Search

Patient-reported outcome measures (PROMs) are widely used in the United Kingdom (UK) and internationally to report and monitor patients' subjective assessments of their symptoms and functional status and also their quality of life. Whilst the importance of involving the public in PROM development to increase the quality of the developed PROM has been highlighted this practice is not widespread. There is a lack of guidance on how public involvement (PI) could be embedded in the development of PROMs, where the roles can be more complex than in other types of research. This paper provides a timely review and sets out an emerging framework for fully incorporating PI into PROM development. [ABSTRACT FROM AUTHOR]

Objective: Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease. Methods: A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008–2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression. Results: Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008–2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5–53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis. Conclusions: This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival. [ABSTRACT FROM AUTHOR]

Hereditary angioedema ( HAE) and acquired angioedema ( AAE) are rare life-threatening conditions caused by deficiency of C1 inhibitor ( C1INH). Both are characterized by recurrent unpredictable episodes of mucosal swelling involving three main areas: the skin, gastrointestinal tract and larynx. Swelling in the gastrointestinal tract results in abdominal pain and vomiting, while swelling in the larynx may be fatal. There are limited UK data on these patients to help improve practice and understand more clearly the burden of disease. An audit tool was designed, informed by the published UK consensus document and clinical practice, and sent to clinicians involved in the care of HAE patients through a number of national organizations. Data sets on 376 patients were received from 14 centres in England, Scotland and Wales. There were 55 deaths from HAE in 33 families, emphasizing the potentially lethal nature of this disease. These data also show that there is a significant diagnostic delay of on average 10 years for type I HAE, 18 years for type II HAE and 5 years for AAE. For HAE the average annual frequency of swellings per patient affecting the periphery was eight, abdomen 5 and airway 0·5, with wide individual variation. The impact on quality of life was rated as moderate or severe by 37% of adult patients. The audit has helped to define the burden of disease in the UK and has aided planning new treatments for UK patients. [ABSTRACT FROM AUTHOR]

This article focuses on a study related to coronary heart disease (CHD) in patients with intermittent claudication. CHD is common among patients with peripheral arterial disease (PAD), and death and major morbidity in PAD are often due to coronary events. Risk factor management should be similar in CHD and PAD. Patients with claudication and evidence of CHD appear to receive more evidence-based treatments than non-CHD patients, but overall patients with claudication referred from primary care in Great Britain are not receiving optimal medical risk factor management.

Introduction: While there is increasing evidence of the effects of cannabis-based medicinal products (CBMPs) on health-related quality of life (HRQoL), a major limitation of the current literature is the heterogeneity of studied CBMPs. This study aims to analyze changes in HRQoL in patients prescribed a homogenous selection of CBMPs., Methods: Primary outcomes were changes in patient-reported outcomes (PROMs) at 1, 3, 6, and 12 months from baseline. The secondary outcome was an adverse events analysis. Statistical significance was defined as p < 0.050., Results: 1378 patients prescribed Adven® CBMPs (Curaleaf International, Guernsey, UK) were included in the final analysis. 581 (42.16%) participants were current users of cannabis at baseline. 641 (46.51%), 235 (17.05%), and 502 (36.43%) patients were treated with oils, dried flowers, or a combination of the two, respectively. Improvements were found in all PROMs in each route of administration at 1, 3, 6, and 12 months from baseline (p < 0.010). Those prescribed dried flower only or both oils and dried flower experienced greater improvements in GAD-7, SQS, and EQ-5D-5L index values at 12 months (p < 0.050). There was no difference in outcomes between those prescribed dried flower only or dried flower with oils (p > 0.050). 3663 (265.82%) adverse events were reported by 297 (21.55%) patients., Conclusion: There was an associated improvement in self-reported anxiety, sleep quality, and HRQoL in patients treated with the CBMPs. Those prescribed treatment formulations including dried flower were most likely to show a clinical improvement. However, these results must be interpreted with caution given the limitations of study design., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background: The following study evaluated the clinical outcomes of patients enrolled in the UK Medical Cannabis Registry, who were treated with inhaled dried flower (Adven® EMT2, Curaleaf International, Guernsey), and sublingual/oral medium-chain triglyceride-based oils (Adven, Curaleaf International, Guernsey) for chronic pain., Methods: In this cohort study, the primary outcomes were changes in validated patient reported outcome measures (PROMs) at 1, 3, and 6 months compared to baseline, and adverse event analysis. Statistical significance was defined as p  < 0.050., Results: Three hundred and forty-eight (45.7%), 36 (4.7%), and 377 (49.5%) patients were treated with oils, dried flower, or both, respectively. Patients treated with oils or combination therapy recorded improvements within health-related quality of life, pain, and sleep-specific PROMs at 1, 3, and 6 months ( p  < 0.050). Patients treated with combination therapy recorded improvements in anxiety-specific PROMs at 1, 3, and 6 months ( p  < 0.050). 1,273 (167.3%) adverse events were recorded, with previously cannabis naïve users, ex-cannabis users, and females more likely to experience adverse events ( p  < 0.050)., Conclusions: This study observed an association between initiation of CBMP treatment and improved outcomes for chronic pain patients. Prior cannabis use and gender were associated with adverse event incidence. Placebo-controlled trials are still necessary to establish the efficacy and safety of CBMPs for chronic pain.

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)

We describe creation and piloting of the PakSurg Collaborative, devised via integration of existing trainee-led collaborative models in the United Kingdom with the resource-limited surgical care in Pakistan. This is the first trainee-lead surgical research collaborative in Pakistan, established by the student-lead Surgery Interest Group from the Aga Khan University. The project involved creation of a model that included a steering committee comprising of five teams which worked in conjunction with collaborators from multiple hospitals. To facilitate this collaboration, a comprehensive and cost-efficient study management pathway was developed. The PakSurg Collaborative has the potential to deliver methodologically robust, high-quality, multicenter surgical evidence from Pakistan. This nationally representative data could inform evidence-based surgical guidelines, potentially translating into improved outcomes for patients undergoing surgery.

Background: The 2016 American Thyroid Association (ATA) guidelines proposed thyroid lobectomy for low-risk differentiated thyroid cancer (DTC); however, this approach is yet to be widely adopted. The aim of the study was to review our practice over three years following the publication of these guidelines identifying patients who underwent lobectomy-only for low-risk DTC in two regional units in the same multidisciplinary team (MDT)., Method: A retrospective review of patients who were operated between January 2016 and December 2018 was carried out., Results: In total, 288 patients undergoing thyroid surgery were included. The preoperative distribution of cytology was: Thy 1 or 2 in 46, THY3a in 57, THY3f in 154, THY4 in 18 and THY5 in 13 patients. Median size of nodules was 26mm (range 1-70mm). DTC was diagnosed in 95 patients (33%). Overall, 39% ( n  = 37) of patients underwent completion thyroidectomy according to ATA recommendations on size or adverse histological features. The only variable associated with likelihood of completion was tumour size ( p  < 0.05, OR 1.14). Ten patients were discharged following surgery with no further follow-up as they had T1a/b well-differentiated DTC with no high-risk histological features., Conclusion: Lobectomy-only appears to be the current surgical practice in two-thirds of patients presenting to our regional units with differentiated thyroid carcinoma. In the context of the current drive to reduce the extent of treatment for low-risk thyroid cancer, there is a need for a more homogeneous approach to these patients and for protocols for long-term follow-up after lobectomy-only.

Background: Advanced hepatocellular carcinoma (HCC) is commonly diagnosed using non-invasive radiological criteria (NIRC) defined by the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases. In 2017, The National Institute for Clinical Excellence mandated histological confirmation of disease to authorise the use of sorafenib in the UK., Methods: This was a prospective multicentre audit in which patients suitable for sorafenib were identified at multidisciplinary meetings. The primary analysis cohort (PAC) was defined by the presence of Child-Pugh class A liver disease and performance status 0-2. Clinical, radiological and histological data were reported locally and collected on a standardised case report form., Results: Eleven centres reported 418 cases, of which 361 comprised the PAC. Overall, 76% had chronic liver disease and 66% were cirrhotic. The diagnostic imaging was computed tomography in 71%, magnetic resonance imaging in 27% and 2% had both. Pre-existing histology was available in 45 patients and 270 underwent a new biopsy, which confirmed HCC in 93.4%. Alternative histological diagnoses included cholangiocarcinoma (CC) and combined HCC-CC. In cirrhotic patients, NIRC criteria had a sensitivity of 65.4% and a positive predictive value of 91.4% to detect HCC. Two patients (0.7%) experienced mild post-biopsy bleeding., Conclusion: The diagnostic biopsy is safe and feasible for most patients eligible for systemic therapy., (© 2021. The Author(s).)

Aim: Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety., Methods: A prospective case series was performed using the UK Medical Cannabis Registry. Primary outcomes were change in patient-reported outcomes measures (EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS)) at 1 and 3 months from baseline. The secondary outcome was the incidence of adverse events. Statistical significance was defined by a P-value <.050., Results: There were 129 patients included in the final analysis with a mean age of 46.23 (±14.51) years. The most common indication was chronic pain of undefined etiology (n = 48; 37.2%). The median initial cannabidiol and (-)-trans-Δ⁹-tetrahydrocannabinol daily dose was 20.0 mg (Range: 0.0-768.0 mg) and 3.9 mg (Range: 0.0-660.0 mg), respectively. Statistically significant improvements in health-related quality of life were demonstrated at 1 and 3 months in GAD-7, SQS, EQ-5D-5L pain and discomfort subscale, EQ-5D-5L anxiety and depression subscale, EQ-VAS and EQ-5D-5L index values(P < .050). There were 31 (24.03%) total reported adverse events., Conclusion: This study suggests that CBMP therapy may be associated with an improvement in health-related quality-of-life outcomes as self-reported by patients. CBMPs are also demonstrated to be relatively safe in the short to medium-term. These findings must be treated with caution given the limited scope of this initial analysis, with no placebo or an active comparator, with further research required., (© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of Neuropsychopharmacology.)

Objective: Atrial fibrillation (AF) is the most common arrhythmia. Undiagnosed and poorly managed AF increases risk of stroke. The Hounslow AF quality improvement (QI) initiative was associated with improved quality of care for patients with AF through increased detection of AF and appropriate anticoagulation. This study aimed to evaluate whether there has been a change in stroke and bleeding rates in the Hounslow population following the QI initiative., Methods: Using hospital admissions data from January 2011 to August 2018, interrupted time series analysis was performed to investigate the changes in standardised rates of admission with stroke and bleeding, following the start of the QI initiative in October 2014., Results: There was a 17% decrease in the rate of admission with stroke as primary diagnosis (incidence rate ratio (IRR) 0.83; 95% CI 0.712 to 0.963; p<0.014). There was an even larger yet not statistically significant decrease in admission with stroke as primary diagnosis and AF as secondary diagnosis (IRR 0.75; 95% CI 0.550 to 1.025; p<0.071). No significant changes were observed in bleeding admissions. For each outcome, an additional regression model including both the level change and an interaction term for slope change was created. In all cases, the slope change was small and not statistically significant., Conclusion: Reduction in stroke admissions may be associated with the AF QI initiative. However, the immediate level change and non-significant slope change suggests a lack of effect of the intervention over time and that the decrease observed may be attributable to other events., Competing Interests: Competing interests: MRC received grants and personal fees from Bayer, personal fees from Pfizer BMS Alliance, outside the submitted work. SK reports grants from Pfizer, during the conduct of the study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome., Patients and Methods: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method., Results: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O 2 ) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission., Conclusion: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity., Competing Interests: Disclosure RJL speaker fees BMS and Astrazeneca, MR honoraria from Astellas Pharma, speaker fees MSD and Servier. CW consultancy and speaker fees Pfizer, Amgen, Novartis, AA conference fee Merck, spouse shares in Astrazeneca. TR financial support to attend educational workshops from Amgen and Daiichi-Sankyo. JT is now working at Astra Zeneca. CD, outside of this scope of work, has received research funding from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, Clearbridge Biomedics, Angle PLC, Menarini Diagnostics, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Thermofisher. CD is on advisory boards for, and has received consultancy fees/honoraria from, AstraZeneca, Biocartis and Merck KGaA. The remaining authors have no conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Adrenocortical carcinomas (ACCs) carry a poor prognosis. This study assessed the comparative performance of existing nomograms in estimating the likelihood of survival, along with the value of conditional survival estimation for patients who had already survived for a given length of time after surgery., Methods: This was an observational study based on a prospectively developed departmental database that recorded details of patients operated for ACC in a UK tertiary referral centre., Results: Of 74 patients with ACC managed between 2001 and 2020, data were analysed for 62 patients (32 women and 30 men, mean(s.d.) age 51(17) years) who had primary surgical treatment in this unit. Laparoscopic (9) or open adrenalectomies (53) were performed alone or in association with a multivisceral resection (27). Most of the tumours were left-sided (40) and 18 were cortisol-secreting.Overall median survival was 33 months, with 1-, 3- and 5-year survival rates of 79, 49, and 41 per cent respectively. Age over 55 years, higher European Network for Study of Adrenal Tumours stage, and cortisol secretion were associated with poorer survival in univariable analyses. Four published nomograms suggested widely variable outcomes that did not correlate with observed overall survival at 1, 3 or 5 years after operation. The 3-year conditional survival at 2 years (probability of surviving to postoperative year 5) was 65 per cent, compared with a 5-year actuarial survival rate of 41 per cent calculated from the time of surgery., Conclusion: Survival of patients with ACC correlates with clinical parameters but not with published nomograms. Conditional survival might provide a more accurate estimate of survival for patients who have already survived for a certain amount of time after resection., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Objective: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease., Design: Systematic review., Data Source: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science., Study Selection: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression., Data Extraction and Synthesis: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies., Results: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2)., Conclusions: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The parasitic nematode Haemonchus contortus is one of the world's most important parasites of small ruminants that causes significant economic losses to the livestock sector. The population structure and selection in its various strains are poorly understood. No study so far compared its different populations using genome-wide data. Here, we focused on different geographic populations of H. contours from China (Tibet, TB; Hubei, HB; Inner Mongolia, IM; Sichuan, SC), UK and Australia (AS), using genome-wide population-genomic approaches, to explore genetic diversity, population structure and selection. We first performed next-generation high-throughput 2b RAD pool sequencing using Illumina technology, and identified single-nucleotide polymorphisms (SNPs) in all the strains. We identified 75,187 SNPs for TB, 82,271 for HB, 82,420 for IM, 79,803 for SC, 83,504 for AS and 78,747 for UK strain. The SNPs revealed low-nucleotide diversity (pi= 0.0092-0.0133) within each strain, and a significant differentiation level (average F st = 0.34264) among them. Chinese populations TB and SC, along with the UK strain, were more divergent populations. Chinese populations IM and HB showed affinities to the Australian strain. We then analysed signature of selection and detected 44 (UK) and 03 (AS) private selective sweeps containing 49 and 05 genes, respectively. Finally, we performed the functional annotation of selective sweeps and proposed biological significance to signature of selection. Our data suggest that 2b-RAD pool sequencing can be used to assess the signature of selection in H. contortus.

Introduction: Redo parathyroidectomy for persistent/recurrent primary hyperparathyroidism is associated with a higher risk of complications and should be planned only with convincing localisation. We assessed whether 18 fluorocholine positron emission tomography/computed tomography could identify parathyroid adenoma(s) in patients with persistent/recurrent primary hyperparathyroidism and negative conventional scans., Materials and Methods: A departmental database was used to identify patients with failed localisation attempts (sestamibi single photon emission computed tomography/computed tomography and/or computed tomography/magnetic resonance imaging and/or selective parathyroid hormone sampling) after previous unsuccessful surgery for primary hyperparathyroidism. 18 Fluorocholine positron emission tomography was performed in all patients and redo surgery offered to those with positive findings., Results: 18 Fluorocholine positron emission tomography incorporating arterial and portal phase enhanced computed tomography was performed in 12 patients with persistent/recurrent primary hyperparathyroidism (four men and eight women). Seven patients (58%) were cured after excision of adenomas located in ectopic positions ( n = 3) or in anatomical position ( n = 4). Five patients (42%) had persistent hypercalcaemia and repeat 18 fluorocholine scan confirmed that the area highlighted on preoperative scans was excised. The arterial phase enhancement of the computed tomography was significantly different between cured and not-cured patients ( P = 0.007). All seven cured patients had either a strong or weak enhancing pattern on computed tomography. Standardised uptake value at 60 minutes in patients with successful surgery (range 2.7-15.7, median 4.05) was higher than in patients with failed surgery (range 1.8-5.8, median 3.2) but was not statistically significant ( P = 0.300)., Discussion: 18 fluorocholine scanning can identify elusive parathyroid adenomas, including those that are ectopic, and is useful in the management of patients with persistent/recurrent primary hyperparathyroidism when first-line scans are negative. The grading of the arterial phase of computed tomography can help to differentiate between true adenomas and false positive targets (lymph nodes).

Background: British Pakistanis are one of the largest ethnic minority groups living in the UK, with high rates of maternal depression being reported in this population. Evidence suggests that culturally-adapted Cognitive Behavioural Therapy (CBT)-based interventions for depression, may improve clinical outcomes and patient satisfaction. This study was conducted to develop and test the feasibility and acceptability of a culturally-adapted, CBT-based, manual-assisted intervention in British Pakistani mothers experiencing maternal depression., Methods: A mixed-method feasibility study that included qualitative interviews followed by the development of a CBT-based intervention for mothers with mild to moderate depression. Following the qualitative interviews, a CBT-based intervention called the Positive Health Program (PHP) was developed and delivered consisting of 12-weekly sessions. A before and after design was used to explore the feasibility and acceptability of the Positive Health Programme., Results: A culturally-adapted CBT-based group intervention (PHP) was acceptable to this group and improvements were reported in depression and health-related quality of life. The women's understanding of 'depression' as a general consensus was in physical terms, but with an onset triggered by psychosocial causes. The most commonly reported factors contributing to depression were marital disharmony, lack of social support, and financial difficulties. Past help offered was primarily antidepressants, which were not welcomed by most of the women. A lack of availability of culturally sensitive interventions and the limited cultural sensitivity of NHS staff was also reported., Conclusion: This study provides preliminary evidence for the feasibility and acceptability of a CBT-based culturally-adapted group psychological intervention for British Pakistani mothers., Trial Registration: Study ethics registration number: 10/H1005/62 (University of Manchester).

Background: Nicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data., Objectives: To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading., Design: Open-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis., Setting: NHS smoking cessation clinics., Participants: People seeking help to stop smoking., Interventions: Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators., Main Outcome Measures: The primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix ® ; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model., Results: In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) -0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; p  = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; p  = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI -£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving., Limitations: The open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified., Conclusions: Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication., Trial Registration: Current Controlled Trials ISRCTN33031001., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 41. See the NIHR Journals Library website for further project information., Competing Interests: All contributors participated in this trial, to which GlaxoSmithKline plc donated free patches. Paul Aveyard is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and CLAHRC. Peter Hajek and Hayden J McRobbie have provided research and consultancy to several manufacturers of smoking cessation treatments and have been paid for doing so. Tim Coleman is a member of the NIHR Health Technology Assessment Clinical Evaluation and Trials Board. Sarah Lewis is a member of the NIHR Health Services and Delivery Research funding board. Peter Hajek reports a research grant to Queen Mary University of London from Pfizer and personal consultancy fees from Pfizer. Andy McEwen reports grants from Pfizer and hospitality from North 51. Hayden J McRobbie reports a grant and honorarium from Pfizer for speaking at education meetings and an honorarium from Johnson & Johnson for speaking at education meetings and an advisory board meeting.

Background: Timely diagnosis of human immunodeficiency virus (HIV) enables access to antiretroviral treatment, which reduces mortality, morbidity and further transmission in people living with HIV. In the UK, late diagnosis among black African people persists. Novel methods to enhance HIV testing in this population are needed., Objectives: To develop a self-sampling kit (SSK) intervention to increase HIV testing among black Africans, using existing community and health-care settings (stage 1) and to assess the feasibility for a Phase III evaluation (stage 2)., Design: A two-stage, mixed-methods design. Stage 1 involved a systematic literature review, focus groups and interviews with key stakeholders and black Africans. Data obtained provided the theoretical base for intervention development and operationalisation. Stage 2 was a prospective, non-randomised study of a provider-initiated, HIV SSK distribution intervention targeted at black Africans. The intervention was assessed for cost-effectiveness. A process evaluation explored feasibility, acceptability and fidelity., Setting: Twelve general practices and three community settings in London., Main Outcome Measure: HIV SSK return rate., Results: Stage 1 - the systematic review revealed support for HIV SSKs, but with scant evidence on their use and clinical effectiveness among black Africans. Although the qualitative findings supported SSK distribution in settings already used by black Africans, concerns were raised about the complexity of the SSK and the acceptability of targeting. These findings were used to develop a theoretically informed intervention. Stage 2 - of the 349 eligible people approached, 125 (35.8%) agreed to participate. Data from 119 were included in the analysis; 54.5% (65/119) of those who took a kit returned a sample; 83.1% of tests returned were HIV negative; and 16.9% were not processed, because of insufficient samples. Process evaluation showed the time pressures of the research process to be a significant barrier to feasibility. Other major barriers were difficulties with the SSK itself and ethnic targeting in general practice settings. The convenience and privacy associated with the SSK were described as beneficial aspects, and those who used the kit mostly found the intervention to be acceptable. Research governance delays prevented implementation in Glasgow., Limitations: Owing to the study failing to recruit adequate numbers (the intended sample was 1200 participants), we were unable to evaluate the clinical effectiveness of SSKs in increasing HIV testing in black African people. No samples were reactive, so we were unable to assess pathways to confirmatory testing and linkage to care., Conclusions: Our findings indicate that, although aspects of the intervention were acceptable, ethnic targeting and the SSK itself were problematic, and scale-up of the intervention to a Phase III trial was not feasible. The preliminary economic model suggests that, for the acceptance rate and test return seen in the trial, the SSK is potentially a cost-effective way to identify new infections of HIV., Future Work: Sexual and public health services are increasingly utilising self-sampling technologies. However, alternative, user-friendly SSKs that meet user and provider preferences and UK regulatory requirements are needed, and additional research is required to understand clinical effectiveness and cost-effectiveness for black African communities., Study Registration: This study is registered as PROSPERO CRD42014010698 and Integrated Research Application System project identification 184223., Funding: The National Institute for Health Research Health Technology Assessment programme and the BHA for Equality in Health and Social Care., Competing Interests: Fiona Burns reports grants from the National Institute for Health Research (NIHR) for other projects during the conduct of the study, and personal fees and other from Gilead Sciences Ltd (London, UK), outside the submitted work. Rachael Hunter reports grants from the NIHR Health Technology Assessment (HTA) programme for other projects, during the conduct of the study. Ibidun Fakoya reports a grant from NIHR for another project, during the conduct of the study. Eleni Nastouli reports personal fees from Roche (Burgess Hill, UK), grants from Viiv Healthcare (London, UK), grants from the European Union (H2020) and personal fees from NIHR, outside the submitted work. Lisa McDaid reports grants from the NIHR HTA programme for other projects, during the conduct of the study. Jane Anderson reports grants and personal fees from Gilead Sciences Ltd, and personal fees from ViiV Healthcare, Merck Sharp & Dohme Limited (Hoddesdon, UK), Bristol-Myers Squibb (Uxbridge, UK), Jansen-Cilag Limited (High Wycombe, UK) and AbbVie (Maidenhead, UK), outside the submitted work.

Background: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer., Objective: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer., Design: A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy., Participants: Patients with suspected pancreatic malignancy., Interventions: All patients to undergo PET/CT following standard diagnostic work-up., Main Outcome Measures: The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours., Results: Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUV max. ) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity ( p  = 0.01) and specificity ( p  = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios ( p  < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients ( p  = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable., Conclusion: PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer., Study Registration: Current Controlled Trials ISRCTN73852054 and UKCRN 8166., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Evidence suggests that general practitioners (GPs) find fitness for work certification and work- related consultations challenging. The Royal College of General Practitioners was commissioned in 2009 to develop and roll out a National Education Programme (NEP) funded by the Department for Work and Pensions for a period of 2 years., Aims: To develop and evaluate a face-to-face educational programme that shifts GPs' attitudes to the management of the consultation about work and health., Methods: A 3 hour interactive programme that addressed both knowledge and skills for the management of the health and work consultation using behaviour-change principles was developed. Evaluation focused on delegates' confidence in managing the work and health consultation and the importance (priority) they gave to the subject. Questionnaires at three time points were constructed: pre, immediately post and 3 months post training., Results: A total of 152 workshops were evaluated across the UK between July 2009 and March 2011. A total of 2865 GPs attended the workshops. Questionnaire response rates were 78% pre workshop, 80% post workshop and 14% 3 months post workshop. Evaluation showed a significant increase in GPs' confidence in managing the consultation regarding work and health, and GPs gave higher priority to these types of consultations after the training., Conclusions: The NEP has brought the training about health and work to prominence in general practice, and has also influenced policy and practice in other medical specialties.