Time-dependent Treatment Research Articles

Non-seasonal and seasonal relapse model for Q fever disease with comprehensive cost-effectiveness analysis

Q fever (query fever) is classified as one of the likely zoonosis that is transmissible to humans from farm animals. The disease may lead to significant economic losses to livestock owners. The deterministic dynamics of direct transmission, different shedding rates, treatment, the effect of relapse, and seasonality of disease remains an open problem. Therefore, this study introduces direct transmission cycle, different shedding rates, treatment, the effect of relapse, and time-dependent parameters. We obtain control reproduction expressions for the model under different scenarios. Using Lyapunov functions, we establish that the non-seasonal model is globally asymptotically stable. The extension of the model to include seasonal trends shows that there exists a positive periodic solution. The global sensitivity method used shows that imperfect treatment reduces the rate of indirect transmission, but, leads to an increase in direct transmission by symptomatic cattle herds. Optimal control model is also utilized to explore the impact of time-dependent treatment, disinfectant, and separate facilities for animal birthing. We show the control efficacies; and also calculated the average cost-effectiveness ratio, and the incremental cost-effectiveness ratio. We hope that this study further enlightens farm owners on the use of other interventions in controlling Q fever disease in livestock.

Progesterone induces apoptosis by activation of caspase-8 and calcitriol via activation of caspase-9 pathways in ovarian and endometrial cancer cells in vitro

Previously we have shown inhibition of endometrial cancer cell growth with progesterone and calcitriol. However, the mechanisms by which the two agents attenuate proliferation have not been well characterized yet. Herein, we investigated how progesterone and calcitriol induce apoptosis in cancer cells. DNA fragmentation was upregulated by progesterone and calcitriol in ovarian and endometrial cancer cells. Time-dependent treatment of ovarian cancer cells, ES-2, and TOV-21G with progesterone enhanced caspase -8 activity after 12h, whereas OV-90, TOV-112D, HEC-1A, and HEC-59 cells showed increased activity after 24h. Caspase 9 activity was increased in all cell lines after 24h treatment with calcitriol. Pretreatment of cancer cells with a caspase-8 inhibitor (z-IETD-fmk) or caspase-9 inhibitor (Z-LEHD-fmk) significantly attenuated progesterone and calcitriol induced caspase-8 and caspase-9 expression, respectively. The expression of FasL, Fas, FAD, and pro-caspase-8, which constitute the death-inducing signaling complex (DISC), was upregulated in progesterone treated cancer cells. Knockdown of FAS or FADD with specific siRNAs significantly blocked progesterone-induced caspase-8. Cleavage of the BID was not affected by caspase-8 activation suggesting the absence of cross-talk between caspase-8 and caspase-9 pathways. Calcitriol treatment decreased mitochondrial membrane potential and increased the release of cancer cytochrome C. These findings indicate that progesterone induces apoptosis through activation of caspase-8 and calcitriol through caspase-9 activation in cancer cells. A combination of progesterone-calcitriol activates both extrinsic and intrinsic apoptotic pathways in cancer cells.

Slump in Hospital Admissions for Stroke, a Fact of an Uncertain Nature That Requires Explanation.

(1) Background: The impact of the health crisis caused by coronavirus disease 2019 (COVID-19) has provoked collateral effects in the attention to pathologies with time-dependent treatments such as strokes. We compare the healthcare activity of two stroke units in the same periods of 2019 and 2020, with an emphasis on what happened during the state of alarm (SA). (2) Materials and methods. Hospitals in the region implemented contingency plans to contain the pandemic; in this planning, the stroke units were not limited in their operational capacity. The SA was declared on 15 March and remained in place for 10 weeks. For the analysis, the data were grouped by consecutive calendar weeks. (3) Results. When the SA was declared the number of calls to the emergency telephone went from 1225 to 3908 calls per week (318% increase). However, the activation of the stroke code went from 6.6 to 5.0 (p = 0.04) and the activity in both stroke units decreased. The largest drop in hospitalizations was for transient ischemic attacks (TIAs) with 35.7% less, 28 vs. 18, (p = 0.05). Reperfusion therapies fell by 37.5%; Poisson regression model 0.64; (95% confidence interval (CI), 0.43–0.95). The overall activity of the telestroke suffered a reduction of 28.9%. We also observed an increase in hospital mortality. (4) Conclusion. The excessive duration of the pandemic precludes any hope of resolving this public health crisis in the short or medium term. Further studies should be conducted to better understand the multifactorial nature of this dramatic decline in stroke admissions and its negative impact.

Hub-and-spoke model for thrombectomy service in UK NHS practice

Mechanical thrombectomy is a highly effective but time dependent treatment for acute ischaemic stroke due to large vessel occlusion. In the UK, the national clinical guidelines for stroke and National Institute for Health and Care Excellence guidance endorses thrombectomy as an acute stroke treatment, and NHS England commissioned thrombectomy services. However, there are no UK 'real-world' data to verify the efficacy of the hub-and-spoke model in thrombectomy. There are currently 24 tertiary neuroscience centres in the UK that can provide thrombectomy treatment and many of these operate only within working hours. This study is the first to demonstrate that a hub-and-spoke thrombectomy service in routine UK 24/7 clinical practice is as effective and safe as in the setting of randomised controlled clinical trials. However, there are 9.3% of patients accepted for transfer to the thrombectomy centre who did not proceed to thrombectomy, mostly due to delays. Fifty-three per cent of thrombectomy cases were performed outside of standard working hours when transfer delays were increased. A 24/7 thrombectomy service is needed to maximise the benefit to all suitable patients. Measures, including improving workflow and optimising work forces, are needed to minimise the delays and continue to improve the service.

Estimating the impact of antiretroviral therapy on HIV-TB co-infection: Optimal strategy prediction

In this paper, a nonlinear population model for HIV-TB co-infection has been proposed. The model is incorporated with the effect of early and late initiation of HIV treatment in co-infectives already on TB treatment, on the occurrence of Immune Reconstitution Inflammatory syndrome (IRIS). A 15-dimensional (15D) mathematical model has been developed in this study. We begin with considering constant treatment rates and thereafter, proceed to time-dependent treatment rates for co-infectives as control parameters. The basic reproduction number, a threshold quantity, corresponding to each HIV and TB sub-model has been computed in case of constant controls. With constant values of control parameters, mathematical analysis shows the existence and local stability of the disease-free equilibrium point and the endemic equilibrium point for the model. Together with time-dependent parameters, an optimal control problem is introduced and solved using Pontryagin’s maximum principle with an objective to minimize the number of infectives and disease induced deaths along with the cost of treatment. Numerical simulations are performed to examine the effect of reproduction numbers on control profiles and to identify, the ideal combination of treatment strategies which provides minimum burden on a society. Numerical results imply that if both HIV and TB are endemic in the population, then in order to bring in minimum burden from the co-infection, optimal control efforts must be enforced rather than constant treatment rate.

CD44 expression changes in MDA-MB-231 cell line of breast cancer after exposure to 2-D clinorotation

Studies have shown that simulated microgravity (SMG) affects tumor cell growth and metastasis. However, the underlying molecular basis is still not known. In recent years, due to the high expression of CD44 in invasive basal breast tumors, it has been the subject of many studies. The aim of present study was to investigate the gene expression of CD44 in MDA-MB-231cell line of breast cancer in microgravity conditioncell line was proliferated under normal gravity and microgravity (1 and 3 days) using 2-D clinostat. Gene expression was measured using real-time PCR technique. SMG increased gene expression (100%) after 1 day and decreased it (15%) during 3 days in comparison to the control samples. It seems that the response of cancer cells to microgravity is time dependent and simulated microgravity treatment for 3 days may have a positive effect on cancer characteristics of MDA-MB-231 cell line in order to decrease the expression of CD44.

Unsynchronized wearable sensor data analytics model for improving the performance of smart healthcare systems

A wearable sensor (WS) is a prominent technology application that senses and gathers information from a user for analyzing changes in physiological signs. Analyzing the physiological sign differences enables the better healthcare solutions. This paper introduces an unsynchronized sensor data analytics (USDA) model for the effective handling of wearable device data regardless of the time factor. Time-dependent healthcare treatments and diagnosis are the themes on which this analytics model focuses. The gathered WS data is classified depending on the time factor and data frequency of occurrence. This occurrence frequency is correlatively analyzed using the diagnosis module to identify defects and to fulfill the missing sensor data consideration. Healthcare diagnoses requiring immediate responses and timely solutions for patients/end-users rely on this model for uncompromising analysis. The vital changes in WS data and time factors are analyzed using sophisticated machine learning methods for previous diagnosis correlation and effective accuracy. Responsive healthcare solutions using unsynchronized WS data help to achieve better efficiency and reduce complications in assessing the performance of the healthcare systems.

Safety and Efficacy of Outpatient Surgical Procedures for the Treatment of Benign Prostatic Enlargement in New York State and California (2005-2016).

We compared outcomes of transurethral prostatectomy and laser prostatectomy in a real-world setting. We present a prospectively collected observational cohort study of 85,682 men with benign prostatic enlargement in New York State and California who received transurethral prostatectomy or laser prostatectomy in outpatient and ambulatory surgery settings from January 2005 to December 2016. We used propensity score matching to adjust for differences in patient characteristics between groups. We analyzed short-term outcomes using mixed-effect logistic regressions and long-term outcomes using Cox regressions with a time-dependent treatment variable to account for nonproportionality. We performed a sensitivity analysis using multivariable regression models. Mean±SD patient age was 70.5±9.7 years, 71% of patients were White, and median followup was 3.8 years (IQR 1.8-6.3). Transurethral prostatectomy recipients had increased risk of 30-day hospital readmission/emergency room visit (OR 1.09, 95% CI 1.04-1.13, p <0.001) and decreased risk of reoperation (HR 0.81, 95% CI 0.76-0.88, p <0.001). Transurethral prostatectomy had a higher rate of urethral stricture (HR 1.47, 95% CI 1.22-1.75, p <0.001). Transurethral prostatectomy was associated with higher risk of short and long-term complications but a lower rate of long-term reoperation than laser prostatectomy for benign prostatic enlargement.

Effect of Early Central Venous Catheterization on Mortality Among Patients with Severe Sepsis: A Nationwide Inpatient Database Study.

Clinical guidelines for the management of sepsis have accelerated the utilization of central venous catheterization (CVC). However, risks associated with CVC may be high in the initial phase of severe sepsis because of patient instability. The timing of CVC itself has not been fully evaluated. Therefore, we aimed to assess the association between CVC in the initial care of patients with severe sepsis and corresponding mortality rates. We conducted a nationwide retrospective analysis using the Japanese Diagnosis Procedure Combination database from April 1, 2014 to March 31, 2016. We identified patients who received CVC within 30 days from hospital admission. We compared the 30-day mortality between two groups: patients who received CVC within 2 days (early) after admission and those who received CVC 3 or more days (delayed) after admission, using marginal structural models with inverse probability treatment weighting. We identified 6,028 eligible patients from 911 hospitals among 27,497 patients with severe sepsis for this study; 4,544 (75.4%) received early CVC. Patients with early CVC had poor prognostic baselines and received more intense treatment than patients with delayed CVC. After adjusting for baseline and time-dependent treatment variables, we found that there were no significant differences between patients who received CVC within 2 days after admission and those who received CVC 3 or more days after admission (hazard ratio 0.83, 95% confidence interval 0.62-1.10). Among patients with severe sepsis, early CVC was not associated with improved in-hospital mortality rates.

Stroke care in Italy at the time of the COVID-19 pandemic: a lesson to learn.

From March to May 2020, the Italian health care system, as many others, was almost entirely devoted to the fight against the COVID-19 pandemic. In this context, a number of questions arose, from the increased stroke risk due to COVID-19 infection to the quality of stroke patient care. The overwhelming need of COVID-19 patient management made mandatory a complete re-organization of the stroke pathways: many health professionals were reallocated and a number of stroke units was turned into COVID-19 wards. As a result, acute stroke care suffered from a shortage of services and delays in time-dependent treatments and diagnostic work-up. In-patient and out-patient care and rehabilitation facilities for stroke survivors were also reduced or slowed down, to direct resources to COVID-19 patients care and to reduce contagion risks. Overall, this is likely to result in a significant future increased burden of complications and disabilities that will impact the health care systems in the coming months. Thus, while still fighting against COVID-19 disease, authorities need to promptly implement robust action plans, including an increase of workforce, without forgetting the assurance of a high level of stroke care. The medical community and the health care administrators should always keep in mind that stroke was before, and will be after the pandemic, a, sometimes, life-threatening condition, and almost always a disease with a severe impact on the quality of life.

Nested g-computation: A causal approach to analysis of censored medical costs in the presence of time-varying treatment.

Rising medical costs are an emerging challenge in policy decisions and resource allocation planning. When cumulative medical cost is the outcome, right-censoring induces informative missingness due to heterogeneity in cost accumulation rates across subjects. Inverse-weighting approaches have been developed to address the challenge of informative cost trajectories in mean cost estimation, though these approaches generally ignore post-baseline treatment changes. In post-hysterectomy endometrial cancer patients, data from a linked database of Medicare records and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute reveal substantial within-subject variation in treatment over time. In such a setting, the utility of existing intent-to-treat approaches is generally limited. Estimates of population mean cost under a hypothetical time-varying treatment regime can better assist with resource allocation when planning for a treatment policy change; such estimates must inherently take time-dependent treatment and confounding into account. In this paper, we develop a nested g-computation approach to cost analysis to address this challenge, while accounting for censoring. We develop a procedure to evaluate sensitivity to departures from baseline treatment ignorability. We further conduct a variety of simulations and apply our nested g-computation procedure to two-year costs from endometrial cancer patients.

Promising anti-sickling and fetal hemoglobin inducing effects of Boerhavia diffusa root extract on sickle cell erythrocytes

Sickle cell disease (SCD) is a genetic blood disorder and currently available drugs are ineffective and come with numerous side effects B. diffusa has been reported as an important herb in the ayurvedic texts. Although studies have shown immunomodulatory and anti-inflammation activities, the anti-sickling activity and fetal hemoglobin (HbF) inducing potential of Boerhavia diffusa have not yet been explored. Therefore, the present study was aimed to assess anti-sickling and HbF induction effects of B. diffusa aqueous root extract in sickle cell erythrocytes obtained from SCD patients. The in vitro anti-sickling activity of the extract was evaluated microscopically via the Emmel Test. The HbF inducing activity of the extract was determined on SCD erythrocytes through HPLC. The different doses and time-dependent treatments of the test extract and drug control (hydroxyurea) suggested that 30 mg/mL extract for 60 min exerts significant anti-sickling effect on SCD erythrocytes compared to the negative control (P < 0.0001). The anti-sickling activity of test extract was comparable to hydroxyurea. Moreover, the test extract showed significant increased HbF% in SCD patients’ erythrocytes at 30 mg/mL concentration for 120 min compared to negative control (P < 0.0001). The test extract showed similar HbF inducing potential when compared to hydroxyurea. In addition, the percentage of sickling was remarkably reduced with treatment of test extract in both severe and less severe SCD groups compared to negative control. The test extract and hydroxyurea were found to have similar anti-sickling effects irrespective of the severity of the disease. Overall, these results show for the first time the potent anti-sickling and HbF inducing activity of aqueous root extract of Boerhaviadiffusa, which may be used as an herb-based alternative therapy in SCD patients, warranting future in vivo studies.

Abstract 4707: Long noncoding RNA FER1L4 is a novel p73 transcriptional target and inhibits colon cancer cell migration and invasion in a p73-dependent manner

Abstract p73 is a member of the p53 tumor suppressor family, which transactivates p53-responsive genes and mediates DNA damage response. Recent evidences suggest that p73 exerts its tumor suppressor functions by suppressing metastasis, but the exact mechanism remains unknown. It is increasingly evident that long non-coding RNAs (lncRNAs) play a significant role in tumor suppression. However, we still have a limited knowledge of the clinical significance of lncRNAs in colorectal cancer. The present study is aimed to identify novel lncRNAs that play a role in p73-mediated suppression of metastasis in colorectal cancer cells. p73 was knocked down in HCT116p53−/−p73+/+ cells and transcriptome analysis was performed to detect the differentially expressed lncRNAs in presence and absence of p73. The top two up-regulated and down-regulated lncRNAs were selected for further analysis based on the false discovery rate (FDR), fold-change (FC) and P-values. Out of these, FER1L4 lncRNA was found to be significantly induced by DNA damage in a p73-dependent manner. Through bioinformatics analysis, we identified two p73-binding sites in FER1L4 promoter. Consistent with this, p73 binding to FER1L4 promoter was confirmed through luciferase reporter assays and Chromatin Immunoprecipitation (ChIP) assays. Site-directed mutagenesis of both the binding sites totally abrogated p73 responsiveness, indicating that both the sites are equally responsible and essential for p73 binding. In addition, Real-time quantitative PCR demonstrated a rapid increase in endogenous FER1L4 mRNA upon induction of p73. Furthermore, knockdown of FER1L4 and p73 significantly increased the invasion and migration rate of colorectal cancer cells as confirmed by wound-healing assay. Also, knockdown of FER1L4 decreased the expression of E-cadherin, a cancer metastasis suppressor, and increased the expression of other prominent EMT markers such as N-cadherin, Snail, Vimentin and Fibronectin. Cell functional assays further revealed that FER1L4 causes a G2/M cell cycle arrest in a p73-dependent manner in HCT116p53−/−p73+/+ colon cancer cells and upon FER1L4kd, normal cell cycle progression was observed. Annexin V/PI and TUNEL apoptosis assays revealed that FER1L4 induced apoptosis in HCT116p53−/−p73+/+ colon cancer cells with increase in time-dependent treatment of etoposide and FER1L4kd inhibited apoptosis even in the presence of p73. The protein expression level of several pro-apoptotic genes such as Bad, Bax, Bik, Bim, BID, Bak and PUMA decreased upon FER1L4kd and p73kd, confirming that FER1L4 plays a role in p73-mediated apoptosis and cell cycle arrest. Taken together, we provide evidence that FER1L4 is a direct transcriptional target of p73 and p73 exerts its anti-metastatic function by inducing the expression of FER1L4 in response to genotoxic stress. Citation Format: Apoorva Uboveja, Yatendra Kumar Satija, Chanchal Bareja, Daman Saluja. Long noncoding RNA FER1L4 is a novel p73 transcriptional target and inhibits colon cancer cell migration and invasion in a p73-dependent manner [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4707.

Lifting the core-collapse supernova bounds on keV-mass sterile neutrinos

We explore the energy and entropy transport as well as the lepton number variation induced from the mixing between electron and sterile neutrinos with keV mass in the supernova core. We develop a radial- and time-dependent treatment of the νs-νe mixing, by including ordinary matter effects, reconversions between sterile and electron antineutrinos, as well as the collisional production of sterile particles for the first time. The dynamical feedback due to the production of sterile particles on the composition and thermodynamic properties of the core only leads to major implications for the supernova physics for large mixing angles (sin2 2θ ≳ 10−10). Our findings suggest that a self-consistent appraisal of the electron-sterile conversion physics in the supernova core would relax the bounds on the sterile neutrino mixing parameters reported in the literature for sin2 2θ ≲ 10−6, leaving the (ms, sin2 2θ) parameter space relevant to dark matter searches unconstrained by supernovae.

Thermalization of large energy release in the early Universe

ABSTRACT Spectral distortions of the cosmic microwave background (CMB) provide a unique tool for learning about the early phases of cosmic history, reaching deep into the primordial Universe. At redshifts z ≲ 106, thermalization processes become inefficient and existing limits from COBE/FIRAS imply that no more than Δρ/ρ ≲ 6 × 10−5 ($95{{\ \rm per\ cent}}$ c.l.) of energy could have been injected into the CMB. However, at higher redshifts, when thermalization is efficient, the constraint weakens and Δρ/ρ ≃ 0.01−0.1 could in principle have occurred. Existing computations for the evolution of distortions commonly assume Δρ/ρ ≪ 1 and thus become inaccurate in this case. Similarly, relativistic temperature corrections become relevant for large energy release, but have previously not been modelled as carefully. Here, we study the evolution of distortions and the thermalization process after single large energy release at z ≳ 105. We show that for large distortions the thermalization efficiency is significantly reduced and that the distortion visibility is sizeable to much earlier times. This tightens spectral distortions constraints on low-mass primordial black holes with masses $M_{\rm PBH}\lesssim 2 \times 10^{11}\, {\rm g}$. Similarly, distortion limits on the amplitude of the small-scale curvature power spectrum at wavenumbers $k\gtrsim 10^4\, {\rm Mpc}^{-1}$ and short-lived decaying particles with lifetimes $t_X\lesssim 10^7\, {\rm s}$ are tightened, however, these still require a more detailed time-dependent treatment. We also briefly discuss the constraints from measurements of the effective number of relativistic degrees of freedom and light element abundances and how these complement spectral distortion limits.

Mesenchymal Stem Cell–Derived Exosomes Improve Functional Recovery in Rats After Traumatic Brain Injury: A Dose-Response and Therapeutic Window Study

Background. Mesenchymal stem cell (MSC)-derived exosomes play a critical role in regenerative medicine. Objective. To determine the dose- and time-dependent efficacy of exosomes for treatment of traumatic brain injury (TBI). Methods. Male rats were subjected to a unilateral moderate cortical contusion. In the dose-response study, animals received a single intravenous injection of exosomes (50, 100, 200 µg per rat) or vehicle, with treatment initiated at 1 day after injury. In the therapeutic window study, animals received a single intravenous injection of 100 µg exosomes or vehicle starting at 1, 4, or 7 days after injury. Neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning was measured on days 31 to 35 after TBI using the Morris water maze test. Results. Compared with the vehicle, regardless of the dose and delay in treatment, exosome treatment significantly improved sensorimotor and cognitive function, reduced hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis, and reduced neuroinflammation. Exosome treatment at 100 µg per rat exhibited a significant therapeutic effect compared with the 50- or 200-µg exosome groups. The time-dependent exosome treatment data demonstrated that exosome treatment starting at 1 day post-TBI provided a significantly greater improvement in functional and histological outcomes than exosome treatments at the other 2 delayed treatments. Conclusions. These results indicate that exosomes have a wide range of effective doses for treatment of TBI with a therapeutic window of at least 7 days postinjury. Exosomes may provide a novel therapeutic intervention in TBI.

Bisphosphonate drug holidays: Risk of fractures and mortality in a prospective cohort study

This study examined osteoporotic fractures and mortality in patients pretreated with bisphosphonates (BPs) during BP holidays and ongoing BP use. Interview-based prospective observational study in a cohort of 1973 patients with BP treatment for at least 80% of the total time of the preceding 4years. Patients were recruited from 146 primarily endocrinological, orthopedic and rheumatological practices and clinics across Germany between May 2013 and June 2015. Outcomes were analyzed by Cox proportional hazards regression in relation to treatment status at the time of the first interview (model 1) or using time-dependent treatment variables (model 2). Temporal changes in fracture risk during BP holidays were evaluated by comparisons among 3 incremental levels of simple moving averages of BP treatment during the preceding 12months (BP-SMA levels 0%, >0% to <50%, and ≥50%). For an observation period of up to 25months, the adjusted hazard ratios (HRs) in model 1 for BP holidays compared to ongoing BP use were 0.87 (95% confidence interval [CI] 0.59-1.28) for major osteoporotic fractures (MOFs), 0.95 (95% CI 0.70-1.28) for any clinical osteoporotic fracture, 0.96 (95% CI 0.55-1.68) for clinical vertebral fractures, and 0.86 (95% CI 0.50-1.48) for mortality. The risk of MOFs was higher for the BP-SMA level 0%, corresponding to a time >12months since the start of a BP holiday, than for the BP-SMA level >0% to <50%, corresponding mainly to a time >6 to ≤12months since the start of a BP holiday (adjusted HR 2.28, 95% CI 1.07-4.86). We found an interaction between prevalent vertebral fractures (PVFs) and BP-SMA-related time to first MOF for BP-SMA as a continuous variable (p for interaction 0.046 in the adjusted model). The adjusted HR for MOFs for the BP-SMA level 0% compared to the BP-SMA level >0% to <50% was 3.53 (95% CI 1.19-10.51) with a PVF but was 1.44 (95% CI 0.49-4.22) without a PVF. Fracture risk and mortality in patients with preceding BP treatment did not significantly differ between BP holidays and ongoing BP use for an observation period up to 25months when outcomes were analyzed in relation to treatment at the time of the first interview. However, in the presence of a PVF, the risk of MOFs was higher for a BP-SMA level corresponding to a time >12months since the start of a BP holiday than for a BP-SMA level corresponding mainly to a time >6 to ≤12months since the start of a BP holiday. The presence of a PVF may increase the relative risk of MOFs associated with a longer BP holiday.

Delay of Antibiotic Administration Greater than 2 Hours Predicts Surgical Site Infection in Open Fractures

AimsAntibiotic administration, severity of injury, and debridement are associated with surgical site infection (SSI) after internal fixation of open fractures. We sought to validate a time-dependent treatment effect of antibiotic administration. PatientsConsecutive open fracture patients at a level 1 trauma center with minimum 30-day follow-up were identified from an orthopaedic registry from 2013-2017. MethodsThe primary endpoint was SSI within 90 days. A threshold time to antibiotic administration associated with SSI was ascertained by receiver-operator analysis. A Cox proportional hazards model adjusted for age, smoking, and drug use determined the treatment effect of antibiotic administration within the threshold period. ResultsTen percent of 230 patients developed a SSI. There was a trend for patients who did not develop an SSI to receive antibiotics earlier than those who did develop an SSI (61 minutes, IQR 33-107 vs 83 minutes, IQR 40-186), p=0.053). Intravenous antibiotic administration after 120 minutes of presentation of an open fracture to emergency department was significantly associated with a 2.4 increased hazard of surgical site infection (p=0.036) within 90 days. ConclusionAntibiotic administration greater than 120 minutes after ED presentation of an open fracture was associated with an increased risk of SSI.

Positive predictive value of stroke identification by ambulance clinicians in North East England: a service evaluation

Introduction/backgroundAccurate prehospital identification of patients who had an acute stroke enables rapid conveyance to specialist units for time-dependent treatments such as thrombolysis and thrombectomy. Misidentification leads to patients who had...

Influence of catecholic ring torsion on hydroxyflavones

Abstract Systematic quantum chemical investigation of quercetin and selected eight mono- and bihydroxyflavonols is presented. Structural analysis based on the Density Functional Theory showed that the energetically preferred conformation of flavonols substituted at the C5 and C3 atoms by a hydroxyl group is stabilised via intramolecular hydrogen bonds occurring between the (C4)O···HO(3 or 5) atomic pairs. Depending on the hydroxyl group positions, energetically preferred torsional orientation of the phenyl ring with respect to the planar benzo-γ-pyrone moiety changed from 0 to 180 degrees. Gas-phase electron transitions were investigated using the time-dependent DFT treatment. The dependence of maximal wavelengths on the torsional deformation of the phenyl ring is of a similar shape, i.e. minima observed for the perpendicular orientation and maxima for the planar one. Shape and energies of the Highest Occupied (HOMO) and Lowest Unoccupied (LUMO) Molecular Orbitals were compared. The obtained theoretical results were compared with available experimental data.