Access to nutrition services and information after active cancer treatment: a mixed methods study.

PURPOSE: Evidence-based guidelines for cancer strongly support nutrition and dietetic services for people with cancer and carers in order to improve patient-centred and health service outcomes. Access to nutrition services and information after completing active cancer treatment is relatively unknown in Australia. This study aimed to determine the availability, accessibility, barriers, and preferences to nutrition services and information after cancer treatment in Australia. METHODS: Utilising mixed methods, people with cancer and carers completed a cross-sectional survey, and a sub-group of participants completed a semi-structured interview. The survey evaluated the availability of nutrition services, nutrition information searched, barriers, and preferences for nutrition information. Semi-structured interviews explored participant experience with nutrition services and information. RESULTS: The 149 participants (including 10 carers) were predominately male and with a diagnosis of prostate cancer (63%). Overall, 23% of participants received nutrition information from a dietitian after cancer treatment. Participants (78%) indicated that accessing a nutrition specialist is the main barrier to receiving nutrition care after treatment. Most searched nutrition information on the internet (55%) and found the information easy to understand (89%), but conflicting (52%). Thematic analysis of interviews in fourteen cancer patients revealed three key themes pertaining to (1) preferred referral and timing of nutrition services, (2) lack of confidence in publicly available nutrition information, and (3) streamlining nutrition services for greater access. CONCLUSION: Access to a dietitian and evidence-based information after cancer treatment is limited for people with cancer and carers in Australia, despite the high interest and need for ongoing nutrition care. IMPLICATIONS FOR CANCER SURVIVORS: Models of care evaluating the provision of appropriate nutrition care and information provision after cancer treatment are needed to address this unmet survivorship need.

Race, language, and neighborhood predict high-risk preterm Infant Follow Up Program participation.

OBJECTIVES: Infant Follow Up Programs (IFUPs) provide developmental surveillance for preterm infants after hospital discharge but participation is variable. We hypothesized that infants born to Black mothers, non-English speaking mothers, and mothers who live in "Very Low" Child Opportunity Index (COI) neighborhoods would have decreased odds of IFUP participation. STUDY DESIGN: There were 477 infants eligible for IFUP between 1/1/2015 and 6/6/2017 from a single large academic Level III NICU. Primary outcome was at least one visit to IFUP. We used multivariable logistic regression to identify factors associated with IFUP participation. RESULT: Two hundred infants (41.9%) participated in IFUP. Odds of participation was lower for Black compared to white race (aOR 0.43, p = 0.03), "Very Low" COI compared to "Very High" (aOR 0.39, p = 0.02) and primary non-English speaking (aOR 0.29, p = 0.01). CONCLUSION: We identified disparities in IFUP participation. Further study is needed to understand underlying mechanisms to develop targeted interventions for reducing inequities.

The value of continuing professional development: A realistic evaluation of a multi-disciplinary workshop for health visitors dealing with children with complex needs.

BACKGROUND: Continuing Professional Development is important for maintaining and developing knowledge and skills. Evidence regarding direct impact on practice is limited. Existing literature often lacks sufficient detail regarding the initiative or its evaluation, making transferability problematic. OBJECTIVE: To explore the impact and perceived value of multi-disciplinary Continuing Professional Development workshops for Health Visitors who support families with children with complex health needs. DESIGN: Realistic Evaluation principles guided the research. Workshop attendees were invited to participate (n.21), 81% (n.17) agreed. Data collection included a questionnaire and semi-structured interviews. Data analysis included descriptive statistics and qualitative thematic analysis. SETTING: One North of England Health Service Trust. FINDINGS: Interrelated temporal themes emerged. Before the workshop expectations included, uncertainty regarding content and ambiguity regarding attendance. During workshops comments focused on networking opportunities, the detail, content and facilitation of the learning experience. 'Emotional safety' enabled interaction, sharing and absorption of information, and potentially increased trust, confidence and social capital. Participants viewed the workshop as informative, enhancing insight regarding roles, services and processes. Post-workshop participants reported examples of practice enhancements attributed to workshop attendance including: confidence building; improved team working; facilitation of early referral and accessing additional support for families. CONCLUSIONS: Findings suggest initiative developers aiming CPD at new or existing teams need to consider nurturing social capital and to pay attention to the context and mechanisms, which can prompt attendance, engagement and subsequent practice application.

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

BACKGROUND AND OBJECTIVES: Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING: A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS: Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES: Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS: Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS: A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341. CONCLUSIONS: There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM. LIMITATIONS: This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle. FUTURE WORK: Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

Assessment of haematological and clinical pathology effects of blood microsampling in suckling and weaned juvenile rats.

UNLABELLED: Tail vein microsampling in juvenile rats for toxicokinetic assessment has the potential to significantly reduce satellite animal use. This paper explores the toxicological consequences of microsampling at various post natal day (PND) ages. METHODS: Microsamples were taken as follows: suckling pups, 10 pups/sex, 3×32µL samples on PND19, euthanased PND20; weaned pups, 10 pups/sex, 6×32µL samples on PND23 and PND37, euthanased PND38; and satellite pups, 3 pups/sex, 5×32µL samples on PND14 and PND35, euthanased on PND36. At termination on PND20 or PND38, clinical pathology samples were obtained and spleen, liver and bone marrow were examined. There were 10 unsampled concurrent control animals for each experiment. RESULTS: Suckling animals: females showed a slight, statistically significant decrease in red blood cell count (0.94× of control; p<0.05) with slight decreases in haemoglobin and haematocrit. The suckling males showed a slight increase in reticulocyte counts (1.05× of control) plus a statistically significant, slight increase in relative splenic weight. Weanling animals: the only effect was decreased liver weight in the microsampled females. In both suckling and weanling experiments, all clinical pathology values were within the age control range. In the satellite pups microsampled on PND14, there was a statistically significant transient increase in bodyweight gain between PND17 and PND21. CONCLUSION: The nature of the toxicological effects of microsampling was as expected. The magnitude of effects does not preclude microsampling main test pups provided care is taken over study design and blood volume loss.

The novel use of a heterozygous knockout mouse for embryofetal development assessment of a glucokinase activator.

Glucokinase activators (GKAs), such as AZD1656, are designed as antihyperglycemic agents for diabetics and can cause dose-limiting hypoglycemia in normal animals used in embryofetal development studies. Genetically modified heterozygous GK knockout (gkdel/wt) mice are less susceptible to severe GKA-induced hypoglycemia than wild-type mice due to their elevated baseline glucose levels. In this study, the gkdel/wt mouse was used as an alternative rodent strain for embryofetal development studies with AZD1656. Heterozygous global knockout gkdel/wt females were dosed with 20, 50, or 130 mg/kg/day of AZD1656 or vehicle for a minimum of 14 consecutive days before mating with wild-type males and throughout organogenesis. Maternal effects were confined to slightly reduced food consumption, reduced body weight gain, and the pharmacologic effect of decreased plasma glucose. Fetuses were genotyped. Fetal weights at the high dose were slightly reduced but there was no effect on fetal survival. There were two specificmajormalformations, omphalocele and right-sided aortic arch, with increased fetal incidence in mid- and high-dose fetuses (e.g., omphalocele fetal incidence of 0.6, 0.7, 4.6, and 2% across the dose groups) plus increased incidences of minor abnormalities and variants indicative of either delayed or disturbed development. Fetal weight and abnormalities were unaffected by fetal genotype. The fetal effects are considered hypoglycemia related. There was no effect on embryofetal survival in the gkdel/wt mouse at AZD1656 exposures, which were 70× higher than those causing 75% fetal death in rabbits. This illustrates the value of genetically modified animals in unraveling target versus chemistry-related effects.

Multicentre cluster randomised controlled trial evaluating implementation of a fire prevention Injury Prevention Briefing in children's centres: study protocol.

BACKGROUND: The UK has one of the highest fatality rates for deaths from fire-related injuries in children aged 0-14 years; these injuries have the steepest social gradient of all injuries in the UK. Children's centres provide children under five years old and their families with a range of services and information, including home safety, but their effectiveness in promoting injury prevention has yet to be evaluated. We developed a fire prevention intervention for use in children's centres comprising an Injury Prevention Briefing (IPB) which provides evidence on what works and best practice from those running injury prevention programmes, and a facilitation package to support implementation of the IPB. This protocol describes the design and methods of a trial evaluating the effectiveness and cost-effectiveness of the IPB and facilitation package in promoting fire prevention. METHODS/DESIGN: Pragmatic, multicentre cluster randomised controlled trial, with a nested qualitative study, in four study centres in England. Children's centres in the most disadvantaged areas will be eligible to participate and will be randomised to one of three treatment arms comprising: IPB with facilitation package; IPB with no facilitation package; usual care (control). The primary outcome measure will be the proportion of families who have a fire escape plan at follow-up. Eleven children's centres per arm are required to detect an absolute difference in the percentage of families with a fire escape plan of 20% in either of the two intervention arms compared with the control arm, with 80% power and a 5% significance level (2-sided), an intraclass correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families per children's centre. Secondary outcomes include the assessment of the cost-effectiveness of the intervention, other fire safety behaviours and factors associated with degree of implementation of the IPB. DISCUSSION: This will be the first trial to develop and evaluate a fire prevention intervention for use in children's centres in the UK. Its findings will be generalisable to children's centres in the most disadvantaged areas of the UK and may also be generalisable to similar interventions to prevent other types of injury. TRIAL REGISTRATION: http://NCT01452191 (date of registration: 13/10/2011).

Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat.

UNLABELLED: Historically, satellite groups are often used for rodent toxicokinetic profiling because of the haematological consequences of blood sampling. If microsampling is shown to be toxicologically benign, its adoption in rat studies would enable comparison of exposure and toxicity in individual animals (as happens in non-rodent studies) as well as obviating need for satellite groups. METHODS: Groups of 10 male (200-300g) and female (150-250g) rats aged 10weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6×200µL) or microsampled (6×32µL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained. RESULTS: All clinical pathology parameters were within background range. However, compared to unsampled controls, conventional volume sampled rats showed a statistically significant (p<0.001) decrease in haemaglobin, haematocrit and red blood cell count, an increase in reticulocytes (at least p<0.01), increased AST and GLDH and, in males only, an increase in monocytes and neutrophils. In contrast, microsampled animals showed no changes except for a slight, toxicologically insignificant decrease in haemoglobin concentration (15.0g/dL compared to the unsampled group mean of 14.4g/dL) in females (p<0.05) and a small increase in monocytes (p<0.05) in males. CONCLUSION: Microsampling of adult rats is possible without adverse toxicological consequences.

Assessment of male rodent fertility in general toxicology 6-month studies.

An outcome and statistical review of male reproductive performance assessed by including a mating phase within 6-month general toxicity studies in the Han Wistar rat was undertaken. The basic study design was 16-20 animals per group dosed for approximately 9 weeks before pairing the male rats with undosed females. This design provides opportunity for remating and automatically includes general toxicity parameters. The dose levels used in the 1- and 6-month studies show that male reproduction was assessed at generally similar doses. The majority of males (compound-dosed and controls) mated within 7 days. All vehicle-dosed males mated and 98.5% of these females were pregnant. Modeling shows that a pregnancy rate of less than 14 out of 16 pregnant animals is very unlikely to occur due to biological variability. Power calculations based on vehicle control data show that group sizes of >10 males have a >80% power of detecting a decrease in median of three embryos per group compared with the control group. Even if the number of pregnancies decreased by a third, a group size of ≥12 would still detect a decrement in the median of three embryos with >80% power. Based on the statistical modeling and inherent strengths of the study design, this review indicates that decrements in male reproductive function can be successfully detected by incorporating a mating phase into a 6-month rat study and that a group size of 12-16 is generally adequate rather than the 16-20 group size indicated as a generic default within ICHS5(R2).

Keeping children safe at home: protocol for three matched case-control studies of modifiable risk factors for falls.

BACKGROUND: Childhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children. OBJECTIVES: To estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity. DESIGN: Three multicentre case-control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0-4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences. MAIN OUTCOME MEASURES: Falls on stairs, on one level and from furniture. DISCUSSION: As the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children.

Preventing bath water scalds: a cost-effectiveness analysis of introducing bath thermostatic mixer valves in social housing.

AIMS: To assess the cost-effectiveness of installing thermostatic mixer valves (TMVs) in reducing risks of bath water scalds and estimate the costs of avoiding bath water scalds. METHODS: The evaluation was undertaken from the perspective of the UK public sector, and conducted in conjunction with a randomised control trial of TMVs installed in social housing in Glasgow. Installation costs were borne by the social housing organisation, while support materials were provided by the UK NHS. Effectiveness was represented by the number of families with at-risk bath water temperatures pre- and post-installation, and the number of bath scalds avoided as a result of installation. Differences in the number of families with at-risk temperatures between groups were derived from the RCT. Cost-effectiveness was assessed and a series of one-way sensitivity analyses were conducted. RESULTS: Unit costs associated with installation were calculated to be £13.68, while costs associated with treating bath water scalds ranged from £25,226 to £71,902. The cost of an avoided bath water scald ranged from net savings to public purse of £1887 to £75,520 and at baseline produced a net saving of £3,229,008; that is, £1.41 saved for every £1 spent. CONCLUSION: It is very likely that installing TMVs as standard in social housing in new buildings and major refurbishments accompanied by educational information represents value for money.

The cynomolgus monkey as a model for developmental toxicity studies: variability of pregnancy losses, statistical power estimates, and group size considerations.

BACKGROUND: This work evaluates pregnancy and infant loss in 1,069 vehicle-treated cynomolgus monkeys from 78 embryo-fetal development (EFD) studies and 14 pre-postnatal development (PPND) studies accrued during 1981-2007. METHODS: Losses were analysed by survival function and hazard ratio using logistic regression for influence of year, study type (e.g., dose duration), and test item route of administration (ig, im, iv, sc). RESULTS: Neither study type nor route of dosing affected pregnancy outcome. Losses were higher pre-1990 (104 losses/347 pregnancies) compared to 1990 onwards (94 losses/722 pregnancies). Losses were greatest before gestation day 50 and at parturition. Using post-1989 data, Monte-Carlo simulations of pregnancy outcomes were created. The power associated with the comparison of vehicle survival curves and simulated adverse survival curves was examined. This showed that EFD studies with initial vehicle group sizes of 16 and 20 have an 80% probability of having 13 and 16 ongoing pregnancies at gestational day 100, respectively. For PPND studies with initial vehicle group sizes of 16, 20, or 28, there is an 80% likelihood of having 9, 11, or 16 infants at day 7 post-partum, respectively. A PPND study initiated with group size 20 could detect a threefold increase of test item-related pregnancy or infant loss. CONCLUSIONS: For designing and managing primate developmental toxicity studies, this type of analysis provides an objective tool to facilitate decisions either by supplementing groups with additional pregnant animals or stopping a group because an adverse effect on offspring survival has already been adequately revealed.

Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure.

BACKGROUND AND RATIONALE: The reinstatement model is widely used to study relapse to drug addiction. However, the model's validity is open to question. OBJECTIVE: We assess the reinstatement model in terms of criterion and construct validity. RESEARCH HIGHLIGHTS AND CONCLUSIONS: We find that the reinstatement model has adequate criterion validity in the broad sense of the term, as evidenced by the fact that reinstatement in laboratory animals is induced by conditions reported to provoke relapse in humans. The model's criterion validity in the narrower sense, as a medication screen, seems promising for relapse to heroin, nicotine, and alcohol. For relapse to cocaine, criterion validity has not yet been established primarily because clinical studies have examined medication's effects on reductions in cocaine intake rather than relapse during abstinence. The model's construct validity faces more substantial challenges and is yet to be established, but we argue that some of the criticisms of the model in this regard may have been overstated.

Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. Should the guidelines be changed?

The Royal College of Obstetricians and Gynaecologists Guidelines for the management of infertility in secondary care (1998) states that stimulated intrauterine insemination (IUI) has Grade A evidence to confirm its effective use in unexplained infertility. This paper challenges that assertion after closer assessment of the papers upon which it was based. With the current appraisal of the Guidelines as part of the 'scope' of the assessment of infertility management by the National Institute of Clinical Excellence it is important that the guidelines are indeed critically reviewed prior to their updated publication. With the emphasis on minimizing the risk of multiple pregnancies, a formal trial of stimulated IUI is called for in order to justify its continued use in this setting. Strict attention to limiting the number of follicles treated in verified unexplained subfertility is necessary to validate such a trial.