Tobacco use in people with severe mental illness: Findings from a multi-country survey of mental health institutions in South Asia.

INTRODUCTION: People with severe mental illness (SMI) tend to die early due to cardiovascular and respiratory diseases, which may be linked to tobacco use. There is limited information on tobacco use in people with SMI in low- and middle-income countries where most tobacco users reside. We present novel data on tobacco use in people with SMI and their access to tobacco cessation advice in South Asia. METHODS: We conducted a multi-country survey of adults with SMI attending mental health facilities in Bangladesh, India, and Pakistan. Using data collected with a standardized WHO STEPS survey tool, we estimated the prevalence and distribution of tobacco use and assessed receipt of tobacco cessation advice. RESULTS: We recruited 3874 participants with SMI; 46.8% and 15.0% of men and women consumed tobacco, respectively. Smoking prevalence in men varied by country (Bangladesh 42.8%, India 20.1% and Pakistan 31.7%); <4% of women reported smoking in each country. Smokeless tobacco use in men also varied by country (Bangladesh 16.2%, India 18.2% and Pakistan 40.8%); for women, it was higher in Bangladesh (19.1%), but similar in India (9.9%) and Pakistan (9.1%). Just over a third of tobacco users (38.4%) had received advice to quit tobacco. Among smokers, 29.1% (n=244) made at least one quit attempt in the past year. There was strong evidence for the association between tobacco use and the severity of depression (OR=1.29; 95% CI: 1.12-1.48) and anxiety (OR=1.29; 95% CI: 1.12-1.49). CONCLUSIONS: As observed in high-income countries, we found higher tobacco use in people with SMI, particularly in men compared with rates reported for the general population in South Asia. Tobacco cessation support within mental health services offers an opportunity to close the gap in life expectancy between SMI and the general population. STUDY REGISTRATION: ISRCTN88485933; https://doi.org/10.1186/ISRCTN88485933 39.

Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics.

Lymphomas are a heterogenous group of lymphoid neoplasms with a wide variety of clinical presentations. Response to treatment and prognosis differs both between and within lymphoma subtypes. Improved molecular and genetic profiling has increased our understanding of the factors which drive these clinical dynamics. Immune and non-immune cells within the lymphoma tumor microenvironment (TME) can both play a key role in antitumor immune responses and conversely also support lymphoma growth and survival. A deeper understanding of the lymphoma TME would identify key lymphoma and immune cell interactions which could be disrupted for therapeutic benefit. Single cell RNA sequencing studies have provided a more comprehensive description of the TME, however these studies are limited in that they lack spatial context. Spatial transcriptomics provides a comprehensive analysis of gene expression within tissue and is an attractive technique in lymphoma to both disentangle the complex interactions between lymphoma and TME cells and improve understanding of how lymphoma cells evade the host immune response. This article summarizes current spatial transcriptomic technologies and their use in lymphoma research to date. The resulting data has already enriched our knowledge of the mechanisms and clinical impact of an immunosuppressive TME in lymphoma and the accrual of further studies will provide a fundamental step in the march towards personalized medicine.

A randomised controlled, feasibility study to establish the acceptability of early outpatient review and early cardiac rehabilitation compared to standard practice after cardiac surgery and viability of a future large-scale trial (FARSTER).

OBJECTIVE: To determine the acceptability and feasibility of delivering early outpatient review following cardiac surgery and early cardiac rehabilitation (CR), compared to standard practice to establish if a future large-scale trial is achievable. METHODS: A randomised controlled, feasibility trial with embedded health economic evaluation and qualitative interviews, recruited patients aged 18-80 years from two UK cardiac centres who had undergone elective or urgent cardiac surgery via a median sternotomy. Eligible, consenting participants were randomised 1:1 by a remote, centralised randomisation service to postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control), or postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention). The primary outcome measures related to trial feasibility including recruitment, retention, CR adherence, and acceptability to participants/staff. Secondary outcome measures included health-rated quality of life using EQ-5D-5L, NHS resource-use, Incremental Shuttle Walk Test (ISWT) distance, 30- and 90-day mortality, surgical site complications and hospital readmission rates. RESULTS: Fifty participants were randomised (25 per group) and 92% declared fit for CR. Participant retention at final follow-up was 74%; completion rates for outcome data time points ranged from 28 to 92% for ISWT and 68 to 94% for follow-up questionnaires. At each time point, the mean ISWT distance walked was greater in the intervention group compared to the control. Mean utility scores increased from baseline to final follow-up by 0.202 for the intervention (0.188 control). Total costs were £1519 for the intervention (£2043 control). Fifteen participants and a research nurse were interviewed. Many control participants felt their outpatient review and CR could have happened sooner; intervention participants felt the timing was right. The research nurse found obtaining consent for willing patients challenging due to discharge timings. CONCLUSION: Recruitment and retention rates showed that it would be feasible to undertake a full-scale trial subject to some modifications to maximise recruitment. Lower than expected recruitment and issues with one of the clinical tests were limitations of the study. Most study procedures proved feasible and acceptable to participants, and professionals delivering early CR. TRIAL REGISTRATION: ISRCTN80441309 (prospectively registered on 24/01/2019).

Financial incentives for quitting smoking in pregnancy: Are they cost-effective?

AIMS: To evaluate whether adding financial incentives to usual care is cost-effective in encouraging pregnant women to quit tobacco smoking, compared with usual care alone. DESIGN: Cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) from a health-care provider's perspective, embedded in the Smoking Cessation in Pregnancy Incentives Trial (CPIT III). Long-term analyses were conducted from the same perspective, using an existing Markov model over a life-time horizon. SETTING: Seven maternity smoking cessation sites in Scotland, England and Northern Ireland in the United Kingdom. PARTICIPANTS: In the short-term analysis, CPIT III participants were assessed: women 16 years or older, self-reporting as smokers, fewer than 24 weeks pregnant and English-speaking (n = 944). The same population was used for the life-time analysis, plus their infants. MEASUREMENTS: Costs included financial incentive vouchers and postage, cessation support and nicotine replacement therapy and neonatal stays. The outcome measure was a biochemically verified quit rate for the CEA and quality-adjusted life-years (QALYs) for CUA. Costs are presented in 2020 GBP sterling (£). Data for the life-time analysis came from the trial and were combined with data from published literature embedded in the model, reporting incremental cost per quitter and QALY. A 3.5% discount rate was applied. FINDINGS: The short-term incremental cost per quitter was £4400 and cost per QALY was £150 000. Results of sensitivity analyses confirmed these results. The long-term analysis combined costs and outcomes for mother and infants; results showed a cost saving of £37 [95% confidence interval (CI]) = £35-106] and increase in QALYs of 0.171 (95% CI = 0.124-0.229). These findings indicate that, over a life-time, financial incentives are cost-saving and improve health outcomes. CONCLUSIONS: In the United Kingdom, offering up to £400 financial incentives, in addition to usual care, to support pregnant women to stop smoking appears to be highly cost-effective over a life-time for mother and infants.

Effect of financial voucher incentives provided with UK stop smoking services on the cessation of smoking in pregnant women (CPIT III): pragmatic, multicentre, single blinded, phase 3, randomised controlled trial.

OBJECTIVE: To examine effectiveness, cost effectiveness, generalisability, and acceptability of financial incentives for smoking cessation during pregnancy in addition to variously organised UK stop smoking services. DESIGN: Pragmatic, multicentre, single blinded, phase 3, randomised controlled trial (Cessation in Pregnancy Incentives Trial phase 3 (CPIT III)). SETTING: Seven UK stop smoking services provided in primary and secondary care facilities in Scotland, Northern Ireland, and England. PARTICIPANTS: 944 pregnant women (age ≥16 years) who self-reported as being smokers (at least one cigarette in the past week) when asked at first maternity visit, less than 24 weeks' gestation, and notified to the trial team by routine stop smoking services. INTERVENTIONS: Participants in the control group were offered the standard stop smoking services, which includes the offer of counselling by specially trained workers using withdrawal orientated therapy and the offer of free nicotine replacement therapy. The intervention was the offer of usual support from the stop smoking services and the addition of up to £400 ($440; €455) of LoveToShop financial voucher incentives for engaging with current stop smoking services or to stop smoking, or both, during pregnancy. MAIN OUTCOME MEASURES: Self-reported smoking cessation in late pregnancy (between 34 and 38 weeks' gestation) corroborated by saliva cotinine (and anabasine if using nicotine replacement products). Results were adjusted for age, smoking years, index of multiple deprivation, Fagerström score, before or after covid, and recruitment site. Secondary outcomes included point and continuous abstinence six months after expected date of delivery, engagement with stop smoking services, biochemically validated abstinence from smoking at four weeks after stop smoking date, birth weight of baby, cost effectiveness, generalisability documenting formats of stop smoking services, and acceptability to pregnant women and their carers. RESULTS: From 9 January 2018 to 4 April 2020, of 4032 women screened by stop smoking services, 944 people were randomly assigned to the intervention group (n=471) or the control group (n=470). Three people asked for their data to be removed. 126 (27%) of 471 participants stopped smoking from the intervention group and 58 (12%) of 470 from the control group (adjusted odds ratio 2.78 (1.94 to 3.97) P<0.001). Serious adverse events were miscarriages and other expected pregnancy events requiring hospital admission; all serious adverse events were unrelated to the intervention. Most people who stopped smoking from both groups relapsed after their baby was born. CONCLUSIONS: The offer of up to £400 of financial voucher incentives to stop smoking during pregnancy as an addition to current UK stop smoking services is highly effective. This bolt-on intervention supports new guidance from the UK National Institute for Health and Care Excellence, which includes the addition of financial incentives to support pregnant women to stop smoking. Continuing incentives to 12 months after birth is being examined to prevent relapse. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15236311.

Convergent and criterion validity of PROMIS anxiety measures relative to six legacy measures and a structured diagnostic interview for anxiety in cancer patients.

BACKGROUND: Detecting anxiety in oncology patients is important, requiring valid yet brief measures. One increasingly popular approach is the Patient Reported Outcomes Measurement Information System (PROMIS); however, its validity is not well established in oncology. We assessed the convergent and criterion validity of PROMIS anxiety measures in an oncology sample. METHODS: 132 oncology/haematology outpatients completed the PROMIS Anxiety Computer Adaptive Test (PROMIS-A-CAT) and the 7 item (original) PROMIS Anxiety Short Form (PROMIS-A-SF) along with six well-established measures: Hospital Anxiety and Depression Scale-Anxiety (HADS-A); Generalised Anxiety Disorder-7 (GAD-7); Depression, Anxiety and Stress Scale-Anxiety (DASS-A) and Stress (DASS-S); Distress Thermometer (DT) and PSYCH-6. Correlations, area under the curve (AUC) and diagnostic accuracy statistics were calculated with Structured Clinical Interview as the reference standard. RESULTS: Both PROMIS measures correlated with all legacy measures at p < .001 (Rho = .56-.83). AUCs (> .80) were good for both PROMIS measures and comparable to or better than all legacy measures. At the recommended mild cut-point (55), PROMIS-A-SF had sensitivity (.67) comparable to or better than all the legacy measures, whereas PROMIS-A-CAT sensitivity (.59) was lower than GAD-7 (.67) and HADS-A (.62), but comparable to PSYCH-6 and higher than DASS-A, DASS-S and DT. Sensitivity for both was .79. A reduced cut-point of 51 on both PROMIS measures improved sensitivity (.83-.84) although specificity was only adequate (.61-.62). CONCLUSIONS: The convergent and criterion validity of the PROMIS anxiety measures in cancer populations was confirmed as equivalent, but not superior to, established measures (GAD-7 and HADS-A). The PROMIS-A-CAT did not demonstrate clear advantages over PROMIS-A-SF.

The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer.

BACKGROUND: The faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme. AIM: To determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC. DESIGN AND SETTING: Patients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation. METHOD: The diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results. RESULTS: In total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively. CONCLUSION: FIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.

A multicentre, randomized, parallel group, superiority study to compare the clinical effectiveness and cost-effectiveness of external frame versus internal locking plate for complete articular pilon fracture fixation in adults.

AIMS: A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients' quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. METHODS: A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. DISCUSSION: The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150-163.

Investigating Changes in Patients' Smoking Behavior, Tobacco Dependence, and Motivation to Stop Smoking Following a "Smoke-Free" Mental Health Inpatient Stay: Results From a Longitudinal Survey in England.

INTRODUCTION: In line with national guidance, mental health Trusts in England are implementing complete smoke-free policies. We investigated inpatients' changes in smoking behavior, tobacco dependence, vaping, and motivation to stop smoking between pre-admission and post-discharge. METHODS: We surveyed acute adult mental health inpatients from 14 wards in three mental health Trusts in England in 2019. Structured face-to-face and telephone interviews with patients who smoked on or during admission were conducted during the admission period and at one week and one month after discharge. Data on smoking status; daily cigarette consumption; Heaviness of Smoking Index (HSI); Strength of Urges to Smoke (SUTS); Motivation to Stop Smoking (MTSS) and vaping were collected and analyzed using regression and probit models. RESULTS: Inpatient smoking prevalence was 51.9%, and a total of 152 of all 555 eligible smokers (27%) were recruited. Attrition was high: 49.3% at the first and 50.7% at the second follow-up interview. Changes in self-reported smoking status, motivation to quit, and vaping did not change significantly over the study period. Cigarette consumption (p < 0.001) and Heaviness of Smoking Index (p < 0.001) modestly reduced. The frequency and strength of urges to smoke (p = 0.011 and 0.012, respectively) decreased modestly after discharge but were scored as high by 57% and 60% of participants during admission respectively. Just over half (56%) reported being offered smoking cessation support on admission. CONCLUSIONS: This study identified very modest changes in smoking-related outcomes during and after admission and indicates major challenges to smoke-free policy implementation, including limited support for patients who smoke. IMPLICATIONS: Despite mental health Trusts in England had developed and implemented smoke-free policies to meet national guidelines, adherence to these policies and provision of effective smoking cessation and temporary abstinence support for inpatients admitted to acute adult mental health wards appear to be limited. Patients who smoke on admission are likely to continue to do so during admission and after discharge, and only a very modest change in smoking behaviors appears to take place. Important opportunities to promote smoking cessation in this population are missed. Barriers to effective support need to be identified and addressed.

A protocol for the economic evaluation of the smoking Cessation in Pregnancy Incentives Trial III (CPIT III).

INTRODUCTION: Smoking results in an average 10-year loss of life, but smokers who permanently quit before age 40 can expect a near normal lifespan. Pregnancy poses a good opportunity to help women to stop; around 80% of women in the UK have a baby, most of whom are less than 40 years of age. Smoking prevalence during pregnancy is high: 17%-23% in the UK. Smoking during pregnancy causes low birth weight and increases the risk of premature birth. After birth, passive smoking is linked to sudden infant death syndrome, respiratory diseases and increased likelihood of taking up smoking. These risks impact the long-term health of the child with associated increase in health costs. Emerging evidence suggests that offering financial incentives to pregnant women to quit is highly cost effective.This protocol describes the economic evaluation of a multi-centre randomised controlled trial (Cessation in Pregnancy Incentives Trial III, CPIT III) designed to establish whether offering financial incentives, in addition to usual care, is effective and cost effective in helping pregnant women to quit. METHODS AND ANALYSIS: The economic evaluation will identify, measure and value resource use and outcomes from CPIT III, comparing participants randomised to either usual care or usual care plus up to £400 financial incentives. Within-trial and long-term analyses will be conducted from a National Health Service and Personal Social Services perspective; the outcome for both analyses will be quality adjusted life-years measured using EQ-5D-5L. Patient level data collected during the trial will be used for the within-trial analysis, with an additional outcome of cotinine validated quit rates at 34-38 weeks gestation and 6 months postpartum. The long-term model will be informed by data from the trial and published literature. ETHICS AND DISSEMINATION: TRIAL REGISTRATION NUMBER: ISRCTN15236311; Pre-results (https://doi.org/10.1186/ISRCTN15236311).

Smoking prevalence among tuberculosis patients: A crosssectional study in Bangladesh and Pakistan.

INTRODUCTION: Smoking has a negative impact on TB outcomes. We estimated the proportion of TB patients who smoke and are willing to quit in two high TB burden countries, Bangladesh and Pakistan. METHODS: A cross-sectional survey was conducted among TB patients to assess their eligibility and recruit them to a smoking cessation randomized controlled trial. Adults diagnosed with TB were recruited from 32 health facilities in Bangladesh and Pakistan. Data on smoking behaviour and willingness to quit were collected and analysed. RESULTS: In total, 13934 TB patients completed the survey between June 2017 and April 2018. The prevalence of smoking in these TB patients was estimated to be 22.5% (95% CI: 21.8, 23.2). Moreover, the prevalence of smoking in TB patient population was 8% (RR=1.49; 95% CI: 7.1-8.9; p<0.01) and 8.3% (RR=1.24; 95% CI: 7.3-9.4; p<0.01) higher than smoking prevalence in the general population in Bangladesh and Pakistan, respectively. Among TB patients who smoke, 97.7% (95% CI: 97.2-98.2) were willing to quit. CONCLUSIONS: The estimated prevalence of smoking was higher in TB patients than the general population; however, a vast majority of TB patients who smoke were willing to quit.

The smoking cessation in pregnancy incentives trial (CPIT): study protocol for a phase III randomised controlled trial.

BACKGROUND: Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? METHODS: The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years, < 24 weeks pregnant, English speaking), who consent via telephone to take part and are willing to be followed-up in late pregnancy and 6 months after birth. The primary outcome is cotinine/anabasine-validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with SSS, quit rates at 4 weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention to treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case-study approach will identify opportunities to improve recruitment and learning for future implementation. Research questions include: what is the therapeutic efficacy of incentives; are incentives cost-effective; and what are the potential facilitators and barriers to implementing incentives in different parts of the UK? DISCUSSION: This phase III trial in Scotland, England and Northern Ireland follows a successful phase II trial in Glasgow, UK. The participating sites have diverse SSS that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective, this trial could demonstrate that financial incentives are effective and transferable to most UK SSS for pregnant women. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN15236311. Registered on 9 October 2017.

A Visual-Analogue Screening Tool for Assessing Mood and Quality of Daily Life Complications in Family Members of People Living With Cancer: Portuguese Version of the Emotion Thermometers: Burden Version.

Cancer is a disease that impacts not only the patient but also affects the entire family. Family members experience high levels of distress. Therefore, screening for cancer-specific distress among family members of people with cancer is important but relatively unexplored. This cross-sectional study aims to analyze the psychometric properties of a screening tool for family members of people with cancer. We examined the usefulness of the emotional thermometers burden version (ET-BV) in detecting caregiver emotional distress. The ET-BV is a simple multidomain visual analogue scale distributed in two major domains: "emotional upset" and "impact." A total of 364 cancer patients' family members completed the ET-BV and Brief Symptom Inventory. Analyses were aimed to examine the diagnostic accuracy (receiver operating characteristic) of the ET-BV. A fair to good diagnostic accuracy was achieved for ET-BV. For emotional upset thermometers, a cutoff of ≥5 was determined and for impact thermometers, a cutoff of ≥4 was established. ET-BV seems to be a useful, quick, and simple tool for distress screening in family members of people with cancer. A revision of a specific thermometer is discussed in order to increase ET screening performance and clinical utility.

Microbial community drivers of PK/NRP gene diversity in selected global soils.

BACKGROUND: The emergence of antibiotic-resistant pathogens has created an urgent need for novel antimicrobial treatments. Advances in next-generation sequencing have opened new frontiers for discovery programmes for natural products allowing the exploitation of a larger fraction of the microbial community. Polyketide (PK) and non-ribosomal pepetide (NRP) natural products have been reported to be related to compounds with antimicrobial and anticancer activities. We report here a new culture-independent approach to explore bacterial biosynthetic diversity and determine bacterial phyla in the microbial community associated with PK and NRP diversity in selected soils. RESULTS: Through amplicon sequencing, we explored the microbial diversity (16S rRNA gene) of 13 soils from Antarctica, Africa, Europe and a Caribbean island and correlated this with the amplicon diversity of the adenylation (A) and ketosynthase (KS) domains within functional genes coding for non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), which are involved in the production of NRP and PK, respectively. Mantel and Procrustes correlation analyses with microbial taxonomic data identified not only the well-studied phyla Actinobacteria and Proteobacteria, but also, interestingly, the less biotechnologically exploited phyla Verrucomicrobia and Bacteroidetes, as potential sources harbouring diverse A and KS domains. Some soils, notably that from Antarctica, provided evidence of endemic diversity, whilst others, such as those from Europe, clustered together. In particular, the majority of the domain reads from Antarctica remained unmatched to known sequences suggesting they could encode enzymes for potentially novel PK and NRP. CONCLUSIONS: The approach presented here highlights potential sources of metabolic novelty in the environment which will be a useful precursor to metagenomic biosynthetic gene cluster mining for PKs and NRPs which could provide leads for new antimicrobial metabolites.

Feasibility study of early outpatient review and early cardiac rehabilitation after cardiac surgery: mixed-methods research design-a study protocol.

INTRODUCTION: Following cardiac surgery, patients currently attend an outpatient review 6 weeks after hospital discharge, where recovery is assessed and suitability to commence cardiac rehabilitation (CR) is determined. CR is then started from 8 weeks. Following a median sternotomy, cardiac surgery patients are required to refrain from upper body exercises, lifting of heavy objects and other strenuous activities for 12 weeks. A delay in starting CR can prolong the recovery process, increase dependence on family/carers and can cause frustration. However, current guidelines for activity and exercise after median sternotomy have been described as restrictive, anecdotal and increasingly at odds with modern clinical guidance for CR. This study aims to examine the feasibility of bringing forward outpatient review and starting CR earlier. METHODS AND ANALYSES: This is a multicentre, randomised controlled, open feasibility trial comparing postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control arm) versus, postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention arm). The study aims to recruit 100 eligible patients, aged 18-80 years who have undergone elective or urgent cardiac surgery involving a full median sternotomy, over a 7-month period across two centres. Feasibility will be measured by consent, recruitment, retention rates and attendance at appointments and CR sessions. Qualitative interviews with trial participants and staff will explore issues around study processes and acceptability of the intervention and the findings integrated with the feasibility trial outcomes to inform the design of a future full-scale randomised controlled trial. ETHICS AND DISSEMINATION: Ethics approval was granted by East Midlands-Derby Research Ethics Committee on 10 January 2019. The findings will be presented at relevant conferences disseminated via peer-reviewed research publications, and to relevant stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN80441309.

Normative values for the distress thermometer (DT) and the emotion thermometers (ET), derived from a German general population sample.

PURPOSE: The distress thermometer (DT) and the emotion thermometers (ET) are short screening instruments for use in oncological practice. The aim of this study was to provide normative values and to analyze the correlational structure of the ET. METHODS: A representative sample of the adult German general population (N = 2437) completed the ET, the PHQ-4, the FACIT-fatigue scale, and the demoralization scale. RESULTS: The percentages of people above the cutoff (≥ 4) and the mean scores of the five ET scales were as follows: distress: 39.0%, M = 3.15 ± 2.62, anxiety: 12.3%, M = 1.36 ± 1.93, depression: 16.1%, M = 1.65 ± 2.11, anger: 24.5%, M = 2.33 ± 2.16, and need for help: 10.7%, M = 1.18 ± 1.90. Women reported significantly higher levels of burden than men, with effect sizes between 0.07 (anger) and 0.36 (anxiety). All ET dimensions were interrelated (r between 0.44 and 0.69) and significantly correlated with the other scales (r between 0.36 and 0.68). CONCLUSIONS: The normative scores can help qualify assessments of groups of patients. The new four dimensions of the ET provide relevant additional information that is not already covered by the DT.

The impact of automated screening with Edmonton Symptom Assessment System (ESAS) on health-related quality of life, supportive care needs, and patient satisfaction with care in 268 ambulatory cancer patients.

PURPOSE: We aimed to assess the impact of implementing Edmonton Symptom Assessment System (ESAS) screening on health-related quality of life (HRQoL) and patient satisfaction with care (PSC) in ambulatory oncology patients. ESAS is now a standard of care in Ontario cancer centers, with the goal of improving symptom management in cancer patients, yet few studies examine impact of ESAS on patient outcomes. METHODS: We compared ambulatory oncology patients who were not screened prior to ESAS site implementation (2011-2012), to a similar group who were screened using ESAS after site implementation (2012-2013), to examine between-group differences in patient HRQoL, PSC outcomes, and supportive care needs (Supportive Care Service Survey). Both no-ESAS (n = 160) and ESAS (n = 108) groups completed these measures: the latter completing them, along with ESAS, at baseline and 2 weeks later. RESULTS: After assessing the impact of implementing ESAS, by matching for potentially confounding variables and conducting univariate analyses, no significant between-group differences were found in HRQoL or PSC. There was significant improvement in symptoms of nausea/vomiting and constipation, after 2 weeks. Lower symptom burden with decreased ESAS scores was significantly correlated with increased HRQoL. There were no between-group differences in knowledge of/access to supportive care. CONCLUSIONS: Significant correlation between change in ESAS and HRQoL implies ESAS could usefully inform healthcare providers about need to respond to changes in symptom and functioning between visits. This study showed no impact of early-ESAS screening on HRQoL or PSC. Further research should explore how to better utilize ESAS screening, to improve communication, symptom management, and HRQoL.

Screening for emotional disorders in patients with cancer using the Brief Symptom Inventory (BSI) and the BSI-18 versus a standardized psychiatric interview (the World Health Organization Composite International Diagnostic Interview).

BACKGROUND: Given the adverse consequences of psychiatric and psychosocial morbidity on the quality of life for patients with cancer, prompt detection of psychological symptoms is mandatory. The authors examined the properties and accuracy of the Brief Symptom Inventory (the 53-item version [BSI] and the 18-item version [BSI-18]) for the detection of psychiatric morbidity compared with the World Health Organization Composite International Diagnostic Interview (CIDI) for International Classification of Diseases-10th Revision psychiatric diagnoses. METHODS: A convenience sample of 498 patients with newly diagnosed cancer who were recruited in cancer outpatient services participated in the CIDI interview and in BSI and BSI-18 assessments. RESULTS: The prevalence of psychiatric morbidity was 39.75%. When participants were classified as cases using the BSI standard case rule, agreement with the CIDI was potentially acceptable (sensitivity, 72.7%; specificity, 88.7%). In contrast, the accuracy of the BSI-18 in identifying cases was poor according to the standard case rule, with very low sensitivity (29.3%) (misclassification rate, 28.7%). By using a first alternative case-rule system (a BSI-18 global severity index [GSI] T-score ≥57), sensitivity marginally improved (45%), whereas a second alternative case-rule system (a GSI T-score ≥50) significantly increased sensitivity (77.3%). In receiver operating characteristic curve analysis, a further cutoff GSI T-score ≥48 exhibited good discrimination levels (sensitivity, 82.3%; specificity, 72.4%). There were some differences in GSI cutoff T-scores according to the International Classification of Diseases-10th Revision diagnosis and sex. CONCLUSIONS: The BSI appeared to have acceptable diagnostic accuracy compared with a standardized psychiatric interview. For the BSI-18, it is mandatory to use alternative case-rule systems, to identify patients with psychiatric morbidity. Cancer 2018;124:2415-26. © 2018 American Cancer Society.

PROMIS depression measures perform similarly to legacy measures relative to a structured diagnostic interview for depression in cancer patients.

PURPOSE: To assess the convergent validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) depression measures relative to legacy measures and criterion validity against a structured diagnostic interview for depression in an oncology sample. METHODS: 132 oncology/haematology outpatients completed the PROMIS Depression Computer Adaptive Test (PROMIS-D-CAT) and PROMIS Depression Short Form (PROMIS-D-SF) along with seven legacy measures: Beck Depression Inventory (BDI); Centre for Epidemiological Studies Depression (CES-D); Depression, Anxiety and Stress Scale; Hospital Anxiety and Depression Scale; Patient Health Questionnaire; Distress Thermometer and PSYCH-6. Correlations, area under the curve (AUC) and diagnostic accuracy statistics were calculated with Structured Clinical Interview as the gold standard. RESULTS: Both PROMIS measures correlated with all legacy measures at p < .001 (ρ = 0.589-0.810) and all AUCs (> 0.800) were comparable. At the cut-off points for mild depression of 53, the PROMIS measures had sensitivity (0.83 for PROMIS-D-CAT and 0.80 for PROMIS-D-SF) similar to or better than 6/7 legacy measures with high negative predictive value (> 90%). At cut-off points of 60 for moderate depression, PROMIS measures had specificity > 90%, similar to or better than all legacy measures and positive predictive value ≥ 0.50 (similar to 5/7 legacy measures). CONCLUSIONS: The convergent and criterion validity of the PROMIS depression measures in cancer populations was confirmed, although the optimal cut-off points are not established. PROMIS measures were briefer than BDI-II and CES-D but do not offer any advance in terms of diagnostic accuracy, reduced response burden or cost over other legacy measures of depression in oncology patients.