Does the length of stay in hospital affect healthcare outcomes of patients without COVID-19 who were admitted during the pandemic? A retrospective monocentric study.

Uncertainties remain if changes to hospital care during the coronavirus disease (COVID-19) pandemic had an adverse impact on the care-quality of non-COVID-19 patients. We examined the association of hospital length of stay (LOS) with healthcare quality indicators in patients admitted with general medical conditions (non-COVID-19). In this retrospective monocentric study at a National Health Service hospital (Surrey), data were collected from 1st April 2019 to 31st March 2021, including the pandemic from 1st March 2020. Primary admissions, in-hospital mortality, post-discharge readmission and mortality were compared between the pre-pandemic (reference group) and pandemic period, according to LOS categories. There were 10,173 (47.7% men) from the pre-pandemic and 11,019 (47.5% men) from the pandemic period; mean (SD) age 68.3 year (20.0) and 68.3 year (19.6), respectively. During the pandemic, primary admission rates for acute cardiac conditions, pulmonary embolism, cerebrovascular accident and malignancy were higher, whilst admission rates for respiratory diseases and common age-related infections, and in-hospital mortality rates were lower. Amongst 19,721 survivors, sex distribution and underlying health status did not significantly differ between admissions before the pandemic and during wave-1 and wave-2 of the pandemic. Readmission rates did not differ between pre-pandemic and pandemic groups within the LOS categories of < 7 and 7-14 days, but were lower for the pandemic group who stayed > 14 days. For patients who died within seven days of admission, in-hospital mortality rates were lower in patients admitted during the pandemic. Mortality rates within 30 days of discharge did not differ between pre-pandemic and pandemic groups, irrespective of the initial hospital LOS. Despite higher rates of admission for serious conditions during the pandemic, in-hospital mortality was lower. Discharge time was similar to that for patients admitted before the pandemic, except it was earlier during the pandemic for those who stayed > 14 days, There were no group differences in quality-care outcomes.

Comparison of characteristics and outcomes of patients admitted to hospital with COVID-19 during wave 1 and wave 2 of the current pandemic.

In this study of patients admitted with COVID-19, we examined differences between the two waves in patient characteristics and outcomes. Data were collected from the first COVID-19 admission to the end of study (01/03/2020-31/03/2021). Data were adjusted for age and sex and presented as odds ratios (OR) with 95% confidence intervals (CI). Among 12,471 admissions, 1452 (11.6%) patients were diagnosed with COVID-19. On admission, the mean (± SD) age of patients with other causes was 68.3 years (± 19.8) and those with COVID-19 in wave 1 was 69.4 years (± 18.0) and wave 2 was 66.2 years (± 18.4). Corresponding ages at discharge were 67.5 years (± 19.7), 63.9 years (± 18.0) and 62.4 years (± 18.0). The highest proportion of total admissions was among the oldest group (≥ 80 years) in wave 1 (35.0%). When compared with patients admitted with other causes, those admitted with COVID-19 in wave 1 and in wave 2 were more frequent in the 40-59 year band: 20.8, 24.6 and 30.0%; consisted of more male patients: 47.5, 57.6 and 58.8%; and a high LACE (Length of stay, Acuity of admission, Comorbidity and Emergency department visits) index (score ≥ 10): 39.4, 61.3 and 50.3%. Compared to wave-2 patients, those admitted in wave 1 had greater risk of death in hospital: OR = 1.58 (1.18-2.12) and within 30 days of discharge: OR = 2.91 (1.40-6.04). Survivors of COVID-19 in wave 1 stayed longer in hospital (median = 6.5 days; interquartile range = 2.9-12.0) as compared to survivors from wave 2 (4.5 days; interquartile range = 1.9-8.7). Patient characteristics differed significantly between the two waves of COVID-19 pandemic. There was an improvement in outcomes in wave 2, including shorter length of stay in hospital and reduction of mortality.

Changes in antibiotic use following implementation of a telehealth stewardship pilot program.

Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.

An Alternative In Vitro Method for Examining Nanoparticle-Induced Cytotoxicity.

Conventional in vitro assays are often used as initial screens to identify potential toxic effects of nanoparticles (NPs). However, many NPs have shown interference with conventional in vitro assays, resulting in either false-positive or -negative outcomes. Here, we report an alternative method for the in vitro assessment of NP-induced cytotoxicity utilizing Fluoro-Jade C (FJ-C). To provide proof of concept and initial validation data, Ag-NPs and Au-NPs were tested in 3 different cell cultures including rat brain microvessel endothelial cells, mouse neural stem cells, and the human SH-SY5Y cell line. Conventional 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase (LDH) assays were run in parallel with the new method and served as references. The results demonstrate for the first time that FJ-C labeling can be a useful tool for assessing NP-induced cytotoxicity in vitro. Using these approaches, it was also demonstrated that removal of Ag-NPs-while keeping the Ag-ions that were released from the Ag-NPs in culture media-abolished the measured cytotoxicity, indicating that Ag-NPs rather than Ag-ions in solution contributed to the observed cytotoxic effects. Further, co-treatment of Ag-NPs with N-acetyl cysteine (NAC) prevented the observed cytotoxicity, suggesting a protective role of NAC in Ag-NP-induced cytotoxicity. Thus, this alternative in vitro assay is well suited for identify potential cytotoxicity associated with exposure to NPs.

A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys.

BACKGROUND: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. METHODS: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing. RESULTS: With the exception of serum myoglobin, there were no statistical differences or apparent dose-response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P = .0006). CONCLUSIONS: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.

Effects of iron oxide nanoparticles on biological responses and MR imaging properties in human mammary healthy and breast cancer epithelial cells.

Superparamagnetic iron oxide nanoparticles (SPIONs, diameters >50 nm) have received great attention due to their promising use as magnetic resonance imaging (MRI) contrast agents. In this study, we evaluated the cellular uptake and biological responses in vitro of ultrasmall SPIONs (USPIONs, diameters < 50 nm). We compared the cellular responses between breast epithelia isolated from healthy and breast cancer donors after exposure to carboxy-terminated USPIONs (10 and 30 nm PEG-coated, 10 and 30 nm non-PEG-coated). The particles were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and gel electrophoresis. Cellular interactions with USPIONs were assessed by confocal microscopy and TEM. Cellular uptake of USPIONs was quantified using ICP-MS. Cell viability was measured by MTT and neutral red uptake assays. T2* weighted MRI scans were performed using a 7T scanner. Results demonstrated that cell association/internalization of USPIONs was size- and surface coating-dependent (PEG vs. non-PEG), and higher cellular uptake of 10 and 30 nm non-coated particles was observed in both cell types compared with PEG-coated particles. Cell uptake for 10 and 30 nm non-coated particles was higher in cancer cells from two of three tested donors compared to healthy cells from three donors. There was no significant cytotoxicity observed for all tested particles. Significantly enhanced MRI contrast was observed following exposure to 10 and 30 nm non-coated particles compared to PEG-coated particles in both cell types. In comparison, cancer cells showed more enhanced MRI signals when compared to normal cells. The data indicate that cell responses following exposure to USPIONs are dependent on particle properties. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1032-1042, 2016.

Iron Oxide Nanoparticles Induce Dopaminergic Damage: In vitro Pathways and In Vivo Imaging Reveals Mechanism of Neuronal Damage.

Various iron-oxide nanoparticles have been in use for a long time as therapeutic and imaging agents and for supplemental delivery in cases of iron-deficiency. While all of these products have a specified size range of ∼ 40 nm and above, efforts are underway to produce smaller particles, down to ∼ 1 nm. Here, we show that after a 24-h exposure of SHSY-5Y human neuroblastoma cells to 10 µg/ml of 10 and 30 nm ferric oxide nanoparticles (Fe-NPs), cellular dopamine content was depleted by 68 and 52 %, respectively. Increases in activated tyrosine kinase c-Abl, a molecular switch induced by oxidative stress, and neuronal α-synuclein expression, a protein marker associated with neuronal injury, were also observed (55 and 38 % percent increases, respectively). Inhibition of cell-proliferation, significant reductions in the number of active mitochondria, and a dose-dependent increase in reactive oxygen species (ROS) were observed in neuronal cells. Additionally, using a rat in vitro blood-brain barrier (BBB) model, a dose-dependent increase in ROS accompanied by increased fluorescein efflux demonstrated compromised BBB integrity. To assess translational implications, in vivo Fe-NP-induced neurotoxicity was determined using in vivo MRI and post-mortem neurochemical and neuropathological correlates in adult male rats after exposure to 50 mg/kg of 10 nm Fe-NPs. Significant decrease in T 2 values was observed. Dynamic observations suggested transfer and retention of Fe-NPs from brain vasculature into brain ventricles. A significant decrease in striatal dopamine and its metabolites was also observed, and neuropathological correlates provided additional evidence of significant nerve cell body and dopaminergic terminal damage as well as damage to neuronal vasculature after exposure to 10 nm Fe-NPs. These data demonstrate a neurotoxic potential of very small size iron nanoparticles and suggest that use of these ferric oxide nanoparticles may result in neurotoxicity, thereby limiting their clinical application.

PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments.

Robo-Slit and Plexin-Semaphorin signaling participate in various developmental and pathogenic processes. During commissural axon guidance in the spinal cord, chemorepulsion by Semaphorin3B and Slits controls midline crossing. Slit processing generates an N-terminal fragment (SlitN) that binds to Robo1 and Robo2 receptors and mediates Slit repulsive activity, as well as a C-terminal fragment (SlitC) with an unknown receptor and bioactivity. We identified PlexinA1 as a Slit receptor and found that it binds the C-terminal Slit fragment specifically and transduces a SlitC signal independently of the Robos and the Neuropilins. PlexinA1-SlitC complexes are detected in spinal cord extracts, and ex vivo, SlitC binding to PlexinA1 elicits a repulsive commissural response. Analysis of various ligand and receptor knockout mice shows that PlexinA1-Slit and Robo-Slit signaling have complementary roles during commissural axon guidance. Thus, PlexinA1 mediates both Semaphorin and Slit signaling, and Slit processing generates two active fragments, each exerting distinct effects through specific receptors.

Silver nanoparticles decrease body weight and locomotor activity in adult male rats.

Silver nanoparticles (Ag-NPs) are widely used in FDA regulated products. The physical-chemical properties of Ag-NPs are characterized using various instruments. The dose-dependent activity and body weight alterations are evaluated after rats were exposed to Ag nanoparticles, suggesting a major human health risk, given the wide application of silver nanomaterials.

The use of fixed appliances in the UK: a survey of specialist orthodontists.

OBJECTIVE: To investigate the use of fixed appliances in the UK. DESIGN: Prospective postal questionnaire. SETTING: UK. PARTICIPANTS: All members of the General Dental Council Specialist List in Orthodontics still in active practice and not in training posts. METHOD: A preemptive letter of explanation was sent inviting orthodontists to participate in the survey. The questionnaire was subsequently posted to 935 specialists. Data analysis investigated differences in clinical practice related to varying provider groups, level of operator experience and geographical region. RESULTS: The response rate achieved was 66.3%. A majority of orthodontists routinely used the 0.022 inch pre-adjusted edgewise system, standard size Siamese pattern stainless steel brackets, conventionally ligated and bonded using standard etch and light cured composite. Nickel titanium and stainless steel were the most popular archwire materials. Anchorage was supported routinely by palatal and lingual arches in up to 25% and by headgear in over a third of respondents. Newer innovations showed variable popularity. Self-etching primer was used routinely by one-third of respondents with 11% use of self-ligating brackets. Banding of first molars was preferred by over 60% of clinicians. Bone screw implants were used by only 0.2% of respondents. Clinicians with less than 10 years experience used more headgear, light curing, MBT prescription and molar bonding. Operators with over 20 years experience used more chemically cured bonding, Roth prescription, banded first molars, 0.018 inch slot size and Tip-Edge(TM), with less use of headgear. Fixed appliance use differed from that reported in the US with lower use in the UK of standard edgewise and Roth systems, aesthetic, miniaturised and 0.018 inch slot brackets and rapid maxillary expansion. CONCLUSION: Most UK orthodontic specialists routinely used the 0.022 inch pre-adjusted edgewise system with standard size Siamese steel brackets bonded using standard etch and light cured composite with conventional ligation. Variations were seen between different provider groups, types of treatment funding, levels of operator seniority and geographical regions. Differences were noted particularly in the use of bracket prescription and design, types of molar attachment and anchorage control.

Post-infectious bronchiolitis obliterans: can CT scan findings at early age anticipate lung function?

BACKGROUND: The image findings of post-infectious bronchiolitis obliterans (PIBO) have been described, however, we do not know if such findings can predict lung function (LF) deterioration with increasing patient age. AIM: To assess whether computed tomography (CT) abnormalities detected at an early stage of the disease can anticipate abnormal LF a decade later in children with PIBO. METHODS: We compared CT scans of 21 children with PIBO, done within their first 3 years of life, and their actual LF. To evaluate CT scans we used a modified Bhalla score and, for LF, FEV1 as percentage of predicted values. We calculated prevalence ratios (PRs) by comparing the proportion of patients with worst CT score and worst LF, with the proportion of those with best CT score and worst LF. RESULTS: PR was 1.17 (CI 1.02; 1.34, P = 0.02). CONCLUSIONS: The CT finding early in the life of children with PIBO, when assessed by the Bhalla, score seem to anticipate future LF status.

Risk assessment of pneumothorax and pulmonary haemorrhage complicating percutaneous co-axial cutting needle lung biopsy.

INTRODUCTION: The primary aim of this study was to evaluate the ability of radiologists to accurately estimate pneumothorax and pulmonary haemorrhage during percutaneous co-axial cutting needle CT-guided lung biopsy. METHODOLOGY: Patients undergoing cutting needle lung biopsy during the study period were identified; the path taken by the cutting needle marked on each pre-biopsy staging CT scan. Each scan was then reviewed independently by two thoracic radiologists blinded to clinical details and complications; pneumothorax and pulmonary haemorrhage risk estimated with a percentage Visual Analogue Scale. RESULTS: In 134 patients, pneumothorax occurred in 24%. The radiologists differed in the estimation of pneumothorax risk in 55% (74 episodes). When pneumothorax risk was estimated <20% by radiologists 1 and 2, 16% and 14% of biopsies resulted in pneumothorax; where risk was estimated at 20-49%, pneumothorax incidence rose to 33% and 31%; where risk was deemed > or =50%, pneumothorax rate was 87% and 100%. Pulmonary haemorrhage occurred in 4%; estimated haemorrhage risk for biopsies complicated by haemorrhage did not differ significantly from where haemorrhage did not occur. CONCLUSION: Radiologists differ markedly in the estimation of pneumothorax risk for a patient undergoing co-axial lung biopsy. Identifying individual patients developing pneumothorax was only possible when risk was estimated at > or =50%. Pulmonary haemorrhage was uncommon and difficult to predict accurately.

T cell responses in dengue hemorrhagic fever: are cross-reactive T cells suboptimal?

Dengue virus infection poses a growing public health and economic burden in a number of tropical and subtropical countries. Dengue circulates as a number of quasispecies, which can be divided by serology into four groups or serotypes. An interesting feature of Dengue, recognized over five decades ago, is that most severe cases that show hemorrhagic fever are not suffering from a primary infection. Instead, they are reinfected with a virus of different serotype. This observation poses considerable problems in vaccine design, and it is therefore imperative to gain a full understanding of the mechanisms underlying this immunological enhancement of disease. In this study, we examined a T cell epitope restricted by HLA-A*24, a major MHC class I allele, in Southeast Asia in a cohort of children admitted to a hospital with acute Dengue infection. The cytokine profiles and the degranulation capacity of T cells generated to this epitope are defined and compared across different viral serotypes. Cross-reactive Dengue-specific T cells seem to show suboptimal degranulation but high cytokine production, which may contribute to the development of the vascular leak characteristic of Dengue hemorrhagic fever.

Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH.

Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5p15. We have identified a mutation in the ANKH gene that segregates with the disease in a family with this condition. ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of ANKH causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition.