Walter Muruet

Introduction: Skeletal fractures are a leading cause of death and disability and a growing global public health concern. Internal fixation is a common surgical treatment indicated for several fractures, yet there are few comprehensive epidemiological studies describing mortality following the procedure. Methods: Data were extracted from an England-wide administrative database (Hospital Episode Statistics, HES) and linked to mortality records from the Office for National Statistics (ONS). All records from patients aged 18 years or older who were admitted due to a non-polytrauma single fracture and underwent internal fixation between 2013 and 2023 were included. Crude and adjusted mortality rates were calculated as well as the restricted mean time lost. Results: A total of 630 758 admissions were included in the primary analysis. Of these, 55% were female, and the mean±SD age was 59±23 years. Primary open reduction internal fixation was the most common procedure (54% of cases), followed by closed reduction internal fixation (35%). Overall, mortality rates following internal fixation were 2% within 30 days, 5% within 90 days and 10% within 365 days. Mortality rates were described by fracture region and reduction procedure. Variation in mortality rates across fracture regions and procedures was attenuated in the case-mix-adjusted estimates. Conclusions: This study described national crude and adjusted mortality rates following internal fixation for the treatment of skeletal fractures. These findings provide population-level descriptive benchmarks for clinical and epidemiological interpretation and may inform decision-making by clinicians and patients as well as the design of randomised controlled trials and other research studies.

Background: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. Methods and findings: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24⁺¹ weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. Conclusions: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. Trial registration: This trial is registered with the ISRCTN registry, ISRCTN67698474.

Background: In the UK, children with high levels of hyperactivity, impulsivity and inattention referred to clinical services with possible attention-deficit/hyperactivity disorder (ADHD) often wait a long time for specialist diagnostic assessment. Parent training (PT) has the potential to support parents during this difficult period, especially regarding the management of challenging and disruptive behaviours that often accompany ADHD. However, traditional face-to-face PT is costly and difficult to organise in a timely way. We have created a low-cost, easily accessible PT programme delivered via a phone app, Structured E-Parenting Support (STEPS), to address this problem. The overall OPTIMA programme will evaluate the efficacy and cost-effectiveness of STEPS as a way of helping parents manage their children behaviour while on the waiting list. To ensure the timely and efficient evaluation of STEPS in OPTIMA, we have worked with children’s health services to implement a remote strategy for recruitment, screening, and assessment of recently referred families. Part of this strategy is incorporated into routine clinical practice and part is OPTIMA specific. Here we present the protocol for Phase 1 of OPTIMA – a study of the feasibility of this remote strategy, as a basis for a large-scale STEPS randomised controlled trial (RCT). Methods: This is a single arm observational feasibility study. Parents of up to 100 children aged 5-11 years with high levels of hyperactivity/impulsivity, inattention and challenging behaviour who are waiting for assessment in one of five UK child and adolescent mental health or behavioural services. Recruitment, consenting and data collection will occur remotely. The primary outcome will be the rate at which the families, who meet inclusion criteria, agree in principle to take part in a full STEPS RCT. Secondary outcomes include acceptability of remote consenting and online data collection procedures; the feasibility of collecting teacher data remotely within the required timeframe, and technical difficulties with completing online questionnaires. All parents in the study will receive access to STEPS. Discussion: Establishing the feasibility of our remote recruitment, consenting and assessment strategy is a pre-requisite for the full trial of OPTIMA. It can also provide a model for future trials conducted remotely. Trial registration: N/A

Objectives: The COVID-19 related lockdowns and distancing measures have presented families with unprecedented challenges. A UK-wide cohort study tracking changes in families’ mental health since early lockdown (Co-SPACE) found a significant rise in primary school-aged children’s behaviour problems and associated family-related stress. Three-quarters of parents in Co-SPACE also reported wanting extra support. In SPARKLE, we will examine whether providing Co-SPACE families with a smartphone application delivering information and parenting support, Parent Positive, can reverse the negative effects of the pandemic on children and parents. The efficacy on child and parent outcomes and cost-effectiveness of Parent Positive will be examined. We will also test whether the effects are moderated by pre-existing levels of child conduct problems and usage of Parent Positive. Exploratory analyses will examine whether other baseline characteristics or lockdown circumstances moderate the effects of Parent Positive. Trial design: SPARKLE is a two-arm superiority parallel group randomised controlled trial embedded in an existing large UK-wide self-selected community cohort – Co-SPACE. Those who consent to SPARKLE will be randomised 1:1 to either Parent Positive or Follow-up As Usual (FAU). Participants: Co-SPACE (a UK-wide longitudinal cohort study) parents aged ≥18 who have children aged 4-10 years will be eligible for SPARKLE. Intervention and comparator: Parent Positive: is a digital public health intervention that can be delivered rapidly at scale to support parents in managing their children’s behaviour to reduce conduct problems and levels of family conflict, which were exacerbated during the first lockdown, and which may increase further in future months as families need to cope with continuous uncertainty and further disruption to their daily lives. Co-designed with parents and based on decades of parenting research, Parent Positive consists of three elements: (i) Parenting Boosters: where advice, delivered in the form of narrated animations, videos, graphics and text is provided to help parents with eight common parenting challenges; (ii) Parenting Exchange: a facilitated parent-to-parent communication and peer support platform and; (iii) Parent Resources: giving access to carefully selected high-quality, evidence-based online parenting resources. Follow-up as Usual: FAU was selected as a comparator because the public health nature meant that an active comparator was not appropriate due to the pragmatic, rapid implementation of the trial. Individuals randomised to FAU will receive no intervention for the first two months while the data for baseline (T1), T2 and T3 are collected. They will then be given full access to the app until 30th November 2021. Main outcomes: Outcome measures will be collected remotely through Qualtrics according to the Co-SPACE schedule at baseline (T1), which will be the Co-SPACE survey data obtained immediately prior to randomisation, and then at one month (T2) and two months (T3) post-randomisation. Measures will be collected to assess group differences in child and parent outcomes, costs and service utilisation, and adverse events. Usage of Parent Positive will also be tracked. The primary outcome is parent-reported child conduct problems at one-month post-randomisation measured using the Strengths and Difficulties Questionnaire conduct problems subscale. Randomisation: Enrolled participants will be allocated to Parent Positive or FAU at the ratio of 1:1 by simple randomisation using the Randomizer function within the Qualtrics programme. Neither blocking nor stratification will be used. Blinding (masking): It is not possible to blind parents enrolled in the study and Qualtrics will automatically inform parents of their group allocation. Blinded members of the research team and the senior statistician will not be given access to the Qualtrics system or the data in order to remain blinded until after the analysis is complete. We do not anticipate any serious harms associated with taking part in the intervention, therefore there will be no need to unblind any blinded staff during the study. The junior statistician will be unblinded throughout. Numbers to be randomised (sample size): A total of 616 will be recruited into the trial with 308 consenting parents randomised to each treatment arm. Trial status: V1.0; 15.03.2021. Not yet recruiting. Anticipated start date: 1^st April 2021. Anticipated end date for recruitment: 31^st July 2021. Trial registration: Clinicaltrial.gov: NCT04786080. The trial was prospectively registered on 8 March 2021. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Background and Purpose—Intravenous thrombolysis with alteplase is one of the few approved treatments for acute ischemic stroke; nevertheless, little is known about its long-term effects on survival and recovery because clinical trials follow-up times are limited. Methods—Patients registered between January 2005 and December 2015, to the population-based South London Stroke Register of first-ever strokes. Propensity score was used to match thrombolyzed and control cases to a 1:2 ratio by demographical and clinical covariates. The primary outcome was survival up to 10 years using Kaplan–Meier estimates, Cox proportional hazards, and restricted mean survival time. Secondary outcomes included stroke recurrence and functional status (Barthel Index and Frenchay Activities Index scores) at 5 years. Results—From 2052 ischemic strokes, 246 treated patients were matched to 492 controls. Median follow-up time 5.45 years (interquartile range, 4.56). Survival was higher in the treatment group (median, 5.72 years) compared with control group (4.98 years, stratified log-rank test Conclusions—Thrombolysis with intravenous alteplase is associated with improved long-term survival and functional status after ischemic stroke.

The objective of this study was to determine the distribution of staphylococcal cassette chromosome mec (SCCmec) elements in meticillin-resistant coagulase-negative staphylococci (MR-CoNS) isolated from a tertiary-care hospital in Mexico and to examine the relationship to drug resistance. Fifty selected MR-CoNS isolates collected from catheters (n=15), blood (n=15), bone (n=9), bronchial lavage (n=2) and urine (n=2) and one isolate each from an abscess, cerebrospinal fluid, eye, pleural effusion, synovial fluid, tracheal aspirate and wound secretion were examined. Susceptibility testing was performed by the broth microdilution method. SCCmec types were determined by multiplex PCR and PFGE was carried out as described previously for Staphylococcus aureus. Among the MR-CoNS strains studied, the most frequently isolated species were Staphylococcus epidermidis (n=26) and Staphylococcus haemolyticus (n=13). Staphylococcus cohnii (n=5), Staphylococcus hominis (n=3), Staphylococcus sciuri (n=1), Staphylococcus pasteuri (n=1) and the recently described species Staphylococcus pettenkoferi (n=1) were also identified. The most frequent MR-CoNS genotype identified was SCCmec type IVa in S. epidermidis isolates, which also showed a high diversity in their PFGE patterns. A clone was found that amplified both SCCmec III and V elements in five isolates examined. The single MR S. pettenkoferi isolate harboured SCCmec type IVd and the single MR S. pasteuri isolate harboured SCCmec type I. The carriage of SCCmec type III was associated with resistance or intermediate resistance to meropenem (P S. epidermidis SCCmec IVa and the high genetic diversity among MR-CoNS strains. As far as is known, this is the first report describing the newly identified S. pettenkoferi possessing SCCmec IVd and S. pasteuri harbouring SCCmec type I. MR-CoNS harbouring SCCmec type III were found to be more resistant to meropenem.