Routine wastewater-based monitoring of antibiotic resistance in two Finnish hospitals: focus on carbapenem resistance genes and genes associated with bacteria causing hospital-acquired infections.

BACKGROUND: Wastewater-based monitoring represents a useful tool for antibiotic resistance surveillance. AIM: To investigate the prevalence and abundance of antibiotic resistance genes (ARGs) in hospital wastewater over time. METHODS: Wastewater from two hospitals in Finland (HUS1 and HUS2) was monitored weekly for nine weeks (weeks 25-33) in summer 2020. A high-throughput real-time polymerization chain reaction (HT-qPCR) system was used to detect and quantify 216 ARGs and genes associated with mobile genetic elements (MGEs), integrons, and bacteria causing hospital-acquired infections (HAIs), as well as the 16S rRNA gene. Data from HT-qPCR were analysed and visualized using a novel digital platform, ResistApp. Eight carbapenem resistance genes (blaGES, blaKPC, blaVIM, blaNDM, blaCMY, blaMOX, blaOXA48, and blaOXA51) and three genes associated with bacteria causing HAIs (Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were studied. FINDINGS: There was a significantly higher number of ARGs at both hospitals in weeks 27-30 (174-191 genes) compared to other sampling weeks (151-171 genes). Our analyses also indicated that the two hospitals, which used different amounts of antibiotics, had significantly different resistance gene profiles. Carbapenem resistance genes were more prevalent and abundant in HUS1 than HUS2. Across both hospitals, blaGES and blaVIM were the most prevalent and abundant. There was also a strong positive association between blaKPC and K. pneumoniae in HUS1 wastewater. CONCLUSION: Routine wastewater-based monitoring using ResistApp can provide valuable information on the prevalence and abundance of ARGs in hospitals. This helps hospitals understand the spread of antibiotic resistance in hospitals and identify potential areas for intervention.

Missing driver in the Sun-Earth connection from energetic electron precipitation impacts mesospheric ozone.

Energetic electron precipitation (EEP) from the Earth's outer radiation belt continuously affects the chemical composition of the polar mesosphere. EEP can contribute to catalytic ozone loss in the mesosphere through ionization and enhanced production of odd hydrogen. However, the long-term mesospheric ozone variability caused by EEP has not been quantified or confirmed to date. Here we show, using observations from three different satellite instruments, that EEP events strongly affect ozone at 60-80 km, leading to extremely large (up to 90%) short-term ozone depletion. This impact is comparable to that of large, but much less frequent, solar proton events. On solar cycle timescales, we find that EEP causes ozone variations of up to 34% at 70-80 km. With such a magnitude, it is reasonable to suspect that EEP could be an important part of solar influence on the atmosphere and climate system.

Smoking strongly predicts disability retirement due to COPD: the Finnish Twin Cohort Study.

No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD. The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers. Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0-48.5) and for smokers with ≥ 12 pack-yrs was 27.3 (95% CI 12.6-59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (< 18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08-2.68). Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.

Prediction of in vivo neutral detergent fiber digestibility and digestion rate of potentially digestible neutral detergent fiber: comparison of models.

Eleven 1-pool, seven 2-pool, and three 3-pool models were compared in fitting gas production data and predicting in vivo NDF digestibility and effective first-order digestion rate of potentially digestible NDF (pdNDF). Isolated NDF from 15 grass silages harvested at different stages of maturity was incubated in triplicate in rumen fluid-buffer solution for 72 h to estimate the digestion kinetics from cumulative gas production profiles. In vivo digestibility was estimated by the total fecal collection method in sheep fed at a maintenance level of feeding. The concentration of pdNDF was estimated by a 12-d in situ incubation. The parameter values from gas production profiles and pdNDF were used in a 2-compartment rumen model to predict pdNDF digestibility using 50 h of rumen residence time distributed in a ratio of 0.4:0.6 between the non-escapable and escapable pools. The effective first-order digestion rate was computed both from observed in vivo and model-predicted pdNDF digestibility assuming the passage kinetic model described above. There were marked differences between the models in fitting the gas production data. The fit improved with increasing number of pools, suggesting that silage pdNDF is not a homogenous substrate. Generally, the models predicted in vivo NDF digestibility and digestion rate accurately. However, a good fit of gas production data was not necessarily translated into improved predictions of the in vivo data. The models overestimating the asymptotic gas volumes tended to underestimate the in vivo digestibility. Investigating the time-related residuals during the later phases of fermentation is important when the data are used to estimate the first-order digestion rate of pdNDF. Relatively simple models such as the France model or even a single exponential model with discrete lag period satisfied the minimum criteria for a good model. Further, the comparison of feedstuffs on the basis of parameter values is more unequivocal than in the case of multiple-pool models.

In vitro gas production profiles to estimate extent and effective first-order rate of neutral detergent fiber digestion in the rumen.

An automatic in vitro gas production technique was evaluated for predicting in vivo fiber (NDF) digestibility and effective first-order digestion rate of potentially digestible NDF (pdNDF) of 15 grass silages. Observed in vivo NDF digestibility of the silages harvested at different stages of maturity during 3 yr was determined by the total fecal collection in sheep fed at the maintenance level of intake. Isolated grass silage NDF was incubated for 72 h in the presence of rumen fluid and buffer to determine the pdNDF digestion kinetics based on cumulative gas production profiles. The digestion kinetic parameters were estimated by a 2-pool Gompertz function. The estimated parameter values were then used in a 2-compartment mechanistic rumen model to predict the in vivo digestibility of pdNDF. A total compartmental mean residence time of 50 h was used in the model, and a further assumption of the distribution of the residence time between the rumen nonescapable and escapable pools in a ratio of 0.4:0.6 was made. To make a distinction between potentially digestible and indigestible NDF, the potential extent of NDF digestion was determined by a 12-d ruminal in situ incubation. The model-predicted in vivo NDF digestibility accurately and precisely (root mean square error = 0.013 units, R(2) = 0.99). Effective first-order digestion rate was estimated from the predicted pdNDF digestibility, and the values were compared with those calculated from the in vivo pdNDF digestibility using the same passage kinetic parameters. The predicted effective first-order digestion rate was strongly correlated with digestion rate estimates derived from in vivo data (root mean square error = 0.006/h, R(2) = 0.86). It can be concluded that a simple first-order digestion rate can be estimated from a complicated gas production kinetic model including 6 parameters. This rate constant can be used in continuous steady-state dynamic mechanistic rumen models predicting the nutrient supply to the host animal.

Toxinogenic Bacillus pumilus and Bacillus licheniformis from mastitic milk.

To elucidate the occurrence of heat-stable toxin-producing strains among mastitic Bacillus isolates, 100 milk samples of mastitic cows from different parts of Finland were screened. Bacillus was identified as the major organism in 23 samples. Toxinogenic Bacillus isolates identified by sperm cell motility inhibition assay were isolated from six samples. Four isolates belonged to the species Bacillus pumilus and two to Bacillus licheniformis. The toxic substances were heat-stable and soluble to methanol thus being of non-protein nature. The methanol extracted substances disrupted the sperm cell plasma membrane permeability barrier at exposure concentrations of 1-15 microg ml(-1) (B. pumilus) or 20-30 microg ml(-1) (B. licheniformis). The toxic properties of the two mastitic B. licheniformis strains were similar to those of B. licheniformis strains known to produce the lipopeptide lichenysin A and the synthetase genes lchAA, lchAB and lchAC for lichenysin were found in the mastitic strains by PCR. Toxin synthetase genes for the syntheses of lichenysin or surfactin were searched but not found in the toxic B. pumilus strains. The ribopatterns of the mastitic B. pumilus and B. licheniformis isolates were similar to those of the toxinogenic strains described earlier from food poisoning incidents and contaminated indoor air. B. licheniformis and B. pumilus survive pasteurization and other heat treatments as spores. Toxin-producing strains of these species in the dairy production chain may thus be of food safety concern.

Rebirth of the university hospital: the Finnish strategy.

Like the academic hospitals worldwide, the Finnish university hospitals are under increasing economical pressures seeking ways to re-assess their traditional missions. It is strongly felt that new solutions within the field of evaluative sciences could bring added value to university hospitals. In this vein, university hospitals must take a leading position in assessing efficacy, (cost-)effectiveness and, ultimately, cost-utility of both traditional and emerging clinical technologies. This will affect the research culture of university hospitals both profoundly and permanently.

Roxithromycin in nongonococcal urethritis.

This presentation is a summary of five different studies on the efficacy and tolerance of roxithromycin in the treatment of non-gonococcal genital infections. Three of the studies were double-blind comparative and two were open studies. Of the 924 out-patients whose data were analysed for clinical efficacy, 637 received treatment with roxithromycin 150 mg bd. The standard dose of roxithromycin, 150 mg bd for ten days, was compared with doxycycline 200 mg daily, lymecycline 300 mg bd and roxithromycin 450 mg once daily. The overall clinical success rate was 90% (576 of 637 patients) for roxithromycin 150 mg bd. In the three comparative trials, no significant difference was found between the clinical success rates of roxithromycin 150 mg bd and the other drugs. The overall clinical success rate with roxithromycin 150 mg bd was 92% (512/558) in nongonococcal urethritis and 81% (64/79) in cervicovaginitis. Taking into account all patients treated with roxithromycin 150 mg bd, the bacteriological success rate was 90% (444/492). In the comparative trials, no significant difference could be found between the treatment groups. Roxithromycin 150 mg bd was effective in eradicating 97% (308/316) of the isolates of Chlamydia trachomatis, 88% (149/170) of Ureaplasma urealyticum, 73% (40/55) of Mycoplasma hominis and 57% (13/23) of Gardnerella vaginalis. The present findings show that a high cure rate can be achieved with a ten-day course of treatment with roxithromycin and that it is at least as effective as the tetracyclines commonly used in the treatment of nongonococcal urethritis. A higher dosage than 300 mg/day of roxithromycin did not offer any clear advantage in terms of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of RU 41.740, an immune modulating compound, in the prevention of acute exacerbations in patients with chronic bronchitis.

The effect of Biostim (RU 41.740), a new non-specific immune modulator, in reducing the number of acute exacerbations in patients with chronic bronchitis, was examined. One hundred and ninety-eight patients with chronic bronchitis stages 2 and 3 entered the study, which was conducted as a multicenter, double-blind, parallel three-group, placebo-controlled trial. The patients were randomised to placebo, Biostim 2 or 8 mg per day, and received treatment for 1 week every other week for 3 successive months during the winter 1983. A significant (p = 0.005) reduction in the number of acute exacerbations was observed in the patients treated with Biostim 2 mg/day, whereas no effect was observed in the placebo or 8 mg/day group. No serious side-effects were encountered.

Tiaprofenic acid in the treatment of primary dysmenorrhoea.

Thirty-one patients with primary dysmenorrhoea were treated in a double-blind, six-period, cross-over clinical trial with tiaprofenic acid, naproxen sodium and a placebo in randomized order, each for 2 consecutive cycles. Complete disappearance of the symptoms or pronounced therapeutic effects were obtained with tiaprofenic acid, naproxen sodium and the placebo in 74%, 65% and 35% of cases, respectively, while these treatments were ineffective in 3%, 6% and 38% of cases, respectively. Tiaprofenic acid was superior to the placebo for relieving pelvic pain and overall discomfort and for reducing the need for bed-rest. Naproxen sodium compared favourably with the placebo with respect to pelvic pain and overall discomfort. The effects of tiaprofenic acid and naproxen sodium were not significantly different. Tiaprofenic acid had no side-effects, whereas tiredness was experienced in 3 cases of naproxen sodium treatment. The results indicate that tiaprofenic acid is a useful alternative for the treatment of primary dysmenorrhoea.

Body burden of cadmium in man at low level of exposure.

Specimens of heart, kidney, liver, lung, pancreas and skeletal muscle were collected at autopsy from 86 traumatic accident victims. The concentration of cadmium in the samples was determined by atomic absorption spectrophotometry. Tissue burdens and the body burden of cadmium were calculated using individual weights of different organs as a function of age. Total body burden reached its maximum level of approximately 8 mg, in the 30-39 year age group. The highest value (8.3 mg) was measured in the 40-49 year age group. The highest average value of tissue burdens at 40-49 years of age was in kidney (4.9 mg), the amount of cadmium diminishing in different tissues in the following order: liver (1.8 mg), muscle (0.15 mg), lung (0.09 mg), pancreas (0.06 mg) and heart (less than 0.01 mg). At a low level of exposure, kidneys and liver alone contain on an average 85% of the total body burden of cadmium. This value differs greatly from earlier reported figures of 45-50%.

Endralazine, a new peripheral vasodilator: absence of effect of acetylator status on antihypertensive effect.

50 patients with confirmed hypertension were treated with endralazine, a new peripheral vasodilator, in addition to the beta-blocker, pindolol, to which they had not responded adequately. The blood pressure was lowered from 173/115 mm Hg to 143/87 mm Hg in the 34 slow acetylators and from 175/111 mm Hg to 140/84 mm Hg in the 16 fast acetylators. The dosages of both pindolol and endralazine were the same in both groups. It is concluded that the acetylator phenotype does not affect the therapeutic efficacy or dosage requirement of endralazine. It is suggested that this is because endralazine is metabolised mainly by hydrazone formation and only to a minor extent by acetylation.

Monitoring perinatal mortality by birth weight specific mortality rates.

The perinatal mortality at University Central Hospital of Turku, Finland decreased significantly from 15.7/1000 in years 1970-75 to 8.9/1000 in years 1976-78. The main decrease has occurred in weight groups of 1000 g and more. In years 1976-78 the perinatal mortality of non-malformed babies in the weight group 1500-1999 g was 93/1000, in the group 2000-2499 g 21/1000 and in the group of 2500 g and over 1.7/1000. The early neonatal mortality of non-malformed infants has decreased significantly only in the weight group of 1500-1999 g. The 1-week survival rate has been 48% in the weight group 500-999 g, but 77% in the weight group 1000-1499 g. The birth weight specific mortality rates are greatly required when the quality of obstetrical care is assessed. Birth weight specific neonatal mortality rates are essential when guidelines for elective termination of third trimester pregnancy are designed.

Evaluation of the toxicity and carcinogenicity of hair dyes.

The chronic toxicological and carcinogenic potential following skin painting in mice was evaluated for nine oxidative and three nonoxidative hair dyes. Groups of male and female Swiss mice were treated one time weekly for at least 20 mo with one dose level of each dye. The oxidative dyes were mixed 1:1 with 6% hydrogen peroxide before treatment and the three semipermanent formulations were applied without dilution. Control groups were shaved only and received no applications. Body weights and survival rates did not differ between appropriate male and female treatment and control groups. Absolute and relative liver and kidney weights were equivalent for treatment and control groups. After 7 and 9 mo of treatment, 10 males and 10 females randomly selected from each group were necropsied and tissues taken for histopathologic evaluation. Animals found dead or sacrificed in moribund condition or at termination of the study were necropsied and evaluated histopathologically. Comparison of incidence of tumors and of nontumor pathology among the various treatment and control groups revealed no biologically significant differences. Toxicological and carcinogenic effects were not induced by the hair dye formulations.

Biologically active metals in human tissues. I. The effect of age and sex on the concentration of copper in aorta, heart, kidney, liver, lung, pancreas and skeletal muscle.

Autopsy specimens of aorta, heart, kidney, liver, lung, pancreas and skeletal muscle were collected from 86 accident victims. The copper concentration in each tissue was determined with atomic absorption spectrophotometry. The descending order of the tissues in respect to copper concentration was: liver, heart, kidney, pancreas, lung, muscle, and aorta. No significant difference was found in the copper levels of samples from male and female autopsies. When the effect of age on the average copper concentration was studied, liver and kidney showed a decreasing concentration up to maturity, the copper concentration in pancreas and skeletal muscle showed a continuous decline with increasing age, and there was no clear-cut effect of age on the copper concentration of heart, lung and aorta. According to the results the Finnish population does not differ, on the average, from other populations with respect to tissue copper concentrations.

Spontaneous rupture of liver tumours.

Five geriatric patients with spontaneous rupture of the liver caused by hepatic malignancies were operated upon without mortality. Liver resection seems to be the treatment of choice, but in selected cases with unresectable tumours ligation of the hepatic artery alone is preferable to an attempt to control haemorrhage by packing and suture.