Evaluation of amoxicillin, metronidazole and gentamicin dosage regimens for use in antibiotic prophylaxis in colorectal surgery.

OBJECTIVES: To evaluate amoxicillin, metronidazole and gentamicin dosage regimens for antibiotic prophylaxis in colorectal surgery. METHODS: The study was conducted in 20 patients undergoing colorectal surgery. Patients received one or two doses of amoxicillin 1000 mg, metronidazole 500 mg and gentamicin 3 mg/kg ideal body weight, banded by height. Antibiotic concentrations were measured up to 7 h post dose. Population pharmacokinetic (PopPK) analysis with NONMEM followed by Monte Carlo simulation of different dosage regimens was used to estimate the PTA for potential organisms associated with surgical site infections (SSIs). RESULTS: A median of 5 (range 3-6) concentrations were available per patient. CL and V of all antibiotics were related to weight; gentamicin CL was also related to CLCR. The administered doses maintained the desired PTA up to 8 h for the Streptococcus anginosus group but not for enterococci, Bacteroides fragilis group, MSSA, and Escherichia coli. An additional 500 mg amoxicillin every 4 h was sufficient to achieve the PTA for most relevant organisms but 2 hourly dosing was required for patients at risk of infective endocarditis. A metronidazole dose of 1000 mg was required for patients >85 kg. In patients with CLCR >50 mL/min, 5 mg/kg gentamicin (with an additional 2.5 mg/kg in prolonged surgery at 6 h) maintained PTA targets for >10 h. CONCLUSIONS: PopPK analysis with Monte Carlo simulation identified prophylactic antibiotic regimens that would maintain the PTA for organisms associated with SSIs during short- and long-duration colorectal surgery.

Net benefits of smallholder dairy cattle farms in Senegal can be significantly increased through the use of better dairy cattle breeds and improved management practices.

Senegal, located in West Africa, is an example of a low- to middle-income country where the government has prioritized improving livestock production self-sufficiency, with a strong focus on dairy. Among other initiatives, the use of exotic dairy cattle has been promoted, despite no evidence for the potential livelihood benefits (or otherwise) to smallholder farmers on adopting the new genetics. The current work fills this evidence gap by performing a farm-level economic study comparing the keeping of different breed and cross-breed types of dairy cattle under different management levels. Data for the study were obtained by monitoring 220 smallholder dairy cattle farms, with a combined cattle population of about 3,000 animals, over an almost 2-yr period. Findings of the study suggest that the most net-beneficial and cost-beneficial dairy cattle enterprise that could be used by the smallholder farmers was to keep crossbred indigenous zebu by exotic Bos taurus animals under management standards that are considered good compared with local standards. This dairy enterprise type was 7.4-fold more net beneficial and had a 1.4-fold more favorable cost-benefit ratio than the traditional system of keeping indigenous zebu animals under poor (low-input) management. Interestingly, the keeping of (near) pure B. taurus dairy cattle resulted in the highest milk yields and thus benefit from milk, but was not the most net beneficial due to the high costs of keeping these animals, particularly in terms of feed. We also found that increasing the management level of any of the breed or cross-breed types under consideration, including the indigenous zebu animals, resulted in an increased net benefit of 2.2- to 2.9-fold. Results of this economic analysis are discussed as part of a broader trade-off analysis, resulting in recommendations to strengthen the Senegal dairy sector. The combined intervention of improved dairy cattle genetics and management is considered a promising intervention to improve livelihoods of the rural poor as well as livestock production self-sufficiency for Senegal; some other system constraints are addressed.

The impact of social deprivation on the response to a randomised controlled trial of a weight management intervention (BeWEL) for people at increased risk of colorectal cancer.

BACKGROUND: Although 45% of colorectal cancer (CRC) cases may be avoidable through appropriate lifestyle and weight management, health promotion interventions run the risk of widening health inequalities. The BeWEL randomised controlled trial assessed the impact of a diet and activity programme in overweight adults who were diagnosed with a colorectal adenoma, demonstrating a significantly greater weight loss at 12 months in intervention participants than in controls. The present study aimed to compare BeWEL intervention outcomes by participant deprivation status. METHODS: The intervention group of the BeWEL trial (n = 163) was classified by the Scottish Index of Multiple Deprivation (SIMD) quintiles into 'more deprived' (SIMD 1-2, n = 58) and 'less deprived' (SIMD 3-5, n = 105). Socio-economic and lifestyle variables were compared at baseline to identify potential challenges to intervention adherence in the more deprived. Between group differences at 12 months in primary outcome (change in body weight) and secondary outcomes (cardiovascular risk factors, diet, physical activity, knowledge of CRC risk and psychosocial variables) were assessed by deprivation status. RESULTS: At baseline, education (P = 0.001), income (P < 0.001), spending on physical activity (P = 0.003) and success at previous weight loss attempts (P = 0.007) were significantly lower in the most deprived. At 12 months, no between group differences by deprivation status were detected for changes in primary and main secondary outcomes. CONCLUSIONS: Despite potential barriers faced by the more deprived participants, primary and most secondary outcomes were comparable between groups, indicating that this intervention is unlikely to worsen health inequalities and is equally effective across socio-economic groups.

Conjugal amyotrophic lateral sclerosis: a case report from Scotland.

BACKGROUND: Conjugal amyotrophic lateral sclerosis is rare, with significant effects on psychological and care needs. We report a case of conjugal amyotrophic lateral sclerosis disease from central Scotland. This case is particularly unusual as both patients were diagnosed within an 18-month period and experienced the disease simultaneously, with similar symptomatology and progression. CASE PRESENTATION: Patient A was a 71-year-old man who presented with unilateral arm weakness and wasting. Patient B was a 68-year-old woman who presented with unilateral shoulder and elbow weakness. Diagnosis of amyotrophic lateral sclerosis was made within a few months of presentation in both cases, based on typical clinical symptomatology together with supportive neurophysiological testing. Interventions included enteral feeding and non-invasive ventilation. The time period between symptom onset and death was 5 years for Patient A and 3.5 years for Patient B. CONCLUSION: This case illustrates two main points: the care issues surrounding cases of conjugal neurological disease, and the psychological issues in these patients. There are significant care issues arising when co-habiting couples both develop severe functionally limiting neurological diseases at the same time. The more slowly progressive nature of Patient A's disease may be at least partially explained by the support he was able to receive from Patient B before she developed symptoms. Secondly, there are important psychological effects of living with someone with the same - but more advanced - progressive and incurable neurological disease. Thus, Patient B was reluctant to have certain interventions that she had observed being given to her husband. Lastly, no plausible shared environmental risk factors were identified, implying that the co-occurrence of ALS in this couple was a random association.

Assessing finasteride-associated sexual dysfunction using the FAERS database.

BACKGROUND: Postmarketing reports suggest that finasteride causes sexual dysfunction despite a low incidence reported in clinical trials. Therefore, the extent of risk remains unknown. OBJECTIVE: To determine whether the risk of sexual dysfunction is higher among individuals treated with finasteride compared to a baseline risk for all other drugs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: A case by non-case disproportionality approach was used whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. The National Ambulatory Medical Care Survey (NAMCS) was used to confirm results. RESULTS: A significant disproportionality in reporting of sexual dysfunction with the use of finasteride was observed whether finasteride was indicated for hair loss (ROR = 138.17, 95% CI: 133.13, 143.4), prostatic hyperplasia (ROR = 93.88, 95% CI: 84.62, 104.16) or any indication (ROR = 173.18, 95% CI: 171.08, 175.31). When these results were stratified by age, disproportionality was strongest at 31-45 years. CONCLUSION: Use of finasteride has led to an increase in reports of sexual dysfunction where it is believed to be the primary suspect.

Integrating livestock health measures into marginal abatement cost curves.

Improving livestock health offers both private and social benefits. Among the potential social benefits is a reduction in the greenhouse gas (GHG) emissions arising from livestock production. Reductions in emissions intensity (the amount of GHG produced per kilogram of meat, milk or eggs) may occur, as improving health can lead to improvements in the parameters that emissions intensity is sensitive to, such as (for ruminants): maternal fertility and abortion rates, calf and lamb mortality rates and growth rates, milk yields and feed conversion rates. However, improved health is not yet widely recognised as a GHG mitigation measure due, in part, to difficulties in reliably quantifying the financial and GHG effects of disease control options. This paper discusses how the GHG effects of disease control can be quantified and included in a marginal abatement cost curve (MACC). To illustrate some of the challenges, it draws on the experience of including health measures in the most recent (2015) agricultural MACCs in the United Kingdom.

L'amélioration de la santé des animaux d'élevage apporte des bénéfices non seulement aux personnes et entreprises privées mais aussi à la société en général. La réduction des émissions de gaz à effet de serre est l'un des bénéfices potentiels apportés à la société par les élevages. Il est ainsi possible de réduire l'intensité des émissions (c'est-à-dire la quantité de gaz à effet de serre générée par kilogramme de viande, de lait ou d'oeufs), dans la mesure où l'amélioration de la santé animale s'accompagne d'une amélioration des paramètres qui influent sur l'intensité de ces émissions ; par exemple, chez les ruminants, le taux de fécondité, le taux d'avortements, le taux de mortalité néonatale et le taux de croissance chez les ovins et les caprins, la production de lait et le taux de conversion des aliments donnés aux animaux. Or, l'amélioration de la santé n'est pas toujours reconnue comme étant une mesure de réduction des gaz à effet de serre, en raison notamment de la difficulté de quantifier de manière fiable les effets des différentes stratégies zoosanitaires en termes financiers et d'émissions de gaz à effet de serre. Les auteurs proposent une méthode permettant de quantifier les effets des mesures de lutte contre les maladies animales sur les émissions de gaz à effet de serre et de les intégrer dans une courbe de coût marginal d'abattement. Afin d'illustrer certains enjeux en la matière, les auteurs présentent l'expérience conduite récemment (2015) au Royaume-Uni pour intégrer les mesures sanitaires dans les courbes de coût marginal d'abattement du secteur agricole.

El hecho de mejorar el estado de salud del ganado reporta beneficios de índole tanto privada como social. Entre los posibles beneficios sociales figura una reducción de las emisiones de gases de efecto invernadero resultantes de la producción pecuaria. Esas emisiones también pueden ser menos intensas (volumen de gases generados por kilogramo de carne, leche o huevos), pues la intensidad de las emisiones es sensible a una serie de parámetros cuyo valor mejora al hacerlo el estado de salud, tales como (en el caso de los rumiantes): tasas de fertilidad materna y de abortos; tasas de mortalidad y crecimiento en terneros y corderos; y tasas de producción de leche y de conversión alimenticia. Sin embargo, todavía no ha arraigado la idea de que la mejora del estado de salud es una medida de lucha contra los gases de efecto invernadero, debido en parte a las dificultades existentes para cuantificar con fiabilidad los efectos de los métodos de lucha zoosanitaria sobre parámetros económicos o sobre las emisiones. Los autores explican cómo cuantificar los efectos del control de enfermedades sobre los gases de efecto invernadero y a partir de ahí incluirlos en una curva del costo marginal de reducción. Para ilustrar algunos de los problemas que pueden surgir se refieren a la experiencia británica destinada a incluir parámetros que miden el estado de salud en las más recientes (2015) curvas del costo marginal de reducción en el ámbito agropecuario.

Lessons learnt from a feasibility study on price incentivised healthy eating promotions in workplace catering establishments.

BACKGROUND: It is recognised that the worksite catering sector is likely to play a pivotal role in influencing dietary intake in adults of working age. The present study aimed to assess the feasibility of engaging worksites in a healthy eating intervention, implementing a price incentivised main meal intervention and measuring indicative intervention responses to inform the design of a future trial. METHODS: Workplaces registered with the Scottish Healthy Living Award were invited to participate. The EatSMART intervention (a reduced price, healthy meal combination plus promotions) was implemented over 10 weeks in two worksites. Implementation was assessed by observational and sales data. Indicative effects on food habits were measured using online pre- and post-intervention questionnaires. Focus group discussions and interviews were used to determine catering staff and consumer acceptability. RESULTS: Thirty-seven worksites were invited to participate and four worksites responded positively. Two sites (with 1600 and 500 employees, respectively) participated. Both required significant implementation support. Estimated sales data indicated that the uptake of promoted items varied by week (range 60-187 items) and by site. A poor response rate from questionnaires limited the evaluation of intervention impact. Consumers reported improved value for money and quality. Both sites reported an intention to continue the intervention delivery. CONCLUSIONS: Significant efforts are required to engage worksite catering teams and implement healthy eating interventions. Evaluation methods require further development to improve data collection. Responses from consumers and catering staff suggest that further work in this area would be welcomed.

Ten-year outcome of early childhood traumatic brain injury: Diffusion tensor imaging of the ventral striatum in relation to executive functioning.

PRIMARY OBJECTIVE: The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity. RESEARCH DESIGN: Between a paediatric group with TBI and a group of typically-developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity. METHODS AND PROCEDURES: Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to-severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests. MAIN OUTCOMES AND RESULTS: The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching). CONCLUSIONS: TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits.

Colorectal adenomas and diabetes: implications for disease prevention.

AIM: This study assessed the baseline type II diabetes mellitus (T2DM) risk status among overweight patients with screen-detected colorectal adenomas and explored the implications of the findings for preventative practice. METHOD: Participants aged between 50 and 74 years (73% of whom were men) were recruited from four Scottish health boards and assessed for diabetes risk. Participants were categorized as at 'high' diabetes risk if glycated haemoglobin (HbA1c) was between 6.0 and 6.4% or fasting plasma glucose (FPG) was between 5.5 and 6.9 mmol/l and as potentially undiagnosed T2DM when HbA1c ≥ 6.5% or FPG ≥ 7 mmol/l. Secondary outcome measures included anthropometric measurements, blood pressure and the plasma lipid profile. The tests were repeated at 12 months and diabetes risk categories were reassessed following intervention procedures. RESULTS: Forty-seven (14.3%) of the 329 participants had a preexisting diagnosis of T2DM. Of the remainder with complete biochemistry results (n = 250), 19 (7.6%) were classified as having potentially undiagnosed T2DM and 125 (50.0%) as being at high risk of developing diabetes. More than a quarter of participants in all categories had raised waist circumference, hypertension and plasma lipids, indicative of raised cardiovascular risk. At 12 months' follow-up, the diabetes risk category diminished in 20% of the intervention group vs 11% in the controls [OR 2.26 (95% CI 1.03-4.96)]. CONCLUSION: Our results suggest that a diagnosis of adenoma in overweight patients provides a health service opportunity for diabetes assessment, prevention and management in a high-risk population at a potentially teachable moment.

Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice.

Most systemic autoimmune diseases occur more frequently in females than in males. This is particularly evident in Sjögren's syndrome, systemic lupus erythromatosis (SLE) and thyroid autoimmunity, where the ratio of females to males ranges from 20:1 to 8:1. Our understanding of the etiology of SLE implies important roles for genetics, environmental factors and sex hormones, but the relative significance of each remains unknown. Using the New Zealand hybrid mouse model system of SLE, we present here a new fetal liver chimera-based system in which we can segregate effects of immune system genes from that of sex hormones in vivo. We show that female hematopoietic cells express an intrinsic capacity to drive lupus-like disease in both male and female recipient mice, suggesting that this capacity is hormone independent. Particularly, only chimeric mice with a female hematopoietic system showed significantly increased numbers of germinal center B cells, memory B cells and plasma cells followed by a spontaneous loss of tolerance to nuclear components and hence elevated serum antinuclear autoantibodies. A protective effect of testosterone was noted with regard to disease onset, but not disease incidence. Thus, genetic factors encoded within the female hematopoietic system can effectively drive lupus-like disease even in male recipients.

Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?

BACKGROUND: Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of in vivo glioma models in predicting clinical efficacy. METHODS: We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias. RESULTS: We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74-2.03) and reduced tumour volume by 50.4% (41.8-58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias. CONCLUSION: These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental in vivo glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine.

Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog.

Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas.

Morbidity experienced by women before and after operative vaginal delivery: prospective cohort study nested within a two-centre randomised controlled trial of restrictive versus routine use of episiotomy.

OBJECTIVE: To explore: (1) the antenatal and postnatal morbidity experienced by women in relation to operative vaginal delivery (OVD); and (2) the impact of restrictive versus routine use of episiotomy. DESIGN: Longitudinal prospective cohort study embedded within a two-centre randomised controlled trial (RCT). SETTING: Two UK tertiary-level maternity units. POPULATION: Antenatally recruited participants of an RCT of restrictive versus routine use of episiotomy at OVD. METHODS: A self-completing questionnaire was administered antenatally, before hospital discharge, at 6 weeks and at 1 year postpartum. MAIN OUTCOME MEASURES: Urinary and anal incontinence, dyspareunia, perineal pain and psychological morbidity. RESULTS: Longitudinal data have revealed that morbidities historically associated with OVD were often as prevalent, if not more prevalent, in the third trimester of pregnancy than postpartum. Restrictive episiotomy use was associated with: a higher incidence of perineal pain in the immediate postpartum period (98.9% restrictive versus 87.8% routine, RR 1.10, 95% CI 1.01-1.21); greater psychological morbidity in the immediate postpartum period (mean scores on the Edinburgh Postnatal Depression Scale, Edinburgh Postnatal Depression Score (EPDS) 6.7 restrictive versus 5.1 routine; P = 0.01 ); and more stress urinary incontinence at 6 weeks postpartum (42.2% restrictive versus 27.2% routine, RR 1.55, 95% CI 1.00-2.40); however, this had resolved by 1 year. No other differences were found between the groups at 6 weeks and 1 year postpartum. CONCLUSIONS: Morbidities previously attributed to OVD may in fact be present antenatally, to a greater or similar degree. A restrictive approach to the use of episiotomy at OVD may increase rates of urinary morbidity, in particular stress incontinence and perineal pain, in the immediate postpartum period.

Maternal and neonatal morbidity in relation to the instrument used for mid-cavity rotational operative vaginal delivery: a prospective cohort study.

OBJECTIVE: To compare the maternal and neonatal morbidity associated with alternative instruments used to perform a mid-cavity rotational delivery. DESIGN: A prospective cohort study. SETTING: Two university teaching hospitals in Scotland and England. POPULATION: Three hundred and eighty-one nulliparous women who had a mid-cavity rotational operative vaginal delivery. METHODS: A data collection sheet was completed by the research team following delivery. MAIN OUTCOME MEASURES: Postpartum haemorrhage, third- and fourth-degree perineal tears, low cord pH, neonatal trauma, and failed or sequential operative vaginal delivery. RESULTS: One hundred and sixty-three women (42.8%) underwent manual rotation followed by non-rotational forceps delivery, 73 (19.1%) had a rotational vacuum delivery, and 145 (38.1%) delivered with the assistance of rotational (Kielland) forceps. The rates of postpartum haemorrhage were similar when comparing manual rotation with rotational vacuum (adjusted OR 1.42, 95% CI 0.66-3.98), and when comparing manual rotation with Kielland forceps (adjusted OR 1.22, 95% CI 0.71-2.88). The results were comparable for third- and fourth-degree perineal tears (adjusted OR 0.85, 95% CI 0.13-1.89; adjusted OR 0.94, 95% CI 0.39-1.82), low cord pH (adjusted OR 1.76, 95% CI 0.44-6.91; adjusted OR 1.12, 95% CI 0.44-2.83), neonatal trauma (adjusted OR 0.50, 95% CI 0.16-1.55; adjusted OR 3.25, 95% CI 0.65-16.17), and admission to the neonatal intensive care unit (adjusted OR 1.47, 95% CI 0.45-4.81; adjusted OR 1.04, 95% CI 0.49-2.19). The sequential use of instruments was less likely with manual rotation and forceps than with rotational vacuum delivery (0.6 versus 36.9%, OR 0.01, 95% CI 0.002-0.090). CONCLUSIONS: Maternal and perinatal outcomes are comparable with Kielland forceps, vacuum extraction, and manual rotation, with few serious adverse outcomes. With appropriate training mid-cavity rotational delivery can be practiced safely, including the use of Kielland forceps.

Value of adding second-trimester uterine artery Doppler to patient characteristics in identification of nulliparous women at increased risk for pre-eclampsia: an individual patient data meta-analysis.

OBJECTIVE: To investigate the value of adding second-trimester uterine artery Doppler ultrasound to patient characteristics in the identification of nulliparous women at risk for pre-eclampsia. METHODS: For this individual patient data meta-analysis, studies published between January 1995 and December 2009 were identified in MEDLINE and EMBASE. Studies were eligible in which Doppler assessment of the uterine arteries had been performed among pregnant women and in which gestational age at ultrasound, Doppler ultrasound findings and data on the occurrence of pre-eclampsia were available. We invited corresponding authors to share their original datasets. Data were included of nulliparous women who had had a second-trimester uterine artery Doppler ultrasound examination. Shared data were checked for consistency, recoded to acquire uniformity and merged into a single dataset. We constructed random intercept logistic regression models for each of the patient and Doppler characteristics in isolation and for combinations. We compared goodness of fit, discrimination and calibration. RESULTS: We analyzed eight datasets, reporting on 6708 nulliparous women, of whom 302 (4.5%) developed pre-eclampsia. Doppler findings included higher, lower and mean pulsatility index (PI) and resistance index (RI) and any or bilateral notching. Of these, the best predictors were combinations of mean PI or RI and bilateral notching, with areas under the receiver-operating characteristics curve (AUC) of 0.75 (95% confidence interval (CI), 0.56-0.95) and 0.70 (95% CI, 0.66-0.74), respectively. Addition of Doppler findings to the patient characteristics blood pressure or body mass index (BMI) significantly improved discrimination. A model with blood pressure, PI and bilateral notching had an AUC of 0.85 (95% CI, 0.67-1.00). CONCLUSIONS: The addition of Doppler characteristics of mean PI or RI and bilateral notching to patient characteristics of blood pressure or BMI improves the identification of nulliparous women at risk for pre-eclampsia.

Uptake of folic acid supplements before and during pregnancy: focus group analysis of women's views and experiences.

BACKGROUND: To reduce risk of neural tube defects, current guidance recommends that all women who could become pregnant should take a daily 400 µg folic acid supplement before conception and until the 12th week of pregnancy. It is recognised that compliance with this guidance is sub-optimal, although little is known about the reasons why. The present study aims to explore the rationale behind women's decision-making on folic acid supplement use to inform health communications. METHODS: Women attending routine health visitor led baby clinics completed a questionnaire to establish their folic acid use in their most recent pregnancy. Participants were then invited to join focus group discussions to explore motivators and barriers to folic acid supplement use before and during pregnancy. RESULTS: Of 292 women approached, 211 (70%) provided information on supplement use. Of these, 67 (31%) reported having taken folic acid supplements as recommended; 118 (56%) only during pregnancy [22 (18%) only intermittently]; and 26 (12%) had not taken folic acid at all. Eight focus group discussions were held comprising 24 participants. Discussions indicated the rationale behind current recommendations was known. Participants often linked folic acid use with morning sickness, and invoked busy lives, competing priorities for concern, and poor memory in accounting for intermittent use. Building a 'lay evidence base' from their own experiences, many cited healthy pregnancy outcomes without supplement use and expressed scepticism about its preventive action. CONCLUSIONS: The findings of the present study highlight the importance of guidance on the importance of daily folic acid supplement use, the severity of neural tube defects and the provision of evidence on risk reduction.

Application of the WFD cost proportionality principle to diffuse pollution mitigation: a case study for Scottish Lochs.

The Water Framework Directive (WFD) aims to deliver good ecological status (GES) for Europe's waters. It prescribes the use of economic principles, such as derogation from GES on grounds of disproportionate costs of mitigation. This paper proposes an application of the proportionality principle to mitigation of phosphorus (P) pollution of 544 Scottish lochs at national and local water body scales. P loading estimates were derived from a national diffuse pollution screening tool. For 293 of these lochs (31% of the loch area), GES already occurred. Mitigation cost-effectiveness was assessed using combined mitigation cost curves for managed grassland, rough grazing, arable land, sewage and septic tank sources. These provided sufficient mitigation (92% of national P load) for GES to be achieved on another 31% of loch area at annualised cost of £2.09 m/y. Mitigation of the residual P loading preventing other lochs achieving GES was considered by using a "mop-up" cost of £200/kg P (assumed cost effectiveness of removal of P directly from lochs), leading to a total cost of £189 m/y. Lochs were ranked by mitigation costs per loch area to give a national scale marginal mitigation cost curve. A published choice experiment valuation of WFD targets for Scottish lochs was used to estimate marginal benefits at national scale and combined with the marginal cost curve. This gave proportionate costs of £5.7 m/y leading to GES in 72% of loch area. Using national mean marginal benefits with a scheme to estimate changes in individual loch value with P loading gave proportionate costs of £25.6 m/y leading to GES in 77% of loch area (491 lochs).

Liver fluke in beef cattle - Impact on production efficiency and associated greenhouse gas emissions estimated using causal inference methods.

We aimed to estimate 1) the marginal effect of liver fluke (Fasciola hepatica) infection on productivity of Scottish beef cattle, and 2) the associated greenhouse gas emissions intensity (GHG EI). Data comprised 240,065 abattoir records from NE Scotland from 2014 to 2017, including the presence or absence of lesions typical of liver fluke in the liver at the time of slaughter, from which we inferred liver fluke infection status. The retrospective analysis of abattoir records to estimate marginal effects of an exposure is complicated by the multi-dimensional, clustered nature of the datasets, which result in confounding of potential causal factors with the exposure. Causal inference methods are required to identify and correct for variation in background exposure. We constructed directed acyclic graphs (DAGs) of observed variables, including the potential confounders, breed, sex, breeder, finisher, season of birth and year of birth. We then applied inverse probability weighting (IPW) to adjust for variation among exposure risk and applied a doubly robust generalized linear model (DRGLM) to the weighted observations to estimate the marginal effect of fluke on the growth rate of animals and total days from birth until slaughter. We compared these estimates with the results of linear mixed effects (LME) models with the same variables, treating breeder and producer as random effects. To estimate GHG EI, we applied IPCC tier-2 type GHG calculations to the marginal effects estimated from IPW with DRGLM. The IPW with DRGLM model estimated that animals with active fluke lesions (adult fluke seen on postmortem inspection) gained 17 (95 % CI 12-22) g/d less saleable beef than animals with no lesions and no visible fluke. Animals with active fluke lesions were 11 (95 % CI 6.5-15) d older at slaughter weight than animals with no lesions. Animals with historic lesions in which there was scarring of the liver but in which no adult fluke were seen showed a wide variation in effect estimates, consistent with some misclassification. The effect estimates from LME models suggested slightly lower effects of fluke on growth rate and days to slaughter but with overlapping 95 % confidence intervals. Calculation of the associated GHG emissions suggest the EI of meat from a herd with no fluke is approximately 1.5 % lower than the same herd with fluke. Sustainably controlling liver fluke would have additional production benefits not included in this estimate and could therefore have a much greater impact on GHG EI in practice than demonstrated here.

Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK.

INTRODUCTION: Establishing an early clinical diagnosis in variant Creutzfeldt-Jakob disease (vCJD) can be difficult, resulting in extended periods of uncertainty for many families and sometimes a view that patients have been subjected to unnecessary investigations. This issue is accentuated by the progressive nature of vCJD and by the difficulty in achieving a confident clinical diagnosis before an advanced stage of illness. Although diagnostic delay may be a result of the non-specific early clinical features, a systematic analysis of the process of diagnosis was undertaken, with the aim of trying to achieve earlier diagnosis of vCJD. METHODS: Retrospective case file analysis was undertaken of the first 150 definite and clinically probable cases of vCJD identified by the UK surveillance system. RESULTS: There is a significant interval between illness onset and presentation to a primary care physician, which is influenced by the nature of the initial clinical features. Neurological review is invariably sought following the development of clinical signs and a diagnosis is then established relatively quickly. Despite the progressive clinical course, a confident clinical diagnosis is not usually achieved until a relatively advanced stage of illness (mean time to diagnosis 10.5 months) with a more rapid clinical progression accounting for those cases diagnosed earlier after symptom onset. CONCLUSIONS: Early clinical diagnosis in vCJD is not possible in the great majority of cases because of non-specific initial symptoms. Once neurological signs develop, a diagnosis is usually made promptly but this is often at a relatively advanced stage of illness. The inherent delays in the diagnosis of vCJD have implications for those involved in both public health and therapeutics.

Short communication: Identifying key parameters for modelling the impacts of livestock health conditions on greenhouse gas emissions.

Improved animal health can reduce greenhouse gas (GHG) emissions intensity in livestock systems while increasing productivity. Integrated modelling of disease impacts on farm-scale emissions is important in identifying effective health strategies to reduce emissions. However, it requires that modellers understand the pathways linking animal health to emissions and how these might be incorporated into models. A key barrier to meeting this need has been the lack of a framework to facilitate effective exchange of knowledge and data between animal health experts and emissions modellers. Here, these two communities engaged in workshops, online exchanges and a survey to i) identify a comprehensive list of disease-related model parameters and ii) test its application to evaluating models. Fifty-six parameters were identified and proved effective in assessing the potential of farm-scale models to characterise livestock disease impacts on GHG emissions. Easy wins for the emissions models surveyed include characterising disease impacts related to feeding.