Uncovering influential factors in human antibiotic prescribing: a meta-synthesis study informed by the Theoretical Domains Framework.

This study aimed to identify modifiable determinants (facilitators and barriers) related to the choice of prescribing antibiotics in human medicine across clinical settings. Enhanced management of antibiotics can help slow the spread of resistant bacteria. A qualitative meta-synthesis approach was used, according to Sandelowski and Barroso's method. Included studies were evaluated using the Critical Appraisal Skills Programme. Findings were extracted and organized to form a qualitative meta-summary. The Theoretical Domains Framework, the Capabilities-Opportunities-Motivation (COM-B) model and the Behaviour Change Wheel were used as a coding matrix for data interpretation. The analysis of 63 included studies revealed barriers and facilitators in 12 of 14 domains specified by the Theoretical Domains Framework. Prescribers' capabilities, motivation and opportunities were found to be the main drivers of antibiotic prescribing behaviour. Knowledge, skills, beliefs, expectations, the influence of patients and colleagues, organizational culture and infrastructure characteristics have a significant impact on prescribing behaviours. A comprehensive inventory of factors related to antibiotic prescribing has been compiled. Interventions to promote appropriate antibiotic prescribing should take a systemic approach rather than focusing solely on individual-level variables. Furthermore, the adoption of co-design approaches for such interventions is desirable to ensure greater applicability and sustainability in the real-world context of organizations.

Detection of benzo[a]pyrene-diol-epoxide-DNA adducts in white blood cells of psoriatic patients treated with coal tar.

An enzyme-linked immunosorbent assay (ELISA) was used to detect BPDE-DNA adducts in white blood cells of 23 psoriatic patients undergoing clinical coal tar therapy. Ten of these patients were reanalyzed 2-5 months after the end of the coal tar treatments. The results show that the mean adduct level during the treatment period was 0.26 +/- 0.16 fmole BPDE/micrograms DNA (7.7 +/- 4.9 adducts/10(8) nucleotides), while 2-5 months later the mean adduct level had decreased significantly (P less than 0.005) to 0.11 +/- 0.08 fmole BPDE/micrograms DNA (3.3 +/- 2.4 adducts/10(8) nucleotides). No relationship could be ascertained between the level of exposure and the amount of BPDE-DNA adducts. In addition, no difference in the level of DNA adducts was found between smoking and non-smoking patients.

Evidence for substantial formation of r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene- deoxyguanosine in human lymphocytes treated in vitro with benzo[a]pyrene.

The possibility that the amounts of r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene- deoxyguanosine (anti-BaP diol epoxide-dGuo) and r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene- deoxyguanosine (syn-BaP diol epoxide-dGuo) may vary in human lymphocyte cultures from different donors was investigated by comparing DNA adducts formed after treatment with [G-3H]benzo[a]-pyrene (4 microM) for 24 h. In most cases, greater than 50% of the DNA adducts were derived from r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (syn-BaP diol epoxide).

Induction of SOS response in Escherichia coli strain PQ37 by 16 chemical compounds and human urine extracts.

The SOS Chromotest on Escherichia coli strain PQ37 was used to detect DNA damage induced by 16 chemical compounds and urine samples from smokers and a non-smoking psoriatic patient treated with mineral coal tar. The results confirmed the strong SOS inducing activity of 2-aminoanthracene and benzo[a]pyrene with metabolic activation and N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C and 4-nitroquinoline-N-oxide without metabolic activation. A weaker response in the absence of microsomal enzymes was observed with hydroxyurea (only at high doses) and the soluble Cr(VI) compounds potassium chromate and potassium dichromate. No effect was observed with ampicillin, cadmium chloride, cyclophosphamide, griseofulvin, the insoluble Cr(VI) compound lead chromate, the soluble Cr(III) compounds chromium nitrate, chromium chloride, chromium potassium sulphate, and the chelating agent sodium nitrilotriacetate. Among the Cr(III) compounds only chromium acetate produced a low but significant increase of SOS inducing activity. Solubilization by nitrilotriacetate of genotoxic Cr(VI) from insoluble lead chromate was observed, whereas no interaction occurred between nitrilotriacetate and the soluble Cr(VI) and Cr(III) compounds. Using urinary XAD-2 extracts, we found the SOS Chromotest poorly sensitive to the mutagens present in urine from tobacco smokers which, on the other hand, were detected by the gene mutation assay in Salmonella typhimurium (Ames test). A urine sample obtained from a psoriatic patient, therapeutically treated with mineral coal tar, had a significant SOS inducing activity with and even without metabolic activation, whereas in the Ames test it was active only in the presence of metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological monitoring of human exposure to coal tar. Urinary excretion of total polycyclic aromatic hydrocarbons, 1-hydroxypyrene and mutagens in psoriatic patients.

Three methods for the biological monitoring of human exposure to coal tar were compared. Levels of 1-hydroxypyrene(1-OH PYR), polycyclic aromatic hydrocarbons (PAH) and mutagens (Ames plate incorporation assay using Salmonella typhimurium strain TA98 in the presence of S9 and beta-glucuronidase) were determined in urinary samples from psoriatic patients undergoing topical treatment with mineral coal tar. A single sample of urine with a high content of PAH was diluted with urine of nonexposed, non-smoking subjects in order to obtain nine samples with a decreasing content of PAh metabolites. Mutagenicity of the extracts was detectable down to the dilution corresponding to a content in 1-OH PYR of about 50 micrograms/g creatinine and total PAH of 7 micrograms/g creatinine. In a second phase the three indicators of exposure to PAH were compared in 16 urinary samples from four psoriatic patients. The total PAH levels determined by the acidic deconjugation/reduction method were confirmed to be nearly always lower than the corresponding levels of 1-OH PYR alone. Most of the extracts were mutagenic, however, some of the samples with a high content in PAh metabolites were not mutagenic. In all the urinary samples analyzed the excretion of 1-OH PYR was markedly greater than in control subjects. 1-OH PYR and urinary mutagenicity levels were well correlated. The present data suggest that both the determination of mutagenicity and 1-OH PYR in urine may be used to monitor occupational exposure to PAH, the latter method being cheaper and of greater specificity and sensitivity.

Nitrilotriacetic acid (NTA) does not induce chromosomal damage in mammalian cells either in vitro or in vivo.

We used human lymphocyte cultures to repeat the experiments under the very particular conditions of nitrilotriacetic acid (NTA) treatments (high doses: up to 10(-2) M; very long exposure times: up to 5 days) which have been described as being able to induce chromosomal aberrations, and we also performed the more conventional treatments (24-48 h of exposure) as suggested in the protocols adopted by the EEC-OECD. Mitomycin C was routinely used as a positive clastogenic control. NTA did not significantly increase the frequency of chromosomal aberrations in any of the different experimental conditions adopted. Furthermore, no induction of micronuclei was observed in mouse polychromatic erythrocytes after treatment in vivo for up to 48 h with NTA (200-400 mg/kg b.w.), whereas the frequency of micronuclei was significantly increased by mitomycin C (1 mg/kg b.w.).

Psychiatry on the prevention of crime.

The main endeavor of Forensic Psychiatry is to find out the causes, to investigate the psychodynamics of crime, hence based on them, to try to prevent or to treat them. In this connection, I will not enter into details today about the position of delinquency into psychodynamics, as they have elsewhere been described; I only would emphasize some cases which take place during the state so-called "hystero-epilepsy" of Charcot.

Etiology and the prevention of wars. (Preliminary thoughts).

There is a suggestion in the previous paper that a way out to convey the overwhelming progress and "heavy" civilization of humanity may be to explore the Space, the Universe, and it, indeeed, results in an excellent job what American and Soviets together are these days endeavoring toward new exploration in Space. Let us see now, is this way out going to give the solution of our problem, hence avoid wars in the world?

Psychiatry on the prevention of crime.

The main endeavor of Forensic Psychiatry is to find out the causes, to investigate the psychodynamics of crime, hence based on them, to try to prevent or to treat them. In this connection, I will not enter into details today about the position of delinquency into psychodynamics, as they have elsewhere been described, I only would emphasize so-called "hystero-epilepsy" of Charcot.

Etiology and the prevention of wars (preliminary thoughts).

There is a suggestion in the previous paper that a way out to convey the overwhelming progress and "heavy" civilization of humanity may be to explore the Space, the Universe, and it, indeed, results in an excellent job what American and Soviets together are these days endeavoring toward new exploration in Space. Let us see now, is this way out going to give the solution of our problem, hence avoid wars in the world?