 19 cases. Avotermin was well tolerated. CONCLUSION: Avotermin administration following scar revision surgery is well tolerated and significantly improves scar appearance compared with placebo. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.(Figure is included in full-text article.).

The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility

Abstract: results: The ECS plays a pivotal role in human reproduction. The enzymes involved in the synthesis and degradation of endocannabi- noids normalize levels of AEA for successful implantation. The AEA degrading enzyme (fatty acid amide hydrolase) activity as well as AEA content in blood may potentially be used for the monitoring of early pregnancies. Progesterone and oestrogen are involved in the mainten- ance of endocannabinoid levels. The ECS plays an important role in the immune regulation of human fertility.

Curcumin ameliorates oxaliplatin‐induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo

Abstract: The aims of this study were to determine potency of oxaliplatin in combination with curcumin in oxaliplatin-resistant cell lines in vitro and to evaluate the efficacy of a novel curcumin formulation (Meriva®) alone and in combination with oxaliplatin in colorectal tumor-bearing mice, exploring relevant pharmacodynamic markers in vivo. Oxaliplatin-resistant HCT116 p53wt and p53(-/-) cell lines were generated, and the effects of oxaliplatin in combination with curcumin on resistance- and proliferation-associated proteins investigated. Eighty nude mice were implanted with HCT116 p53wt colorectal cancer cells before randomization into the following treatment groups: control; Meriva only; oxaliplatin only; Meriva + oxaliplatin. Tumor volume was assessed, as was the expression of Ki-67, cleaved caspase-3 and Notch-1. Curcumin in combination with oxaliplatin was able to decrease proliferative capacity of oxaliplatin-resistant p53 wildtype and p53(-/-) cell lines more effectively than oxaliplatin alone. It also decreased markers associated with proliferation. After 21 days of treatment in the xenograft model, the order of efficacy was combination > Meriva > oxaliplatin > control. The decrease in tumor volume when compared to vehicle-treated animals was 53, 35 and 16%, respectively. Ki-67 and Notch-1 immunoreactivity was decreased by the combination when compared to vehicle-treated animals, with cleaved caspase-3 rising by 4.4-fold. Meriva did not adversely affect the DNA-platinating ability of oxaliplatin. Curcumin enhanced the cytotoxicity of oxaliplatin in models of oxaliplatin resistance in vitro. In vivo, Meriva greatly enhanced oxaliplatin efficacy, without affecting the mode of action of oxaliplatin. Addition of formulated curcumin to oxaliplatin-based chemotherapy regimens has the potential for clinical benefit.

Patient preferences for the delivery of bad news - the experience of a UK Cancer Centre.

Abstract: The primary aim of this study was to assess how patients would prefer to be given their cancer diagnosis in a typical UK cancer centre. Two hundred and forty-four patients attending the oncology outpatient department at the Leicester Royal Infirmary, UK, were recruited. Patients were invited to complete the Measure of Patients' Preferences questionnaire, write comments on their own experience of the breaking bad news consultation and choose their preferred role in decision making. Over 90% of questionnaires were completed. Patients rated the items addressing the message content of the consultation as more important than the facilitative or the supportive aspects. Over 80% of patients wrote a detailed account of their experiences, of which 60% were satisfied with the consultation. Most of the patients who were dissatisfied commented on the unsympathetic or pessimistic manner of the doctor. The majority of patients wanted a collaborative role in decision making. Regarding the cancer diagnosis, the majority of patients have information needs, want to be involved in treatment decisions and know their prognosis. The difficulty for physicians is how to meet individual information needs, give hope, but not deliver unrealistic expectations.

Screening for cancer-related distress: Summary of evidence from tools to programmes

Abstract: Introduction. A number of studies have addressed the development and testing of tools for measuring cancer-related distress. Except for studies of diagnostic validity, knowledge on the effect of screening for psychological distress on psychological well-being is limited. We aimed to describe and critically discuss the findings of randomized trials of the effect of screening and to identify components necessary for future studies of the effectiveness of screening programmes. Methods. A search was made of the Embase/Medline and Web of Knowledge abstract databases from inception to September 2010. Our inclusion criterion was randomized controlled trials concerning the effect of screening for psychological distress on psychological outcomes. We compared the randomized trials on the following aspects: design and methods, setting and sample, screening and intervention, effects on psychological distress, staff utilization of screening results, possible confounding factors and other methodological limitat...

Curcumin: the potential for efficacy in gastrointestinal diseases

Abstract: Curcumin is a naturally occurring phytochemical and an extract of Turmeric. Extensive in vitro and in vivo data have paved the way for curcumin to become the subject of clinical trials. Curcumin modulates key signalling pathways important in cellular processes. Numerous mechanisms of action have been elucidated. The potential for clinical efficacy is apparent from benign and malignant disease models. Curcumin has potent anti-inflammatory and anti-neoplastic properties used alone and in combination with standard therapies. Early-phase trials have ascertained pharmacological properties and consistently demonstrate it to be safe and well tolerated. However, bioavailability is limited and efficacious doses have not yet been determined. Evidence of efficacy has been derived from animal models or small clinical trials. There is only finite data supporting the use of curcumin in phase III trials with specific diseases (e.g. ulcerative colitis). However, for the vast majority of conditions additional early-phase studies are required to justify larger trials determining efficacy.

The Functional Significance Of Foveal Abnormalities In Albinism Measured Using Spectral-domain Optical Coherence Tomography

Abstract: PURPOSE The relationship between foveal abnormalities in albinism and best-corrected visual acuity (BCVA) is unclear. High-resolution spectral-domain optical coherence tomography (SD OCT) was used to quantify foveal retinal layer thicknesses and to assess the functional significance of foveal morphologic features in patients with albinism. DESIGN Cross-sectional study. PARTICIPANTS Forty-seven patients with albinism and 20 healthy control volunteers were recruited to the study. METHODS Using high-resolution SD OCT, 7×7×2-mm volumetric scans of the fovea were acquired (3-μm axial resolution). The B scan nearest the center of the fovea was identified using signs of foveal development. The thickness of each retinal layer at the fovea and foveal pit depth were quantified manually using ImageJ software and were compared with BCVA. MAIN OUTCOME MEASURES Total retinal thickness, foveal pit depth, photoreceptor layer thickness, and processing layer thickness in relation to BCVA. RESULTS Total photoreceptor layer thickness at the fovea was correlated highly to BCVA (P = 0.0008; r = -0.501). Of the photoreceptor layers, the outer segment length was correlated most strongly to BCVA (P<0.0001; r = -0.641). In contrast, there was no significant correlation between either total retinal thickness or pit depth and BCVA (P>0.05). This was because of an inverse correlation between total photoreceptor layer thickness and total processing layer thickness (P<0.0001; r = -0.696). CONCLUSIONS Neither the total retinal thickness nor the pit depth are reliable indicators of visual deficit, because patients with similar overall retinal thickness had widely varying foveal morphologic features. In albinism, the size of the photoreceptor outer segment was found to be the strongest predictor of BCVA. These results suggest that detailed SD OCT images of photoreceptor anatomic features provide a useful tool in assessing the visual potential in patients with albinism. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Identification of patient-reported distress by clinical nurse specialists in routine oncology practice: a multicentre UK study.

Abstract: Background: There is uncertainty regarding how well clinical nurse specialists are able to identify distress in cancer settings. Methods: We examined recognition of patient-reported distress by nurse specialists across three sites in the East Midlands (UK). Clinicians were asked to report on their clinical opinion regarding the presence of distress or any mental health complication after routine assessment of 401 mixed cancer patients. Patient-reported distress was defined by the distress thermometer at a cut-off of 4 or higher. Results: We found that the prevalence of patient-reported distress was 45.4%. The rates for mild, moderate and severe distress were: 23.4, 13.7 and 8.2, respectively. When looking for distress (or any mental health complication) nurse practitioners had a detection sensitivity of 50.5% and specificity 80.0%. Cohen's kappa suggested fair agreement between staff and patients. Examining predictors of distress, clinicians were better able to recognise higher severities of distress (adjusted R2=0.87 P=0.001). There was lower sensitivity in palliative stages but no differences according to the type of cancer. There was also higher sensitivity but lower specificity in those clinicians with high self-rated confidence. Conclusions: Nurses working in cancer settings have difficulty identifying distress using their routine clinical judgement and tend to make more false-negative than false-positive errors. Evidence-based strategies that improve detection of mild and moderate distress are required in routine cancer care. Copyright © 2010 John Wiley & Sons, Ltd.

Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial.

Abstract: Summary Background Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa. Methods The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840. Findings 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2·4, 95% CI 1·3–4·2, p=0·003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug. Interpretation Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence. Funding Meningitis Research Foundation.

Screening for diabetes using an oral glucose tolerance test within a western multi-ethnic population identifies modifiable cardiovascular risk: the ADDITION-Leicester study.

Abstract: Aims/hypothesis The aim of this study was to determine the frequency of undiagnosed glucose abnormalities and the burden of cardiovascular disease (CVD) risk among south Asians and white Europeans attending a systematic screening programme for type 2 diabetes (ADDITION-Leicester) and to estimate the achievable risk reduction in individuals identified with glucose disorders.