A Powerful P-N Connection: Preparative Approaches, Reactivity, and Applications of P-Stereogenic Aminophosphines.

For more than five decades, P-stereogenic aminophosphine chalcogenides and boranes have attracted scientific attention and are still in the focus of ongoing research. In the last years, novel transition metal-based synthesis methods have been discovered, in addition to the long-known use of chiral auxiliaries. Enantiomerically pure compounds with N-P+-X- (X=O, S, BH3) motifs served as valuable reactive building blocks to provide new classes of organophosphorus derivatives, thereby preserving the stereochemical information at the phosphorus atom. Over the years, intriguing applications in organocatalysis and transition metal catalysis have been reported for some representatives. Asymmetric reductions of C=C, C=N, and C=O double bonds were feasible with selected P-stereogenic aminophosphine oxides in the presence of hydrogen transfer reagents. P-stereogenic aminophosphine boranes could be easily deprotected and used as ligands for various transition metals to enable catalytic asymmetric hydrogenations of olefins and imines. This review traces the emergence of a synthetically and catalytically powerful functional compound class with phosphorus-centered chirality in its main lines, starting from classical approaches to modern synthesis methods to current applications.

The Epidemiology of Antibiotic-Related Adverse Events in the Treatment of Diabetic Foot Infections: A Narrative Review of the Literature.

The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative review was to summarize the most frequent and most severe AEs reported in prospective trials and observational studies at the global level in DFI. Gastrointestinal intolerances were the most frequent AEs, from 5% to 22% among all therapies; this was more common when prolonged antibiotic administration was combined with oral beta-lactam or clindamycin or a higher dose of tetracyclines. The proportion of symptomatic colitis due to Clostridium difficile was variable depending on the antibiotic used (0.5% to 8%). Noteworthy serious AEs included hepatotoxicity due to beta-lactams (5% to 17%) or quinolones (3%); cytopenia's related to linezolid (5%) and beta-lactams (6%); nausea under rifampicin, and renal failure under cotrimoxazole. Skin rash was found to rarely occur and was commonly associated with the use of penicillins or cotrimoxazole. AEs from prolonged antibiotic use in patients with DFI are costly in terms of longer hospitalization or additional monitoring care and can trigger additional investigations. The best way to prevent AEs is to keep the duration of antibiotic treatment short and with the lowest dose clinically necessary.

Evaluation of a multi-component training programme for employees aged 50.

Lifelong learning offers an opportunity for mature employees to stay adept in the light of changing demands, to promote health and counteract physical and cognitive decline. This intervention study evaluates the effects of a multi-component training programme for employees aged 50+ , focussing on competence expectations, stress management, cognitive, metacognitive and psychomotoric training. Effects were evaluated in a longitudinal control group design with follow-up after six months (24 training groups, n = 247, participants per group: M = 13.04, SD = 2.44; control group, n = 199). To control for experimenter effects the same programme was administered to 6 additional groups by trained instructors (n = 54, participants per group: M = 11.83, SD = 3.37). To validate effects of the multi-component training 12 supplementary groups were included, with 4 groups each focusing on either the competence (n = 49, participants per group: M = 15.00, SD = 0.00) or cognitive (n = 43, participants per group: M = 14.25, SD = 1.50) or stress management components (n = 41, participants per group: M = 14.50, SD = 0.58). Data of 633 adults (mean age: M = 55.03, SD = 3.71 years) were analysed. Participants reported high acceptance of the programme. The multi-component training programme was effective regarding improvements in subjective health, self-concept of professional competence, self-efficacy, coping with stress and cognitive abilities with long-term effects for the latter four. Trainings administered by trained instructors had similar effects to those administered by the programme's designers. The single-component trainings led to specific effects in the focused areas, overall comparable to those of the multi-component training. Unexpectedly, cognitive effects were obtained by all single-component trainings. Subjective health and self-efficacy were only promoted by the multi-component training, indicating broader effects. The results are discussed with respect to strengths and limitations of the study, possible mechanisms underlying the effects, suggestions for further research as well as for the training's implementation in business practice.

Access to Enantiomerically Pure P-Stereogenic Primary Aminophosphine Sulfides under Reductive Conditions.

Stereochemically pure phosphines with phosphorus-heteroatom bonds and P-centered chirality are a promising class of functional building blocks for the design of chiral ligands and organocatalysts. A route to enantiomerically pure primary aminophosphine sulfides was opened through stereospecific reductive C-N bond cleavage of phosphorus(V) precursors by lithium in liquid ammonia. The chemoselectivity of the reaction as a function of reaction time, substrate pattern, and chiral auxiliary was investigated. In the presence of exclusively aliphatic groups bound to the phosphorus atom, all competing reductive side reactions are totally prevented. The absolute configurations of all P-stereogenic compounds were determined by single-crystal X-ray diffraction analysis. Their use as synthetic building blocks was demonstrated. The lithium salt of (R)-BINOL-dithiophosphoric acid proved to be a useful stereochemical probe to determine the enantiomeric purity. Insights into the coordination mode of the lithium-based chiral complex formed in solution was provided by NMR spectroscopy and DFT calculations.

Osteoarticular infections: a specific program for older patients?

BACKGROUND: With the increasing number of elderly patients, arthroplasties, fractures and diabetic foot infections, the worldwide number of osteoarticular infections (OAI) among the elderly is concomitantly expected to rise. AIMS: We explore existing scientific knowledge about OAI in the frail elderly population. METHODS: We performed a literature search linking OAIs to geriatric patients and comparing elderly patients (> 65 years) with average adults (range 18-65 years). RESULTS: In this literature, financial aspects, comparison of diverse therapies on quality of life, reimbursement policies, or specific guidelines or nursing recommendations are missing. Age itself was not an independent factor related to particular pathogens, prevention of OAI, nursing care, and outcomes of OAI. However, geriatric patients were significantly more exposed to adverse events of therapy. They had more co-morbidities and more conservative surgery for OAI. CONCLUSION: Available literature regarding OAI management among elderly patients is sparse. In recent evaluations, age itself does not seem an independent factor related to particular epidemiology, pathogens, prevention, nursing care, rehabilitation and therapeutic outcomes of OAI. Future clinical research will concern more conservative surgical indications, but certainly reduce inappropriate antibiotic use.

Oral Flucloxacillin for Treating Osteomyelitis: A Narrative Review of Clinical Practice.

Flucloxacillin (FLU) administered by the oral route is widely used for treating various infections, but there are no published retrospective or prospective trials of its efficacy, or its advantages or disadvantages compared to parenteral treatment or other antibiotics for treating osteomyelitis. Based on published in vitro data and expert opinions, other non-ß-lactam oral antibiotics that have better bone penetration are generally preferred over oral FLU. We reviewed the literature for studies of oral FLU as therapy of osteomyelitis (OM), stratified by acute versus chronic and pediatric versus adult cases. In striking contrast to the prevailing opinions and the few descriptive data available, we found that treatment of OM with oral FLU does not appear to be associated with more clinical failures compared to other oral antibiotic agents. Because of its narrow antibiotic spectrum, infrequent severe adverse effects, and low cost, oral FLU is widely used in clinical practice. We therefore call for investigators to conduct prospective trials investigating the effectiveness and potential advantages of oral FLU for treating OM.

Optimization of the antibiotic management of diabetic foot infections: protocol for two randomized controlled trials.

BACKGROUND: Few studies have addressed the appropriate duration of antibiotic therapy for diabetic foot infections (DFI) with or without amputation. We will perform two randomized clinical trials (RCTs) to reduce the antibiotic use and associated adverse events in DFI. METHODS: We hypothesize that shorter durations of postdebridement systemic antibiotic therapy are noninferior (10% margin, 80% power, alpha 5%) to existing (long) durations and we will perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022. The primary outcome for both RCTs is remission of infection after a minimal follow-up of 2 months. The secondary outcomes for both RCTs are the incidence of adverse events and the overall treatment costs. The first RCT will allocate the total therapeutic amputations in two arms of 50 patients each: 1 versus 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 versus 4 days for remaining soft tissue infection. The second RCT will randomize the conservative approach (only surgical debridement without in toto amputation) in two arms with 50 patients each: 10 versus 20 days of antibiotic therapy for soft tissue infections; and 3 versus 6 weeks for osteomyelitis. All participants will have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, podiatric, internist and infectiology care. During the surgeries, we will collect tissues for BioBanking and future laboratory studies. DISCUSSION: Both parallel RCTs will respond to frequent questions regarding the duration of antibiotic use in the both major subsets of DFIs, to ensure the quality of care, and to avoid unnecessary excesses in terms of surgery and antibiotic use. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04081792. Registered on 4 September 2019.

Oral amoxicillin-clavulanate for treating diabetic foot infections.

AIM: To assess amoxicillin-clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO). METHODS: We performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases. RESULTS: The median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days). Oral AMC was prescribed for a median of 20 days (interquartile range, 12-30 days). The median ratio of oral AMC among the entire antibiotic treatment was 0.9 (interquartile range, 0.7-1.0). After a median follow-up of 3.3 years, 178 DFIs (22%) overall recurred (DFO, 75; 22%). Overall, oral AMC led to 74% remission compared with 79% with other regimens (χ2 -test; P = 0.15). In multivariate analyses and stratified subgroup analyses, oral AMC resulted in similar clinical outcomes to other antimicrobial regimens, when used orally from the start, after an initial parenteral therapy, or when prescribed for DFO. CONCLUSIONS: Oral AMC is a reasonable option when treating patients with DFIs and DFOs.

Implementation of an IT-guided checklist to improve the quality of medication history records at hospital admission.

Background Medication discrepancies often occur at transition of care such as hospital admission and discharge. Obtaining a complete and accurate medication history on admission is essential as further treatment is based on it. Objective The goal of this study was to reduce the proportion of patients with at least one medication discrepancy in the medication history at admission by implementing an IT-guided checklist. Setting Surgery ward focused on vascular and visceral surgery at a Swiss Cantonal Hospital. Method The study was divided into two phases, before and after implementation of an IT-guided checklist. For both phases a pharmacist collected and compared the medication history (defined as gold standard) with that of the admitting physician. Medication discrepancies were subdivided in omissions and commissions, incorrect medications or dose changes, and incorrect dosage forms or strength. Main outcome measure The proportion of patients with at least one medication discrepancy in the medication history before and after intervention was assessed. Results Out of 415 admissions, 228 patients that met the inclusion criteria were enrolled in the study, 113 before and 115 patients after intervention. After intervention, medication discrepancies declined from 69.9 to 29.6% (p < 0.0001) of patients, the mean medication discrepancy per patient was reduced from 2.3 to 0.6 (p < 0.0001), and the most common error, omission of a regularly used medication, was reduced from 76.4 to 44.1% (p < 0.001). Conclusion The implementation of the IT-guided checklist is associated with a significant reduction of medication discrepancies at admission and potentially improves the medication safety for the patient.