Budget Processes: Theory and Experimental Evidence

This paper studies budget processes, both theoretically and experimentally. We compare the outcomes of bottom-up and top-down budget processes. It is often presumed that a top-down budget process leads to a smaller overall budget than a bottom-up budget process. Ferejohn and Krehbiel (1987) showed theoretically that this need not be the case. We test experimentally the theoretical predictions of their work. The evidence from these experiments lends strong support to their theory, both at the aggregate and the individual subject level

The Parents under Pressure parenting programme for families with fathers receiving treatment for opioid dependency: the PuP4Dads feasibility study

Background: The impact of parental drug use on children is a major public health problem. However, opioid-dependent fathers have been largely ignored in parenting research. Objective: Implement and test the feasibility and acceptability of the ‘Parents under Pressure’ parenting programme for opioid-dependent fathers and their families (PuP4Dads) and determine whether a full scale evaluation could be conducted. Design: Mixed methods feasibility study. Setting: Two non-NHS family support services for parents who use drugs in Scotland. Participants: Fathers prescribed Opioid Substitution Therapy (n=25), their partners (n=17) and children; practitioners; supervisors, service managers; referrers. Intervention: Home-visiting programme, including an integrated theoretical framework, case formulation, collaborative goal setting, and modules designed to improve parenting, the caregiving environment and child welfare. Delivered flexibly over six months by accredited practitioners. Main outcome measures: Feasibility progression criteria: recruitment target (n=24 fathers); acceptability of PUP; father engagement in the study (66% complete programme; minimum 10 complete baseline and post-treatment interviews); engagement in qualitative interviews (fathers n=10 minimum; practitioners 90% uptake; managers 80% uptake); focus groups (referrers 80% uptake); adequate fidelity; no adverse events. Data sources: Researcher administered validated questionnaires: Brief Child Abuse Potential; Parenting Sense of Competence; Difficulties in Emotion Regulation; Paternal/Maternal Antenatal Attachment; Emotional Availability (video); Infant Toddler Social Emotional Assessment/Strengths and Difficulties; Conflict Tactics Scale; Treatment Outcomes Profile; EQ-5D-5L. Other sources: Parent-completed service use (economic measure); Social work child protection data; NHS opioid substitution therapy prescription data. Practitioner reported attendance data. Interviews with fathers, mothers, practitioners (n=8), supervisors (n=2), service managers (n=7); focus groups with referrers (n=28); ‘expert event’ with stakeholders (n=39). Results: PuP was successfully delivered within non-NHS settings and acceptable and suitable for the study population. Referrals (n=44) resulted in 38 (86%) eligible fathers, of whom 25 (66%) fathers and 17 partners/mothers consented to participate. Most fathers reported no previous parenting support. Intervention engagement: 248 sessions delivered to 20 fathers and 14 mothers who started the intervention; 14 fathers (10 mothers) completed ≥ six sessions; six fathers (4 mothers) completed ≤ five sessions. Father and mother attendance rates were equal (mean: 71%). Median length of engagement: fathers 26 weeks, mothers 30 weeks. Research interview completion rates for fathers: 23 at baseline, 16 follow-up one, 13 follow-up two. Measures: well tolerated; suitability of some measures dependent on family circumstances; researcher administered questionnaires resulted in little missing data. Perceived benefits of PuP4Dads from parent, practitioner and manager perspectives: therapeutic focus on fathers, improved parental emotion regulation; understanding and responding to child’s needs; better multi-agency working; programme a good fit with practice ‘ethos’ and policy agenda. Learning highlighted importance of: service-wide adoption and implementation support; strategies to improve recruitment and retention of fathers; managing complex needs of both parents concurrently; understanding contextual factors affecting programme delivery and variables affecting intervention engagement and outcomes. Limitations: Lack of emotional availability and economic (service use) data. Conclusions: A larger evaluation of PuP4Dads is feasible. Future work: Demonstrating the effectiveness of PuP4Dads and the cost implications. Better understanding of how the intervention works, for whom, under what circumstances, and why

A protective role for FGF-23 in local defence against disrupted arterial wall integrity?

Increasing interest is focusing on the role of the FGF-23/Klotho axis in mediating vascular calcification. However, the underpinning mechanisms have yet to be fully elucidated. Murine VSMCs were cultured in calcifying medium for a 21d period. FGF-23 mRNA expression was significantly up-regulated by 7d (1.63 fold; P<0.001), with a concomitant increase in protein expression. mRNA and protein expression of both FGFR1 and Klotho were confirmed. Increased FGF-23 and Klotho protein expression was also observed in the calcified media of Enpp1(−/−) mouse aortic tissue. Reduced calcium deposition was observed in calcifying VSMCs cultured with recombinant FGF-23 (10ng/ml; 28.1% decrease; P<0.01). Calcifying VSMCs treated with PD173074, an inhibitor of FGFR1 and FGFR3, showed significantly increased calcification (50nM; 87.8% increase; P<0.001). FGF-23 exposure induced phosphorylation of ERK1/2. Treatment with FGF-23 in combination with PD98059, an ERK1/2 inhibitor, significantly increased VSMC calcification (10μM; 41.3% increase; P<0.01). Use of FGF-23 may represent a novel therapeutic strategy for inhibiting vascular calcification

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T-and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30 min of left ascending coronary I/R. Benidipine was administered orally at 3 mg kg -1daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2′ deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels. © 2012 The Japanese Society of Hypertension All rights reserved

ESHRE good practice recommendations for add- ons in reproductive medicine

The draft of the paper “ESHRE Good practice recommendations for add-ons in reproductive medicine” was published for public review for 4 weeks, between 1 November and 1 December 2022. This report summarizes all reviewers, their comments and the reply of the working group and is published on the ESHRE website as supporting documentation to the paper. During the stakeholder review, a total of 274 comments (including 24 duplicates) were received from 46 reviewers. Reviewers included professionals and representatives of donor-conceived offspring organisations. The comments were focussed on the content of the guideline (209 comments), language and style (31 comments), or were remarks that did not require a reply (10 comments). All comments to the language and format were checked and corrected where relevant. The comments to the content of the paper (n=209) were assessed by the working group and where relevant, adaptations were made in the paper (n=94; 45%). Adaptations included revisions and/or clarifications of the text, and amendments to the recommendations. For a number of comments, the working group considered them outside the scope of the paper or not appropriate/relevant (n=115; 55%).peer-reviewe

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe