Long-acting PGE2 and Lisinopril Mitigate H-ARS.

Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.

Developing a complex intervention to support pregnant women with mild to moderate anxiety: application of the Medical Research Council framework.

BACKGROUND: To design and develop an intervention to support women with symptoms of mild to moderate anxiety in pregnancy. METHODS: The development followed the MRC framework for complex interventions, utilising psychological theory, review level evidence and professional and public involvement. Two systematic reviews were completed which helped identify potentially beneficial intervention components. The theory underpinning the components was explored to consider the potential benefit for women with mild to moderate anxiety symptoms in pregnancy. Methods of delivering the intervention within maternity services were explored. The intervention comprised: group discussions, one to one support and assisted self-help resources. Midwives were identified as ideally placed to facilitate the intervention supported by midwifery support workers. A bespoke training package was provided by subject experts to prepare the facilitators. RESULTS: The absence of established interventions and a paucity of evidence based approaches for pregnant women with symptoms of mild to moderate anxiety indicated the need for a rigorous and systematic approach to the intervention design. This approach led to the development of an intervention feasible for implementation in maternity care systems tailored to the needs of pregnant women. The involvement of a multi-professional advisory team and active engagement of service users helped to consider the acceptability of the intervention for women and the feasibility of delivering the intervention in the context of maternity care. CONCLUSION: The MRC Framework provided useful overarching guidance to develop a midwife facilitated intervention for women with symptoms of anxiety in pregnancy. The framework assisted the development of a robust rationale for each intervention component and considered the processes of evaluation and implementation into maternity care systems.

The effectiveness of exercise-based interventions for preventing or treating postpartum depression: a systematic review and meta-analysis.

Postpartum depression can have detrimental effects on both a mother's physical and mental health and on her child's growth and emotional development. The aim of this study is to assess the effectiveness of exercise/physical activity-based interventions in preventing and treating postpartum depressive symptoms in primiparous and multiparous women to the end of the postnatal period at 52 weeks postpartum. Electronic databases were searched for published and unpublished randomised controlled trials of exercise/physical activity-based interventions in preventing and treating depressive symptoms and increasing health-related quality of life in women from 4 to 52 weeks postpartum. The results of the studies were meta-analysed and effect sizes with confidence intervals were calculated. The Grading of Recommendations Assessment and Development and Evaluation (GRADE) system was used to determine the confidence in the effect estimates. Eighteen trials conducted across a range of countries met the inclusion criteria. Most of the exercise interventions were aerobic and coaching compared to usual care, non-intervention and active controls. Small effect sizes of exercise-based interventions in reducing depressive symptoms were observed collectively and the quality of evidence was low across the individual studies. Although exercise-based interventions could create an alternative therapeutic approach for preventing major depression in postpartum women who experience subthreshold elevated depressive symptoms, the clinical effectiveness and the cost-effectiveness of exercise-based and physical activity interventions need to be better established. There is a need for further more rigorous testing of such interventions in high-quality randomised controlled trials against active control conditions before large-scale roll-out of these interventions in clinical practice is proposed.

Cost-effectiveness of PoNDER health visitor training for mothers at lower risk of depression: findings on prevention of postnatal depression from a cluster-randomised controlled trial.

BACKGROUND: There is evidence for the cost-effectiveness of health visitor (HV) training to assess postnatal depression (PND) and deliver psychological approaches to women at risk of depression. Whether this approach is cost-effective for lower-risk women is unknown. There is a need to know the cost of HV-delivered universal provision, and how much it might cost to improve health-related quality of life for postnatal women. A sub-study of a cluster-randomised controlled trial in the former Trent region (England) previously investigated the effectiveness of PoNDER HV training in mothers at lower risk of PND. We conducted a parallel cost-effectiveness analysis at 6-months postnatal for all mothers with lower-risk status attributed to an Edinburgh Postnatal Depression Scale (EPDS) score <12 at 6-weeks postnatal. METHODS: Intervention HVs were trained in assessment and cognitive behavioural or person-centred psychological support techniques to prevent depression. Outcomes examined: quality-adjusted life-year (QALY) gains over the period between 6 weeks and 6 months derived from SF-6D (from SF-36); risk-of-depression at 6 months (dichotomising 6-month EPDS scores into lower risk (<12) and at-risk (⩾12). RESULTS: In lower-risk women, 1474 intervention (63 clusters) and 767 control participants (37 clusters) had valid 6-week and 6-month EPDS scores. Costs and outcomes data were available for 1459 participants. 6-month adjusted costs were £82 lower in intervention than control groups, with 0.002 additional QALY gained. The probability of cost-effectiveness at £20 000 was very high (99%). CONCLUSIONS: PoNDER HV training was highly cost-effective in preventing symptoms of PND in a population of lower-risk women and cost-reducing over 6 months.

Systematic review and meta-analysis of non-pharmacological interventions to reduce the symptoms of mild to moderate anxiety in pregnant women.

AIM: To assess the effectiveness of non-pharmacological interventions for pregnant women with symptoms of mild to moderate anxiety. BACKGROUND: Many pregnant women experience mild to moderate symptoms of anxiety and could benefit from additional support. Non-pharmacological interventions have been suggested for use during pregnancy. DESIGN: A systematic review of randomized controlled trials. DATA SOURCES: Randomized controlled trials published since 1990, identified from electronic databases: Medline; CINAHL; Maternity and Infant Care; PsycINFO; Cochrane Database of Systematic Reviews; CENTRAL; EMBASE; Centre for Reviews and Dissemination; Social Sciences Citation Index; ASSIA; HTA Library; Joanna Briggs Institute Evidence-Based Practice database; Allied and Complementary Medicine. REVIEW METHODS: Conducted according to the Centre for Reviews and Dissemination procedure. Papers were screened (N = 5,222), assessed for eligibility (N = 57) and selected for inclusion (N = 25). The Cochrane Collaboration's tool for assessing risk of bias was used. Papers were assessed for clinical and statistical heterogeneity and considered for meta-analysis. Descriptive analysis of the data was conducted. RESULTS: Psychological, mind-body, educational and supportive interventions were delivered individually and to groups of pregnant women over single or multiple sessions. The State-Trait Anxiety Inventory was the most commonly used anxiety measure. In 60% of studies there were fewer than 40 participants. Meta-analysis of three studies indicated no observed beneficial effect in the reduction of anxiety. CONCLUSION: There was insufficient evidence from which to draw overall conclusions regarding the benefit of interventions. Results were predominantly based on small samples. Many papers provided an inadequate description of methods which prevented a full assessment of methodological quality.

Perceptions and experiences of interventions to prevent postnatal depression. A systematic review and qualitative evidence synthesis.

BACKGROUND: More women experience depressive symptoms antenatally than postnatally. Supporting women through the antenatal period is recognised as important in mitigating negative outcomes and in preventing postnatal depression (PND). A systematic review was conducted which aimed to provide a detailed service user and service provider perspective on the uptake, acceptability, and perception of harms of antenatal interventions and postnatal interventions for preventing PND. METHODS: A comprehensive literature search was conducted in 12 major bibliographic databases in November 2012 and updated in December 2014. Studies were included if they contained qualitative evidence on the perspectives and attitudes of pregnant women and postnatal women who had taken part in, or healthcare professionals (HCPs) involved in delivering, preventive interventions for PND. RESULTS: Twenty-two studies were included. Support and empowerment through education were identified as particularly helpful to women as intervention components, across all intervention types. Implications for accessing the service, understanding the remit of the service and women's preferences for group and individual care also emerged. LIMITATIONS: The majority of the included studies were of moderate or low quality, which may result in a lack of rich data consistently across all studies, limiting to some degree interpretations that can be made. CONCLUSION: The synthesis demonstrated important considerations for devising new interventions or adapting existing interventions. Specifically, it is important that individual or group interventions are carefully tailored to women's needs or preferences and women are aware of the remit of the HCPs role to ensure they feel able to access the support required.

Women's views on anxiety in pregnancy and the use of anxiety instruments: a qualitative study.

OBJECTIVE: To explore women's experience of anxiety in pregnancy and views on the use of anxiety instruments in antenatal care. BACKGROUND: Anxiety in pregnancy is associated with adverse birth outcomes, developmental and behavioural problems in infants and postnatal depression. Despite recommendations for routine psychological assessment in pregnancy, the optimal methods to identify anxiety in pregnancy have not been confirmed. METHODS: A qualitative study using two focus group discussions was undertaken. Focus group one included women in a community setting and focus group two included women in a hospital clinic setting who had received additional support for anxiety in pregnancy. Participants were women who had given birth within the past nine months and considered themselves to have been anxious during their pregnancy. RESULTS: Three main themes were identified using template analysis: sources of support, administration of anxiety instruments and the use of instruments to prompt discussion. Women stated that anxiety instruments could help them to identify their anxious feelings and prompt a discussion around those feelings. However, they expressed concerns surrounding the administration of anxiety instruments and questioned how useful they would be in helping women access help and support. CONCLUSIONS: The introduction of anxiety instruments in antenatal care may present an opportunity to discuss women's emotional health and anxieties. Providing women with sufficient time to discuss their anxious feelings, identified by such instruments, could facilitate access to additional support.

A systematic review, evidence synthesis and meta-analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost-effectiveness, safety and acceptability of interventions to prevent postnatal depression.

BACKGROUND: Postnatal depression (PND) is a major depressive disorder in the year following childbirth, which impacts on women, their infants and their families. A range of interventions has been developed to prevent PND. OBJECTIVES: To (1) evaluate the clinical effectiveness, cost-effectiveness, acceptability and safety of antenatal and postnatal interventions for pregnant and postnatal women to prevent PND; (2) apply rigorous methods of systematic reviewing of quantitative and qualitative studies, evidence synthesis and decision-analytic modelling to evaluate the preventive impact on women, their infants and their families; and (3) estimate cost-effectiveness. DATA SOURCES: We searched MEDLINE, EMBASE, Science Citation Index and other databases (from inception to July 2013) in December 2012, and we were updated by electronic alerts until July 2013. REVIEW METHODS: Two reviewers independently screened titles and abstracts with consensus agreement. We undertook quality assessment. All universal, selective and indicated preventive interventions for pregnant women and women in the first 6 postnatal weeks were included. All outcomes were included, focusing on the Edinburgh Postnatal Depression Scale (EPDS), diagnostic instruments and infant outcomes. The quantitative evidence was synthesised using network meta-analyses (NMAs). A mathematical model was constructed to explore the cost-effectiveness of interventions contained within the NMA for EPDS values. RESULTS: From 3072 records identified, 122 papers (86 trials) were included in the quantitative review. From 2152 records, 56 papers (44 studies) were included in the qualitative review. The results were inconclusive. The most beneficial interventions appeared to be midwifery redesigned postnatal care [as shown by the mean 12-month EPDS score difference of -1.43 (95% credible interval -4.00 to 1.36)], person-centred approach (PCA)-based and cognitive-behavioural therapy (CBT)-based intervention (universal), interpersonal psychotherapy (IPT)-based intervention and education on preparing for parenting (selective), promoting parent-infant interaction, peer support, IPT-based intervention and PCA-based and CBT-based intervention (indicated). Women valued seeing the same health worker, the involvement of partners and access to several visits from a midwife or health visitor trained in person-centred or cognitive-behavioural approaches. The most cost-effective interventions were estimated to be midwifery redesigned postnatal care (universal), PCA-based intervention (indicated) and IPT-based intervention in the sensitivity analysis (indicated), although there was considerable uncertainty. Expected value of partial perfect information (EVPPI) for efficacy data was in excess of £150M for each population. Given the EVPPI values, future trials assessing the relative efficacies of promising interventions appears to represent value for money. LIMITATIONS: In the NMAs, some trials were omitted because they could not be connected to the main network of evidence or did not provide EPDS scores. This may have introduced reporting or selection bias. No adjustment was made for the lack of quality of some trials. Although we appraised a very large number of studies, much of the evidence was inconclusive. CONCLUSIONS: Interventions warrant replication within randomised controlled trials (RCTs). Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. FUTURE WORK RECOMMENDATIONS: Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. Future research conducting RCTs to establish which interventions are most clinically effective and cost-effective should be considered. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003273. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Can community midwives prevent antenatal depression? An external pilot study to test the feasibility of a cluster randomized controlled universal prevention trial.

BACKGROUND: Repeated epidemiological surveys show no decline in depression although uptake of treatments has grown. Universal depression prevention interventions are effective in schools but untested rigorously in adulthood. Selective prevention programmes have poor uptake. Universal interventions may be more acceptable during routine healthcare contacts for example antenatally. One study within routine postnatal healthcare suggested risk of postnatal depression could be reduced in non-depressed women from 11% to 8% by giving health visitors psychological intervention training. Feasibility and effectiveness in other settings, most notably antenatally, is unknown. METHOD: We conducted an external pilot study using a cluster trial design consisting of recruitment and enhanced psychological training of randomly selected clusters of community midwives (CMWs), recruitment of pregnant women of all levels of risk of depression, collection of baseline and outcome data prior to childbirth, allowing time for women 'at increased risk' to complete CMW-provided psychological support sessions. RESULTS: Seventy-nine percent of eligible women approached agreed to take part. Two hundred and ninety-eight women in eight clusters participated and 186 termed 'at low risk' for depression, based on an Edinburgh Perinatal Depression Scale (EPDS) score of <12 at 12 weeks gestation, provided baseline and outcome data at 34 weeks gestation. All trial protocol procedures were shown to be feasible. Antenatal effect sizes in women 'at low risk' were similar to those previously demonstrated postnatally. Qualitative work confirmed the acceptability of the approach to CMWs and intervention group women. CONCLUSION: A fully powered trial testing universal prevention of depression in pregnancy is feasible, acceptable and worth undertaking.

Glutamate Receptor Interacting Protein 1 Regulates CD4(+) CTLA-4 Expression and Transplant Rejection.

PDZ domains are common 80- to 90-amino-acid regions named after the first three proteins discovered to share these domains: postsynaptic density 95, discs large, and zonula occludens. PDZ domain-containing proteins typically interact with the C-terminus of membrane receptors. Glutamate receptor interacting protein 1 (GRIP1), a seven-PDZ domain protein scaffold, regulates glutamate receptor surface expression and trafficking in neurons. We have found that human and mouse T cells also express GRIP1. T cell-specific GRIP1(-/-) mice >11 weeks old had prolonged cardiac allograft survival. Compared with wild-type T cells, in vitro stimulated GRIP1(-/-) T cells had decreased expression of activation markers and increased apoptotic surface marker expression. Surface expression of the strong T cell inhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4) was increased on GRIP1(-/-) T cells from mice >11 weeks old. CTLA-4 increases with T cell stimulation and its surface expression on GRIP1(-/-) T cells remained high after stimulation was removed, indicating a possible internalization defect in GRIP1-deficient T cells. CTLA-4-blocking antibody treatment following heart transplantation led to complete rejection in T cell GRIP1(-/-) mice, indicating that increased CTLA-4 surface expression contributed to the extended graft survival. Our data indicate that GRIP1 regulates T cell activation by regulating CTLA-4 surface expression.

A psychometric systematic review of self-report instruments to identify anxiety in pregnancy.

AIMS: To report a systematic review of the psychometric properties of self-report instruments to identify the symptoms of anxiety in pregnancy to help clinicians and researchers select the most suitable instrument. BACKGROUND: Excessive anxiety in pregnancy is associated with adverse birth outcomes, developmental and behavioural problems in infants and postnatal depression. Despite recommendations for routine psychological assessment in pregnancy, the optimal methods to identify anxiety in pregnancy have not been confirmed. DESIGN: Psychometric systematic review. DATA SOURCES: A systematic literature search of the multiple databases (1990-September 2014). REVIEW METHODS: Identification of self-report instruments to measure anxiety in pregnancy using COSMIN guidelines to assess studies reporting a psychometric evaluation of validity and reliability. RESULTS: Thirty-two studies were included. Studies took place in the UK, Australia, Belgium, Canada, Germany, Italy, Scandinavia, Spain and the Netherlands. Seventeen different instruments were identified. Measures of validity were reported in 19 papers and reliability in 16. The overall quality of the papers was rated as fair to excellent using the COSMIN checklist. Only one paper scored excellent in more than one category. CONCLUSION: Many instruments have been adapted for use in different populations to those for which they were designed. The State Trait Anxiety Inventory, Edinburgh Postnatal Depression Scale and the Hospital Anxiety and Depression Scale have been tested more frequently than other instruments, yet require further assessment to confirm their value for use in pregnancy.

The burden of obesity on blood pressure is reduced in older persons: the SardiNIA study.

INTRODUCTION: Being overweight or obese increases the risk of elevated blood pressure. However differences of their effects on blood pressure in different age groups are not clear. OBJECTIVE: The aim of the present study was to evaluate differences of the effects of adiposity on the odds of having hypertension in different age groups. DESIGN AND METHODS: Three thousand fifty-six subjects (1,532 women and 1,524 men) consist of the drug naïve subjects from the SardiNIA study. Logistic regression models with backward elimination were used to determine and compare the association between categories of obesity on hypertension within young (≤ 39), middle aged (40-59), and older (60+) subjects. Additional terms controlled for in the model were smoking and alcohol intake status. RESULTS: The relationship of body mass index (BMI) on hypertension differed by age, as indicated by the significant interaction term of age with BMI (P <0.01). Older subjects had higher odds of having hypertension than younger subjects but these odds were lower for obese than for lean subjects (OR 10.45, 95% CIs 4.58-23.85 in obese versus OR 33.89, 95% CIs 17.94-64.02 in lean subjects). A similar trend was also observed in middle aged subjects. CONCLUSIONS: This study shows that among men and women, older age was associated with a lesser effect of BMI on the odds of having hypertension.

Identification of depressive disorder among older people in care homes - a feasibility study.

BACKGROUND: Depression is common among older people but more common among those living in care homes. Depression is not easily detected among older adults because of the presentation, and the tendency for older people not to complain of depression, particularly those living in care homes. In general, care home staff have limited training in recognising depression. Depression is undertreated and residents may not receive a therapeutic dose of antidepressant. The true prevalence of depression among care home residents is uncertain. METHOD: This feasibility study aimed to explore the level of depression among older people in care homes by comparing the outcome of an assessment by care home staff with the outcome of a diagnostic clinical interview, using ICD-10 criteria and the 30-item Geriatric Depression Scale (GDS), conducted by a psychiatrist. RESULTS: In all, 47 older people from four care homes were interviewed by a psychiatrist. Of them, 39.1% (18/46) of residents were prescribed an antidepressant and were no longer depressed; 8.7% (4/46) were prescribed an antidepressant and remained depressed; and 6.5% (3/46) of residents assessed as being depressed, had not been prescribed an antidepressant. That is, 54% (25/46) of residents had been or were currently depressed. Using ICD-10 criteria, the sensitivity of the GDS at a threshold of 10 and 11 was 100%. In total, 89.4% of residents received a correct diagnosis (presence or absence of depression) using the GDS at the 11 threshold. SUMMARY: The prevalence of depression in these homes was 54%. Of the residents with depression, 72% (18/25) were managed with an antidepressant and 28% (7/25) were receiving ineffective or no treatment. The 30-item GDS can provide more useful information than a home care staff assessment for identifying depression. More research should explore the value of training home care staff to administer the 30-item GDS to optimise the management of depression in older people in care homes.

The development of two postnatal health instruments: one for mothers (M-PHI) and one for fathers (F-PHI) to measure health during the first year of parenting.

PURPOSE: To develop and psychometrically evaluate two questionnaires measuring both positive and negative postnatal health of mothers (M-PHI) and fathers (F-PHI) during the first year of parenting. METHODS: The M-PHI and the F-PHI were developed in four stages. Stage 1: Postnatal women's focus group (M-PHI) and postnatal fathers' postal questionnaire (F-PHI); Stage 2: Qualitative interviews; Stage 3: Pilot postal survey and main postal survey; and Stage 4: Test-retest postal survey. RESULTS: The M-PHI consisted of a 29-item core questionnaire with six main scales and five conditional scales. The F-PHI consisted of a 27-item questionnaire with six main scales. All scales achieved good internal reliability (Cronbach's α 0.66-0.87 for M-PHI, 0.72-0.90 for F-PHI). Intraclass correlation coefficients demonstrated high test-retest reliability (0.60-0.88). Correlation coefficients supported the criterion validity of the M-PHI and the F-PHI when tested against the Short-Form-12 (SF-12), Edinburgh Postnatal Depression Scale (EPDS) and the Warwick and Edinburgh Mental Well-Being Scale (WEMWBS). CONCLUSION: The M-PHI and F-PHI are valid, reliable, parent-generated instruments. These unique instruments will be invaluable for practitioners wishing to promote family-centred care and for trialists and other researchers requiring a validated instrument to measure both positive and negative health during the first postnatal year, as to date no such measurement has existed.

Training health visitors in cognitive behavioural and person-centred approaches for depression in postnatal women as part of a cluster randomised trial and economic evaluation in primary care: the PoNDER trial.

AIM: This paper aims to describe the training preparation for health visitors who took part in the intervention arm of a cluster randomised controlled trial and economic evaluation of training for health visitors - the POstNatal Depression Economic evaluation and Randomised (the PoNDER) trial. A secondary aim is to make available, by electronic links, the training manuals developed for and used for the cognitive behavioural approach (CBA) and the person-centred approach (PCA) training for the health visitors. The paper is of relevance to health visitors, general practitioners, nurse practitioners, midwives, clinical psychologists, mental health nurses, community psychiatric nurses, counsellors, and service commissioners. BACKGROUND: The trial clinical outcomes have been published, indicating the pragmatic effectiveness of the package of training for health visitors to identify depressive symptoms and provide a psychologically informed intervention. The training was associated with a reduction in depressive symptoms at six months postnatally among intervention group women and some evidence of a benefit for the intervention group for some of the secondary outcomes at 18 months follow-up. METHODS: The two experimental interventions examined in the PoNDER trial built upon promising work on the potential for psychological interventions to help women recover from postnatal depression as an alternative to pharmaceutical interventions and to address the limitations of previous research in the area. FINDINGS: The package of health visitor training comprised the development of clinical skills in assessing postnatal women and identifying depressive symptoms, and the delivery of a CBA or a PCA for eligible women. This was the largest trial a health visitor intervention and of postnatal depression ever conducted. We are aware of no other rigorously performed trial that has published details of an extensively tested training programme for the benefit of health-care professionals and clients.

Universal prevention of depression in women postnatally: cluster randomized trial evidence in primary care.

BACKGROUND: To test whether receiving care from a health visitor (HV) trained in identification and psychological intervention methods prevents depression 6-18 months postnatally in women who are not depressed 6 weeks postnatally. METHOD: The study was a prospective cluster trial, randomized by GP practice, with follow-up for 18 months in 101 primary care teams in the Trent area of England. The participants were women scoring <12 on the postal Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks postnatally (1474 intervention and 767 control women). Intervention HVs (n=89, 63 clusters) were trained in identifying depressive symptoms using the EPDS and face-to-face clinical assessment and in providing psychologically orientated sessions based on cognitive behavioral or person-centered principles. The control group comprised HVs (n=49, 37 clusters) providing care as usual (CAU). The primary outcome measure was the proportion of women scoring ≥ 12 on the EPDS at 6 months postnatally. Secondary outcomes were mean EPDS score, Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) score, State-Trait Anxiety Inventory (STAI), 12-item Short Form Health Survey (SF-12) and Parenting Stress Index Short Form (PSI-SF) scores at 6, 12 and 18 months. RESULTS: After adjusting for individual-level covariates, living alone, previous postnatal depression (PND), the presence of one or more adverse life events and the 6-week EPDS score, the odds ratio (OR) for EPDS ≥ 12 at 6 months was 0.71 [95% confidence interval (CI) 0.53-0.97, p=0.031] for the intervention group (IG) women compared with the control (CAU) group women. Two subgroups were formed by baseline severity: a 'subthreshold' subgroup with a 6-week EPDS score of 6-11 (n=999) and a 'lowest severity' subgroup with a 6-week EPDS score of 0-5 (n=1242). There was no difference in psychological effectiveness by subgroup (interaction term: z=-0.28, p=0.782). CONCLUSIONS: This study provides new evidence of a universal, enduring preventive effect for depression in women who screen negative for depression postnatally.

Postnatal women's experiences of management of depressive symptoms: a qualitative study.

BACKGROUND: Postnatal depression is a public health problem requiring intervention. To provide effective care, information is needed on the experiences of those with high levels of depressive symptoms who are offered and accept, or decline, psychological intervention postnatally. AIM: To provide the first integrated in-depth exploration of postnatal women's experiences of the identification and management of symptoms of depression and the offer and acceptance of postnatal care by health visitors taking part in the PoNDER trial. SETTING: General practice: primary care within the former Trent regional health authority, England. METHOD: Thirty women with 6-week Edinburgh Postnatal Depression Scale (EPDS) scores ≥ 18 and probable depression completed semi-structured interviews. All women had taken part in the Post-Natal Depression Economic Evaluation and Randomised controlled (PoNDER) trial where intervention group health visitors received training in identification of depressive symptoms and provided psychologically informed sessions based on cognitive-behavioural therapy or person-centred counselling principles. RESULTS: When accepted, psychological sessions were experienced as positive, effective, and 'ideal care'. Women approved of using the EPDS but did not understand the health visitor's role in supporting women. Seeking help and accepting sessions depended on women's perspectives of their health visitor as an individual. CONCLUSION: Women's experience of their health visitors providing psychological sessions to help with postnatal depressive symptoms is highly positive. Women will better accept support from health visitors if they recognise their role in postnatal depression and find them easy to relate to on personal matters. There is a case for specific enhancement of interpersonal skills in health visiting, or alternatively offering a choice of health visitors to women.

Platelet functions beyond hemostasis.

Although their central role is in the prevention of bleeding, platelets probably contribute to diverse processes that extend beyond hemostasis and thrombosis. For example, platelets can recruit leukocytes and progenitor cells to sites of vascular injury and inflammation; they release proinflammatory and anti-inflammatory and angiogenic factors and microparticles into the circulation; and they spur thrombin generation. Data from animal models suggest that these functions may contribute to atherosclerosis, sepsis, hepatitis, vascular restenosis, acute lung injury, and transplant rejection. This article represents an integrated summary of presentations given at the Fourth Annual Platelet Colloquium in January 2009. The process of and factors mediating platelet-platelet and platelet-leukocyte interactions in inflammatory and immune responses are discussed, with the roles of P-selectin, chemokines and Src family kinases being highlighted. Also discussed are specific disorders characterized by local or systemic platelet activation, including coronary artery restenosis after percutaneous intervention, alloantibody-mediated transplant rejection, wound healing, and heparin-induced thrombocytopenia.

Psychological interventions for postnatal depression: cluster randomised trial and economic evaluation. The PoNDER trial.

OBJECTIVES: To investigate outcomes for postnatal women attributed to special training for health visitors (HVs) in systematically identifying postnatal depression and delivering psychologically informed interventions, and to establish the cost-effectiveness of the intervention. DESIGN: A pragmatic randomised cluster trial with clusters allocated to experimental HV training arms or control, with an 18-month follow-up. SETTING: GP practices in the former Trent Regional Health Authority. PARTICIPANTS: Women registered with participating GP practices who became 36 weeks pregnant during the recruitment phase of the trial, had a live baby and were on a collaborating HV's caseload for 4 months postnatally. INTERVENTION: HV training in the assessment of postnatal women, combined with either cognitive behavioural approach (CBA) or person-centred approach (PCA) sessions for eligible women, plus the option of a selective serotonin reuptake inhibitor if indicated. MAIN OUTCOME MEASURES: The primary outcome was the proportion of at-risk women with a 6-month Edinburgh Postnatal Depression Scale (EPDS) score > or = 12. The primary comparison was between at-risk women in the combined clusters randomised to HV training and women in practices randomised to provide HV usual care. The secondary comparison was to determine any differences between the proportions of women with a 6-month EPDS score > or = 12 in the CBA and PCA groups. RESULTS: HVs in 101 clusters in 29 primary care trusts collaborated in the study. From 7649 eligible women 4084 (53.4%) consented to take part: 17.3% (595/3449) of women who returned a 6-week questionnaire had a 6-week EPDS score > or = 12 and were at-risk women; 70.3% (418/595) of at-risk women had a 6-month EPDS score available. In total, 45.6% (67/147) of control group (CG) at-risk women had a 6-month EPDS score > or = 12 versus 33.9% (93/271) of intervention group (IG) women (p = 0.036). A total of 32.9% (46/140) of at-risk women in the CBA group versus 35.1% (46/131) in the PCA group had a 6-month EPDS score > or = 12 (p = 0.74). The CG mean 6-month EPDS score for at-risk women was 11.3 (SD 5.8) versus 9.2 (SD 5.4) for the IG (p = 0.002) and this remained statistically significant after adjusting for 6-week variables (p = 0.001). In total, 16.4% (150/914) of all women in the CG had a 6-month EPDS score > or = 12 compared with 11.7% (205/1745) in the IG (p = 0.003). The CG mean 6-month EPDS score for all women was 6.4 (SD 5.2) compared with 5.5 (SD 4.7) for the IG (p < 0.001). The economic analysis results showed a consistent pattern of psychological approaches being cost-effective at funding levels used by the National Institute for Health and Clinical Excellence. CONCLUSIONS: HV training was effective compared with HV usual care in reducing the proportion of at-risk women with a 6-month EPDS score > or = 12, with a wide confidence interval for the estimated intervention effect, suggesting that the true treatment effect may be small. The effect remained for 1 year. The economic evaluation demonstrated that the HV intervention was highly likely to be cost-effective compared with the control. There was no difference in outcomes between the CBA and the PCA groups.