While existing literature has begun to explore risk factors which may predict differential response to marriage education, a history of couple infidelity has not been examined to determine whether infidelity moderates the impacts of marriage education. The current study evaluated self-report marital satisfaction and communication skills in a sample of 662 married Army couples randomly assigned to marriage education (i.e., PREP) or a no-treatment control group and assessed prior to intervention, post intervention and at 1 year after intervention. Of these, 23.4% couples reported a history of infidelity in their marriage. Multilevel modeling analyses indicated that having a history of infidelity significantly moderated the impact of PREP for marital satisfaction, with a trend for a similar effect on communication skills. However, couples with a history of infidelity assigned to PREP did not reach the same levels of marital satisfaction after intervention seen in the group of couples without infidelity assigned to PREP, although they did show comparable scores on communication skills after intervention. Implications of these findings for relationship education with couples with a history of infidelity are discussed.

Background

Best formats for summarising and presenting evidence for use in clinical guideline development remain less well defined. We aimed to assess the effectiveness of different evidence summary formats to address this gap.

Methods

Healthcare professionals attending a one-week Kenyan, national guideline development workshop were randomly allocated to receive evidence packaged in three different formats: systematic reviews (SRs) alone, systematic reviews with summary-of-findings tables, and ‘graded-entry’ formats (a ‘front-end’ summary and a contextually framed narrative report plus the SR). The influence of format on the proportion of correct responses to key clinical questions, the primary outcome, was assessed using a written test. The secondary outcome was a composite endpoint, measured on a 5-point scale, of the clarity of presentation and ease of locating the quality of evidence for critical neonatal outcomes. Interviews conducted within two months following completion of trial data collection explored panel members’ views on the evidence summary formats and experiences with appraisal and use of research information.

Results

65 (93%) of 70 participants completed questions on the prespecified outcome measures. There were no differences between groups in the odds of correct responses to key clinical questions. ‘Graded-entry’ formats were associated with a higher mean composite score for clarity and accessibility of information about the quality of evidence for critical neonatal outcomes compared to systematic reviews alone (adjusted mean difference 0.52, 95% CI 0.06 to 0.99). There was no difference in the mean composite score between SR with SoF tables and SR alone. Findings from interviews with 16 panelists indicated that short narrative evidence reports were preferred for the improved clarity of information presentation and ease of use.

Conclusions

Our findings suggest that ‘graded-entry’ evidence summary formats may improve clarity and accessibility of research evidence in clinical guideline development.

Trial Registration

Controlled-Trials.com ISRCTN05154264

Few studies have investigated the possible role of higher-level cognitive mechanisms in color constancy. Following-up on previous work with successive color constancy (Allen, Beilock, & Shevell, J. Exp. Psychol. Learn. 37, 1014, 2011), the current study examined the relation between simultaneous color constancy and working memory – the ability to maintain a desired representation while suppressing irrelevant information. Higher working-memory was associated with poorer simultaneous color constancy for a chromatically complex stimulus, but was not associated with simultaneous color constancy for a chromatically simple stimulus. Ways in which the executive attention mechanism of working memory may play a role in color constancy when observers are not required to maintain a representation of a color in memory (as was the case here) are discussed. This finding supports a role for higher-level cognitive mechanisms in color constancy, and is the first to demonstrate a relation between simultaneous color constancy and a complex cognitive ability.

Although earlier studies have demonstrated promising effects of relationship education for military couples, these studies have lacked random assignment. The current study evaluated the short-term effects of relationship education for Army couples in a randomized clinical trial at two sites (476 couples at Site 1 and 184 couples at Site 2). At both sites, participant satisfaction with the program was high. Intervention and control couples were compared on relative amounts of pre-intervention to post-intervention change. At Site 1, not all variables showed the predicted intervention effects, although we found significant and positive intervention effects for communication skills, confidence that the marriage can survive over the long haul, positive bonding between the partners, and satisfaction with sacrificing for the marriage or the partner. However, at Site 2, we found significant and positive intervention effects for communication skills only. Possible site differences as moderators of intervention effects are discussed.

Purpose

A multidisciplinary workshop was convened at the National Institutes of Health (NIH) to discuss the management of the orthopedic and other complications of Proteus syndrome (PS), a progressive, disproportionate overgrowth disorder. While PS poses many complex challenges, the focus of the workshop was the management of the asymmetric and disorganized skeletal overgrowth that characterizes this multisystem disorder.

Methods

Workshop participants developed recommendations for clinical research and patient management and surveillance to maximize the benefits and reduce the risks of surgical and other interventions.

Results

Recommendations for clinical care and management included assessments of skeletal overgrowth and its progression with modalities such as X-ray, magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry, and computerized tomography (CT) imaging. The recommendations also cover the assessment of non-orthopedic complications of PS that significantly impact surgical risk, such as pulmonary embolism and lung bullae. Surgical considerations in PS include assessment of the contribution of contractures to deformities and prophylactic soft-tissue release, aggressive and early use of epiphysiodesis and epiphysiostasis, amputation, and spinal bracing.

Conclusion

Decisions on the timing of orthopedic procedures in children with PS are challenging because they entail balancing the risks of intervention in this high-risk and complex population against the increasing morbidity that patients experience with progressive bony overgrowth. If surgery is delayed too long, the condition may become inoperable. We hope that these recommendations will help clinicians gather appropriate data and assist their patients in making timely treatment decisions.

Background

The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.

Methods/Design

Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.

Discussion

In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improves maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.

Combat-related posttraumatic stress disorder (PTSD) is linked with elevated psychological distress in service members’/veterans’ spouses. Researchers use a variety of terms to describe this distress, and recently, secondary traumatic stress and secondary traumatic stress disorder (STS/STSD) have become increasingly commonly used. Although STS/STSD connotes a specific set of symptoms that are linked to service members’/veterans’ symptoms, researchers often use general measures of distress or generically worded measures of PTSD symptoms to assess STS/STSD. To determine how often scores on such measures appear to be an accurate reflection of STS/STSD, we examined responses to a measure of PTSD symptoms in 190 wives of male service members with elevated levels of PTSD symptoms. Wives rated their own PTSD symptoms, and then answered questions about their attributions for the symptoms they endorsed. Fewer than 20% of wives who endorsed symptoms on the PTSD measure attributed these symptoms completely to their husbands’ military experiences. Moreover, compared with wives who attributed symptoms only to events in their own lives, wives who attributed symptoms completely or partially to their husbands’ military experiences had a greater overlap between some of their responses on the PTSD measure and their responses to a measure of general psychological distress. These results suggest that most wives of service members/veterans with PTSD experience generic psychological distress that is not conceptually consistent with STS/STSD, although a subset does appear to endorse a reaction consistent with this construct. Implications of these findings for intervention and research with this vulnerable population are discussed.

We explored the relation between individual differences in working memory (WM) and color constancy, the phenomenon of color perception that allows us to perceive the color of an object as relatively stable under changes in illumination. Successive color constancy (measured by first viewing a colored surface under a particular illumination and later recalling it under a new illumination) was better for higher-WM individuals than for lower-WM individuals. Moreover, the magnitude of this WM difference depended on how much contextual information was available in the scene, which typically improves color constancy. By contrast, simple color memory, measured by viewing and recalling a colored surface under the same illumination, showed no significant relation to WM. This study reveals a relation between WM and a low-level perceptual process not previously thought to operate within the confines of attentional control, and provides a first account of the individual differences in color constancy known about for decades.

In neurons, a highly regulated microtubule cytoskeleton is essential for many cellular functions. These include axonal transport, regional specialization and synaptic function. Given the critical roles of microtubule-associated proteins (MAPs) in maintaining and regulating microtubule stability and dynamics, we sought to understand how this regulation is achieved. Here, we identify a novel LisH/WD40 repeat protein, tentatively named nemitin (neuronal enriched MAP interacting protein), as a potential regulator of MAP8-associated microtubule function. Based on expression at both the mRNA and protein levels, nemitin is enriched in the nervous system. Its protein expression is detected as early as embryonic day 11 and continues through adulthood. Interestingly, when expressed in non-neuronal cells, nemitin displays a diffuse pattern with puncta, although at the ultrastructural level it localizes along the microtubule network in vivo in sciatic nerves. These results suggest that the association of nemitin to microtubules may require an intermediary protein. Indeed, co-expression of nemitin with microtubule-associated protein 8 (MAP8) results in nemitin losing its diffuse pattern, instead decorating microtubules uniformly along with MAP8. Together, these results imply that nemitin may play an important role in regulating the neuronal cytoskeleton through an interaction with MAP8.

Background

Increasing demand for qualitative research within global health has emerged alongside increasing demand for demonstration of quality of research, in line with the evidence-based model of medicine. In quantitative health sciences research, in particular clinical trials, there exist clear and widely-recognised guidelines for conducting quality assurance of research. However, no comparable guidelines exist for qualitative research and although there are long-standing debates on what constitutes 'quality' in qualitative research, the concept of 'quality assurance' has not been explored widely. In acknowledgement of this gap, we sought to review discourses around quality assurance of qualitative research, as a first step towards developing guidance.

Methods

A range of databases, journals and grey literature sources were searched, and papers were included if they explicitly addressed quality assurance within a qualitative paradigm. A meta-narrative approach was used to review and synthesise the literature.

Results

Among the 37 papers included in the review, two dominant narratives were interpreted from the literature, reflecting contrasting approaches to quality assurance. The first focuses on demonstrating quality within research outputs; the second focuses on principles for quality practice throughout the research process. The second narrative appears to offer an approach to quality assurance that befits the values of qualitative research, emphasising the need to consider quality throughout the research process.

Conclusions

The paper identifies the strengths of the approaches represented in each narrative and recommend these are brought together in the development of a flexible framework to help qualitative researchers to define, apply and demonstrate principles of quality in their research.

Background

There are few reports of interventions to reduce the common but irrational use of antibiotics for acute non-bloody diarrhoea amongst hospitalised children in low-income settings. We undertook a secondary analysis of data from an intervention comprising training of health workers, facilitation, supervision and face-to-face feedback, to assess whether it reduced inappropriate use of antibiotics in children with non-bloody diarrhoea and no co-morbidities requiring antibiotics, compared to a partial intervention comprising didactic training and written feedback only. This outcome was not a pre-specified end-point of the main trial.

Methods

Repeated cross-sectional survey data from a cluster-randomised controlled trial of an intervention to improve management of common childhood illnesses in Kenya were used to describe the prevalence of inappropriate antibiotic use in a 7-day period in children aged 2-59 months with acute non-bloody diarrhoea. Logistic regression models with random effects for hospital were then used to identify patient and clinician level factors associated with inappropriate antibiotic use and to assess the effect of the intervention.

Results

9, 459 admission records of children were reviewed for this outcome. Of these, 4, 232 (44.7%) were diagnosed with diarrhoea, with 130 of these being bloody (dysentery) therefore requiring antibiotics. 1, 160 children had non-bloody diarrhoea and no co-morbidities requiring antibiotics-these were the focus of the analysis. 750 (64.7%) of them received antibiotics inappropriately, 313 of these being in the intervention hospitals vs. 437 in the controls. The adjusted logistic regression model showed the baseline-adjusted odds of inappropriate antibiotic prescription to children admitted to the intervention hospitals was 0.30 times that in the control hospitals (95%CI 0.09-1.02).

Conclusion

We found some evidence that the multi-faceted, sustained intervention described in this paper led to a reduction in the inappropriate use of antibiotics in treating children with non-bloody diarrhoea.

Trial registration

International Standard Randomised Controlled Trial Number Register ISRCTN42996612

A 17-year-old female patient with pyridoxine non-responsive homocystinuria, treated with 20 g of betaine per day, developed a strong body odour, which was described as fish-like. Urinary trimethylamine (TMA) was measured and found to be markedly increased. DNA mutation analysis revealed homozygosity for a common allelic variant in the gene coding for the TMA oxidising enzyme FMO3. Without changing diet or betaine therapy, riboflavin was given at a dose of 200 mg per day. An immediate improvement in her odour was noticed by her friends and family and urinary TMA was noted to be greatly reduced, although still above the normal range.

Gradual further reductions in TMA (and odour) have followed whilst receiving riboflavin. Throughout this period, betaine compliance has been demonstrated by the measurement of dimethylglycine (DMG) excretion, which has been consistently increased. Marked excretions of DMG when the odour had subsided also demonstrate that DMG was not the source of the odour.

This patient study raises the possibility that betaine may be converted to TMA by intestinal flora to some degree, resulting in a significant fish odour when oxidation of TMA is compromised by FMO3 variants. The possibility exists that the body odour occasionally associated with betaine therapy for homocystinuria may not be related to increased circulating betaine or DMG, but due to a common FMO3 mutation resulting in TMAU. Benefits of riboflavin therapy for TMAU for such patients would allow the maintenance of betaine therapy without problematic body odour.

Background

Russia has particularly low life expectancy for an industrialised country, with mortality at working ages having fluctuated dramatically over the past few decades, particularly among men. Alcohol has been identified as the most likely cause of these temporal variations. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. Very few studies to evaluate the efficacy of brief interventions in Russia have been conducted. Motivational Interviewing (MI) is a person-centred counselling style which can be adapted to brief interventions in which help is offered in thinking through behaviour in the context of values and goals, to decide whether change is needed, and if so, how it may best be achieved.

Methods

This paper reports on an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous and harmful drinking at 3 months. Participants were drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous and harmful drinking in the past year. All participants underwent a health check, with MI subsequently delivered to those in the intervention arm. Signed consent was obtained from those in the intervention arm only at this point. Both groups were then invited for 3 and 12 month follow ups. The control group did not receive any additional intervention.

Results

441 men were randomised. Of these 61 did not have a health check leaving 190 in each trial arm. Follow up at 3 months was high (97% of those having a health check), and very similar in the two trial arms (183 in the intervention and 187 in the control).

No significant differences were detected between the randomised groups in either the primary or the secondary outcomes at three months in the intention to treat analyses. The unadjusted odds ratio (95% CI) for the effect of MI on hazardous and harmful drinking was 0.77 (0.51, 1.16). An adjusted odds ratio of 0.52 (0.28, 0.94) was obtained in the pre-specified per protocol analysis.

Conclusions

This trial demonstrates that it is possible to engage Russian men who drink hazardously in a brief intervention aimed at reducing alcohol related harm. However the results with respect to the efficacy are equivocal and further, larger-scale trials are warranted.

Trial Registration

ISRCTN: ISRCTN82405938

Background

There is now convincing evidence that in industrialized countries therapeutic hypothermia for perinatal asphyxial encephalopathy increases survival with normal neurological function. However, the greatest burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic hypothermia is safe and effective.

Aims

Under the UCL Uganda Women's Health Initiative, a pilot randomized controlled trial in infants with perinatal asphyxia was set up in the special care baby unit in Mulago Hospital, a large public hospital with ~20,000 births in Kampala, Uganda to determine:

(i) The feasibility of achieving consent, neurological assessment, randomization and whole body cooling to a core temperature 33-34°C using water bottles

(ii) The temperature profile of encephalopathic infants with standard care

(iii) The pattern, severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with outcome

(iv) The feasibility of neurodevelopmental follow-up at 18-22 months of age

Methods/Design

Ethical approval was obtained from Makerere University and Mulago Hospital. All infants were in-born. Parental consent for entry into the trial was obtained. Thirty-six infants were randomized either to standard care plus cooling (target rectal temperature of 33-34°C for 72 hrs, started within 3 h of birth) or standard care alone. All other aspects of management were the same. Cooling was performed using water bottles filled with tepid tap water (25°C). Rectal, axillary, ambient and surface water bottle temperatures were monitored continuously for the first 80 h. Encephalopathy scoring was performed on days 1-4, a structured, scorable neurological examination and head circumference were performed on days 7 and 17. Cranial ultrasound was performed on days 1, 3 and 7 and scored. Griffiths developmental quotient, head circumference, neurological examination and assessment of gross motor function were obtained at 18-22 months.

Discussion

We will highlight differences in neonatal care and infrastructure that need to be taken into account when considering a large safety and efficacy RCT of therapeutic hypothermia in low and mid resource settings in the future.

Trial registration

Current controlled trials ISRCTN92213707

Using a sample of 434 couples consisting of active duty Army husbands married to civilian wives, relationships between recent deployment, current PTSD symptoms, and a range of marital outcomes were investigated. Self-reports from both husbands and wives regarding relationship functioning did not differ between couples who were and were not separated due to deployment in the prior year. However, deployment in the past year was related to higher levels of current PTSD symptoms for husbands, and husbands' current PTSD symptoms were associated with lower marital satisfaction, confidence in the relationship, positive bonding between the spouses, parenting alliance, and dedication to the relationship for both husbands and wives. In addition, husbands' current PTSD symptoms were associated with higher levels of negative communication for both husbands and wives, and lower satisfaction with sacrifice for the relationship for husbands. Once positive bonding, negative communication, and parenting alliance were controlled, husband PTSD symptoms no longer significantly predicted marital satisfaction for wives. Husband PTSD symptoms continued to exert a significant, but reduced, unique effect on husband marital satisfaction once these variables were accounted for. The results provide greater understanding of the relationship of deployment/PTSD symptoms and marital functioning and suggest areas for intervention with military couples.

Alan Dangour and colleagues report results from the CENEX (Cost-effectiveness Evaluation of a Nutritional supplement and EXercise program for older people) trial, which evaluates a nutritional and exercise program aiming to prevent pneumonia and physical decline in Chilean people.

Background

Ageing is associated with increased risk of poor health and functional decline. Uncertainties about the health-related benefits of nutrition and physical activity for older people have precluded their widespread implementation. We investigated the effectiveness and cost-effectiveness of a national nutritional supplementation program and/or a physical activity intervention among older people in Chile.

Methods and Findings

We conducted a cluster randomized factorial trial among low to middle socioeconomic status adults aged 65–67.9 years living in Santiago, Chile. We randomized 28 clusters (health centers) into the study and recruited 2,799 individuals in 2005 (∼100 per cluster). The interventions were a daily micronutrient-rich nutritional supplement, or two 1-hour physical activity classes per week, or both interventions, or neither, for 24 months. The primary outcomes, assessed blind to allocation, were incidence of pneumonia over 24 months, and physical function assessed by walking capacity 24 months after enrolment. Adherence was good for the nutritional supplement (∼75%), and moderate for the physical activity intervention (∼43%). Over 24 months the incidence rate of pneumonia did not differ between intervention and control clusters (32.5 versus 32.6 per 1,000 person years respectively; risk ratio = 1.00; 95% confidence interval 0.61–1.63; p = 0.99). In intention-to-treat analysis, after 24 months there was a significant difference in walking capacity between the intervention and control clusters (mean difference 33.8 meters; 95% confidence interval 13.9–53.8; p = 0.001). The overall cost of the physical activity intervention over 24 months was US$164/participant; equivalent to US$4.84/extra meter walked. The number of falls and fractures was balanced across physical activity intervention arms and no serious adverse events were reported for either intervention.

Conclusions

Chile's nutritional supplementation program for older people is not effective in reducing the incidence of pneumonia. This trial suggests that the provision of locally accessible physical activity classes in a transition economy population can be a cost-effective means of enhancing physical function in later life.

Trial registration

Current Controlled Trials ISRCTN 48153354

Please see later in the article for the Editors' Summary

Editors' Summary

Background

By 2050, about a quarter of the world's population will be aged 60 years or over, with Asia and Latin America experiencing the most dramatic increases in the proportion of older people. For example, in Chile, which has recently undergone rapid demographic transition, the proportion of the population aged 60 years or over has increased from 8% to 12% over the past 25 years.

Current global policy initiatives that promote healthy ageing include an emphasis on adequate nutrient intakes, as longitudinal studies (conducted in high-income countries) suggest that achieving nutritional sufficiency and maintaining moderate levels of physical activity both decrease risk of mortality by preserving immune function and lean body mass and so reduce the numerous risk factors for disability and chronic disease in later life. Such interventions may also decrease the risk of infection, particularly pneumonia, a common cause of death in older people. However, older people in low- and middle-income countries frequently have diets with insufficient calories (energy) and/or micronutrients.

Why Was This Study Done?

Currently, there is no high-quality evidence to support the benefits of improved nutrition and increased physical activity levels from low-income or transition economies, where the ongoing demographic trends suggest that the needs are greatest. National policies aimed at preserving health and function in older people with interventions such as cash-transfers and provision of “food baskets” are often used in Latin American countries, such as Chile, but are rarely formally evaluated. Therefore, the purpose of this study (the Cost-effectiveness Evaluation of a Nutritional supplement and EXercise program for older people—CENEX) was to evaluate Chile's national nutritional supplementation program and/or physical exercise, to investigate whether this program prevented pneumonia and physical functional decline in older people in Santiago, and also to investigate whether these interventions were cost-effective.

What Did the Researchers Do and Find?

The researchers randomly allocated 28 participating health centers in Santiago, Chile, into one of four arms: (1) nutritional supplementation; (2) nutritional supplementation+physical activity; (3) physical activity alone; (4) control. From May to December 2005, 2,799 eligible adults aged 65–67.9 years and living in low to middle socioeconomic circumstances, who attended each health center, were recruited into the study and received the allocated intervention—daily micronutrient-rich nutritional supplement, or two 1-hour physical activity classes per week, or both interventions or neither—for 24 months. The researchers did not know the allocation arm of each patient and over the course of the study assessed the incidence of pneumonia (viral and bacterial as based on diagnosis at the health center or hospital) and physical function was measured by walking capacity (meters walked in 6 minutes). The researchers used administrative records and interviews with staff and patients to estimate the cost-effectiveness of the interventions.

Participant retention in the study was 84%, although only three-quarters of patients receiving the nutritional intervention and less than half (43%) of patients in the physical activity intervention arm adhered to their respective programs. Over 24 months, the incidence rate of pneumonia did not differ between intervention and control groups (32.5 versus 32.6 per 1,000 person years, respectively), but at the end of the study period, there was a significant difference in walking capacity between the intervention and control clusters (mean difference 33.8 meters). The number of falls and fractures in the study arms were similar. The overall costs over 24 months were US$91.00 and US$163.70 per participant for the nutritional supplement and physical activity interventions, respectively. The cost of the physical activity intervention per extra meter walked at 24 months was US$4.84.

What Do These Findings Mean?

The results of this trial suggest that there is little evidence to support the effectiveness of Chile's national nutritional supplementation program in reducing the incidence of pneumonia for 65.0–67.9 year olds. Therefore, given Chile's high burden of infectious and nutrition-related chronic diseases and the associated high health costs, this program should not be considered as a priority preventive public health intervention. However, the provision of locally available physical activity classes to older people could be of clinical benefit, especially in urban settings such as Santiago, although future challenges include increasing the uptake of, and retention to, such programs.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001023.

The World Health Organization provides information about the state of health in Chile

Wikipedia also provides information about health and health care in Chile (please note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)

Findings from a large, randomized controlled trial of couple education are presented in this brief report. Married Army couples were assigned to either PREP for Strong Bonds (n = 248) delivered by Army chaplains or to a no-treatment control group (n = 228). One year after the intervention, couples who received PREP for Strong Bonds had 1/3 the rate of divorce of the control group. Specifically, 6.20% of the control group divorced while 2.03% of the intervention group divorced. These findings suggest that couple education can reduce the risk of divorce, at least in the short run with military couples.

Background

Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain.

Methods

The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol.

Conclusions

In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.

Purpose

North American research finds increased sexual risk-taking among teenagers with same-sex partners, but understanding of underlying processes is limited. The research carried out in the United Kingdom compares teenagers' early sexual experiences according to same- or opposite-sex partner, focusing on unwanted sex in addition to risk-taking, and exploring underlying psychosocial differences.

Methods

Multivariate analyses combined self-reported data from two randomized control trials of school sex education programs (N = 10,250). Outcomes from sexually experienced teenagers (N = 3,766) were partner pressure to have first sex and subsequent regret, and sexual risk measures including pregnancy. Covariates included self-esteem, future expectations, substance use, and communication with mother.

Results

By the time of follow-up (mean age, 16), same-sex genital contact (touching or oral or anal) was reported by 2.3% of teenagers, with the majority also reporting heterosexual intercourse. A total of 39% reported heterosexual intercourse and no same-sex genital contact. Boys were more likely to report partner pressure (Odds ratio [OR] = 2.56, 95% confidence intervals [CI] = 1.29–5.08) and regret (OR = 2.32; 95% CI = 1.39–3.86) in relation to first same-sex genital contact than first heterosexual intercourse, but girls showed no differences according to partner type. Teenagers with bisexual behavior reported greater pregnancy or partner pregnancy risk than teenagers with exclusively opposite-sex partners (girls, OR = 4.51, 95% CI = 2.35–8.64; boys, OR = 4.43, 95% CI = 2.41–8.14), partially reduced by attitudinal and behavioral differences.

Conclusions

This UK study confirms greater reporting of sexual risk-taking among teenagers with same-sex partners, and suggests that boys in this group are vulnerable to unwanted sex. It suggests limitations to the interpretation of differences, in terms of psychosocial risk factors common to all adolescents.

Background

The subject of death and bereavement in the context of randomised controlled trials in neonatal or paediatric intensive care is under-researched. The objectives of this phase of the Bereavement and RAndomised ControlLEd Trials (BRACELET) Study were to determine trial activity in UK neonatal and paediatric intensive care (2002-06); numbers of deaths before hospital discharge; and variation in mortality across intensive care units and trials and to determine whether bereavement support policies were available within trials. These are essential prerequisites to considering the implications of future policies and practice subsequent to bereavement following a child's enrolment in a trial.

Methods

The units survey involved neonatal units providing level 2 or 3 care, and paediatric units providing level II care or above; the trials survey involved trials where allocation was randomized and interventions were delivered to intensive care patients, or to parents but designed to affect patient outcomes.

Results

Information was available from 191/220 (87%) neonatal units (149 level 2 or 3 care); and 28/32 (88%) paediatric units. 90/177 (51%) eligible responding units participated in one or more trial (76 neonatal, 14 paediatric) and 54 neonatal units and 6 paediatric units witnessed at least one death. 50 trials were identified (36 neonatal, 14 paediatric). 3,137 babies were enrolled in neonatal trials, 210 children in paediatric trials. Deaths ranged 0-278 (median [IQR interquartile range] 2 [1, 14.5]) per neonatal trial, 0-4 (median [IQR] 1 [0, 2.5]) per paediatric trial. 534 (16%) participants died post-enrolment: 522 (17%) in neonatal trials, 12 (6%) in paediatric trials. Trial participants ranged 1-236 (median [IQR] 21.5 [8, 39.8]) per neonatal unit, 1-53 (median [IQR] 11.5 [2.3, 33.8]) per paediatric unit. Deaths ranged 0-37 (median [IQR] 3.5 [0.3, 8.8]) per neonatal unit, 0-7 (median [IQR] 0.5 [0, 1.8]) per paediatric unit. Three trials had a formal policy for responding to bereavement.

Conclusions

A substantial number of deaths after trial enrolment were identified, distributed over many trials and units. Few trial teams had responses to bereavement in place. Those with the largest numbers of deaths might be best placed to collaborate in developing and assessing responses to bereavement.

SUMMARY

Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies.

Background

Holistic profiling and systems biology studies of nutrient availability are providing more and more insight into the mechanisms by which gene expression responds to diverse nutrients and metabolites. Less is known about the mechanisms by which gene expression is affected by endogenous metabolites, which can change dramatically during development. Multivariate statistics and correlation network analysis approaches were applied to non-targeted profiling data to investigate transcriptional and metabolic states and to identify metabolites potentially influencing gene expression during the heterotrophic to autotrophic transition of seedling establishment.

Results

Microarray-based transcript profiles were obtained from extracts of Arabidopsis seeds or seedlings harvested from imbibition to eight days-old. 1H-NMR metabolite profiles were obtained for corresponding samples. Analysis of transcript data revealed high differential gene expression through seedling emergence followed by a period of less change. Differential gene expression increased gradually to day 8, and showed two days, 5 and 7, with a very high proportion of up-regulated genes, including transcription factor/signaling genes. Network cartography using spring embedding revealed two primary clusters of highly correlated metabolites, which appear to reflect temporally distinct metabolic states. Principle Component Analyses of both sets of profiling data produced a chronological spread of time points, which would be expected of a developmental series. The network cartography of the transcript data produced two distinct clusters comprising days 0 to 2 and days 3 to 8, whereas the corresponding analysis of metabolite data revealed a shift of day 2 into the day 3 to 8 group. A metabolite and transcript pair-wise correlation analysis encompassing all time points gave a set of 237 highly significant correlations. Of 129 genes correlated to sucrose, 44 of them were known to be sucrose responsive including a number of transcription factors.

Conclusions

Microarray analysis during germination and establishment revealed major transitions in transcriptional activity at time points potentially associated with developmental transitions. Network cartography using spring-embedding indicate that a shift in the state of nutritionally important metabolites precedes a major shift in the transcriptional state going from germination to seedling emergence. Pair-wise linear correlations of transcript and metabolite levels identified many genes known to be influenced by metabolites, and provided other targets to investigate metabolite regulation of gene expression during seedling establishment.

Background

Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage.

Methods

The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose.

The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy.

Trial registration

Current Controlled Trials: ISRCTN76912190 and Clinicaltrials.gov ID: NCT00872469