Background
Excessive and inappropriate use of antibiotics is the most important driver of antimicrobial resistance. The aim of the HAPPY PATIENT project is to evaluate the adaptation of European Union (EU) recommendations on the prudent use of antimicrobials in human health by evaluating the impact of a multifaceted intervention targeting different categories of healthcare professionals (HCPs) on common community-acquired infectious diseases, especially respiratory and urinary tract infections.
Methods/design
HAPPY PATIENT was initiated in January 2021 and is planned to end in December 2023. The partners of this project include 15 organizations from 9 countries. Diverse HCPs (doctors, nurses, pharmacists, and pharmacy technicians) will be audited by the Audit Project Odense (APO) method before and after an intervention in four different settings: general practice, out of hours services, nursing homes and community pharmacies in four high antibiotic prescribing countries (France, Poland, Greece, and Spain) and one low prescribing country (Lithuania). About 25 individuals from each professional group will be recruited in each country, who will register at least 25 patients with community-acquired infections during each audit period. Shortly before the second registration participants will undertake a multifaceted intervention and will receive the results from the first registration to allow the identification of possible quality problems. At these meetings participants will receive training courses on enhancement of communication skills, dissemination of clinical guidelines with recommendations for diagnosis and treatment, posters for the waiting rooms, and leaflets for patients. The results of the second registration will be compared with those obtained in the first audit.
Discussion
HAPPY PATIENT is an EU-funded project aimed at contributing to the battle against antibiotic resistance through improvement of the quality of management of common community-acquired infections based on interventions by different types of HCPs. It is hypothesized that the use of multifaceted strategies combining active intervention will be effective in reducing inappropriate prescribing and dispensing of antibiotics.
Study registration
EU Health programmes project database https://webgate.ec.europa.eu/chafea_pdb/health/projects/900024/summary; date of registration: 1 January 2021.
The unsaturated cobalamin binding capacity of transcobalamin and haptocorrin was studied in cerebrospinal fluid (CSF) and plasma (P) from 37 reference individuals. These comprised 27 males and 10 females who underwent minor surgery in spinal anaesthesia.
The 5th and 95th percentiles were as follows:
P‐Transcobalamin 300 ‐ 870 pmol/l (median 550 pmol/l)
CSF‐Transcobalamin 90 ‐ 540 pmol/l (median 194 pmol/l)
P‐Haptocorrin 75 ‐ 290 pmol/l (median 159 pmol/l)
CSF‐Haptocorrin 10 ‐ 41 pmol/l (median 21 pmol/l)
No sex difference was found between the levels of haptocorrin or transcobalamin in plasma or cerebrospinal fluid. A positive correlation between P‐Transcobalamin and CSF‐Transcobalamin was found, whereas no correlation between P‐Haptocorrin and CSF‐Haptocorrin values was found. The plasma/CSF ratios of transcobalamin, haptocorrin, albumin and IgG indicated that the binders may be synthetized into the cerebrospinal fluid or are actively being transported into the cerebrospinal fluid.
Transcobalamin (TC) and haptocorrin (HC) are present in normal seminal plasma in substance concentrations ten- to twenty-fold that in blood. The results are given in range and (median). The substance concentration of seminal plasma TC is 3.6-21.9 (8.4) nmol l-1 and of seminal plasma HC 1.4-8.6 (3.0) nmol l-1. Compared to normals the substance concentration of TC is significantly lowered in post-vasectomy seminal plasma 2.2-2.9 (5.3) nmol l-1. The Stokes radius and the isoelectric points of seminal plasma TC are identical to TC in blood.
SUMMARY1. The pH-and voltage-dependent Cl-conductance in frog muscle may be related to the chloride equilibrium potential, Vc1,eq, rather than to the absolute membrane potential, Vm. This hypothesis was tested in thin depolarized frog muscle fibre bundles by investigating the influence of pH on 36Cl-efflux during Cl-net efflux upon removal of external Cl-, which offers a state far from Cl-equilibrium by changing Vc1,eq instead of Vm.2. Upon the change from Cl-equilibrium at 20 mM-ClJ to Cl-net efflux at zero [Cl-]0, Vm changed only -10 mV, but the 36Cl-efflux rate increased about three times at pH 5-5 and decreased to less than one tenth of the equilibrium efflux rate at pH 9-8. The switch between 'acid' and 'alkaline' responses occurs at a pH between 6-4 ('acid response') and 7-2 ('alkaline response').3. Changing pH between 5-5 and 9'8 during Cl-net efflux showed an increase of 36Cl-net flux rate upon acidification and a decrease upon alkalination. The reactions are opposite to those seen by pH shifts at chloride equilibrium.4. The changes of net flux rate coefficients upon changes of pH were transient, especially the activation at low pH that relaxed significantly during about 10 min.5. The results are consistent with the notion that the state of the gcl mechanism in frog muscle is related to (VmVC1ejq) rather than to the absolute potential alone.
We investigated the mechanism of interference of mucosal application of the short-chain phospholipid didecanoyl-L-alpha-phosphatidylcholine (DDPC; 0.1-0.5%) with ion transport pathways in isolated rabbit nasal airway epithelium (RNAE). Transports of Na+ and Cl- were evaluated from tracer ion fluxes, short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in Ussing chambers. DDPC rapidly and reversibly abolished net Na+ absorption, reduced control Isc (approximately 110 microA/cm2) by approximately 80%, and induced a small Cl secretion. Intracellular Ca2+ concentration ([Ca2+]i) increased dose dependently and transiently (measured by fura 2 in cultured rabbit airway epithelium), but ionomycin failed to mimic the decrease in Isc. The rise in [Ca2+]i may explain a Ba(2+)-sensitive transient activation of a basolateral K+ conductance. Indomethacin-sensitive prostaglandin E2 production in RNAE increased severalfold, but cyclooxygenase and lipoxygenase inhibitors did not prevent DDPC-induced changes in Isc. DDPC initially decreased control Gt (approximately 13 mS/cm2) by approximately 25% due to inhibition of amiloride-sensitive Na+ channels, and then reversibly increased Gt to approximately 45% above control values. Passive Na+ fluxes increased more than Cl fluxes, suggesting that the increase in Gt is due to formation of a paracellular shunt conductance in parallel with unaffected, anion-selective tight junction channels. The results suggest that DDPC inhibits apical membrane Na+ channels and causes structural changes in tight junctions after incorporation in apical cell membranes.
SUMMARY1. Inhibition of 36Cl-efflux in frog muscle by the stilbene disulphonates (SD) SITS (4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonate) and DNDS (4,4'-dinitro-stilbene-2,2'-disulphonate) depends on the external pH, while the blocking of Clconductance with SITS is independent of pH. The 36Cl-efflux inhibition with DNDS has been studied in thin depolarized muscle fibre bundles in order to examine whether this difference is consistent with one transporter or reflects the existence of two mutually independent conductive and non-conductive SD-sensitive Clpathways.2. The 36Cl-efflux response to a sudden inward KCl gradient was studied. At high pH the efflux decreased as predicted for dominant conductive Cl-single-filing, and at low pH the efflux increased in agreement with dominant non-conductive Clantiport. DNDS inhibition resulted in the same response, an efflux decrease, at both high and low pH, suggesting a selective reduction of the non-conductive contribution at low pH.3. The inhibition of 36Cl-efflux as a function of the DNDS concentration at an external pH of 6-9 showed complex kinetics, which could be described as the sum of two Michaelis-Menten functions with different half-inhibition concentrations of DNDS.4. The results support the hypothesis that the stilbene disulphonate-sensitive Cltransport is mediated by two separate transporters rather than one.
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