Project description:BackgroundThe management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.MethodsWe enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points.ResultsAmong the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%).ConclusionsOral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).
Project description:The first intermolecular early main group metal-alkene complexes were isolated. This was enabled by using highly Lewis acidic Mg centers in the Lewis base-free cations (Me BDI)Mg+ and (tBu BDI)Mg+ with B(C6 F5 )4 - counterions (Me BDI=CH[C(CH3 )N(DIPP)]2 , tBu BDI=CH[C(tBu)N(DIPP)]2 , DIPP=2,6-diisopropylphenyl). Coordination complexes with various mono- and bis-alkene ligands, typically used in transition metal chemistry, were structurally characterized for 1,3-divinyltetramethyldisiloxane, 1,5-cyclooctadiene, cyclooctene, 1,3,5-cycloheptatriene, 2,3-dimethylbuta-1,3-diene, and 2-ethyl-1-butene. In all cases, asymmetric Mg-alkene bonding with a short and a long Mg-C bond is observed. This asymmetry is most extreme for Mg-(H2 C=CEt2 ) bonding. In bromobenzene solution, the Mg-alkene complexes are either dissociated or in a dissociation equilibrium. A DFT study and AIM analysis showed that the C=C bonds hardly change on coordination and there is very little alkene→Mg electron transfer. The Mg-alkene bonds are mainly electrostatic and should be described as Mg2+ ion-induced dipole interactions.
Project description:Approximately 20% of the US population primarily speaks a language other than English at home. Yet the effect of language preference on treatment of acute ischemic stroke (AIS) patients remains unknown. We aimed to evaluate the influence of language preference on AIS patients' receipt of intravenous (IV) thrombolysis. We analyzed data from 3894 AIS patients who participated in the American Heart Association "Get With The Guidelines®-Stroke" program at our hospital from January 1, 2003 to April 30, 2014. Information included patients' language in which they preferred to receive medical care. We used descriptive statistics and stepwise logistic regression models to examine associations between patients' language preference and receipt of IV thrombolysis, adjusting for relevant covariates. A total of 306/3295 (9.3%) AIS patients preferred to speak a non-English language and represented 25 different languages. Multivariable analyses adjusting for other socioeconomic factors showed that non-English-preferring patients were more likely than English-preferring patients to receive IV thrombolysis (OR=1.64; CI=1.09-2.48; P=0.02). However, in models that also included age, sex, and initial NIH Stroke Scale, patients' language preference was no longer significant (OR 1.38; CI=0.88-2.15; P=0.16), but NIH Stroke Scale was strongly associated with receiving IV thrombolysis (OR=1.15 per point; CI=1.13-1.16; P<0.0001). Contrary to our hypothesis, non-English-preferring was not associated with lower rates of IV thrombolysis among AIS patients once initial stroke severity was accounted for.
Project description:BackgroundSurgical-site infection (SSI) is a potentially serious complication following colorectal surgery. The present systematic review and meta-analysis aimed to investigate the effect of preoperative oral antibiotics and mechanical bowel preparation (MBP) on SSI rates.MethodsA systematic review of PubMed, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials was performed using appropriate keywords. Included were RCTs and observational studies reporting rates of SSI following elective colorectal surgery, in patients given preoperative oral antibiotic prophylaxis, in combination with intravenous (i.v.) antibiotic prophylaxis and MBP, compared with patients given only i.v. antibiotic prophylaxis with MBP. A meta-analysis was undertaken.ResultsTwenty-two studies (57 207 patients) were included, of which 14 were RCTs and eight observational studies. Preoperative oral antibiotics, in combination with i.v. antibiotics and MBP, were associated with significantly lower rates of SSI than combined i.v. antibiotics and MBP in RCTs (odds ratio (OR) 0·45, 95 per cent c.i. 0·34 to 0·59; P < 0·001) and cohort studies (OR 0·47, 0·44 to 0·50; P < 0·001). There was a similarly significant effect on SSI with use of a combination of preoperative oral aminoglycoside and erythromycin (OR 0·40, 0·25 to 0·64; P < 0·001), or preoperative oral aminoglycoside and metronidazole (OR 0·51, 0·39 to 0·68; P < 0·001). Preoperative oral antibiotics were significantly associated with reduced postoperative rates of anastomotic leak, ileus, reoperation, readmission and mortality in the cohort studies.ConclusionOral antibiotic prophylaxis, in combination with MBP and i.v. antibiotics, is superior to MBP and i.v. antibiotic prophylaxis alone in reducing SSI in elective colorectal surgery.
Project description:We introduced domiciliary intravenous (IV) antibiotic therapy in patients with bronchiectasis to promote patient-centred domiciliary treatment instead of hospital inpatient treatment.To assess the efficacy and safety of domiciliary IV antibiotic therapy in patients with non-cystic fibrosis bronchiectasis.In this prospective study conducted over 5 years, we assessed patients' eligibility for receiving domiciliary treatment. All patients received 14 days of IV antibiotic therapy and were monitored at baseline/day 7/day 14. We assessed the treatment outcome, morbidity, mortality and 30-day readmission rates.A total of 116 patients received 196 courses of IV antibiotics. Eighty courses were delivered as inpatient treatment, 32 as early supported discharge (ESD) and 84 as domiciliary therapy. There was significant clinical and quality of life improvement in all groups, with resolution of infection in 76% in the inpatient group, 80% in the ESD group and 80% in the domiciliary group. Morbidity was recorded in 13.8% in the inpatient group, 9.4% in the ESD group and 14.2% in the domiciliary IV group. No mortality was recorded in either group. Thirty-day readmission rates were 13.8% in the inpatient group, 12.5% in the ESD group and 14.2% in the domiciliary group. Total bed days saved was 1443.Domiciliary IV antibiotic therapy in bronchiectasis is clinically effective and was safe in our cohort of patients.
Project description:Methicillin-susceptible Staphylococcus aureus (MSSA) is a common pathogen associated with a range of clinically important infections. MSSA can cause deep-seated infections requiring prolonged courses of intravenous antibiotic therapy to achieve effective resolution. The move toward ambulatory or outpatient delivery of parenteral antibiotics has led to an increase in the use of ceftriaxone as a pragmatic first choice given its advantageous single daily dosing schedule. To compare the efficacy of once daily ceftriaxone in the treatment of infections due to confirmed or suspected MSSA to multiple dosing regimes of anti-staphylococcal antibiotics. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Global Health, PubMed, EMBASE and CINAHL for randomised controlled trials as well as prospective and retrospective cohort studies that compared ceftriaxone to any multiple dosing regime of anti-staphylococcal antibiotics. Outcome measures were the proportion of patients with a resolution of infection based on time after initiation of therapy, adverse reactions, recurrence and duration of hospital admission. We included two randomized controlled trials, one prospective observational study and three retrospective cohort studies (643 participants; 246 children, 397 adults). There was no difference in time to resolution of symptoms. The number of adverse reactions, recurrence of bacteraemia and duration of hospital stay were not significantly different between ceftriaxone and other anti-staphylococcal antibiotics. Based on a small number of low-quality studies, ceftriaxone is as effective as multiple dosing regimes for the treatment of infections due MSSA. An appropriately powered randomized trial is required to demonstrate equivalence and cost effectiveness.
Project description:An effort to develop smaller, well-dispersed catalytic materials electrochemically on high-surface-area carbon supports is required for improved fuel cell performance. A high-surface-area carbon material of interest is carbon nano-onions (CNOs), also known as multilayer fullerenes. The most convenient synthesis method for CNOs is annealing nanodiamond particles, thus retaining the size of the precursors and providing the possibility to prepare very small nanocatalysts using electrochemical techniques. In terms of pure metal catalysts, platinum is the most common catalyst used in fuel cells. The combination of Pt nanoparticles with CNOs could lead to new catalytic nanomaterials. In this work, this was accomplished by using a rotating disk-slurry electrode (RoDSE) technique. The Pt/CNO catalysts were prepared from slurries that contained functionalized CNOs and K(2)PtCl(6) as the platinum precursor in aqueous 0.1 M H(2)SO(4) solution. X-ray photoelectron spectroscopy results showed that 37% of the Pt on the CNOs is metallic Pt whereas 63% had higher binding energies, which is evidence of higher oxidation states or the presence of Pt atoms and clusters on CNOs. However, aberration-corrected scanning transmission electron microscopy of the Pt/CNOs confirmed the presence of Pt atoms and clusters on CNOs. Thermal gravimetric analysis showed the excellent thermal stability of the Pt/CNOs and a lower onset potential for the electrochemical oxidation of methanol compared to that of commercial Pt/Vulcan catalyst material. The computational method confirmed the Pt atoms' location at CNOs surface sites. Geometric parameters for distances between Pt atoms in the 3Pt/CNOs molecular system from our theoretical calculations are in agreement with the respective parameters obtained experimentally. The combination of CNO with RoDSE presents a new highly dispersed catalyst nanomaterial.
Project description:The thermo-catalytic synthesis of hydrocarbons from CO2 and H2 is of great interest for the conversion of CO2 into valuable chemicals and fuels. In this work, we aim to contribute to the fundamental understanding of the effect of alloying on the reaction yield and selectivity to a specific product. For this purpose, Fe-Co alloy nanoparticles (nanoalloys) with 30, 50 and 76 wt% Co content are synthesized via the Inert Gas Condensation method. The nanoalloys show a uniform composition and a size distribution between 10 and 25 nm, determined by means of X-ray diffraction and electron microscopy. The catalytic activity for CO2 hydrogenation is investigated in a plug flow reactor coupled with a mass spectrometer, carrying out the reaction as a function of temperature (393-823 K) at ambient pressure. The Fe-Co nanoalloys prove to be more active and more selective to CO than elemental Fe and Co nanoparticles prepared by the same method. Furthermore, the Fe-Co nanoalloys catalyze the formation of C2-C5 hydrocarbon products, while Co and Fe nanoparticles yield only CH4 and CO, respectively. We explain this synergistic effect by the simultaneous variation in CO2 binding energy and decomposition barrier as the Fe/Co ratio in the nanoalloy changes. With increasing Fe content, increased activation temperatures for the formation of CH4 (from 440 K to 560 K) and C2-C5 hydrocarbons (from 460 K to 560 K) are observed.
Project description:Background:Most users of unsupported Internet interventions visit that site only once, therefore there is a need to create interventions that can be offered as a single brief interaction with the user. Objective:The main goal of this study was to compare the effect of a one-session unsupported Internet intervention on participants' clinical symptoms (depressive and anxiety symptoms) and related variables (mood, confidence and motivation). Method:A total of 765 adults residing in the United States took part in a randomized controlled trial. Participants were randomly assigned to one of five brief plain text interventions lasting 5-10 min. The interventions designed to address depressive symptoms were: thoughts (increasing helpful thoughts), activities (increasing activity level), sleep hygiene, assertiveness (increasing assertiveness awareness), Own Methods (utilizing methods that were previously successful). They were followed-up one week after consenting. Results:A main effect of time was observed for both depression (F(1, 563) = 234.70, p < 0.001) and anxiety (F(1, 551) = 170.27, p < 0.001). In all cases, regardless of assigned condition and Major Depressive Episode status, mean scores on both positive outcomes (mood, confidence and motivation) and negative outcome scores (depression and anxiety) improved over time. Conclusions:Brief unsupported Internet interventions can improve depressive symptoms at one-week follow-up. Further outcome data and research implications will be discussed.
Project description:ImportanceGram-negative bacteremia is a global health concern, and optimizing the transition from intravenous (IV) to oral antibiotics is a critical step in improving patient treatment and resource utilization.ObjectiveTo assess the association of switching to oral antibiotics within 4 days after initial blood culture with 90-day all-cause mortality compared with prolonged IV antibiotic treatment for patients with uncomplicated gram-negative bacteremia.Design, setting, and participantsThis cohort study conducted using the target trial emulation framework included observational data from adults with uncomplicated gram-negative bacteremia in 4 hospitals in Copenhagen, Denmark, from January 1, 2018, through December 31, 2021. The duration of follow-up was 90 days. Eligibility criteria included a blood culture positive for growth of gram-negative bacteria, clinical stability within 4 days of initial blood culture, an available susceptibility report on day 4, and initiation of appropriate empirical IV antibiotic treatment within 24 hours of blood culture.ExposureSwitching to oral antibiotics within 4 days after initial blood culture compared with continuing IV antibiotic treatment for at least 5 days after initial blood culture.Main outcomes and measuresThe main outcome was 90-day all-cause mortality. Inverse probability of treatment weighting was applied to adjust for confounding. Intention-to-treat and per-protocol analyses were performed using pooled logistic regression to estimate absolute risk, risk difference (RD), and risk ratio (RR); 95% CIs were computed using bootstrapping.ResultsA total of 914 individuals were included in the target trial emulation analysis (512 [56.0%] male; median age, 74.5 years [IQR, 63.3-83.2 years]); 433 (47.4%) transitioned early to oral antibiotic treatment, and 481 (52.6%) received prolonged IV treatment. Ninety-nine individuals (10.8%) died during follow-up. The proportion of individuals who died was higher in the group receiving prolonged IV treatment (69 [14.3%] vs 30 [6.9%]). In the intention-to-treat analysis, 90-day all-cause mortality risk was 9.1% (95% CI, 6.7%-11.6%) for the early-switch group and 11.7% (95% CI, 9.6%-13.8%) for the group receiving prolonged IV treatment; the RD was -2.5% (95% CI, -5.7% to 0.7%) and RR was 0.78 (95% CI, 0.60-1.10). In the per-protocol analysis, the RD was -0.1% (95% CI, -3.4% to 3.1%) and RR was 0.99 (95% CI, 0.70-1.40).Conclusions and relevanceIn this cohort study of uncomplicated gram-negative bacteremia, early transition to oral antibiotics within 4 days of initial blood culture was associated with 90-day all-cause mortality risk comparable to that of continuing IV antibiotic treatment and may be an effective alternative to prolonged IV treatment.