Transferring inpatients between wards drives large nosocomial COVID-19 outbreaks, Wales, 2020-22: a matched case-control study using routine and enhanced surveillance data.

BACKGROUND: The role of the hospital environment in the spread of COVID-19 is unclear. AIM: To measure associations between ward characteristics and outbreak size to inform mitigations. METHODS: Wards with large (case wards) and small (control wards) outbreaks in three acute hospitals were compared. Cases were healthcare-associated COVID-19 inpatients (positive polymerase chain reaction test ≥8 days post admission). Case wards were adult medical/surgical wards with ≥10 cases within rolling 14-day periods, between April 1st, 2020 and April 30th, 2022. Control wards were equivalents with 2-9 cases. Demographic and laboratory data were extracted from routine surveillance systems. Continuous data were aggregated fortnightly and analysed as binary variables according to median values. Each case ward was compared with two control wards matched on outbreak start date (±14 days) to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) using univariable and conditional multivariable logistic regression. FINDINGS: From 170 outbreaks (median: 5 cases; interquartile range: 2-9), 35 case wards were identified. Community admissions were lower in case wards vs control wards (5 vs 10 median admissions; P<0.01, respectively), whereas transfers between wards within the same hospital were higher (58 vs 29 median transfers; P<0.01, respectively). Wards with more transfers in the preceding fortnight were significantly more likely to experience a large outbreak (≥35 vs <35 transfers; adjusted OR: 9.08; 95% CI: 2.5-33). CONCLUSION: We recommend safely minimizing patient movements, such as by asking clinicians to record the rationale for transfer, to reduce the likelihood of disease transmission.

A review of atypical subtrochanteric femoral fractures in Northern Ireland between 2010 and 2014.

The term atypical femoral fractures most commonly occur in the subtrochanteric area. Concerns exist regarding the role of bisphosphonate treatment in their aetiology. Which surgical intervention provides the best outcome remains contentious. We reviewed all atypical subtrochanteric femoral fractures treated in Northern Ireland over 5 years, specifically investigating incidence, prodromal symptoms, association with bisphosphonates and optimal fixation methods. All subtrochanteric fractures treated in the region were identified and reviewed for atypical features. Case notes and imaging were then reviewed for each patient. A total of 364 subtrochanteric femoral fractures were identified during the 5-year study period. Twenty-six of these met the criteria for an atypical fracture (7%). Thirteen patients (50%) had presented with prodromal symptoms prior to complete fracture, six of which had radiological evidence of an incomplete fracture of the lateral cortex. Thirteen patients had a history of bisphosphonate treatment. All were treated operatively, with twenty-five cephalomedullary nails and one dynamic hip screw. Twenty-one patients had follow-up for greater than 2 months, nine of which (42.9%) achieved radiological union with a mean time to union of 297 days. Dynamically locked nails had a higher union rate than statically locked (80% versus 33.3%). Four patients required major revision surgery (15.4%). The quality of reduction was statistically significant in predicting need for revision. Atypical fractures often present with prodromal symptoms. Complete fractures are difficult to successfully manage with longer than expected times to union. Treatment with a dynamically locked, cephalomedullary with a good reduction provided the best results.

The changing face of fractures of the hip in Northern Ireland: a 15-year review.

AIMS: We reviewed all patients who sustained a fracture of the hip and were treated in Northern Ireland over a period of 15 years to identify trends in incidence, the demographics of the patients, the rates of mortality, the configuration of the fracture and the choice of implant. PATIENTS AND METHODS: Since 01 January 2001 data about every fracture of the hip sustained in an adult have been collected centrally in Northern Ireland. All adults with such a fracture between 2000 and 2015 were included in the study. Temporal changes in their demographics, the mode of treatment, and outcomes including mortality were analysed. RESULTS: The incidence of fractures of the hip, in Northern Ireland, rose from 54 in 100 000 in 2000 to 86 in 100 000 in 2015. If these trends continue, we predict this rising to 128 in 100 000 in 2030. We found that these patients are becoming older and increasingly frail, as assessed by the American Association of Anesthesiology grade. Complex extracapsular fractures have become more common since 2009, which may explain the increased use of cephalomedullary nails. Despite increasing frailty, the 30-day and 12-month rates of mortality fell significantly (p = 0.002 and 0.001, respectively). CONCLUSION: Fractures of the hip are becoming more common and more complex in an aging, increasingly frail population. We expect these trends to continue. This will place an increasing economic and clinical strain on healthcare systems. Forward planning is essential to put systems in place that can deal with the increasing demand. Cite this article: Bone Joint J 2017;99-B:1223-31.

Avoidable Compartment Syndrome! High Index of Suspicion for a Newly Presenting Haemophiliac: A Case Series.

Bleeding disorders can present at any age and vary in their severity. Haemophilia, which is characterised by its x-linked recessive inheritance, can present with a spontaneous mutation and therefore no family history will be evident. Three cases of trauma induced thigh haematomas as an initial presenting feature for people with haemophilia are discussed. The cases highlight the importance of a coagulation screen if the patients bleeding phenotype does not match the injury sustained. An isolated prolonged APTT with no offending anticoagulant cause should always be investigated to look for underlying haemophilia. Interestingly the cases demonstrate the limitations of a coagulation screen. Factor VIII being an acute phase reactant can result in the fact that the initial coagulation screen may be temporarily normal. Therefore, if there is a high index of suspicion for a bleeding disorder, consider repeating the coagulation screen and seeking haematology opinion. Early diagnosis and appropriate specific factor replacement for an injured haemophiliac prevent haematomas expanding thus avoiding potential complications like compartment syndrome or unnecessary surgical input.

Delayed diagnosis of developmental dysplasia of the hip in Northern Ireland: can we do better?

Developmental dysplasia of the hip (DDH) should be diagnosed as early as possible to optimise treatment. The current United Kingdom recommendations for the selective screening of DDH include a clinical examination at birth and at six weeks. In Northern Ireland babies continue to have an assessment by a health visitor at four months of age. As we continue to see late presentations of DDH, beyond one year of age, we hypothesised that a proportion had missed an opportunity for earlier diagnosis. We expect those who presented to our service with Tonnis grade III or IV hips and decreased abduction would have had clinical signs at their earlier assessments. We performed a retrospective review of all patients born in Northern Ireland between 2008 and 2010 who were diagnosed with DDH after their first birthday. There were 75 856 live births during the study period of whom 645 children were treated for DDH (8.5 per 1000). The minimum follow-up of our cohort from birth, to detect late presentation, was four years and six months. Of these, 32 children (33 hips) were diagnosed after their first birthday (0.42 per 1000). With optimum application of our selective screening programme 21 (65.6%) of these children had the potential for an earlier diagnosis, which would have reduced the incidence of late diagnosis to 0.14 per 1000. As we saw a peak in diagnosis between three and five months our findings support the continuation of the four month health visitor check. Our study adds further information to the debate regarding selective versus universal screening.

Does K-wire position in tension band wiring of olecranon fractures affect its complications and removal of metal rate?

BACKGROUND: Despite the recognised complications of migration of wires and soft tissue irritation, tension band wiring (TBW) remains the gold standard for fixation of displaced, minimally comminuted olecranon fractures. There is much variation in placement of the K-wires with current AO guidance stating that each wire should be drilled through the anterior cortex and then backed up by 1 cm. The aim of this study was to examine the effect of K-wire position (intramedullary vs. transcortical) on stability of the construct and significant local complications. METHODS: All patients who underwent TBW for an isolated olecranon fracture in our trauma unit between 1/1/2009 and 31/12/2011 were included in this retrospective study. Mean follow-up was 14 months (range 5-29 months). Data was gathered from medical records and radiographs. The outcome measured was removal of metal due to complications such as wound problems or proximal migration of wires as standard practice within out trauma unit. RESULTS: Sixty-three patients met the inclusion criteria. Forty-seven had an intramedullary compared with 16 with transcortical configuration (ratio 3:1). Nine patients (19%) with intramedullary K-wires required removal of metalwork - seven due to prominent metalwork and two with wound infection. Four patients (25%) with transcortical K-wires required removal of metalwork - three due to prominent metalwork and one with failure of metalwork. There was no significant statistical difference between transcortical and intramedullary K-wire placement with regards to complication rates following tension band wiring of an isolated olecranon fracture requiring removal of metal (Chi squared test with Yates' correction p = 0.89). CONCLUSION: We concluded that we found no difference in complications or metalwork removal rate in the placement of K-wire in tension band wiring for isolated olecranon fracture. We recognise our study was limited by small numbers and is based on the experience of one trauma unit.

Post-injection sciatic neuropathy in a cynomolgus macaque (Macaca fascicularis).

BACKGROUND: Intramuscular injection is a common route parenteral used in primates. METHODS: A cynomolgus macaque was evaluated for acute lameness and atrophy of the left leg with no evidence of trauma. RESULTS: History revealed ketamine injection 12 days prior. CONCLUSIONS: Histologic examination supported traumatic injection neuropathy due to intramuscular injection.

Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis.

In a subset of patients with cystic fibrosis (CF), nonsense mutations (premature stop codons) disrupt production of full-length, functional CF transmembrane conductance regulator (CFTR). Ataluren (PTC124) allows ribosomal readthrough of premature stop codons in mRNA. We evaluated drug activity and safety in patients with nonsense mutation CF who took ataluren three times daily (morning, midday and evening) for 12 weeks at either a lower dose (4, 4 and 8 mg·kg(-1)) or higher dose (10, 10 and 20 mg·kg(-1)). The study enrolled 19 patients (10 males and nine females aged 19-57 yrs; dose: lower 12, higher seven) with a classic CF phenotype, at least one CFTR nonsense mutation allele, and an abnormal nasal total chloride transport. Both ataluren doses were similarly active, improving total chloride transport with a combined mean change of -5.4 mV (p<0.001), and on-treatment responses (at least -5 mV improvement) and hyperpolarisations (values more electrically negative than -5 mV) in 61% (p<0.001) and 56% (p = 0.002) of patients. CFTR function was greater with time and was accompanied by trends toward improvements in pulmonary function and CF-related coughing. Adverse clinical and laboratory findings were uncommon and usually mild. Chronic ataluren administration produced time-dependent improvements in CFTR activity and clinical parameters with generally good tolerability.

Wildlife toxicology: biomarkers of genotoxic exposures at a hazardous waste site.

A large number of hazardous waste sites in the United States have undergone the initial stages of remediation or containment. At many of the remaining sites, the potential for exposure to ecological receptors is a primary concern. This manuscript reports on studies to investigate the impact on ecological receptors exposed to complex mixtures at a former creosote facility. Currently there are isolated areas on-site that were not addressed in the initial removal action that appear to be releasing polycyclic aromatic hydrocarbons (PAHs) to the surrounding environment. The U.S. EPA collected environmental samples and performed ex situ sediment bioassays to measure chronic toxicity; whereas, this study describes an in situ study to measure biomarkers of effect in two ecological receptors. Mosquitofish (Gambusia affinis) and cricket frogs (Acris crepitans) were collected from a small intermittent creek adjacent to the site, and reference stations. A weight-of-evidence ecological risk assessment was completed for the amphibian and fish communities. The ecological risk assessment was developed using analysis of media chemistry, body burden of specific PAHs, bioassay results, community surveys, and cellular genome size variation as a biomarker of genotoxicity. Flow cytometric estimates of chromosomal damage were significantly elevated for both mosquitofish and cricket frogs inhabiting the contaminated site, relative to at least one reference site. Surface water screening values for fish and amphibians exceeded screening values for PAHs by more than one order of magnitude in the on-site creek, and sediment PAH concentrations were extremely high (up to 1,549 microg/dry g). Tissue concentrations of PAHs were below screening values. Media chemistry, bioassay and genotoxicity data all support the same conclusion that on-site PAHs continue to impact aquatic receptors. The genotoxicity findings are consistent with and contribute to results of the weight-of-evidence ecological risk assessment. The results support continuing efforts to incorporate biomarkers as valuable lines of evidence within ecological risk assessment.

Bioreactors for guiding muscle tissue growth and development.

Muscle tissue bioreactors are devices which are employed to guide and monitor the development of engineered muscle tissue. These devices have a modern history that can be traced back more than a century, because the key elements of muscle tissue bioreactors have been studied for a very long time. These include barrier isolation and culture of cells, tissues and organs after isolation from a host organism; the provision of various stimuli intended to promote growth and maintain the muscle, such as electrical and mechanical stimulation; and the provision of a perfusate such as culture media or blood derived substances. An accurate appraisal of our current progress in the development of muscle bioreactors can only be made in the context of the history of this endeavor. Modern efforts tend to focus more upon the use of computer control and the application of mechanical strain as a stimulus, as well as substrate surface modifications to induce cellular organization at the early stages of culture of isolated muscle cells.

Bilateral capacity for speech sound processing in auditory comprehension: evidence from Wada procedures.

Data from lesion studies suggest that the ability to perceive speech sounds, as measured by auditory comprehension tasks, is supported by temporal lobe systems in both the left and right hemisphere. For example, patients with left temporal lobe damage and auditory comprehension deficits (i.e., Wernicke's aphasics), nonetheless comprehend isolated words better than one would expect if their speech perception system had been largely destroyed (70-80% accuracy). Further, when comprehension fails in such patients their errors are more often semantically-based, than-phonemically based. The question addressed by the present study is whether this ability of the right hemisphere to process speech sounds is a result of plastic reorganization following chronic left hemisphere damage, or whether the ability exists in undamaged language systems. We sought to test these possibilities by studying auditory comprehension in acute left versus right hemisphere deactivation during Wada procedures. A series of 20 patients undergoing clinically indicated Wada procedures were asked to listen to an auditorily presented stimulus word, and then point to its matching picture on a card that contained the target picture, a semantic foil, a phonemic foil, and an unrelated foil. This task was performed under three conditions, baseline, during left carotid injection of sodium amytal, and during right carotid injection of sodium amytal. Overall, left hemisphere injection led to a significantly higher error rate than right hemisphere injection. However, consistent with lesion work, the majority (75%) of these errors were semantic in nature. These findings suggest that auditory comprehension deficits are predominantly semantic in nature, even following acute left hemisphere disruption. This, in turn, supports the hypothesis that the right hemisphere is capable of speech sound processing in the intact brain.

Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

Quantitative analysis of the EEG posterior-dominant rhythm in healthy adolescents.

OBJECTIVE: Pivotal studies of the normal EEG posterior-dominant rhythm (PDR) typically relied on visual inspection of a few seconds of EEG data from a relatively small number of subjects in each age category. We sought to analyze and characterize the PDR in a large cohort of healthy 15-year-olds, and to determine if PDR characteristics mature over the following year. METHODS: Seventy-nine healthy 15-year-olds free of neurologic and psychiatric disease underwent a resting-awake EEG, which was repeated 1 year later. In each study, PDR frequency was determined with fast Fourier transform analysis of a continuous 2-min EEG segment. t-Tests were used to compare relevant variables. RESULTS: From age 15 to 16 the mean PDR frequency increased from 9.9 to 10.0Hz, a small but statistically significant difference. The PDR frequency range at both ages was 8.9-11.0Hz, similar to values reported in prior studies on healthy young adults. There was no significant difference in PDR frequency between genders or hemispheres. CONCLUSIONS: Maturation of the PDR is nearly complete at age 16. The frequency range of the PDR in healthy adolescents and adults is substantially narrower than the alpha band. SIGNIFICANCE: Based on this and prior studies, a PDR frequency of less than 8.5 or greater than 11.5Hz should be considered abnormal in adolescents and adults.

A comparison of concentrations of polycyclic aromatic compounds detected in dust samples from various regions of the world.

Settled house dust can be a source of human exposure to toxic polycyclic aromatic hydrocarbons (PAHs) through non-dietary ingestion and dermal contact. Information regarding the concentrations of various contaminants in house dust would be useful in estimating the risk associated with exposure to these compounds. This study reports on the surface loading, variability and distribution of PAHs in settled house dust collected from homes in three locations: Sumgayit, Azerbaijan; Shanxi Province, China; and southern Texas, United States. The highest PAH floor surface loadings were observed in China, followed by Azerbaijan and Texas. Median concentrations of high molecular weight (four ring and larger) PAHs ranged from a low of 0.11 microg/m(2) in Texas, to 2.9 microg/m(2) in Azerbaijan and 162 microg/m(2) in China. These trends in total surface loading and relative carcinogenicity indicate that the risk of health effects from exposure to PAHs in house dust is highest in the Chinese population and lowest in the Texas population. As anticipated, variability among dust samples from different houses within the same region was high, with coefficients of variation greater than 100%. Alkylated PAHs comprised 30-50% of the total mass of PAHs. Based on a comparison of the composition of specific components, PAHs in China and Azerbaijan were determined to be derived mainly from combustion sources rather than from unburned fossil fuels such as petroleum. These results, coupled with ongoing investigation of appropriate PAH exposure biomarkers in humans, will guide future efforts to identify ways to reduce exposures in the study areas.

Genotoxicity of organic extracts of house dust from Shanxi, China.

Indoor combustion of solid fuel such as coal may generate respirable particles containing polycyclic aromatic hydrocarbons (PAH) that may adhere to settled dust. Dust might therefore present a major source of PAH exposure in humans. This study evaluated the in vitro and in vivo genotoxicity of PAH mixtures extracted from house dust samples. Four dust samples (E1-4) were collected from houses in Shanxi, China, where coal is heavily used for heating and cooking. For comparison, a coal sample was also collected from one of the houses and included in the analyses. The samples were extracted with methylene chloride:acetone (95:5 v/v), dried, and redissolved in appropriate solvents for assessment in genotoxicity assays. Samples were evaluated for their ability to induce point mutations in bacteria and DNA adducts in vivo. DNA adduct levels were analyzed by nuclease P1-enhanced 32P-postlabeling. PAH were quantified using gas chromatography/mass spectrometry. Based on chemical analysis, sample E1 had the highest concentration by sampling area of benzo[a]pyrene (BaP) (181 microg/m2) and total PAH (10100 microg/m2). However, based on the microbial genotoxicity assay, sample E3, with the highest carcinogenic PAH/total PAH ratio (26%), produced the greatest number of revertants. In mice, administration of the extract of coal induced more adducts (9.81 adducts per 10(9) nucleotides) than dust extracts. The results of this study confirm the presence of genotoxic chemicals in residential dust. Inhalation of respirable particles containing similar mixtures of PAH represents a cancer risk for humans.

In vitro models for assessing neurotoxicity of mixtures.

Rapid and inexpensive methods are needed to investigate the interactions of complex mixtures. This commentary addresses the use of cell cultures to detect neurotoxicity of simple binary mixtures, which is a first step in the development of such methods. A small number of recent studies from our laboratory are examined. Though such studies are few, they offer guidance for optimizing the value of cell cultures as systems for chemical toxicity screening and mechanistic research. The same issues that apply to in vitro neurotoxicity studies of single agents also apply to the study of mixtures, such as relevance of endpoints tested, biological usefulness and limitations of cell culture models, and relevance of exposures tested. In this commentary we will focus on several aspects of these issues.

Biomonitoring of exposure in farmworker studies.

Although biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process--from study design, to sample collection, to chemical analysis--and with interpreting the resulting data. We present an overview of concepts that should be considered when using biomonitoring or biomonitoring data, assess the current status of biomonitoring, and detail potential advancements in the field that may improve our ability to both collect and interpret biomonitoring data. We discuss issues such as the appropriateness of biomonitoring for a given study, the sampling time frame, temporal variability in biological measurements to nonpersistent chemicals, and the complex issues surrounding data interpretation. In addition, we provide recommendations to improve the utility of biomonitoring in farmworker studies.

Improving treatment response of cognitively impaired veterans with neuropsychological rehabilitation.

This pilot study examined the effect of computerized neuropsychological rehabilitation (NR) on cognitively impaired veterans' behavior while in treatment for polysubstance abuse. A group of 10 veterans participated in a 10-session adjunctive program of NR. This group was rated for length of stay in treatment and behavioral change and participation in treatment. Comparisons were made with a group of nine veterans who were in the standard substance abuse treatment with no adjunctive NR. Mild to moderate neuropsychological impairments were present in both groups in the areas of immediate and delayed memory, prospective memory, problem solving, and visual scanning and tracking. Relative to controls, the group that participated in NR was found to remain in treatment significantly longer and rated as having a better overall attitude in the general treatment program. These data suggest that NR may have positive treatment implications in patients with mild to moderate neuropsychological impairment.

DEHP, bis(2)-ethylhexyl phthalate, alters gene expression in human cells: possible correlation with initiation of fetal developmental abnormalities.

Diethylhexylphthalate (DEHP) is a widely distributed phthalate, to which humans are exposed to due to its variety of commercial and manufacturing uses. As a plasticiser, it is found in a wide number of products, and metabolites of DEHP have been detected in urine samples from a high percentage of the people screened for phthalates. We utilised DNA microarray analysis to evaluate DEHP for gene expression disrupting activity using the human cell line MCF-7, and found that DEHP significantly dysregulated approximately 34% of the 2400 genes spotted on the NEN2400 chip we used. The results suggest that DEHP, a known estrogen agonist and probable androgen antagonist, alters the expression of a number of genes, many of which are critical for fetal development. Down-regulation of two genes, FGD1 and PAFAH1B1, related in that both are essential for fetal brain development, was corroborated using quantitative real time PCR. These studies show DEHP to be a highly effective human gene expression-altering chemical, and that, at appropriate concentrations, it has the possibility of altering fetal central nervous system development, resulting in the birth defects lissencephaly and/or faciodigitogenital dysplasia.

A multi-perspective concept mapping study of problems associated with traumatic brain injury.

OBJECTIVE: To develop a model of the problems of persons with traumatic brain injury that includes multiple perspectives as well as the multi-dimensional nature of the phenomena. DESIGN: Concept mapping, a multi-variate modelling strategy, was employed to produce an exhaustive inventory and concept map of TBI-related problems based on input from patients, family caregivers and professional providers. RESULTS: The eight-cluster concept map included the following dimensions: social competence, intimacy, behavioural, maturity/independence, neurophysiological, mood, executive functions and non-executive functions. CONCLUSIONS: An underlying two-dimensional conceptual model of TBI problems is proposed with relevance for theory, practice and further research.