Post-traumatic stress disorder following childbirth: an update of current issues and recommendations for future research

Objective: This paper aimed to report the current status of research in the field of post-traumatic stress disorder following childbirth (PTSD FC), and to update the findings of an earlier 2008 paper. Background: A group of international researchers, clinicians and service users met in 2006 to establish the state of clinical and academic knowledge relating to PTSD FC. A paper identified four key areas of research knowledge at that time. Methods: Fourteen clinicians and researchers met in Oxford, UK to update the previously published paper relating to PTSD FC. The first part of the meeting focused on updating the four key areas identified previously, and the second part on discussing new and emerging areas of research within the field. Results: A number of advances have been made in research within the area of PTSD FC. Prevalence is well established within mothers, several intervention studies have been published, and there is growing interest in new areas: staff and pathways; prevention and early intervention; impact on families and children; special populations; and post-traumatic growth. Conclusion: Despite progress, significant gaps remain within the PTSD FC knowledge base. Further research continues to be needed across all areas identified in 2006, and five areas were identified which can be seen as ‘new and emerging’. All of these new areas require further extensive research. Relatively little is still known about PTSD FC

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Background: The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments. Methods: The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed. Findings: Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15–1·22] in men and 1·10 [1·06–1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval −0·84 g/L [95% CI −0·99 to −0·70] in men and −0·45 g/L [–0·59 to −0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval −6·5% [95% CI −7·6 to −5·5] in men and −5·3% [–6·5 to −4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001). Interpretation: During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores. Funding: NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Low-dose induction of micronuclei by lindane.

Environmental contaminants possessing hormonal activity have long been suspected of playing a role in cancer causation. What is unclear is whether such agents elicit their effects through genotoxic and/or epigenetic mechanisms. -Hexachlorocyclohexane (-HCH, lindane) was tested in the 10-12–10-4 M range. Chromosomal damage in MCF-7 breast cells and PC-3 prostate cells was assessed using the cytokinesis block micronucleus assay. Micronuclei (MNi) were scored in 1000 binucleate cells per treatment. Cell viability and cell cycle kinetics were also assessed, along with immunocytochemical and quantitative gene expression analyses of CDKN1A (P21WAF1/CIP1), BCL-2 and BAX. Following 24 h treatment, lindane (10-12–10-10 M) induced increases (up to 5-fold) in MNi in both cell lines. Increases in MNi occurred in the absence of DNA single-strand breaks or cytotoxicity and, compared with benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, at low concentrations. Lindane induced more MNi than the or ß stereoisomers of HCH. Low dose lindane (10-12–10-10 M) significantly elevated the percentage of MCF-7 cells staining positive for Bcl-2 and of PC-3 cells staining positive for Bax. Only high dose lindane (10-4 M) disrupted cell cycle kinetics with increases in percentage of cells in G1 and decreases in percentage of cells in G2/M. Despite a comparable high dose lindane induction of cell cycle arrest, marked increases in expression of P21WAF1/CIP1 were observed only in MCF-7 cells, although in PC-3 cells a significant increase (P < 0.0005) in the percentage of cells staining positive for p21Waf1/Cip1 was seen. These results suggest that ‘environmental’ concentrations of lindane can induce a number of subtle alterations in breast and prostate cells in the absence of cytotoxicity

Evaluating the effectiveness of e‐cigarettes compared with usual care for smoking cessation when offered to smokers at homeless centres: Protocol for a multi‐centre cluster randomised controlled trial in Great Britain

Background and aims: Smoking is extremely common among adults experiencing homelessness but there is lack of evidence for treatment efficacy. E-cigarettes are an effective quit aid, but they have not been widely tested in smokers with complex health and social needs. Here we build on our cluster feasibility trial and evaluate the offer of an e-cigarette or usual care to smokers accessing a homeless centre. Design: Multi-centre two-arm cluster randomised controlled trial with mixed-method embedded process and economic evaluation. Setting: Homeless centres in England, Scotland and Wales. Participants: Adult smokers (18+ years; n= 480) accessing homeless centres and who are known to centre staff and willing to consent. Intervention and comparator: Clusters (n=32) will be randomised to either an e-cigarette starter pack with weekly allocations of nicotine containing e-liquid for 4-weeks (choice of flavours (menthol, fruit and tobacco) and strengths 12 mg/mL and 18mg/mL), or the usual care intervention which comprises very brief advice and a leaflet signposting to the local stop smoking service. Measurements: The primary outcome is 24-week sustained CO validated smoking cessation (Russell Standard defined, intention-to-treat analysis). Secondary outcomes: i) Fifty percent smoking reduction (cigarettes per day) from baseline to 24 weeks; ii) 7-day point prevalence quit rates at 4-, 12- and 24-week follow-up; iii) changes in risky smoking practices (e.g. sharing cigarettes, smoking discarded cigarettes) from baseline to 4-, 12- and 24-weeks; iv) cost-effectiveness of the intervention; v) fidelity of intervention implementation; mechanisms of change; contextual influences and sustainability. Comments: This is the first study to randomly assign smokers experiencing homelessness to an e-cigarette and usual care intervention to measure smoking abstinence with embedded process and economic evaluations. If effective, the results will be used to inform the larger scale implementation of offering e-cigarettes across homeless centres to aid smoking cessation

Inter-individual differences in the ability of human milk-fat extracts to enhance the genotoxic potential of the procarcinogen benzo[a]pyrene in MCF-7 breast cells.

Environmental factors are believed to play an important role in cancer aetiology. Whether environmental pollutants act in isolation or in combination within mixtures remains unclear. Four human milk-fat extracts (from resident U.K. women) were screened for levels of organochlorinated and brominated compounds prior to being tested (1−50 mg-equiv) for micronucleus (MN)-forming activity in MCF-7 cells. Using the cytokinesis-block micronucleus assay, micronuclei (MNi) were scored in 1000 binucleate cells per treatment. Cell viability (% plating efficiency) and immunohistochemical detection of p53 induction were also measured. The effects of treatment with 1 mg-equiv of extract in combination with benzo[a]pyrene (BP) were also examined. BP−DNA adducts were detected and quantified by 32P-postlabeling analysis. Dose-related increases in MNi independent of pollutant concentrations were induced by milk-fat extracts. All four extracts elevated the percentage of p53 positive cells, although not always in a dose-related fashion. Some combinations resulted in profound low-dose-induced increases in MNi and significant elevations in the percentage of p53 positive cells, which occurred without further reduction in cell viability or mitotic rate. When one particular extract was combined with BP, a 100-fold increase in BP−DNA adducts was detected as compared with the levels induced by BP alone; an effect not induced by other extracts. This adduct-enhancing extract was fractionated into 14 fractions that were subsequently tested (1 mg-equiv of original extract) in combination with 0.01 μM BP. Fraction 1, into which nonpolar pollutants mostly eluted, enhanced MN-forming activity with BP. Surprisingly, the more polar and less likely to contain fat-soluble pollutants fractions 5 and 8 also enhanced MN-forming activity. No identifiable pollutants were present in these fractions. The results suggest that different environmental pollutants present in human tissue may influence the susceptibility of target cells to initiating events

Carnivalesque collaborations: reflections on ‘doing’ multi-disciplinary research

Many funding bodies emphasise the advantages of using multi-disciplinary approaches; in response, in this paper we consider our reflections on doing such a project. We contribute to the multi-disciplinary literature by considering the standardizing effect of collaboration on multifarious research approaches. We argue that greater attention should be paid to ‘doing’ qualitative multi-disciplinary research. We find that elements of ‘letting go’ and ‘coming together’ are important when new perspectives and knowledge are engaged. Therefore, we call for clarity on the multi-disciplinary approaches and discuss how we came to understand the collaborative processes of researching, thinking, and writing. The paper begins with vignettes about our ontological journeys during the research project. In developing our argument, we consider the retrospective and reflexive qualities expressed in our vignettes and examine how our collaborative theorizing shaped the research project