No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA: n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations. (C) 2008 Elsevier Ltd. All rights reserved.

The structure of the Beck Hopelessness Scale: A confirmatory factor analysis in UK students

The aim of this paper was to confirm the factor structure of the 20-item Beck Hopelessness Scale in a non-clinical population. Previous research has highlighted a lack of clarity in its construct validity with regards to this population.

Based on previous factor analytic findings from both clinical and non-clinical studies, 13 separate confirmatory factor models were specified and estimated using LISREL 8.72 to test the one, two and three-factor models.

Psychology and medical students at Queen's University, Belfast (n = 581) completed both the BHS and the Beck Depression Inventory (BDI).

All models showed reasonable fit, but only one, a four-item single-factor model demonstrated a nonsignificant chi-squared statistic. These four items can be used to derive a Short-Form BHS (SBHS) in which increasing scores (0-4) corresponded with increasing scores in the BDI. The four items were also drawn from all three of Beck's proposed triad, and included both positively and negatively scored items.

This study in a UK undergraduate non-clinical population suggests that the BHS best measures a one-factor model of hopelessness. It appears that a shorter four-item scale can also measure this one-factor model. (C) 2011 Elsevier Ltd. All rights reserved.

Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

PURPOSE: Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.

METHODS: Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality.

RESULTS: Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.

CONCLUSIONS: There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Post-diagnostic oral bisphosphonate use and colorectal cancer mortality: a population-based cohort study within the UK Clinical Practice Research Datalink

Background:We conducted the first study to investigate post-diagnostic oral bisphosphonates use and colorectal cancer-specific mortality.

Methods:Colorectal cancer patients were identified from the National Cancer Data Repository (1998–2007) and linked to the UK Clinical Practice Research Datalink, providing prescription records, and Office of National Statistics mortality data. Time-dependent Cox regression models investigated colorectal cancer-specific mortality in post-diagnostic bisphosphonate users.

Results:Overall, in 4791 colorectal cancer patients, there was no evidence of an association between bisphosphonate use and colorectal cancer-specific mortality (adjusted hazard ratio=1.11; 95% confidence interval 0.80, 1.54) or with drug frequency or type.

Conclusions:In this novel population-based cohort study, post-diagnostic bisphosphonate use was not associated with longer rates of colorectal cancer survival.

The adaptations of a quality of life questionnaire for routine use in clinical practice: the Chronic Respiratory Disease Questionnaire in Cystic Fibrosis.

The assessment of quality of life (QOL) is necessary to monitor the course of disease and to assess the effect of new and existing interventions in clinical practice. This will only be achieved if QOL can be measured accurately and routinely. The aim of this study was to demonstrate the methodology involved in the adaptation and shortening of the Chronic Respiratory Disease Questionnaire (CRDQ) in a population of adults with cystic fibrosis (CF). A single interviewer administered the CRDQ to a sample of 45 adult patients (32 males) with CF prior to assessment of spirometric measures of lung function. Those patients whose lung function was stable at the time of study, and who could attend for a retest within 14 days, were asked to complete the questionnaire at a subsequent visit (n=10). The average interval between visits was 7 days (range 5-14 days). Correlations between spirometry and CRDQ dimensions ranged from -0.003 to 0.426. The fatigue, emotion and mastery dimensions showed high internal consistency, and adequate construct validity. In the small number of patients suitable for retest, the results indicated that the dimensions exhibited adequate test retest reliability. In contrast low internal consistency was demonstrated for the dyspnoea dimension. The fatigue, emotion and mastery dimensions could be reduced, in terms of their number of items without a substantial loss in explanatory power. This study suggests that QOL measurement can be made convenient, and so more easily accessible for routine clinical assessment.

A descriptive study of the usage of spinal manipulative therapy techniques within a randomised clinical trial in acute low back pain

The majority of randomized clinical trials (RCTs) of spinal manipulative therapy have not adequately de?ned the terms ‘mobilization’ and ‘manipulation’, nor distinguished between these terms in reporting the trial interventions. The purpose of this study was to describe the spinal manipulative therapy techniques utilized within a RCT of manipulative therapy (MT; n=80), interferential therapy (IFT; n=80), and a combination of both (CT; n=80) for people with acute low back pain (LBP). Spinal manipulative therapy was de?ned as any ‘mobilization’ (low velocity manual force without a thrust) or ‘manipulation’ (high velocity
thrust) techniques of the spine described by Maitland and Cyriax.
The 16 physiotherapists, all members of the Society of Orthopaedic Medicine, utilized three spinal manipulative therapy patterns in the RCT: Maitland Mobilization (40.4%, n=59), Maitland Mobilization/Cyriax Manipulation (40.4%, n=59) and Cyriax Manipulation (19.1%, n=28). There was a signi?cant difference between the MT and CT groups in their usage of spinal manipulative therapy techniques (w2=9.178; df=2;P=0.01); subjects randomized to the CT group received three times more Cyriax Manipulation (29.2%, n=21/72) than those randomized to the MT group (9.5%, n=7/74; df=1; P=0.003).
The use of mobilization techniques within the trial was comparable with their usage by the general population of physiotherapists in Britain and Ireland for LBP management. However, the usage of manipulation techniques was considerably higher than reported in physiotherapy surveys and may re?ect the postgraduate training of trial therapists.

Interleukin 18 promoter polymorphisms are not strongly associated with type 1 diabetes in a UK population

Interleukin 18 (IL18) is a proinflammatory cytokine whose levels are increased in the subclinical stage of insulin-dependent (type I) diabetes mellitus. Previous case-control studies have reported associations between IL18 -607C>A and -137G>C promoter polymorphisms and type I diabetes. We performed case-control and family-based association studies employing Pyrosequencing to assess if these IL18 polymorphisms are also associated with the development of type I diabetes in the Northern Ireland population. The chi2 analysis of genotype and allele frequencies for the IL18 polymorphisms in cases (n=433) vs controls (n=426) revealed no significant differences (P>0.05). Assessment of allele transmission distortion from informative parents to affected offspring also failed to confirm previously reported associations. Stratification of these analyses for age-at-onset and HLA-DR type did not reveal any significance associations. In conclusion, our data do not support the strong positive associations of IL18 promoter polymorphisms with type I diabetes reported in previous smaller studies.

Human marrow mesenchymal stem Cells (MSCs) in the peplated non-adherent cell population serve as a complementary source of osteogenic cells

To obtain enough quantity of osteogenic cells is a challenge for successful cell therapy in bone defect treatment, and cell numbers were usually achieved by culturing bone marrow cells in a relatively long duration. This study reported a simple and cost effective method to enhance the number of MSCs by collecting and replating the non-adherent cell population of marrow MSCs culture. Bone marrow MSCs were isolated from 11 patients, cultured at a density of 1×105/cm2 to 1×106/cm2 in flasks. For the first three times of media change, the floating cells were centrifuged and replated in separate flasks. The total number of cells in both the primary and replating flasks were counted at day 21. Cell proliferation rate, potentials for osteogenic, chondrognenic, and adipogenic differentiation were examined in both cell types in vitro. In-vivo osteogenic potentials of the cells were also tested in mice implantation model. The results showed that MSCs derived from non-adherent cell population of marrow cell cultures have similar cell proliferation and differentiation potentials as the originally attached MSCs in vitro. When implanted with HA-TCP materials subcutaneously in SCID mice, newly formed bony tissues were found in both cell type groups with osteocalcin expression. We have obtained 36.6% (20.70%-44.97%) more MSCs in the same culture period when the non-adherent cell populations were collected. The findings confirmed that the non-adherent cell population in the bone marrow culture is a complementary source of MSCs, collecting these cells is a simple and cost-effective way to increase MSCs numbers and reduce the time required for culturing MSCs for clinical applications.