Predicted waiting times for orthopaedic surgery : an urgent need to address the deficit in capacity.

Cite this article: Bone Joint Res 2022;11(12):890-892.

Formalising the Pathways to Life Using Assembly Spaces.

Assembly theory (referred to in prior works as pathway assembly) has been developed to explore the extrinsic information required to distinguish a given object from a random ensemble. In prior work, we explored the key concepts relating to deconstructing an object into its irreducible parts and then evaluating the minimum number of steps required to rebuild it, allowing for the reuse of constructed sub-objects. We have also explored the application of this approach to molecules, as molecular assembly, and how molecular assembly can be inferred experimentally and used for life detection. In this article, we formalise the core assembly concepts mathematically in terms of assembly spaces and related concepts and determine bounds on the assembly index. We explore examples of constructing assembly spaces for mathematical and physical objects and propose that objects with a high assembly index can be uniquely identified as those that must have been produced using directed biological or technological processes rather than purely random processes, thereby defining a new scale of aliveness. We think this approach is needed to help identify the new physical and chemical laws needed to understand what life is, by quantifying what life does.

Current recommendations/practices for anonymising data from clinical trials in order to make it available for sharing: A scoping review.

BACKGROUND/AIMS: There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community, and differing recommendations exist on how to perform anonymisation prior to sharing. We aimed to systematically identify, describe and synthesise existing recommendations for anonymising clinical trial datasets to prepare for data sharing. METHODS: We systematically searched MEDLINE®, EMBASE and Web of Science from inception to 8 February 2021. We also searched other resources to ensure the comprehensiveness of our search. Any publication reporting recommendations on anonymisation to enable data sharing from clinical trials was included. Two reviewers independently screened titles, abstracts and full text for eligibility. One reviewer extracted data from included papers using thematic synthesis, which then was sense-checked by a second reviewer. Results were summarised by narrative analysis. RESULTS: Fifty-nine articles (from 43 studies) were eligible for inclusion. Three distinct themes are emerging: anonymisation, de-identification and pseudonymisation. The most commonly used anonymisation techniques are: removal of direct patient identifiers; and careful evaluation and modification of indirect identifiers to minimise the risk of identification. Anonymised datasets joined with controlled access was the preferred method for data sharing. CONCLUSIONS: There is no single standardised set of recommendations on how to anonymise clinical trial datasets for sharing. However, this systematic review shows a developing consensus on techniques used to achieve anonymisation. Researchers in clinical trials still consider that anonymisation techniques by themselves are insufficient to protect patient privacy, and they need to be paired with controlled access.

School-Based Surveillance of Respiratory Pathogens on "High-Touch" Surfaces.

In order to assess the presence of respiratory pathogens on "high-touch" surfaces and inform sanitation practices at schools, pre-selected surfaces in elementary schools in Seattle, WA, USA were sampled weekly and tested by RT-PCR for 25 viral respiratory pathogens (including SARS-CoV-2 retrospectively) and S. pneumoniae during 2019-2020 winter respiratory illness season. Viral pathogens (rhinovirus, adenovirus, influenza) known to cause respiratory illness were detected on commonly touched surfaces, especially wooden surfaces, and matched the patterns of circulating virus in the community.

RSV, Antibodies and the Developing World.

Respiratory syncytial virus remains a major cause of infantile respiratory illness globally. Infants in the developing world experience the highest burden of mortality and morbidity. Risk factors associated with respiratory syncytial virus infection and progression to severe disease include household crowding, preterm birth and low birth weight. Maternally-derived antibody has a role in protection of infants through transplacental antibody transfer and breast milk antibody. Promising prevention strategies that are under development include vaccination during pregnancy and monoclonal antibody administration at birth.

Infant Pneumococcal Carriage During Influenza, RSV, and hMPV Respiratory Illness Within a Maternal Influenza Immunization Trial.

In this post-hoc analysis of midnasal pneumococcal carriage in a community-based, randomized prenatal influenza vaccination trial in Nepal with weekly infant respiratory illness surveillance, 457 of 605 (75.5%) infants with influenza, respiratory syncytial virus (RSV), or human metapneumovirus (hMPV) illness had pneumococcus detected. Pneumococcal carriage did not impact rates of lower respiratory tract disease for these 3 viruses. Influenza-positive infants born to mothers given influenza vaccine had lower pneumococcal carriage rates compared to influenza-positive infants born to mothers receiving placebo (58.1% versus 71.6%, P = 0.03). Maternal influenza immunization may impact infant acquisition of pneumococcus during influenza infection. Clinical Trials Registration. NCT01034254.

A Multicenter Consortium to Define the Epidemiology and Outcomes of Pediatric Solid Organ Transplant Recipients With Inpatient Respiratory Virus Infection.

BACKGROUND: Respiratory virus infection (RVI) in pediatric solid organ transplant (SOT) recipients poses a significant risk; however, the epidemiology and effects of an RVI after pediatric SOT in the era of current molecular diagnostic assays are unclear. METHODS: A retrospective observational cohort of pediatric SOT recipients (January 2010 to June 2013) was assembled from 9 US pediatric transplant centers. Charts were reviewed for RVI events associated with hospitalization within 1 year after the transplant. An RVI diagnosis required respiratory symptoms and detection of a virus (ie, human rhinovirus/enterovirus, human metapneumovirus, influenza virus, parainfluenza virus, coronavirus, and/or respiratory syncytial virus). The incidence of RVI was calculated, and the association of baseline SOT factors with subsequent pulmonary complications and death was assessed. RESULTS: Of 1096 pediatric SOT recipients (448 liver, 289 kidney, 251 heart, 66 lung, 42 intestine/multivisceral), 159 (14.5%) developed RVI associated with hospitalization within 12 months after their transplant. RVI occurred at the highest rates in intestine/abdominal multivisceral (38%), thoracic (heart/lung) (18.6%), and liver (15.6%) transplant recipients and a lower rate in kidney (5.5%) transplant recipients. RVI was associated with younger median age at transplant (1.72 vs 7.89 years; P < .001) and among liver or kidney transplant recipients with the receipt of a deceased-donor graft compared to a living donor (P = .01). The all-cause and attributable case-fatality rates within 3 months of RVI onset were 4% and 0%, respectively. Multivariable logistic regression models revealed that age was independently associated with increased risk for a pulmonary complication (odds ratio, 1.24 [95% confidence interval, 1.02-1.51]) and that receipt of an intestine/multivisceral transplant was associated with increased risk of all-cause death (odds ratio, 24.54 [95% confidence interval, 1.69-327.96]). CONCLUSIONS: In this study, hospital-associated RVI was common in the first year after pediatric SOT and associated with younger age at transplant. All-cause death after RVI was rare, and no definitive attributable death occurred.

Measles and Rubella Seroprevalence in Mother-Infant Pairs in Rural Nepal and the United States: Pre- and Post-Elimination Populations.

We sought to compare seroprevalence of protective measles and rubella-specific antibody in mother-infant pairs across two populations: a pre-disease elimination Nepal population with recently introduced rubella vaccine and post-disease elimination U.S. population. Qualitative measles and rubella immunoglobulin G was assessed in maternal serum and cord blood from 258 pairs in Nepal, 2012-2013 and 49 pairs in Seattle, WA, 2014-2015. High rates of protective antibody were observed in both populations. Two hundred and forty-four (95%) pregnant women in Nepal had protective measles antibody versus 44 (92%) in Seattle (P = 0.42). Ninety-six percent of infants in Nepal (N = 246) and Seattle (N = 43) had protective measles antibody (P = 0.75). Ninety-four percentage of pregnant women in Nepal (N = 242) and Seattle (N = 45) had protective rubella antibody (P = 0.23). Two hundred and thirty-eight (93%) infants in Nepal had protective rubella antibody versus 44 (98%) in Seattle (P = 0.12). Continued surveillance will be necessary to ensure protective immunity, inform progress toward disease elimination in Nepal and avoid reemergence in the United States.

Enhanced detection services for developmental dysplasia of the hip in Scottish children, 1997-2013.

BACKGROUND: Developmental dysplasia of the hip (DDH) remains common. If detected early, DDH can usually be corrected with conservative management. Late presentations often require surgery and have worse outcomes. OBJECTIVE: We estimated the risk of undergoing surgery for DDH by age 3 years before and after the introduction of enhanced DDH detection services. DESIGN: Retrospective cohort study. SETTING: Scotland, 1997/98-2010/11. PATIENTS: All children. METHODS: Using routinely collected national hospital discharge records, we examined rates of first surgery for DDH by age 3 by March 2014. Using a difference in difference analysis, we compared rates in two areas of Scotland before (to April 2002) and after (from April 2005) implementation of enhanced DDH detection services to those seen in the rest of Scotland. RESULTS: For children born in the study period, the risk of first surgery for DDH by age 3 was 1.18 (95% CI 1.11 to 1.26) per 1000 live births (918/777 375).Prior to April 2002, the risk of surgery was 1.13 (95% CI 0.88 to 1.42) and 1.31 (95% CI 1.16 to 1.46) per 1000 live births in the intervention and non-intervention areas, respectively. In the intervention areas, from April 2005, this risk halved (RR 0.47; 95% CI 0.32 to 0.68). The risk remained unchanged in other areas (RR 1.01; 95% CI 0.86 to 1.18). The ratio for the difference in change of risk was 0.46 (95% CI 0.31 to 0.70). CONCLUSIONS: The implementation of enhanced DDH detection services can produce substantial reductions in the number of children having surgical correction for DDH.

A probabilistic framework for identifying biosignatures using Pathway Complexity.

One thing that discriminates living things from inanimate matter is their ability to generate similarly complex or non-random structures in a large abundance. From DNA sequences to folded protein structures, living cells, microbial communities and multicellular structures, the material configurations in biology can easily be distinguished from non-living material assemblies. Many complex artefacts, from ordinary bioproducts to human tools, though they are not living things, are ultimately produced by biological processes-whether those processes occur at the scale of cells or societies, they are the consequences of living systems. While these objects are not living, they cannot randomly form, as they are the product of a biological organism and hence are either technological or cultural biosignatures. A generalized approach that aims to evaluate complex objects as possible biosignatures could be useful to explore the cosmos for new life forms. However, it is not obvious how it might be possible to create such a self-contained approach. This would require us to prove rigorously that a given artefact is too complex to have formed by chance. In this paper, we present a new type of complexity measure, which we call 'Pathway Complexity', that allows us not only to threshold the abiotic-biotic divide, but also to demonstrate a probabilistic approach based on object abundance and complexity which can be used to unambiguously assign complex objects as biosignatures. We hope that this approach will not only open up the search for biosignatures beyond the Earth, but also allow us to explore the Earth for new types of biology, and to determine when a complex chemical system discovered in the laboratory could be considered alive.This article is part of the themed issue 'Reconceptualizing the origins of life'.

Microbiological characteristics of acute osteoarticular infections in children.

This study aimed to describe the microbiological characteristics of acute septic arthritis (SA) and osteomyelitis (OM) in children. Cases of children (0-15 years) with SA/OM were identified through a retrospective search of hospital discharge codes over a six-year period. In addition, a systematic literature search and meta-analysis of studies reporting culture results of children with SA/OM was performed. In our retrospective chart review, we identified 65 cases of OM and 46 cases of SA. The most frequently cultured organisms in both conditions were Gram-positive cocci, primarily Staphylococcus aureus. On admission, most patients had a normal white blood cell count (WCC) but elevated C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR). Bacteraemia was associated with a longer mean length of hospitalization for both infections. Considering our results and the meta-analysis, we found low rates of culture-positivity in cases of clinically confirmed infection. In SA, articular fluid was culture-positive in 42.49% [95% confidence interval (CI) 28.39-57.23]. In OM, intra-operative samples were culture-positive in 52.65% (95% CI 30.54-74.22). Bacteraemia was detected in 23.91% (95% CI 8.40-44.24) of children with SA and 21.48% (95% CI 10.89-34.47) with OM. Despite appropriate sampling, a positive microbiological diagnosis is often lacking in paediatric acute osteoarticular infection using standard culture-based methods. This highlights the need for validation and use of more sensitive diagnostic methods, such as PCR.

Paediatric intrasubstance posterior cruciate ligament rupture.

The authors present the case of a 4-year-old boy who sustained an intrasubstance posterior cruciate ligament (PCL) tear whist trampolining. He was managed non-operatively with return to full function by 8 months. A high index of suspicion is required when assessing paediatric hyperflexion/extension injuries at the knee as ligamentous injury may occur without osteochondral fracture and may be missed on routine radiographs. Early MRI can identify such injuries in addition to osteochondral avulsions which are often amenable to acute internal fixation. In the case of paediatric intrasubstance PCL tears, it appears that non-operative management yields a good functional outcome in the short term in the skeletally immature.

Do children who in-toe need to be referred to an orthopaedic clinic?

The objective of this study was to investigate the outcome of in-toeing referrals to a paediatric orthopaedic department. Two hundred and two patients referred to the Royal Hospital for Sick Children, Edinburgh between July 2005 and March 2008 were retrospectively reviewed. Increased femoral anteversion and internal tibial torsion formed the majority of diagnoses. The median age of referral was 4 years. No patient in the audit period required surgery. Eighty-six percent of children were discharged after their first visit. No significant pathology was identified in the 14% reviewed. Management and outcome for these children were not affected by referral to the orthopaedic clinic.

Pretibial subcutaneous soft tissue lesions presenting to a paediatric orthopaedic clinic.

Pretibial swellings in children usually represent erythema nodosum which exhibits characteristic skin changes. Three cases of pretibial subcutaneous lesions are presented which had no skin involvement or bony abnormalities on plain radiographs. At initial presentation, concerns of malignancy were raised but these lesions were ultimately diagnosed as granuloma annulare, fat necrosis and subcutaneous infection. In combination with clinical assessment and plain radiographs, MRI proved invaluable in reaching diagnosis and excluding neoplasia. Biopsy was only required in one case in this series after MRI. A tissue diagnosis, however, remains mandatory if there is any doubt over the nature of such lesions.

10-16 year results of Leeds-Keio anterior cruciate ligament reconstruction.

Following initial enthusiasm in the late 1980s, the use of artificial ligament substitutes for anterior cruciate ligament (ACL) reconstruction has declined. However, the disadvantages of donor site morbidity for autologous graft and concerns about cross-infection from allogenic material have resulted in a maintained interest in prosthetic ligament substitutes. This study presents the outcome of ACL substitution using the Leeds-Keio (LK) polyester ligament at a mean of 13.3 years (range 10-16 years). Outcome was assessed using the International Knee Documentation Committee score, the Lysholm knee score, Tegner activity scale and American Knee Society Score and laxity by clinical examination and the Stryker Knee Laxity Tester. Standardized radiographs were taken to assess for evidence of degenerative change. The objective scoring tests showed that all patients experienced some degree of symptoms from their knee but functional impairment varied widely. Of the group, 28% were known to have ruptured their LK ligament and 56% had increased laxity compared with their opposite knee but no correlation could be shown between rupture, increased laxity and poor function. Of particular concern, all post-operative knees had radiographic signs of degenerative change compared with a rate of 39% in the contralateral knees.