Cost-effectiveness of Paediatric Surgery: An Economic Evaluation of World Paediatric Project Surgical Interventions in St. Vincent and the Grenadines (2002–2019)

Objectives The purpose of this study is to examine the cost-effectiveness of six types of surgical interventions as part of a sustained paediatric surgical programme in St.Vincent and the Grenadines from 2002 to 2019. Design In this economic model, six paediatric surgical interventions (ophthalmic, orthopaedic, plastic, general, urology, neurosurgery) were compared with no surgery in a deterministic cost-effectiveness model. We assessed health benefits as averted disability-adjusted life-years (DALYs). Costs were included from the programme perspective and measured using standard micro-costing methods. Incremental cost-effectiveness ratios (ICERs) were calculated for each type of surgical intervention. Interventions with ICERs of \u3c50% of gross domestic product (GDP) per capita were considered cost-effective. Costs are reported in 2019 US$. Univariate sensitivity analyses were conducted to assess the effect of uncertainty. Results The average cost per procedure was US$16 685 (range: US$9791.78–US$72 845.76). The cumulative discounted 18-year health impact was 5815 DALYs averted with a cost per DALY averted of US$2622. Most paediatric surgical interventions were cost-effective, yielding cost per DALY estimates less than 50% of GDP per capita of St. Vincent and the Grenadines. When undiscounted, only orthopaedic surgeries had cost per DALY more than 50% GDP per capita. When considering discounting, orthopaedic and urology surgeries exceeded the adopted threshold for cost-effectiveness. Conclusions We found that short-term, recurrent surgical interventions could yield substantial economic benefits in this limited resource setting. This research indicates that investment in paediatric surgical interventions is cost-effective for the majority of specialties. These findings are of clinical significance given the large burden of disease attributable to surgically treatable diseases. This work demonstrates that scaling up dedicated surgical programmes for children is a cost-effective and essential component to improve paediatric health

Statistics on indigenous peoples: International effort needed

In 2007, the UN General Assembly endorsed the United Nations Declaration on the Rights of Indigenous Peoples. In the following years, there has been a strong call from a range United Nations agencies and spokespersons for countries to act to improve their statistics relating to Indigenous peoples as part of their response to the Declaration. These calls have emphasised the need for a holistic approach, describing strengths and resilience of Indigenous peoples and not just a focus on gaps and disadvantage. National responses have been mixed and overall statistics remain inadequate. Significantly, there has been no international statistical effort through the United Nations statistical structures to respond to the Declaration and the increasing array of calls for improved statistics. The United Nations Statistical Commission in particular has an array of mechanisms to study statistical needs and develop solutions across a broad international statistical agenda. It is time for countries to make a concerted effort to improve their own statistics on Indigenous peoples, and to insist that the Statistical Commission work in partnership with the Permanent Forum on Indigenous Issues and other stakeholders to lead a major international drive to improve statistics on and for Indigenous peoples

International Group for Indigenous Health Measurement: Recommendations for best practice for estimation of Indigenous mortality

AIM: To provide a best practice guide on Indigenous mortality reporting based on recommendations from the International Group for Indigenous Health Measurement. METHOD: A workshop of the International Group for Indigenous Health Measurement was held in Montreal in 2013 during which best practices in determining Indigenous mortality were discussed. A subsequent discussion paper and draft recommendations were further refined at a meeting in Vancouver in 2014. A working group finalized this best practice guide in follow-up to the two meetings. OUTCOME: Ten final recommendations are made regarding identification, community engagement and ownership, data linkage, uncertainty in official statistics and a timeline for implementation. In this paper we review and discuss these recommendations drawing on examples of best practice in Australia, Canada, New Zealand and the United States of America and highlighting some shortcomings in the current practices of official statistical agencies

Principles of patient partnership:integrating patient perspectives into ERS Clinical Research Collaborations

Patient and public involvement in research is increasingly considered a cornerstone of good research practice, and the research community recognises people with lived experience as valuable stakeholders within the research process. European Respiratory Society (ERS) strongly encourages patient input into its research programme and scientific activities, working in partnership with the European Lung Foundation (ELF) to facilitate this. Based on the ERS and ELF experience and best practice in the field of patient and public involvement, we developed a set of principles to which future ERS and ELF collaborations should adhere. These principles provide guidance on how to address key challenges when planning and conducting patient and public involvement in order to develop successful partnerships with patients and drive forward patient-centred research.</p

Constraining symmetron fields with atom interferometry

We apply the new constraints from atom-interferometry searches for screening mechanisms to the symmetron model, finding that these experiments exclude a previously unexplored region of the parameter space. We discuss the possibility of networks of domain walls forming in the vacuum chamber, and how this could be used to discriminate between models of screening

Final Protocol and Statistical Analysis Plan for the SNAP Trial - a randomised, double-blind, placebo-controlled trial of nicotine replacement therapy in pregnancy

This NIHR HTA-funded smoking, nicotine and pregnancy (SNAP) trial investigated whether or not nicotine replacement therapy (NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. We randomised 1050 women who were between 12 and 24 weeks pregnant as they attended hospital for ante-natal ultrasound scans. Women received either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure was biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within 2 weeks of this) and delivery. At 6 months after childbirth self-reported maternal smoking status was ascertained and 2 years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial were compared in both groups. This repository contains the final approved version of the protocol plus the statistical analysis plan (SAP) for both outcomes at delivery and following the 2 year follow up period after birth

Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

Background: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy ( SNAP) trial will investigate whether or not nicotine replacement therapy ( NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date ( defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion: This trial is designed to ascertain whether or not standard doses of NRT ( as transdermal patches) are effective and safe when used for smoking cessation during pregnancy

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations