Seventy-two-hour antibiotic retrieval from the ED: a randomized controlled trial of discharge instructional modality.

BACKGROUND: Limited health literacy is a risk factor for poor outcomes in numerous health care settings. Little is known about the impact of instructional modality and health literacy on adherence to emergency department (ED) discharge instructions. PURPOSE: To examine the impact of instructional modality on 72-hour antibiotic retrieval among ED patients prescribed outpatient antibiotics for infections. METHODS: English-speaking ED patients diagnosed as having acute infections and prescribed outpatient antibiotics were randomized to standard discharge instructions, standard instructions plus text-messaged instructions, or standard instructions plus voicemailed instructions targeting ED prescriptions. Health literacy was determined by validated instrument. Seventy-two-hour antibiotic retrieval, 30-day report of prescription completion, and discharge instructional modality preference were assessed. RESULTS: Nearly one-quarter of the 2521 participants demonstrated low health literacy. Low health literacy predicted decreased 72-hour antibiotic retrieval (χ(2) = 9.56, P=.008). No significant association with antibiotic retrieval was noted across the 3 treatment groups (χ(2) = 5.112, P=.078). However, patients randomized to the text message group retrieved antibiotic prescriptions within 72 hours more frequently than did those randomized to the voicemail treatment group (χ(2) = 4.345, P=.037), and patients with low health literacy randomized to voicemailed instructions retrieved their antibiotic prescriptions less frequently than did those randomized to standard of care instructions (χ(2) = 5.526, P=.019). Reported instructional modality preferences were inconsistent with the primary findings of the study. CONCLUSIONS: Discharge instructional modality impacts antibiotic retrieval in patients with low health literacy. Preference for discharge instructional modality varies by degree of health literacy, but does not predict which modality will optimize 72-hour antibiotic retrieval.

Preparation of new surface coating based on modified oil-based polymers blended with ZnO and CuZnO NPs for steel protection.

In our paper, we have synthesized modified PEA and alkyd resin by replacing the new source of polyol (SDEA) which was confirmed by different analyses such as IR, and 1HNMR spectra. A series of conformal, novel, low-cost, and eco-friendly hyperbranched modified alkyd and PEA resins were fabricated with bio ZnO, CuO/ZnO) NPs through an ex-situ method for mechanical and anticorrosive coatings. The synthesized biometal oxides NPs and its composite modified alkyd and PEA were confirmed by FTIR, SEM with EDEX, TEM, and TGA, and can be stably dispersed into modified alkyd and PEA resins at a low weight fraction of 1%. The nanocomposite coating was also subjected to various tests to determine their surface adhesion, which ranged from (4B-5B), physico-mechanical characteristics such as scratch hardness, which improved from < 1.5 to > 2 kg, gloss (100-135) Specific gravity (0.92-0.96) and also chemical resistance test which passed for water, acid, and solvent except alkali, was poor because of the hydrolyzable ester group in the alkyd and PEA resins. The anti-corrosive features of the nanocomposites were investigated through salt spray tests in 5 wt % NaCl. The results indicate that well-dispersed bio ZnO and CuO/ZnO) NPs (1.0%) in the interior of the hyperbranched alkyd and PEA matrix improve the durability and anticorrosive attributes of the composites, such as degree of rusting, which ranged from 5 to 9, blistering size ranged from 6 to 9, and finally, scribe failure, which ranged from 6 to 9 mm. Thus, they exhibit potential applications in eco- friendly surface coatings. The anticorrosion mechanisms of the nanocomposite alkyd and PEA coating were attributed to the synergistic effect of bio ZnO and (CuO/ZnO) NPs and the prepared modified resins are highly rich in nitrogen elements, which might be regarded as a physical barrier layer for steel substrates.

Charged oxygen defects in SiO2: going beyond local and semilocal approximations to density functional theory.

The long-standing problem of the oxygen self-diffusion mechanism in silicon dioxide, a prototypical oxide, both in the crystalline and in the amorphous phase, is studied from first principles. We demonstrate that the widely used local-density approximation to density functional theory (DFT) predicts a kinetic behavior of oxygen in strong disagreement with available experiments. Applying a recently developed scheme that combines DFT with quasiparticle energy calculations in the G0W0 approximation considerably improves defect energetics and gives gratifying agreement with experiment.

Correlation between subjective labour pain and uterine contractions: a clinical study.

Fifteen primiparous women underwent tocography during the second phase of the first stage of labour in order to evaluate the main characteristics of their uterine contractions (intensity, duration and pattern). At the end of each contraction, for a total of about 8 contractions per woman and an overall total of 125 tocographic curves, each woman was asked to make a subjective evaluation of the pain felt during that contraction using a 10 cm visual analogue scale (VAS). All the tocographic curves corresponding to the contractions studied were elaborated mathematically to determine the peak (intensity), base (duration) and area under the curve (AUC). Lastly, correlations between the mathematical parameters of the curves and corresponding VAS scores were sought. In the population a general positive correlation between the 3 main parameters of tocographic curves and the VAS score was demonstrated; the AUC and the peak tended to be better correlated with VAS than duration. Within-subject comparison showed the existence of a significant correlation with VAS score in 12/15 women as far as peaks are concerned, in 10/15 as far as AUC is concerned and in 0/15 women as regards duration. The findings support the concept that perceived labour pain depends in most of the women on the intensity and pattern of the uterine contractions. The possible clinical and experimental applications of this finding are discussed.

Effect of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (AP155) on human platelets in vitro.

The effect on human platelets of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimi din-4-one (AP155) was tested in vitro by measuring cyclic adenosine monophosphate (cAMP) level, cytosolic Ca++, [(125I)]fibrinogen binding as well as aggregation induced by several agonists. AP155 dose-dependently inhibited aggregation both in platelet rich plasma (PRP) and in washed platelets (WP), exerting its maximal power in the presence of collagen, ADP and platelet activating factor (PAF). It specifically inhibited the activity of cAMP high affinity phosphodiesterase (PDE), resulting in a sufficient increase in cAMP levels to activate cAMP-dependent protein kinase. AP155 was able to inhibit aggregation, the increase in cytosolic Ca++ induced by thrombin, and fibrinogen binding to ADP or thrombin-stimulated platelets. Thus, this new pyridopyrimidine derivative exerts its antiplatelet activity by increasing cAMP intracellular concentration.

Double-blind placebo-controlled trial of baclofen, alone and in combination, in patients undergoing voluntary abortion.

This study evaluated the analgesic efficacy of baclofen in relation to specific pain stimuli in 83 women (27 nulliparas and 56 multiparas) undergoing voluntary abortion (clamping of the cervix and dilatation and curettage). The patient population was divided into five treatment groups as follows: group 1, placebo; group 2, baclofen, 0.3 mg/kg, administered intravenously (IV); group 3, baclofen, 0.6 mg/kg IV; group 4, baclofen, 0.3 mg/kg IV, and fentanyl, 1.5 mg IV; and group 5, baclofen, 0.3 mg/kg IV, and diazepam, 5 mg given orally and 5 mg IV. In each case the surgical intervention was started using analgesia only. When the first sensation of pain was recorded, a paracervical anesthetic block was performed to provide pain relief for completion of the operation. The results showed that baclofen had significantly better analgesic properties than did placebo, with no important side effects. Its analgesic action seemed to be dose-dependent, since better results were obtained with the higher dose. The analgesic effect was slightly potentiated when baclofen was combined with fentanyl, but not when it was combined with diazepam. Factors independent of the pain stimuli and drugs used--the most important being parity--influenced the results.

1,8-Naphthyridines IV. 9-substituted N,N-dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4]triazolo[4,3-a][1, 8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities.

The title compounds (8) were synthesized through the cyclocondensation of the corresponding N-substituted 4-amino-2-chloro-1,8-naphthyridine-3-carboxamides (4) with the proper hydrazides, in order to evaluate their anti-inflammatory and anti-aggressive properties. Several compounds 8 exhibited high anti-inflammatory activity (carrageenin-induced paw edema assay in the rat) along with appreciable anti-aggressive properties (isolation-induced aggressiveness test in mice). With respect to anti-inflammatory activity, the most active compounds (8n and 8c) produced a 61% edema inhibition at the 25 mg/kg dose, and 50 or 35% inhibition, respectively, at the 12.5 mg/kg dose. The structure-activity relationships are discussed.

1,5-Benzodiazepines. Part XII. Synthesis and biological evaluation of tricyclic and tetracyclic 1,5-benzodiazepine derivatives as nevirapine analogues.

A number of properly substituted 5H-pyrimido[4,5-b][1,5]benzodiazepines (2) and pyrazolo[3,4-b][1,5]benzodiazepines (3 and 4), as well as compounds 5-7, which are derivatives of new tetracyclic systems, were prepared as nevirapine analogues through multistep synthetic routes. The cytotoxic and anti-HIV-1 properties of compounds 2-7 were evaluated in cell-based assays, together with their inhibitory activity against the HIV-1 recombinant reverse transcriptase (rRT) in enzyme assays. The modifications introduced into nevirapine heterocyclic skeleton proved to have a negative effect for the anti-HIV-1 activity. It is worth noting that some of the new derivatives proved to be cytotoxic in the low micromolar range.

Acid-catalysed hydrolysis and benzodiazepine-like properties of 5-(dialkylamino)- and 5-(alkylthio)-substituted 8-chloro-6-phenyl-6H-[1,2,4]triazolol[4,3-a][1,5]benzodiazepines in mice.

The in-vitro and in-vivo hydrolysis of two benzodiazepine compounds has been studied to evaluate their in-vivo activity in mice. Compounds RL 218 and RL 236, selected as representative examples of N,N-dialkyl-8-chloro-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiaz epin-5-amines (1) and of their 5-(alkylthio) substituted analogues (2), were rapidly hydrolysed to the corresponding 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H )-one 3 (RL 214) in aqueous acidic solution at pH 1.5. This reaction also occurred extensively in mice when compounds RL 218 and RL 236 were given orally but not intraperitoneally. Both compounds were active against pentylenetetrazole-induced lethal convulsions in mice only when administered orally. After administration of pharmacologically effective oral doses (ED50, the dose protecting 50% of mice), at the time of assessment of the anti-pentylenetetrazole activity, mean brain concentrations of RL 218 and RL 236 were below the limits of sensitivity of the analytical procedure whereas brain concentrations of their metabolite RL 214 were comparable with that present after an oral equiactive dose of this compound itself. RL 214 but not RL 218 or RL 236 had in-vitro affinity for brain benzodiazepine receptors. These results indicate that the anticonvulsant activity of RL 218 and RL 236 in mice depends essentially on their in-vivo transformation into the common active metabolite RL 214 which most probably arises as a result of acid catalysed hydrolysis in the gastric juice.

Solid and cystic tumor of the pancreas--case report.

Pancreatic tumors are rarely present in childhood. The authors present a case of papillary-cystic tumor in a 13-year-old girl, treated by partial pancreatoduodenectomy, with preservation of the pylorus. The histologic pattern was of a papillary cystic tumor without evident atypical nuclei. One year after operation, the girl is well without any finding of disease.

Pyran derivatives XIX. (Dialkylamino) substituted 1-benzopyranones and naphthopyranones with platelet antiaggregating activity.

2-(Dialkylamino)chromones 4 and 4-(1-piperazinyl)coumarins 11, as well as their angular benzo-fused derivatives 1, 2 and 12, 13, respectively, were synthesized and tested in vitro for their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP (5.0 microM), collagen (10.0 micrograms/ml), and A 23187 (calcimycin) (20.0 microM). Among the dialkylamino substituents used, and the ring systems examined, 1-piperazinyl and 1-benzopyran or naphtho[2,1-b]pyran, respectively, resulted the most effective ones for antiplatelet activity, both in the chromone and coumarin fields. 7-Ethoxy-4-(1-piperazinyl)coumarin 11b showed the highest activity, and higher than those of all reference compounds (ASA, trifluoperazine, propranolol, and dipyridamole) towards all platelet aggregation inducers.

1,8-Naphthyridines. III. N,N-dialkyl-5-chloro[1,2,4]-triazolo[4,3-a][1,8]naphthyridine-6-carboxa mides with anti-inflammatory activity.

Fifteen N,N-dialkyl-5-chloro[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxami des (7a-o) were synthesized through the cyclocondensation of the corresponding N,N-dialkyl-2,4-dichloro-1,8-naphthyridine-3-carboxamides with proper hydrazides, in order to evaluate their anti-inflammatory, antiaggressive, and analgesic properties. Four of the compounds tested showed a statistically significant and dose-dependent anti-inflammatory activity.

1,8-naphthyridines II. 2,4-disubstituted N,N-dialkyl-1,8-naphthyridine-3-carboxamides with anti-inflammatory and/or antiaggressive activities.

The preparation of the novel N,N-dialkyl-2,4-dichloro-1,8-naphthyridine-3-carboxamides 1c, e and N,N-dialkyl-2-(alkylamino or cycloalkylamino)-4-chloro-1,8-naphthyridine-3- carboxamides 2b, d-g, j-p is described. These compounds and the previously obtained analogs 1a, b, d, f and 2a, c, h, i have been tested for their anti-inflammatory and antiaggressive activities, as well as for their gross behavioral effects and acute toxicity. Nine of the twenty-two tested compounds exhibited a statistically significant anti-inflammatory activity in the carrageenin-induced edema assay in the rat (1e, f and 2h, o were the most active compounds). On the other hand, an interesting antiaggressive activity was displayed by ten compounds in the isolation-induced aggressiveness test in mice (compounds 2d, i, k showed the highest activity). Structure-activity relationships are briefly discussed.

[Synthesis and preliminary pharmacological screening of 2,4-disubstituted N,N-dialkyl-1,8-naphthyridine-3-carboxamides]. / Sintesi ed esame farmacologico preliminare di N,N-dialchil-1,8-naftiridin-3-carbossammidi 2,4-disostituite.

By treating at 100 degrees C 2-aminonicotinic acid with ethyl N,N-dialkylmalonamate (I) and phosphorus oxychloride N,N-dialkyl-4-chloro-1,2-dihydro-2-oxo-1,8-naphthyridine- 3-carboxamides (II) were obtained. The reaction of compounds (II) with an excess of refluxing phosphorus oxychloride afforded N,N-dialkyl-2,4-dichloro-1,8-naphthyridine-3-carboxamides (III), which in turn were treated at room temperature with excess primary amines to give a mixture of isomeric N,N-dialkyl-2-(alkylamino or cycloalkylamino)-4-chloro-1,8-naphthyridine-3-carboxamides (IV) and N,N-dialkyl-4-(alkylamino or cycloalkylamino)-2-chloro-1,8-naphthyridine-3-carboxamides (V). When this last reaction was performed at 160 degrees C, only N,N-dialkyl-2,4-bis(alkylamino or cycloalkylamino)-1,8-naphthyridine-3-carboxamides (VI) were obtained; under the same conditions (IV c) or (V c) reacted with methylamine to give isomeric 2,4-bis(alkylamino)derivatives (VII) or (VIII), respectively. Compounds (II b), (III b), (IV a,c,d), (V a,c,d) were submitted to a wide preliminary pharmacological screening. Some of them, depending on the structure, showed antihypertensive [(IV c)], anti-inflammatory [(IV c) greater than (III b)], or, in the behavioral test, anti-aggressive [(IV d) greater than (III b)] activity. Furthermore compound (III b) caused moderate inhibition of the 5-HT induced contraction of the guinea-pig ileum.

HPLC analysis of the nitrosation products of chlordiazepoxide.

Products originated from Chlordiazepoxide (I) hydrochloride/sodium nitrite interaction were analyzed by HPLC. The studied reactions were carried out in diluted hydrochloric acid solutions at pH values ranging between 0.5-5.0. Depending on the reaction pH values and molar ratios it was possible to find and assess variable amounts of the N-nitrosochlordiazepoxide (II), the dihydroquinazoline (III) and the lactam (IV). The highest degree of N-nitrosation was found at pH 3.5. At this pH value the yields of (II) were respectively 54.8% and 18.3% when the drug (I)/nitrite molar ratios were correspondingly 0.41 and 0.25. When the reaction was performed in concentrations which is possible to find in the gastric juice of patients taking (I) together with nitrite-rich foods the yield of (II) at pH 3.5 was 2.5%. Since in the meantime the genotoxicity of (II) was proved, "in vivo" formation of N-nitrosochlordiazepoxide (II) represents a potential risk not to be underestimated.

1,2-fused pyrimidines. VI. Substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones with antiplatelet activity.

The N-substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 2 d,g-i,l-p,r,s and derivatives 4,5 b,6 a,b, 7 a,b were prepared. Both these novel compounds (except the insoluble 7a) and compounds 2 a-c,e,f,j,k,q, 5a, previously prepared by us, were tested in vitro for their inhibitory activity on human platelet aggregation induced by ADP, collagen, or A23187. On the whole, the compounds tested proved to be more active towards collagen than towards ADP and A23187. The 2-(4-methyl-1-piperazinyl)derivative 2 g was the most active compound both towards ADP and collagen, whereas the 2-(diethylamino)derivative 2 b proved to be the most active one towards A23187.

Pyran derivatives. XX. 2-Aminochromone benzo-fused derivatives with antiproliferative properties.

The N-substituted 2-aminochromones 1 and their benzo-fused derivatives 2-4 described herein were mostly prepared by treating the corresponding (methylthio) derivatives 10-13 with an excess of the proper amines. Only the morpholino derivatives 3d and 4c were obtained from the reaction of the ethyl 3-morpholino-3-oxopropanoate/POCl3 reagent with 1-naphthol or 1-methyl-2-naphthol, respectively. The amino derivatives 1-4, as well as their methylthio analogues 10-13, were tested in vitro for their inhibitory activity on the infectivity of T2 bacteriophage, on the macromolecular synthesis in Ehrlich cells and on the clonal growth capacity of HeLa cells. Several of the angular or linear aminonaphthopyranones 2 and 3 or 4, respectively, and the (methylthio) derivatives 10, 11 and 13 induced a significant inhibition of DNA synthesis, but usually a clearly lower inhibition of clonal growth. Only the linear 2-amino-10-methyl-4H-naphtho[2,3-b]pyran-4-ones 4a and 4b significantly inhibited the clonal growth in HeLa cells and T2 bacteriophage infectivity, respectively.

[Chemistry and pharmacology of pyrane derivatives. XVII. Synthesis of substituted 2-(dialkylamino)-3-formylchromones and their tricyclic derivatives]. / Ricerche chimiche e farmacologiche su derivati piranici nota XVIII - sintesi di 2-(dialchilammino)-3-formilcromoni sostituti e di loro derivati triciclici.

Substituted 2-(dialkylamino)-3-formylchromones (II) were obtained from the reaction of substituted 2-(dialkylamino)chromones (I) either with the N,N-dimethylformamide-POCl3 reagent [compounds (IIa-e)] or with dichloromethylmethylether in the presence of TiCl4 [compounds (IIf-i)]. By treating (IIa,f) with hydroxylamine the oximes (IIIa,f) were prepared, which in turn were converted into the nitriles (IVa,f) by treatment with acetic anhydride. Compound (IIa), selected for the smallest steric hindrance of the 2-dialkylamino substituent, by reaction with hydrazines afforded [1]benzopyrano [2,3-c]pyrazole derivatives (VI), whereas reaction of (IIa) with guanidine, benzamidine or S-methylisothiourea gave rise to the formation of 5H-[1]benzopyrano[2,3-d]pyrimidine derivatives (IX). Among the compounds tested for their antiallergic properties, (IIf) showed an appreciable activity, but also high toxicity.

1,5-Benzodiazepines. X. Dialkylamino substituted 1,5-benzodiazepine and [1,2,4]triazolo [4,3-a][1,5] benzodiazepine derivatives with inhibitory activity on PAF-induced platelet aggregation.

Novel 4-(dialkylamino) substituted (4, 5 c, 8) and 2,4-bis(dialkylamino) substituted (6) 1,5-benzodiazepine derivatives were synthesized. Both these new compounds and the substituted 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine-5-amines 2 a-h, recently described by us, were tested in vitro for their inhibitory activity on the PAF-induced aggregation of human platelets. Actually, bicyclic compounds 4 d, 5 c and tricyclic compounds 2 g, h showed a significant activity: in all them the dialkylamino substituent was the 4-(ethoxycarbonyl)-1-piperazinyl group. On the contrary, compounds 4 d, 5 c, 2 g,h showed practically no inhibitory activity when platelet aggregation was induced by ADP, A23187, or collagen.