Helen Coelho

Mindfulness-Based Cognitive Therapy: Evaluating Current Evidence and Informing Future Research.

Mindfulness-based cognitive therapy (MBCT) is a recently developed class-based program designed to prevent relapse or recurrence of major depression (Z. V. Segal, J. M. G. Williams, & J. Teasdale, 2002). Although research in this area is in its infancy, MBCT is generally discussed as a promising therapy in terms of clinical effectiveness. The aim of this review was to outline the evidence that contributes to this current viewpoint and to evaluate the strengths and weaknesses of this evidence to inform future research. By systematically searching 6 electronic databases and the reference lists of retrieved articles, the authors identified 4 relevant studies: 2 randomized clinical trials, 1 study based on a subset of 1 of these trials, and 1 nonrandomized trial. The authors evaluated these trials and discussed methodological issues in the context of future research. The current evidence from the randomized trials suggests that, for patients with 3 or more previous depressive episodes, MBCT has an additive benefit to usual care. However, because of the nature of the control groups, these findings cannot be attributed to MBCT-specific effects. Further research is necessary to clarify whether MBCT does have any specific effects.

Complementary and alternative medicine use in England: results from a national survey.

Objectives:  In many countries, recent data on the use of complementary and alternative medicine (CAM) are available. However, in England, there is a paucity of such data. We sought to determine the prevalence and predictors of CAM use in England.

Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis

Objective To obtain summary estimates of the accuracy of a single baseline measurement of the Elecsys Troponin T high-sensitive assay (Roche Diagnostics) for the diagnosis of acute myocardial infarction in patients presenting to the emergency department. Design Systematic review and meta-analysis of diagnostic test accuracy studies. Data sources Medline, Embase, and other relevant electronic databases were searched for papers published between January 2006 and December 2013. Study selection Studies were included if they evaluated the diagnostic accuracy of a single baseline measurement of Elecsys Troponin T high-sensitive assay for the diagnosis of acute myocardial infarction in patients presenting to the emergency department with suspected acute coronary syndrome. Study appraisal and data synthesis The first author screened all titles and abstracts identified through the searches and selected all potentially relevant papers. The screening of the full texts, the data extraction, and the methodological quality assessment, using the adapted QUADAS-2 tool, were conducted independently by two reviewers with disagreements being resolved through discussion or arbitration. If appropriate, meta-analysis was conducted using the hierarchical bivariate model. Results Twenty three studies reported the performance of the evaluated assay at presentation. The results for 14 ng/L and 3-5 ng/L cut-off values were pooled separately. At 14 ng/L (20 papers), the summary sensitivity was 89.5% (95% confidence interval 86.3% to 92.1%) and the summary specificity was 77.1% (68.7% to 83.7%). At 3-5 ng/L (six papers), the summary sensitivity was 97.4% (94.9% to 98.7%) and the summary specificity was 42.4% (31.2% to 54.5%). This means that if 21 of 100 consecutive patients have the target condition (21%, the median prevalence across the studies), 2 (95% confidence interval 2 to 3) of 21 patients with acute myocardial infarction will be missed (false negatives) if 14 ng/L is used as a cut-off value and 18 (13 to 25) of 79 patients without acute myocardial infarction will test positive (false positives). If the 3-5 ng/L cut-off value is used, <1 (0 to 1) patient with acute myocardial infarction will be missed and 46 (36 to 54) patients without acute myocardial infarction will test positive. Conclusions The results indicate that a single baseline measurement of the Elecsys Troponin T high-sensitive assay could be used to rule out acute myocardial infarction if lower cut-off values such as 3 ng/L or 5 ng/L are used. However, this method should be part of a comprehensive triage strategy and may not be appropriate for patients who present less than three hours after symptom onset. Care must also be exercised because of the higher imprecision of the evaluated assay and the greater effect of lot-to-lot reagent variation at low troponin concentrations. Systematic review registration PROSPERO registration number CRD42013003926.

A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome.

BACKGROUND Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes. OBJECTIVE To evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified. DATA SOURCES AND METHODS Systematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed. RESULTS Inconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing. The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI and BRAF testing [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing). LIMITATIONS The absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation. CONCLUSIONS Results suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL. STUDY REGISTRATION This study is registered as PROSPERO CRD42012002436. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Systematic review of topical capsaicin in the treatment of pruritus.

Objective  To determine the efficacy of topical capsaicin in treating pruritus in any medical condition.

The relationship between patients' experiences of continuity of cancer care and health outcomes: a mixed methods study.

It is difficult to define continuity of care or study its impact on health outcomes. This study took place in three stages. In stage I we conducted qualitative research with patients, their close relatives and friends, and their key health professionals from which we derived a number of self completion statements about experienced continuity that were tested for reliability and internal consistency. A valid and reliable 18-item measure of experienced continuity was developed in stage II. In stage III we interviewed 199 patients with cancer up to five times over 12 months to ascertain whether their experiences of continuity were associated with their health needs, psychological status, quality of life, and satisfaction with care. The qualitative data revealed that experienced continuity involved receiving consistent time and attention, knowing what to expect in the future, coping between service contacts, managing family consequences, and believing nothing has been overlooked. Transitions between phases of treatment were not associated with changes in experienced continuity. However, higher experienced continuity predicted lower needs for care, after adjustment for other potential explanatory factors (standardised regression coefficients ranging from −0.12 (95% CI −0.20, −0.05) to −0.32 (95% CI −0.41, −0.23)). Higher experienced continuity may be linked to lower health care needs in the future.

Antenatal anxiety disorder as a predictor of postnatal depression: A longitudinal study

Previous research has implicated high levels of antenatal anxiety as a predictor of postnatal depression, but there is a paucity of evidence on the relationship between the various forms of anxiety and postnatal depression. A longitudinal study of 246 mothers (56 with antenatal generalised anxiety disorder (GAD), 68 with antenatal generalised social phobia, 28 with both disorders in the antenatal period, and 94 with no antenatal GAD or social phobia) allowed us to explore whether antenatal social phobia and GAD predict high Edinburgh Postnatal Depression Scale (EPDS) scores (probable depression >12) at 10-14 days, 10-12 weeks, 10 months, 14 months, and 24 months postnatally. We found that, after accounting for the presence of other antenatal anxiety disorders, antenatal depression, maternal age at childs birth, socio-economic status and ethnicity in the models, antenatal GAD independently predicted depression at all time points after delivery. A less robust relationship was found for antenatal social phobia, which predicted postnatal depression at only 10 months after birth. One possibility consistent with our findings is that there may be differences in the timing of postnatal depression with different forms of antenatal anxiety disorders.

Massage therapy for the treatment of depression: a systematic review

Background:  People with depressive disorders or subsyndromal symptoms of depression (SSD) often use complementary and alternative therapies, including massage therapy (MT). This systematic review evaluates the evidence, from randomised clinical trials (RCTs), for the effectiveness of multiple sessions of classical European (Swedish) MT for the treatment of depression.

A model-based assessment of the cost–utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients

BackgroundLynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost–utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS.MethodsA decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum.ResultsAll strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh the health benefits of testing, resulting in overall QALY loss.ConclusionsReflex testing for Lynch syndrome in early-onset colorectal cancer patients is predicted to be a cost-effective use of limited financial resources in England and Wales. Research is recommended into the cost-effectiveness of reflex testing for Lynch syndrome in other associated cancers and into the impact of prophylactic H-BSO on HRQoL.

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Associations electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time-state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY. LIMITATIONS For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled. FUTURE WORK High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome. CONCLUSION Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000-30,000 per QALY. STUDY REGISTRATION This study is registered as PROSPERO CRD42014013189. FUNDING The National Institute for Health Research Health Technology Assessment programme.