Stigmatisation impedes health and quality of life. Evidence regarding stigma reduction interventions is, albeit growing, limited. There is a gap in the availability and evidence of interventions for ...reducing stigma among children and adolescents, especially in low- and middle-income countries. This paper describes the process that led to a stigma reduction intervention impacting children and adolescents in low- and middle-income countries, following previously conducted formative research. In this study, we conducted (i) online stakeholder consultations (FGD) (n = 43), including a survey assessing intervention acceptability, appropriateness, feasibility and scalability (n = 16); and (ii) preliminary field-testing of intervention content online and in a refugee settlement in Uganda. Stakeholder consultation showed the initial version of STRETCH (Stigma Reduction to Trigger Change for Children), albeit positively received, required adaptations. We made adjustments to i) take into account implementation duration, intervention flexibility and intersectionality; (ii) strengthen the involvement of individuals, including adolescents/youth, with lived stigma experience; (iii) target people close to individuals with lived stigma experience; and (iv) address feasibility and sustainability concerns. Preliminary field-testing simplified STRETCH while adding a community outreach component and revisiting the intervention setup, to ensure STRETCH can also be applied from a modular perspective. We conducted a process to develop a child-focused multi-component stigma reduction intervention, with intended applicability across stigmas and settings. This paper provides an overview of the intervention development process, generating intervention-specific learnings with generic value. STRETCH aims to reduce stigmatisation at the implementing organisation, create community-wide reflection and stigma reduction demand, and reduce stigmatisation among various target groups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although evolutionary transitions from sexual to asexual reproduction are frequent in eukaryotes, the genetic bases of these shifts remain largely elusive. Here, we used classic quantitative trait ...analysis, combined with genomic and transcriptomic information to dissect the genetic basis of asexual, parthenogenetic reproduction in the brown alga Ectocarpus. We found that parthenogenesis is controlled by the sex locus, together with two additional autosomal loci, highlighting the key role of the sex chromosome as a major regulator of asexual reproduction. We identify several negative effects of parthenogenesis on male fitness, and different fitness effects of parthenogenetic capacity depending on the life cycle generation. Although allele frequencies in natural populations are currently unknown, we discuss the possibility that parthenogenesis may be under both sex-specific selection and generation/ploidally-antagonistic selection, and/or that the action of fluctuating selection on this trait may contribute to the maintenance of polymorphisms in populations. Importantly, our data provide the first empirical illustration, to our knowledge, of a trade-off between the haploid and diploid stages of the life cycle, where distinct parthenogenesis alleles have opposing effects on sexual and asexual reproduction and may help maintain genetic variation. These types of fitness trade-offs have profound evolutionary implications in natural populations and may structure life history evolution in organisms with haploid-diploid life cycles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Periacetabular osteotomy (PAO) is the most common treatment for symptomatic acetabular dysplasia, or developmental dysplasia of the hip (DDH), in skeletally mature patients. The purpose of ...this multicenter cohort study was to delineate the long-term radiographic natural history of the dysplastic hip following PAO.
METHODS:We evaluated all patients undergoing PAO from 1996 to 2012 at 3 academic institutions in the United States. Inclusion criteria were PAO for DDH with a minimum 5-year radiographic follow-up. Exclusion criteria were PAO for isolated acetabular retroversion, neurogenic dysplasia, Legg-Calvé-Perthes disease, and prior hip surgery including osteotomies and arthroscopy. There were 288 patients, 83% of whom were women; the mean age and body mass index (BMI) were 29 years and 25 kg/m, respectively. The mean clinical and radiographic follow-up was 9.2 years (range, 5.0 to 21.1 years). Every preoperative and postoperative hip radiograph was assessed to determine the degree of osteoarthritis according to the Tönnis classification. Survivorship was analyzed by multistate modeling, enabling assessment of progression through the Tönnis grades rather than just individual transitions as with Kaplan-Meier techniques.
RESULTS:At the time of final follow-up, 144 patients (50%) had progressed at least 1 Tönnis grade, with 42 patients (14.6%) undergoing total hip arthroplasty. The mean number of years spent in each Tönnis grade following PAO was 19 for Tönnis grade 1, 8 for Tönnis grade 2, and 4 for Tönnis grade 3. The probability of progression to total hip arthroplasty increased significantly on the basis of a higher initial Tönnis grade (p < 0.001). The most marked difference occurred between Tönnis grade 0 or 1 and Tönnis grade 2; for Tönnis grade 1, the probability of progression to total hip arthroplasty at 5 and 10 years was 2% and 11%, respectively, compared with 23% and 53%, respectively, for Tönnis grade 2.
CONCLUSIONS:PAO effectively alters the natural history of DDH. Precise radiographic progression based on the Tönnis grade can now be used to ascribe prognosis for the native hip. Importantly, this investigation demonstrates a stark increase in progression to total hip arthroplasty within 10 years of PAO for patients with preoperative Tönnis grade-2 osteoarthritis compared with those with Tönnis grade-0 or 1 osteoarthritis.
LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
ObjectiveTo determine the feasibility of Fluids in Shock, a randomised controlled trial (RCT) of restricted fluid bolus volume (10 mL/kg) versus recommended practice (20 mL/kg).DesignNine-month pilot ...RCT with embedded mixed-method perspectives study.Setting13 hospitals in England.PatientsChildren presenting to emergency departments with suspected infection and shock after 20 mL/kg fluid.InterventionsPatients were randomly allocated (1:1) to further 10 or 20 mL/kg fluid boluses every 15 min for up to 4 hours if still in shock.Main outcome measuresThese were based on progression criteria, including recruitment and retention, protocol adherence, separation, potential trial outcome measures, and parent and staff perspectives.ResultsSeventy-five participants were randomised; two were withdrawn. 23 (59%) of 39 in the 10 mL/kg arm and 25 (74%) of 34 in the 20 mL/kg arm required a single trial bolus before the shock resolved. 79% of boluses were delivered per protocol in the 10 mL/kg arm and 55% in the 20 mL/kg arm. The volume of study bolus fluid after 4 hours was 44% lower in the 10 mL/kg group (mean 14.5 vs 27.5 mL/kg). The Paediatric Index of Mortality-2 score was 2.1 (IQR 1.6–2.7) in the 10 mL/kg group and 2.0 (IQR 1.6–2.5) in the 20 mL/kg group. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) admissions and PICU-free days at 30 days did not differ significantly between the groups. In the perspectives study, the trial was generally supported, although some problems with protocol adherence were described.ConclusionsParticipants were not as unwell as expected. A larger trial is not feasible in its current design in the UK.Trial registration numberISRCTN15244462.
Noninvasive respiratory support modalities such as high-flow nasal cannula (HFNC) therapy and continuous positive airway pressure (CPAP) are used frequently in pediatric critical care to support ...acutely ill children with respiratory failure (step-up management) and children following extubation (step-down management). Although there are several observational studies and database analyses comparing the efficacy of HFNC and CPAP, and a few small randomized clinical trials (RCTs), until recently, there were no large RCTs comparing the two modalities in a mixed group of critically ill children. In the first half of 2022, results from the First-Line Support for Assistance in Breathing in Children (FIRST-ABC) trials were published; these comprised a master protocol of two trials: one in acutely ill children (step-up RCT) and one in extubated children (step-down RCT). Each of these pragmatic trials randomized 600 children to either HFNC or CPAP when the treating clinician decided that noninvasive respiratory support beyond standard oxygen therapy was required. The primary outcome was time to liberation from all forms of respiratory support (invasive and noninvasive), excluding supplemental oxygen. The FIRST-ABC trials represent a significant advance in the field of noninvasive respiratory support, which has traditionally been evidence-poor and associated with considerable variability in clinical practice. In this article, we provide an overview of how the FIRST-ABC trials were conceived and conducted, our view on the results, and how the trial findings have changed our clinical practice.
Background. Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously ...defined, and associations with sepsis outcomes have not been subjected to multivariable analysis. Methods. We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection. Results. XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 ≪g/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30–3.43). In intensive care unit–based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90–2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27–24.92) after adjustment for bacteremia, comorbidities, and age. Conclusions. We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein.
The Children’s Oxygen Administration Strategies Trial (COAST) was an ambitious project based in Uganda and Kenya. The target population was children with severe pneumonia as assessed by presentation ...of peripheral oxygen saturation into two strata (hypoxaemia: SpO2 80–92% and severe hypoxaemia: SpO2 < 80%). The comparisons were between high-flow humidified nasal therapy (HFNT) and standard low-flow nasal oxygen in the severe hypoxaemia stratum, but also in a fractional factorial design of more liberal oxygen use vs. permissive hypoxaemia in the less severe stratum. The primary outcome measure was mortality at 48 h. The trial was conducted by a team with an outstanding track record of delivering large pragmatic and practice-changing trials in low-income settings. We had the privilege of being independent members of the Trial Steering Committee (TSC).
This article estimates a dynamic structural model of discrete Research and Development (R&D) investment and quantifies its cost and long-run benefit for German manufacturing firms. The model ...incorporates linkages between R&D choice, product and process innovations, and future productivity and profits. The long-run payoff to R&D is the proportional difference in expected firm value generated by the investment. It increases firm value by 6.7% for the median firm in high-tech industries but only 2.8% in low-tech industries. Simulations show that reductions in maintenance costs of innovation significantly raise investment rates and productivity, whereas reductions in startup costs have little effect.
Abstract Context Early and accurate recognition of the deteriorating hospitalised child is complex. Paediatric track and trigger systems (PTTS) support clinical decision-making by ‘tracking’ the ...child’s condition through monitoring of clinical signs and ‘triggering’ a request for an appropriate review when pre-determined criteria are breeched. Objective To describe the number and nature of published PTTS and appraise the evidence on their validity, calibration, and effect on important patient outcomes (death, cardiac and/or respiratory arrest, unplanned transfer to intensive/high dependency care, immediate/urgent request for review, rapid response system activation). Method GRADE methodology. Papers identified through electronic database and citation searching. Results Thirty-three PTTS were identified from 55 studies. There was considerable variety in the number and type of parameters, although all contained one or more vital signs. The evidence to support PTTS implementation was very low and the majority of outcomes did not achieve statistical significance. When PTTS was implemented as part of a rapid response system, the evidence was moderate to low but there was some evidence of a statistically significant improvement in outcome. Conclusion There is now some limited evidence for the validity and clinical utility of PTTS scores. The high (and increasing) number of systems is a significant confounder. Further research is needed particularly around the thresholds for the vital signs and the reliability, accuracy and calibration of PTTS in different settings.
PDF
