Responsible antibiotic use and diagnostic challenges in infectious diseases : studies in a resource-limited setting and a high-income setting

Background Antibiotic resistance is a globally emerging health challenge. In resource-limited settings, the burdens of infectious diseases and of antibiotic resistance are the highest. The World Health Organization (WHO) has stated that high and uncontrolled use of antibiotics in resource-limited settings contributes to the increasing prevalence of antibiotic resistance in such areas. Improvements should be based on knowledge about current antibiotic use, preventing the spread of infections, and the implementation and/or development of diagnostic methods for the improved management of infectious diseases. Limited access to diagnostic methods complicates the management of infectious diseases in resource-limited settings and increases the risk of disregarding severe infectious diseases, such as infective endocarditis (IE). Therefore, it is important to evaluate diagnostic methods that can improve the management of infectious diseases in such settings. Evaluating whether the findings of echocardiography (ECHO) could give a suggestion of the bacterial aetiology in patients with IE in a high-income setting might provide valuable information for the implementation of ECHO in resource-limited settings. Aims To map and describe the antibiotic prescribing practices and to highlight areas of improvement in the management of in-patients with infectious diseases in a resource-limited setting in India. Further to assess whether specific manifestations detected by ECHO were associated with certain bacterial species in patients with IE in a high-income setting in Sweden. Methods The studies for Papers I-III were conducted in a teaching hospital (TH) and a non-teaching (NTH) hospital in India. Two were prospective, cross-sectional studies (I and II) and one was a time series analysis (III). Paper IV was conducted in Stockholm, Sweden, as a register-based cohort study. For Paper I, antibiotic use was analysed at the medical intensive care units (ICUs) at the two hospitals in India. For Paper II, antibiotic prescribing practices were analysed with a focus on infectious diagnoses at the paediatric departments at the two hospitals in India. For Paper III, time series analyses over a 10-year period (2008–2017) were conducted to follow antibiotic prescribing over time among patients with severe infections at the NTH and the TH in India. For Paper IV, associations between IE manifestations detected by ECHO and bacterial species were assessed from a cohort of patients with IE obtained from the Swedish National Registry of Infective Endocarditis (SRIE). Main findings High percentages of patients at the medical ICUs were prescribed antibiotics at both hospitals (4,843 of 6,141 patients, 70%) although less than 25% of the patients were registered with an infection-associated diagnosis (I). At the paediatric departments, antibiotic use among patients with either acute gastroenteritis, respiratory tract infections, enteric fever, viral fever or unspecified fever was more common at the NTH (2,088 patients, 84%) compared with the TH (224 patients, 44%; P < 0.001). Broad-spectrum antibiotics were commonly prescribed at both hospitals, and less than 40% of the prescribed antibiotics at both hospitals were compliant to the national list of essential medicines (37% at the TH and 24% at the NTH; P < 0.05) (II). From 2008 to 2017, the overall rate of antibiotic prescribing for patients with severe infections, as well as prescribing of first- and second-line antibiotics and so-called fixed-dose combinations (FDCs) of antibiotics increased in the NTH (P < 0.05). In the TH, the overall antibiotic prescribing did not change significantly, although the prescribing of second- and third-line antibiotics and FDCs of antibiotics increased during the study period (P < 0.05) (III). Among patients with IE, associations were seen between aortic valve vegetation and Enterococcus faecalis among patients with native aortic valves, between mitral valve vegetation and streptococci of group B or viridans group streptococci, between tricuspid valve vegetation and Staphylococcus aureus among patients with intravenous drug abuse, and between perivalvular abscesses as well as cardiovascular implantable electronic device (CIED)-associated IE and coagulase-negative staphylococci (all P < 0.05) (IV). Conclusions Antibiotic prescribing was high at the ICUs and paediatric departments at the NTH and the TH, also among patients presenting with no infection-associated diagnoses or with diagnoses for which antibiotic treatments are not recommended. Broad-spectrum antibiotics were commonly prescribed at both hospitals. From 2008 to 2017, prescribing of second-line antibiotics and FDCs of antibiotics among patients with severe infections increased at both hospitals. The findings suggest that there is a need for improved antibiotic prescribing and management of infectious diseases. A major problem in this setting as well as in similar resource-limited settings is the limited use of diagnostics, which are needed to guide the treatment and follow-up of infectious diseases. Limited use of diagnostics also increases the risk of underdiagnosing infectious diseases. Very few cases of IE were registered at the NTH and TH, which might be a result of the limited use of diagnostics. ECHO is an effective method for the diagnosis, evaluation and follow-up of patients with IE, successfully implemented in high-income settings. ECHO can be used to identify cardiac manifestations of IE but might also give a suggestion of bacterial aetiology as some IE manifestations detected by ECHO have been shown to be associated with certain bacterial species. These findings could possibly be useful also in resource-limited settings, where ECHO might improve the management of patients with IE

Effect of Oxidants on Properties of Electroactive Ultrathin Polyazulene Films Synthesized by Vapor Phase Polymerization at Atmospheric Pressure

A non-benzenoid aromatic hydrocarbon azulene, naturally found in plants and mushrooms, is known for its derivatives applications in medicines. However, the processability of its chemically synthesized high-capacitance polymer is constrained by the sparingly soluble nature of its polymeric form. Oxidative chemical synthesis on a desirable substrate overcomes this difficulty. In this report, polyazulene (PAz) thin films are synthesized by vapor phase polymerization at atmospheric pressure using oxidants, such as CuCl2, CuBr2, FeCl3, and FeTOS. The effect of oxidants on morphologies of PAz films is studied using atomic force microscopy and microscope imaging. Each oxidant produced distinct microstructures in the films. The films synthesized using Cu(II) salts showed organized and knitted structures, whereas Fe(III) salts formed casted sheet-like disordered arrangements. The films synthesized using CuCl2 created uniform porous film assemblies. The pre-peak formations and their splitting observed in the cyclic voltammograms revealed phase segregations in the films. Oxidant-dependent structural and chemical differences such as charge carrier formation, doping levels, and polymer chain length in the PAz films are studied by using UV-Vis and FTIR spectroscopy. The results indicated that 240 and 180 mM are the optimum concentration of CuCl2 to produce high capacitance and well-organized single-and triple-layered PAz films, respectively.</p

Improved long term cycling of polyazulene/reduced graphene oxide composites fabricated in a choline based ionic liquid

To improve the energy density of supercapacitors, novel electronically conducting polymers should be introduced to the research field. Polyazulene is a well-suitable candidate as it exhibits good capacitive behavior both in organic solvents as well as in various ionic liquids, but especially its long term cycling stability should be improved. Previously, enhanced properties have been obtained by combining conducting polymers with carbon nanomaterials to fabricate composites. This work presents an ionic liquid assisted electrochemical polymerization and characterization of polyazulene-reduced graphene oxide composites. The ionic liquid of our choice is choline-based liquid salt. We prepared stable dispersions of graphene oxide in this ionic liquid and performed potentiodynamic electropolymerization of azulene in the mixture. Changing the concentration of graphene oxide between 0.1 and 2 mg mL(-1) had no remarkable effect on the polymerization or electrochemical behavior of the composite materials. The composites exhibit higher capacitances compared to neat polymer films determined by cyclic voltammetry and electrochemical impedance spectroscopy. The obtained films also exhibit excellent cycling stabilities retaining over 90% of their initial capacitance with tendency towards improved cycling stability when combined with reduced graphene oxide. The successful incorporation and reduction of graphene oxide was determined by several spectroscopic techniques

Same-day discharge after percutaneous closure of persistent foramen ovale using intracardiac echocardiography and the Gore Septal Occluder

AimPeriprocedural and postinterventional care of patients undergoing closure of patent foramen ovale (PFO) varies significantly across care providers. Same-day discharge (SDD) after transcatheter interventions is an evolving concept. This study aimed to assess the same-day discharge rate and incidence of complications in patients undergoing PFO closure with intracardiac echocardiography (ICE) using the Gore®Cardioform Septal Occluder (GSO) device. The secondary aim was to analyse the efficacy of femoral vein closure with Perclose ProGlide.MethodsPatients who underwent PFO closure with the GSO device at a university hospital in Stockholm, Sweden, were retrospectively included between March 1, 2017, and June 30, 2020, all with cryptogenic stroke as the indication for the procedure. All patients underwent PFO closure with conscious sedation and local anaesthesia. The indication for all patients was a cryptogenic stroke. Periprocedural imaging was performed using ICE and fluoroscopy in all patients. Patient characteristics and periprocedural data were collected from patient charts. Patients were kept on bed rest for 4–6 h post-intervention. Transthoracic echocardiography and clinical examination, including groin status, were performed before discharge. No clinical routine follow-up was performed the day following the intervention. Clinical follow-up was done by phone call two weeks after the procedure, and echocardiographic follow-up was done after 12 months. Data were analysed using linear and logistic regression models.ResultsIn total, 262 patients were included, of which 246 (94%) had SDD. 166 patients (63%) received the ProGlide™ system for femoral vein access closure. Post-procedural arrhythmias occurred in 17 (6%) patients, and vascular complications in 9 patients (3%). The overall closure rate at follow-up was 98.5%. 25 out of 264 patients (9.5%) had to be readmitted within the first eight weeks after PFO closure, 16 due to atrial fibrillation warranting electric cardioversion, one due to an arteriovenous fistula that was operated, four due to chest pain/pain at the access site, and four patients developed fever. There was no difference in SDD among patients who received ProGlide™ vs. patients who did not receive ProGlide™.ConclusionSDD appears safe after transcatheter PFO closure with the GSO device with high procedural success rates. Low rates of complications and readmissions make the intervention suitable for this patient-friendly and cost-effective concept

Fabrication of electroactive multi-layered polyazulene thin films by atmospheric pressure-vapor phase polymerization

Thin films of polyazulene (PAz) are produced by using an optimized atmospheric pressure–vapor phase polymerization (AP-VPP) method. Method optimization is carried out by studying the effect of cell temperature, substrate temperature, polymerization time, and washing-solvent on film properties like optical bandgap, sheet resistance, surface roughness, and % transmittance (%T). Multi-layered PAz films were produced by layer-by-layer engineering. The effects of thin, electroactive multiple layers on film properties are investigated. UV–Vis, IR, and Raman analysis are utilized to understand the extended conjugation length and nature of the charge carriers. The spectroscopic data revealed the anomalous behaviour of PAz at a high level of doping. The proportion and amount of quinoid conformation is discussed. The addition of layers changes the transport of ions across the electroactive PAz films, which is studied using cyclic voltammetry at various scan rates. AFM and SEM images reveal a change in structural properties which is further correlated with a deviation of capacitance values at elevated scan rate. Comparison with earlier reported literature on electrochemically and chemically synthesized PAz is also provided. The conductivity, transparency and high capacitance show a promising application of AP-VPP PAz in various fields.</p

Synthesis of Layered Double Hydroxides and TiO2 Supported Metal Nanoparticles for Electrocatalysis

In the present work, solution-phase synthesis was employed to prepare two sets of catalysts with different transition metals as active sites. One set contained Au or Pd supported on TiO2 (Au-TiO2, Pd-TiO2), whereas the other set contained layered double hydroxides (NiFe-LDH and CuFe-LDH). The electrocatalytic performance of these composite materials was investigated by cyclic voltammetry (CV) using a model compound 4-nitrophenol (4-NP). Composite materials were characterized by various analytical techniques to gain insight into the catalysts active sites. The morphology and structure of the prepared samples were investigated by X-ray diffraction, attenuated total reflectance Fourier transform infrared, X-ray photoelectron spectroscopy, transmission scanning electron microscope, and field emission scanning electron microscope. Metal nanoparticles loading on TiO2 was measured by inductively coupled plasma - optical emission spectrometry. CV measurements were performed in acetonitrile solution containing 0.1 m tetrabutylammonium hexafluorophosphate (TBAPF(6)) and 1 mm 4-NP. Among all dioxides (Au-TiO2, Pd-TiO2) and hydroxides (NiFe-LDH and CuFe-LDH) studied, Pd-TiO2 shows the lowest onset potential (-0.32 V vs. Ag/AgCl) for the electrocatalytic reduction of 4-NP. This is the first comparative study of such materials for 4-NP electrocatalysis in aprotic solvent, thus demonstrating the suitability of dioxide and hydroxide based materials as electrocatalysts

AVR: Reducing Memory Traffic with Approximate Value Reconstruction

This paper describes Approximate Value Reconstruction (AVR), an architecture for approximate memory compression. AVR reduces the memory traffic of applications that tolerate approximations in their dataset. Thereby, it utilizes more efficiently off-chip bandwidth improving significantly system performance and energy efficiency. AVR compresses memory blocks using low latency downsampling that exploits similarities between neighboring values and achieves aggressive compression ratios, up to 16:1 in our implementation. The proposed AVR architecture supports our compression scheme maximizing its effect and minimizing its overheads by (i) co-locating in the Last Level Cache (LLC) compressed and uncompressed data, (ii) efficiently handling LLC evictions, (iii) keeping track of badly compressed memory blocks, and (iv) avoiding LLC pollution with unwanted decompressed data. For applications that tolerate aggressive approximation in large fractions of their data, AVR reduces memory traffic by up to 70%, execution time by up to 55%, and energy costs by up to 20% introducing less than 1% error to the application output

PHOTO CHROMATIC SENSORS OF MULTINARY MIXED VALENCE INORGANIC MICRO NEEDLES

The recent I-U measurements on the individual micro needle-shaped crystals, of the ternary mixed valence compound In5Se5Cl, crystallizing in the monoclinic crystal system (P21/m), showed significant light sensitivities. Micro needles of In5Se5Cl “glued” on Si- and Cu- substrates were measured under five different wavelengths with various irradiation intensities to investigate their photo chromatic sensing behavior along with the substrate’s influence. In the measuring voltage range 0 – 3 V and maximal LED illumination intensity, current jumps above two orders of magnitude were observed for white light (4100 K; 200 lm), followed by the blue light (460 nm; 976 mW). The amber light (590 nm; 203 mW) exhibited the lowest response. Green- and blue light were selected to determine the substrate’s effect. The micro-needles chips prepared with Si-substrates displayed higher currents for the same voltages in comparison to those prepared with Cusubstrates. These differences decreased with the voltage increase for both employed wavelengths. The mutual structural substitution of a selenium with sulfur, led to the compound In5Se4Cl. The later crystallizes similarly to In5Se5Cl. Its I-U measurements recorded with green and blue light, on Cu-substrate chips within the voltage range 0 -3 V, revealed more pronounced photo chromatic sensorial for both wavelengths used. These differences increased with the voltage increase for both employed wavelengths. At 3 V, current increases up to 2.2 times and 2.4 times were observed for the green light and blue light respectively. Typically high and better distinguishable sensorial activity was observed for all the employed wavelengths using chips with In5Se4Cl crystals on Cu-substrate, even at minimal irradiation LED power (0.25 %). The micro-reflection measurements of both needle-shaped crystals displayed a substitution dependent band-gap. For In5Se5Cl the band gap was estimated at 580 nm. Thickness interference oscillations strongly damped due to structural inhomogeneity or defect-related absorption suggest two possible band gaps for In5Se4Cl; at 540 nm or at 620 nm

Exploring amide linkage in a polyviologen derivative towards simultaneous voltammetric determination of Pb(II), Cu(II) and Hg(II) ions

In this study, we report reductive electrosynthesis of a polyviologen derivative bearing amide linkage in its side chain, derived from a cyanopyridinium based monomer with amide functionality. The as grown film was characterized by cyclic voltammetry which displays a well-defined and reversible two step redox response characteristic of viologen. FTIR analysis show evidence of amide linkage and successful reduction of cyanopyridinium moieties to polyviologen. In situ multi ESR/UV-Vis-NIR spectroelectrochemistry show a single line in ESR signal, thereby suggesting polarons as the only charge carrier involved during charging/discharging process. Furthermore, a characteristic UV&ndash;Vis absorption spectra confirms viologen formation. Finally, the polyviologen film is subjected to simultaneous voltammetric determination of heavy metal ions, Pb(II), Cu(II) and Hg(II). The amide linkage in the polyviologen derivative is supposedly complexing these divalent metal ions, enabling their sensitive and simultaneous determination with low detection limits.</div