Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis: a prospective, multicenter, observational study (AVANTI)

Background

Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies.

Methods

AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients?>?35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected.

Results

In the efficacy population (N?=?2536), chronic bronchitis had been prevalent for?>?10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4?±?1.9 days. Symptom improvement was reported after a mean of 3.4?±?1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N?=?2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin.

Conclusions

A significant number of patients in this observational study had risk factors for poor outcome, justifying use of moxifloxacin. The safety profile of moxifloxacin and its value as an antibiotic treatment were confirmed. Physicians complied with the recommended 400 mg once-daily dose in a large proportion of patients, confirming the advantages of this simple dosing regimen.

Trial registration

ClinicalTrials.gov identifier: NCT00846911     

Wearable defibrillator use in heart failure (WIF): results of a prospective registry

Background

In patients with non-valvular atrial fibrillation (NVAF) at high risk for stroke guidelines consistently recommend long-term oral anticoagulation (OAC) with a vitamin K antagonist. However recommendations remain ambiguous in respect to the precise OAC initiation regimens. Based on the clinical observation, that the initiation of OAC for NVAF varies considerably in daily practice, we aimed to assess the current practice in Switzerland.

Methods

Cross-sectional survey of randomly selected general practitioners, internists and cardiologists from different health care settings in an urban Swiss region that covers 1.4 million inhabitants. The main outcome measures were the preferred antithrombotic initiation regimen and long-term treatment in patients with newly diagnosed NVAF at high risk for stroke.

Results

We received 226 out of 388 (58.2%) surveys. Compared to physicians working in a hospital setting (33.6% of respondents) physicians in ambulatory care reported more years of experience and claimed lower-use (never or seldom) of guidelines in general (47.6 vs. 12.2%). Regarding long-term thromboembolic prophylaxis 93.7% of all responders followed current recommendation by choosing an OAC. When focussing on guideline-consistent correct OAC initiation (either low-dose initial OAC or a combination of LMWH and OAC) adherence dropped to 60.6% with hospital physicians demonstrating a significantly higher use of guideline-conform OAC regimens (79.7 vs. 51.0%). Medical speciality in non-hospital physicians was not related to correct guideline-use. Hospital setting remained independently associated with a guideline-conform OAC initiation regimen (OR 2.8, p = 0.023) when controlled for medical speciality, physicians' characteristics and clinical experience. Problems when starting an anticoagulation treatment were seldom reported (never or seldom accounting for 94.1% of all responses).

Conclusions

The guideline adherence with respect to OAC initiation regimens in NVAF was significantly lower when compared to long-term treatment and health care setting rather than medical speciality explained guideline-conform OAC initiation. The majority of the physicians did not consider the initiation of anticoagulation to be a major obstacle in outpatient care.     

Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated. CgA levels were measured with two different methods, a two-step immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA). CgA was measured centrally by two reference laboratories, one of which used IRMA and the other ELISA, and it was measured by the participating institutions with the method routinely used by each of them. The major findings of the present study were: (i) the two assays for the determination of CgA present good diagnostic performance; (ii) both assays are robust and guarantee comparable results when applied in different settings (central vs local laboratory); (iii) the negative/positive cutoff points (87 ng/mL for IRMA and 21.3 U/L for ELISA) were established according to standardized criteria; (iv) the results obtained with the two assays in basal clinical samples of patients affected by NETs show an apparently satisfactory correlation (rs = 0.843, p < 0.0001). However, a possibly clinically meaningful 36% discordance rate was found. These findings support the hypothesis that the two CgA kits might provide partially different information.     

Troponin elevation in acute ischemic stroke (TRELAS) - protocol of a prospective observational trial

Background  

Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup.     

The psychological effect of mastectomy with or without breast reconstruction: a prospective,multicenter study

A multicenter, prospective study ( = 103) examined the psychological implications of women's decisions for or against breast reconstruction. Recognized measures of anxiety, depression, body image, and quality of life were completed before the operation, and 6 and 12 months later. A reduction in psychological distress over the year following the operation was evident in each surgical group (mastectomy alone or immediate or delayed reconstruction), indicating that reconstructive surgery can offer psychological benefits to some women; however, others report improved psychological functioning without this surgical procedure. In contrast to existing retrospective research, the prospective design enabled the process of adjustment during the first year after the operation to be examined. The results indicate that breast reconstruction is not a universal panacea for the emotional and psychological consequences of mastectomy. Women still reported feeling conscious of altered body image 1 year postoperatively, regardless of whether or not they had elected breast reconstruction. Health professionals should be careful of assuming that breast reconstruction necessarily confers psychological benefits compared with mastectomy alone.     

The cryopreservation of spermatozoa of the burbot,Lota lota (Gadidae,Teleostei)

The cryopreservation of spermatozoa of a teleost fish, the burbot, Lota lota (Gadidae) was investigated. Cryopreserved semen had the highest motility rate (46.6+/-8.0%, fresh semen control 86.5+/-8.2%) and fertility (78.1+/-2.7% embryo survival in hatching stage, fresh semen control 82.2+/-2.9%) when 10% methanol, 1.5% glucose and 7% hen egg yolk were used as cryoprotectants. Freezing was performed in 0.5-ml straws in the vapour of liquid nitrogen at 1cm above the level of liquid nitrogen and thawing in water at 25 degrees C for 20s. For optimal fertilization cryopreserved semen was first mixed with the eggs and then 25 or 50 mmol/L NaCl solution (pH 8.5) was added at a ratio of 1:24 (semen:saline solution). Under these conditions fertilization ratios in the range of fresh semen control were obtained at minimal sperm to egg ratios of 1.7 x 10(6):1. Fertilization with cryopreserved semen had no influence on the embryonic development, as the ratio of embryos which stopped development and the ratio of embryonic malformations were similar to fresh semen.     

Semen collection,characterization, and cryopreservation in a Magellanic penguin (Spheniscus magellanicus)

A cooperative method was developed for collecting semen from a Magellanic penguin. Ejaculate parameters and semen production during a breeding season were characterized. Experiments were performed to study the effect on penguin spermatozoa of two temperatures (4°C and 21°C) for short‐term storage, and two cryoprotectants (dimethylsulfoxide [DMSO] and ethylene glycol [EG]) for long‐term storage (cryopreservation). All dilutions were made using modified Beltsville Poultry Semen Extender. Sperm quality was assessed by evaluating motility and forward progression (sperm motility index [SMI]), viability, and morphology. A total of 39 ejaculates was collected over the 40‐day study period. Thirty‐eight ejaculates contained spermatozoa, but semen quality decreased toward the end of the study period. Varying levels of urate contamination were present in all ejaculates. Sperm quality parameters were similar for diluted samples held at 4°C and 21°C, and samples maintained high numbers of viable (77.8 ± 5.4%) and morphologically normal (67.9 ± 2.5%) spermatozoa at 3 hr. SMI and percentage of viable sperm decreased (P < 0.05) and the number of spermatozoa with a bent head or midpiece increased (P < 0.05) for both temperature groups over the 3‐hr storage interval. DMSO and EG were equally effective in maintaining penguin sperm quality parameters during the cryopreservation and thawing process. Frozen‐thawed semen maintained 69 ± 5 and 78 ± 3% of its pre‐freeze SMI and viability, respectively. SMI and viability decreased slightly during the cooling and equilibration phases but remained relatively stable during the 3‐hr storage interval post‐thaw. Frozen‐thawed semen also exhibited an increase (P < 0.05) in spermatozoa with a bent head or midpiece over time. The pre‐freeze SMI was higher (P < 0.05) for ejaculates with low levels of urates (clean ejaculates) compared with ejaculates with high levels of urate contamination, but sperm viability and morphology were similar (P > 0.05). Both SMI and viability of frozen‐thawed spermatozoa were higher (P < 0.05) for clean than for contaminated ejaculates. This is the first report on penguin ejaculate parameters, semen production, and preliminary methods for short‐ and long‐term semen storage. Zoo Biol 18:199–214, 1999. © 1999 Wiley‐Liss, Inc.     

Human basement membrane collagen (type IV). The amino acid sequence of the alpha 2(IV) chain and its comparison with the alpha 1(IV) chain reveals deletions in the alpha 1(IV) chain

The cDNA and protein sequences of the N-terminal 60% of the alpha 2(IV) chain of human basement membrane collagen have been determined. By repeated primer extension with synthetic oligodeoxynucleotides and mRNA from either HT1080 cells or human placenta overlapping clones were obtained which cover 3414 bp. The derived protein sequence allows for the first time a comparison and alignment of both alpha chains of type IV collagen from the N terminus. This alignment reveals an additional 43 amino acid residues in the alpha 2(IV) chain as compared to the alpha 1(IV) chain. 21 of these additional residues form a disulfide-bridged loop within the triple helix which is unique among all known collagens.     

Steroidogenesis in the Ovarian Follicle of Medaka (Oryzias latipes, a daily spawner) during Oocyte Maturation

The metabolism of ¹⁴C-labeled steroid precursors by cell-free homogenates of medaka ( Oryzias latipes , a daily spawner) ovarian follicles at 12 different developmental stages was examined using thin layer chromatography (TLC). The radioactive metabolites produced were identified and tested for their ability to induce germinal vesicle breakdown (GVBD) in oocytes in an in vitro homologous bioassay. When homogenates of follicles isolated during oocyte maturation were incubated with ¹⁴C-labeled 17α-hydroxyprogesterone, 13 metabolites were detected in TLC. Among these metabolites, one metabolite exhibited very high maturation inducing activity by the in vitro bioassay. This metabolite was identified as 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-DP) by its chromatographic mobility in TLC and recrystallization to constant specific activity. 17α,20β-DP production was high in follicles collected between 10 and 6 hr before spawning. A much less biologically active metabolite, 17α,20β-dihydroxy-5β-pregnane-3-one appeared in follicles immediately after the formation of 17α,20β-DP. A similar pattern of steroidogenesis was observed when the follicles were incubated with ¹⁴C-labeled pregnenolone and progesterone. The timely synthesis of 17α,20β-DP in medaka at the onset of oocyte maturation, together with the demonstration that this progestogen is the most potent inducer of oocyte maturation in vitro , provides further evidence that 17α,20β-DP is the naturally occurring maturation-inducing hormone in the medaka. The results also suggest that the conversion of 17α,20β-DP to its 5β-reduced metabolite may be an inactivation process.     

The preparation,spectral studies,and the crystal structure of dimethylbis(O-ethylxanthato)tin(IV)

Tin-119 NMR data indicate that the tin atom in (CH₃)₂Sn(S₂COC₂H₅)₂ is four co-ordinated in dichloromethane solution. However, single crystal X-ray analysis shows the tin atom to be six co-ordinated in the solid state in which the bidentate xanthate ligands display gross asymmetry in their mode of co-ordination to the tin. The crystals are molecular and there is no association between neighbouring molecules. The unit cell of Me₂Sn(exa)₂ is orthorhombic, Pnma, a = 14.165(1), b = 7.675(9), c = 13.977(2) Å with Z = 4. The structure was refined by conventional least squares methods with final R 0.041 and R_w 0.043 for 1229 unique reflections with 1 ? 2σ(I).     

Amino-terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV)

Increased concentrations of procalcitonin (PCT) are found in the plasma of patients with thermal injury and in patients with sepsis and severe infection, making this molecule important as a diagnostic and prognostic marker in these diseases. Interestingly, only the truncated form of PCT, PCT(3-116), is present in the plasma of these patients. The enzyme responsible for this truncation is unknown as yet. Here, using capillary zone electrophoresis, mass spectrometry and Edman sequence analysis, we demonstrate that dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) is capable of catalyzing the hydrolysis of PCT(1-116), releasing the N-terminal dipeptide Ala-Pro. We hypothesize that PCT(3-116) is the result of the hydrolysis of PCT(1-116) by soluble DP IV of the blood plasma or by DP IV expressed on the surface of cells.     

Inhibition of dipeptidyl peptidase IV (DPP IV) by 2-(2-amino-1-fluoro-propylidene)-cyclopentanecarbonitrile,a fluoroolefin containing peptidomimetic

Novel, potent inhibitors of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5, CD26), containing the fluoroolefin peptide isostere psi [CFz.dbnd6;C], have been prepared via the intermediacy of the Peterson fluoroolefination reaction. The nitrile containing inhibitors were found to inhibit dipeptidyl peptidase IV competitively with K(i) values for the l-3 and u-3 inhibitors of 7.69 and 6.03 microM, respectively. In contrast to earlier reported fluoroolefin containing inhibitors, the nitriles underwent no detectable degradation at pH 7.6 under buffered conditions.     

Preservation, mass production and storage ofStagonospora convolvuli, a bioherbicidecandidate for field bindweed (Convolvulusarvensis)

Different solid substrates were investigated as spore production methods for Stagonospora convolvulistrain LA39, a potential bioherbicide for field bindweed (Convolvulusarvensis L.). Up to 4 × 10⁸ spores/g of substratewere yielded on cous-cous (cracked hard wheat). Thespores were as pathogenic as those grown on artificial medium (V-8-juice agar). The air-drying on kaolin and storage at 3 °C kept spores viable and pathogenic for 180 days. Spore germination exceeded70% for the first 140 days and then declined to 50%after 175 days. Less than 5% of spores were still viable after 17 months. The preservation of stock cultures in 10% glycerine at −80 ° C and in liquid nitrogen did not affect viability orpathogenicity of the spores. This revised version was published online in July 2006 with corrections to the Cover Date.     

Analysis and Preservation of Pleistocene Human and Animal Footprints: An Example from Toluquilla,Valsequillo Basin (Central Mexico)

Human and animal footprints found in the Valsequillo Basin were formed on the upper bedding planes surfaces of a volcanic ash (Xalnene Ash) deposited by a subaqueous volcano along the shores of a Pleistocene lake. The footprints were made on lake shorelines and the exposed lake floor during low stands associated, either with water displacement during the volcanic eruption, or due to climatically-driven fluctuations in the water balance. The Xalnene Ash has been dated to at least 40 K BP and consequently the human footprints provide evidence for much earlier colonization of the Americas than is often accepted. The methodology used to record, analyze and conserve these footprints used three-dimensional laser scanning, with sub-millimeter precision. This data were used to reproduce polymer models of individual footprints using the application of rapid-prototyping technology. This technology has wide significance for the study of ichnofacies in general. The characteristics of the human footprints and some problems associated with the volcanic ash as a molding medium for the clarity of these characteristics are given. These human footprints and their dating resolve the controversy related to the age of the archaeological and associated megafaunal remains that were reported in the Valsequillo Gravels in the 1960s and 1970s.     

The development of Spongilla lacustris from the oocyte to the free larva (Porifera,Spongillidae)

Summary During June and July oocytes appear in well-developed specimens of Spongilla lacustris. These differentiate from archeocytes, and during the first growth phase they reach a diameter of ca. 50 m. At this time each oocyte is enclosed in a single-layered follicle epithelium, which is retained until emergence of the larva.In the second phase the oocytes grow to about 220 m by phagocytosis of trophocytes. When phagocytosis has come to an end, there is a distinct layering of the yolk material that has formed within the cytoplasm of the oocyte. Small yolk granules surround the centrally located nucleus, and peripheral to these is a layer of larger spheres of yolk.Cleavage is totally equal to unequal. Some blastomeres are binucleate. In the 15-cell staged micro- and macromeres appear.The embryo consists of uniform cells with high yolk content; at the periphery they are slightly flattened rather than spherical. In this stage of development the first scleroblasts appear.Further development to the young larva is marked by the appearance of a cavity (the larval cavity) lined with pinacocytes. The cavity expands to occupy about half the volume of the larva at emergence, becoming hemispheric in shape. The cells at the periphery of the larva form a columnar, single-layered, multiseriate ciliated epithelium with teardrop-shaped nuclei.The emerging larva breaks through its follicle and the wall of the excurrent canal system; occasionally larvae can be found in the canals. At this time the larva has developed a few flagellated chambers, which may already be integrated into the primordia of the excurrent canal system. The previously discernible scleroblasts have now formed isolated spicules, which may adhere to form spicule-spongin complexes.     

Diphenylethanediamine (DPEDA) derivatives as chiral selectors: IV. A comparison of 3,5-dinitrobenzoylated (S,S)- and (S,R)-DPEDA-derived chiral stationary phases with Pirkle's standard (R)-phenylglycine-derived phase in normal phase HPLC

Undecanoyl bound 3,5-dinitrobenzoyl-(S,R)-1,2-diphenylethane-1,2-diamine [(1S,2R)-DNB-DPEDA] as chiral selector (SO) has been synthesized and used as a chiral stationary phase (CSP II) for normal-phase enantioselective HPLC. It is compared with the already published diastereomeric (1S,2S)-DNB-DPEDA-derived CSP I and with the “standard” Pirkle DNB-(R)-phenylglycine-derived CSP III. Chromatographic data for about 100 racemic analytes reveal that CSP II is able to separate especially well enantiomers of derivatized aromatic carboxylic acids and analytes having a benzyl substituent bound at the chiral center. However, CSP I was found to be superior to CSP II and III in its general applicability and its ability to resolve enantiomers of heterocyclic drugs. © 1994 Wiley-Liss, Inc.     

The antitumor activity of di-n-butyltin(IV) glycylglycinate,and the correlation with the structure of dialkyltin(IV) glycylglycinates in solution

The in vivo activity of Bu₂ⁿSnGlyGly, Na(CI₂GaGlyGly), and CIGaGlyGly (GlyGly^2?- = glycylglycinate) has been investigated in connection with a number of tumors. Positive results have been obtained only for the Bu₂ⁿSn^IV complex in the case of leukemia P-388 In order to try to interpret the pharmacological data on a molecular basis, the nature of the species present in solutions of AIK₂Sn GlyGly complexes, as well as the reactivity of aqueous Me₂SnGlyGly, have been studied. The presence of chelated species (I), Figure 1, in organic solvents, and the equilibrium (I) ? (II), Figure 1, in water and mixed water-organic solvent systems, have been inferred from conductance measurements, as well as from studies by Mössbauer (in frozen solution), ¹H, ¹³C, and ¹¹⁹Sn NMR, and ir spectroscopy. Moreover, solvated (II) would release AlK₂Sn^IV moieties, as evidenced by the slow formation of (Me₂SnO)_n from aqueous Me₂Sn GlyGly. The involvement of (I) and (II) in the transportation of these drugs across cell membranes is discussed.     

Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: a prospective multicenter study

In a prospective multicenter study 42 thrombocytopenic (less than 30 X 10(9) platelets/l) children with chronic idiopathic thrombocytopenic purpura (ITP) or with acute ITP, dependent on or refractory to corticosteroids, were given 0.4 g i.v. IgG/kg body weight/day on 5 consecutive days and thereafter once a week if the platelet count fell to less than 20 X 10(9)/l or if the patient bled. After the initial 5 days of i.v. IgG the platelets rose within a mean of 7-8 days to greater than 30 X 10(9)/l in all and to greater than 150 X 10(9)/l in 33 of 42 patients (79%). After a mean observation time of 26.6 months 26 of 42 patients (62%) showed a satisfactory long-term effect, i.e. no need for treatment for at least 6 months without bleeding and with no platelet counts below 20 X 10(9)/l. No difference in response rate was found between children with chronic and those with previously treated acute ITP. These results indicate that i.v. IgG could be used to control emergency situations, e.g. to stop bleeding or to prepare a patient for surgery. I.v. IgG also represents a good alternative to treatment modalities, such as splenectomy and/or the administration of cytostatic immunosuppressants with potentially serious side effects. In addition to the expected transient rise in serum IgG levels, i.v. IgG induced a more prolonged elevation of serum IgM. Platelet associated IgG, elevated before therapy, was correlated with the clinical long-term outcome.