Intervention to reduce excessive alcohol consumption and improve comorbidity outcomes in hypertensive or depressed primary care patients: two parallel cluster randomized feasibility trials

Wilson, G. B. Wray, C. McGovern, R. Newbury-Birch, D. McColl, E. Crosland, A. Background Many primary care patients with raised blood pressure or depression drink potentially hazardous levels of alcohol. Brief interventions (BI) to reduce alcohol consumption may improve comorbid conditions and reduce the risk of future alcohol problems. However,research has not established their effectiveness in this patient population. This study aimed to establish the feasibility of definitive trials of BI to reduce excessive drinking in primary care patients with hypertension or mild to moderate depression. Methods Thirteen general practices in North East England were randomized to the intervention or control arm of one of two parallel pilot trials. Adult patients drinking excessively and diagnosed with hypertension or mild-to-moderate depression received the Alcohol Use Disorders Identification Test (AUDIT) by postal survey. Consenting respondents scoring more than 7 on AUDIT (score range 0 to 40) received brief alcohol consumption advice plus an information leaflet (intervention) or an information leaflet alone(control) with follow-up at six months. Measurements included the numbers of patients eligible, recruited, and retained, and the AUDIT score and systolic/diastolic blood pressure of each patient or the nine-item Patient Health Questionnaire (PHQ-9) score. Acceptability was assessed via practitioner feedback and patient willingness to be screened, recruited, and retained at follow-up. Results In the hypertension trial, 1709 of 33,813 adult patients(5.1%) were eligible and were surveyed. Among the eligible patients, 468 (27.4%) returned questionnaires; 166 (9.6% of those surveyed) screened positively on AUDIT and 83 (4.8% of those surveyed) were recruited (50.0% of positive screens). Sixty-seven cases (80.7% of recruited patients)completed follow-up at six months. In the depression trial, 1,044 of 73,146 adult patients(1.4%)were eligible and surveyed. Among these eligible patients, 215(20.6%)responded;104(10.0% of those surveyed)screened positively on AUDIT and 29 (2.8% of those surveyed) were recruited (27.9% of positive screens). Nineteen cases(65.5% of recruited patients)completed follow-up at six months. Conclusions Recruitment and retention rates were higher in the hypertension trial than in the depression trial. A full brief intervention trial appears feasible for primary care patients with hypertension who drink excessively. High AUDIT scores in the depression trial suggest the importance of alcohol intervention in this group. However, future work may require alternative screening and measurement procedures

A pilot feasibility cluster randomised controlled trial of screening and brief alcohol intervention to prevent hazardous drinking in young people aged 14-15 years in a high school setting (SIPS JR-HIGH)

Background: Approximately 33% of 15- to 16-year-olds in England report alcohol intoxication in the past month. This present work builds on the evidence base by focusing on Alcohol Screening and Brief Intervention (ASBI) to reduce hazardous drinking in younger adolescents. Objectives: To explore the feasibility and acceptability of a future definitive cluster randomised controlled trial (cRCT) of ASBI in a school setting to staff, young people and parents; to explore the fidelity of the interventions as delivered by school learning mentors; to estimate the parameters for the design of a definitive cRCT of brief alcohol intervention, including rates of eligibility, consent, participation and retention at 12 months; and to pilot the collection of cost and resource-use data to inform the cost-effectiveness/utility analysis in a definitive trial. Setting: Seven schools across one geographical area in North East England. Methods: Feasibility of trial processes, recruitment and retention and a qualitative evaluation examined facilitators and barriers to the use of ASBI approaches in the school setting in this age group. A three-arm pilot cRCT (with randomisation at the school level) with qualitative evaluation to assess the feasibility of a future definitive cRCT of the effectiveness and cost-effectiveness of ASBI in a school setting, with an integrated qualitative component. The trial ran in parallel with a repeated cross-sectional survey, which facilitated screening for the trial. Participants: Year 10 school pupils (aged 14–15 years). Interventions: Young people who screened positive on a single alcohol screening question, and consented to take part, were randomised to one of three groups: (1) feedback that their drinking habits may be risky and provision of an advice leaflet (control condition, n?=?two schools); (2) feedback as for the control condition plus a 30-minute brief interactive session, which combined structured advice and motivational interviewing techniques, delivered by the school learning mentor (intervention 1, n?=?two schools); or (3) feedback as for the control condition plus a 30-minute brief interactive session as for intervention 1 plus a 60-minute session involving family members delivered by the school learning mentor (intervention 2, n?=?three schools). Young people were followed up at 12 months. Main outcome measures: Feasibility and acceptability. Randomisation: Randomisation was carried out at the school level. Randomisation achieved balance on two school-level variables (numbers of pupils in school year and proportion receiving free school meals). Blinding: School staff, young people and researchers were not blind to the intervention allocated. Results: A total of 229 young people were eligible for the trial; 182 (79.5%) were randomised (control, n?=?53; intervention 1, n?=?54; intervention 2, n?=?75). Of the 75 randomised to intervention 2, 67 received intervention 1 (89%). Eight received both intervention 1 and intervention 2 (11%). In total, 160 out of 182 were successfully followed up at 12 months (88%). Interviews were carried out with six school lead liaisons, 13 learning mentors, 27 young people and seven parents (n?=?53). Analysis shows that the school setting is a feasible and acceptable place to carry out ASBI, with learning mentors seen as suitable people to do this. Intervention 2 was not seen as feasible or acceptable by school staff, parents or young people. Outcomes/conclusions: It is feasible and acceptable to carry out a trial of the effectiveness and cost-effectiveness of single-session ASBI with young people in the school setting, with learning mentors delivering the intervention. Future work should include a definitive study that does not include a parental arm

Bartonella seropositivity in children with Henoch-Schonlein purpura

BACKGROUND: An association between Henoch-Schonlein purpura (HSP) and seropositivity for Bartonella henselae (BH) has been described. The objective of this study was to see if such an association exists in northern Alberta. METHODS: Immunofluorescent antibody testing utilizing an antigen prepared from B. henselae was undertaken on sera from six children with current HSP, 22 children with remote HSP, and 28 controls that were matched for age. Blood from the six children with current HSP was analysed by polymerase chain reaction (PCR) assay with primers derived from the citrate synthase (gltA) gene for the detection of Bartonella DNA. RESULTS: The seropositivity rate for BH was 61% in cases versus 21% in controls (p < 0.03). The PCR assay was negative in all six current cases. CONCLUSION: There is an increased seropositivity rate for BH in children with HSP. However, it is not clear if infection with B. henselae or a related Bartonella species can result in HSP, or if the increased seropositivity is from non-specific or cross-reacting antibodies

Brief intervention to reduce risky drinking in pregnancy: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Risky drinking in pregnancy by UK women is likely to result in many alcohol-exposed pregnancies. Studies from the USA suggest that brief intervention has promise for alcohol risk reduction in antenatal care. However, further research is needed to establish whether this evidence from the USA is applicable to the UK. This pilot study aims to investigate whether pregnant women can be recruited and retained in a randomized controlled trial of brief intervention aimed at reducing risky drinking in women receiving antenatal care.</p> <p>Methods</p> <p>The trial will rehearse the parallel-group, non-blinded design and procedures of a subsequent definitive trial. Over 8 months, women aged 18 years and over (target number 2,742) attending their booking appointment with a community midwife (n = 31) in north-east England will be screened for alcohol consumption using the consumption questions of the Alcohol Use Disorders Identification Test (AUDIT-C). Those screening positive, without a history of substance use or alcohol dependence, with no pregnancy complication, and able to give informed consent, will be invited to participate in the trial (target number 120). Midwives will be randomized in a 1:1 ratio to deliver either treatment as usual (control) or structured brief advice and referral for a 20-minute motivational interviewing session with an alcohol health worker (intervention). As well as demographic and health information, baseline measures will include two 7-day time line follow-back questionnaires and the EuroQoL EQ-5D-3 L questionnaire. Measures will be repeated in telephone follow-ups in the third trimester and at 6 months post-partum, when a questionnaire on use of National Health Service and social care resources will also be completed. Information on pregnancy outcomes and stillbirths will be accessed from central health service records before the follow-ups. Primary outcomes will be rates of eligibility, recruitment, intervention delivery, and retention in the study population, to inform power calculations for a definitive trial. The health-economics component will establish how cost-effectiveness will be assessed, and examine which data on health service resource use should be collected in a main trial. Participants’ views on instruments and procedures will be sought to confirm their acceptability.</p> <p>Discussion</p> <p>The study will produce a full trial protocol with robust sample-size calculations to extend evidence on effectiveness of screening and brief intervention.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN43218782</p

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Blue Ball Properties – initiating responsible environmental stewardship

The Blue Ball Properties Area Transportation Improvement Project encompasses roadway and associated transit improvements surrounding the expansion of the AstraZeneca Headquarters at U.S. 202 (Concord Pike) and Delaware Route 141 near Wilmington, Delaware. Delaware secured 232 acres bordering the Zeneca site, known as the Blue Ball Properties and offered to provide land for the company’s expansion, as well as transportation, recreation, and other improvements that would benefit both AstraZeneca employees as well as the local community. Leaders from the Delaware Department of Transportation (DelDOT), the Delaware Department of Natural Resources and Environmental Control (DNREC), and the Delaware Economic Development Office (DEDO) became equal partners with the community in developing a master plan for the Blue Ball Properties. Project development included preparation of an environmental assessment (EA) document under NEPA, and identification of sensitive historic, cultural and natural resource areas. The project development process underwent a comprehensive minimization and avoidance evaluation to reduce impacts to natural and cultural resources on the project site and incorporated a proactive, environmental stewardship approach to mitigate for the impacts. A comprehensive mitigation package was developed for the project, including extensive stream restoration and wetland replacement initiatives. Agency coordination and frequent agency meetings were held to discuss and enhance the proposed package. The project incurred approximately 500 linear feet of encroachment at various crossing areas of Alapocas Run. Through coordination with the resource agencies, approximately 800 linear feet of incised and eroding channels was restored by raising the channel bed to its historically correct elevation and stabilized with the use of natural bed and bank materials. As mitigation compensation for the proposed impacts to approximately 1.12 acres of wetlands associated with the proposed improvement project, wetland replacement design has been completed on a 2.1-acre site adjacent to an existing wetland along the Alapocas Run corridor. Another priority during Blue Ball Properties development planning was to provide a regional system for stormwater management. Features include bioswales, detention basins and meadow depressions to improve water quality and enhance habitat

Characterization and expression of the Neurospora crassa nmt-1 gene

The Neurospora crassa homologue of the yeast no message in rtiiamine (nmt-1) gene was characterized. The deduced 342-amino-acid gene product has more than 60% identity with other fungal homologues and 42% similarity to a putative bacterial permease. In addition to three introns disrupting the coding sequence, a differentially spliced intron in the 5′ untranslated region was also detected. Unlike other fungi, the N. crassa nmt-1 gene is repressed only 6- to 8-fold by exogenous thiamine concentrations above 0.5 μM and a high basal level of nmt-1 mRNA persists even at 5 μM thiamine. Immuno-blotting with purified antibodies detected two variants of NMT-1 which differ in size and charge. The more abundant 39-kDa form is more strongly repressed by thiamine than the 37-kDa protein. NMT-1 abundance modulates slowly in response to changes in the concentration of exogenous thiamine, suggesting that N. crassa maintains thiamine reserves in excess of immediate needs. Disruption of the nmt-1 gene demonstrated that it is essential for growth in the absence of exogenous thiamine. NMT-1-deficient strains had a growth rate and colony density which was about 70% of the wild type, despite supplementation with a wide range of exogenous thiamine. These results suggest that the nmt-1 gene plays some other role in addition to thiamine biosynthesis