Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR Alliance.

Strontium ranelate use, compared with oral bisphosphonates, is not associated with increased risk of AMI in patients with no contraindications for SR use. However, current strontium ranelate (compared with current bisphosphonate) appears associated with 25-30% excess risk of VTE and 35% excess risk of CVDeath. INTRODUCTION: Evaluate the risk of cardiac and thromboembolic events among new users of SR and oral BPs without contraindications for SR. METHODS: We conducted three multi-national, multi-database (Aarhus-Denmark, HSD-Italy, IPCI-Netherlands, SIDIAP-Spain, THIN-UK) case-control studies nested within a cohort of new users of SR/BP. We matched cases of acute myocardial infarction (AMI), venous thromboembolism (VTE), and cardiovascular death (CVDeath), up to 10 controls on gender, year of birth, index date, and country. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) according to current SR vs current BP use and current vs past SR use, adjusting for potential confounders. Data were pooled using random effects meta-analysis. RESULTS: No excess risk of AMI (5477 cases/54,674 controls) was found with current SR vs current BP (OR 0.89 (95%CI 0.70, 1.12)) nor with current vs past SR use (0.71(0.56, 0.91)). For VTE (5614 cases/6036 controls), an excess risk was found with current SR compared with current BP use, 1.24 (0.96, 1.61), and current vs past SR use, 1.30 (1.04, 1.62). For CVDeath (3019 cases/29,871 controls), an increased risk was seen with current SR vs current BP use, 1.35 (1.02, 1.80), but not with current vs past SR use (0.68 (0.48, 0.96)). CONCLUSION: In patients without contraindications for SR, we found no evidence of an increased risk of AMI but a 25-30% excess risk of VTE and a 35% excess risk of CVDeath with current SR vs current BP users. This is despite a reduction in risk in CVDeath with current vs past SR users. The latter disparity could still be partially explained by cessation of preventative therapies in end-of-life or residual confounding by indication.

Correction to: Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance.

The original version of this article, published on 26 November 2019 contained a mistake.

Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance.

INTRODUCTION: In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). PARTICIPANTS: the database source populations were included for population-based analyses, and SR users for patient-level analyses. INTERVENTION: New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy. METHODS: Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016). RESULTS: The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4-62.9) in the reference to 8.5 (8.5-8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4-7.4) to 0.2 (0.2-0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period. CONCLUSIONS: Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

Diatom motility and nuclear alterations are affected by sediment elutriates of agricultural streams.

Diatoms respond to toxicants in lotic systems, and they are commonly considered to be sensitive indicators in environmental safety assessment. In addition to the structural characteristics of the algal populations, recent studies have shown that endpoints such as nuclear anomalies or diatom motility measures can be affected quickly by environmental changes. We sought to determine if cell density, cell size, nuclear anomalies and motility of the diatom Nitzschia palea were useful indicators of sediment quality from agricultural streams. For this purpose, we exposed cultures of the diatom to elutriates from sediments of a stream that flows through an intensive agricultural area, and measured the responses of the populations for 7 days in laboratory tests. The bioassays showed that motility measures in Nitzschia palea and the condition of their nuclear membranes rapidly reflected the effects of sediment quality after only 48 h of exposure; mean cell density and length were affected by day 7. The sediment elutriates affected cell movements by shortening the total path length and decreasing cell velocity; they also increased the number of cells with nuclear membrane breakage. Our results from these bioassays show that diatom motility measurements and the condition of the nuclei might be indicators that respond faster to impacts than the traditional structural parameters, such as cell density, specific composition of the assemblage or diversity metrics of the algal communities more often used in biomonitoring.

Non-tuberculous mycobacteria: epidemiological pattern in a reference laboratory and risk factors associated with pulmonary disease.

The diseases caused by non-tuberculous mycobacteria (NTM), in both AIDS and non-AIDS populations, are increasingly recognized worldwide. Although the American Thoracic Society published the guidelines for diagnosis of NTM pulmonary disease (NTM-PD), the diagnosis is still difficult. In the first part of the study, we collected data on NTM isolates in the Mycobacteriology Laboratory of Careggi Hospital (Florence, Italy) and analysed the epidemiological data of NTM isolates. Then, to analyse the risk factors associated to NTM-PD, we studied the presence of ATS/IDSA criteria for NTM-PD in patients who had at least one positive respiratory sample for NTM and were admitted to the Infectious Disease Unit and the Section of Respiratory Medicine. We selected 88 patients with available full clinical data and, according to ATS/IDSA criteria, classified 15 patients (17%) as NTM-PD cases and 73 as colonized patients (83%). When comparing colonized and NTM-PD patients we did not find significant differences of age, gender and comorbidity. We observed that Mycobacterium avium and M. intracellulare were statistically associated with NTM-PD (P = 0·001) whereas M. xenopi was statistically associated with colonization. Although the number of studied patients is limited, our study did not identify risk factors for NTM-PD that could help clinicians to discriminate between colonization and disease. We underline the need of close monitoring of NTM-infected patients until the diagnosis is reasonably excluded. Further larger prospective studies and new biological markers are needed to identify new useful tools for the diagnosis of NTM-PD.

Risk of prostate cancer in low-dose aspirin users: A retrospective cohort study.

A growing body of evidence indicates that use of low-dose aspirin (LDA) reduces the risk of certain adenocarcinomas. While there are several and consistent findings on the protective effect of LDA on colorectal and other cancers, few and conflicting evidence is available on prostate cancer (PCa). The aim of this study was to assess whether LDA reduces the incidence rate of PCa. We conducted a nationwide, population-based, retrospective cohort study by using Health Search IMS Health Longitudinal Patient Database (HSD). Patients with ischemic cardio- or cerebrovascular disease (index date) were identified. Time-dependent multivariable Cox proportional hazard models were adopted to estimate Hazard Ratios (HRs) and related 95% confidence intervals (95% CI) of PCa associated with use of LDA. The exposure was lagged by one year to consider the latency of drug effect on the outcome onset. Within a cohort 13,453 patients, the overall incidence rate of PCa was 2.5 per 1,000 person-years. Use of LDA was associated with a decreased incidence rate of PCa (HR = 0.64; 95% CI: 0.48-0.86), which was primarily driven by a frequency of LDA use equal to or higher than twice per week (HR = 0.60; 95% CI: 0.43-0.83). Such an association was more pronounced (HR = 0.43; 95% CI: 0.21-0.91) when LDA was used for five or more years. Our findings indicate that LDA use might be associated with a reduction of risk of PCa in patients with cardio- or cerebrovascular diseases.

Synchronization of time of ovarian follicular development in llamas (Lama glama) using a protocol based on GnRH and PGF2α.

The aim of this study was to evaluate the effectiveness of a protocol based on GnRH and PGF2α to synchronize the emergence of a new wave of ovarian follicular development in llamas and, therefore, when a new dominant follicle develops. Llamas (n = 18) were assigned to growing, mature or regressing follicle groups according to the phase of the follicular wave at the beginning of treatment. The protocol was initiated with a GnRH analogue (GnRHa) injection on Day 0 followed 7 days later with a d-cloprostenol injection and a second GnRHa injection on Day 10. Ovulation rate after the first GnRHa treatment, day of new follicle emergence, mean plasma progesterone concentration and percentage of animals with a newly developed dominant follicle ≥ 7 mm on Day 10 were evaluated. Ovulation rate after the first GnRHa was less in the regressing than mature and growing follicle groups and new follicular wave emergence occurred earlier in the regressing follicle group than in the other two groups. Mean plasma progesterone concentration in females that had ovulations after the first GnRHa injection was similar. The percentage of animals that had a new follicle ≥ 7 mm on Day 10 was not different among groups and the overall percentage was 66.6%. The total synchronization rate for development of a new wave of follicular development on Day 10 was greater in females having ovulations after the first GnRHa injection than in those that did not have ovulations. In conclusion, the protocol used in the present study was useful for synchronizing ovarian follicular development in 66% of the llamas regardless of the phase of the follicular wave development at the beginning of treatment.

Changes in extra-virgin olive oil added with Lycium barbarum L. carotenoids during frying: Chemical analyses and metabolomic approach.

In this work, an Italian extra-virgin olive oil (EVOO) sample and the same sample added with a carotenoid-rich nutraceutical extract from Lycium barbarum L. (EVOOCar) were subjected to a frying process to comparatively assess chemical and physical changes and heat stability. Oxidation progress was monitored by measuring oil quality changes such as peroxide value, free acidity, K232, K268, and fatty acid composition as well as minor compound content, phenols, α-tocopherol, and carotenoids. An UHPLC/QTOF-MS metabolomics approach discriminated the two oil samples based on their chemical changes during frying, identifying also the phenolic classes most exposed to statistically significant variations. Partial least square discriminant analysis and volcano analysis were applied together to identify the most significant markers allowing group separation. The decrease in total phenolic content was lower in EVOOCar than in EVOO during frying. Monounsaturated and polyunsaturated fatty acids showed a significant percentage loss, 3.7% and 17.2%, respectively, in EVOO after 180min frying at 180°C, while they remained constant or slightly changed in EVOOCar. Zeaxanthin added to the oil rapidly decreased during the frying process. These findings showed that the addition of a carotenoid extract from L. barbarum can help to improve the oxidative stability of extra-virgin olive oil.

HPLC separation and NMR structural elucidation of sn-1,2-, 2,3-, and 1,3-diacylglycerols from olive oil as naphthylethylurethane derivatives.

In this study, sn-1,2-, sn-2,3-, and sn-1,3-diacylglycerols were isolated from olive oil, and their urethane derivatives (urethanes) were prepared. Normal-phase high-performance liquid chromatography (NP-HPLC) separation of the urethane isomers was performed and the separate classes were studied by nuclear magnetic resonance (NMR). The use of 1H NMR and homo- and heteronuclear 2D techniques provided a great amount of information in a very short time, particularly when a high-field NMR instrument (700 MHz) was used. Particularly diagnostic for this kind of compound was the glyceridic moiety that presents typical chemical shifts both for carbon and hydrogen. These studies show the usefulness of NMR spectroscopy to recognize clearly the sn-1,3- and, moreover, sn-1,2- with respect to sn-2,3-diacylglycerols, although very minor differences occur between them.

First case of Mycobacterium marseillense lymphadenitis in a child.

BACKGROUND: Nontuberculous mycobacteria (NTM) are pathogens that commonly affect the paediatric population and its most frequent manifestation is a cervicofacial lymphadenopathy. With the improvement of technologies, new species have been recently identified. CASE PRESENTATION: We report the first case of NMT lymphadenitis in a child caused by Mycobacterium marseillense, a newly described species belonging to Mycobacterium avium complex. CONCLUSIONS: Improving the identification of these newly discovered mycobacteria, further information will be available about their clinical involvement and their best treatment.

Authentication of Coffea arabica according to Triacylglycerol Stereospecific Composition.

Stereospecific analysis is an important tool for the characterization of lipid fraction of food products. In the present research, an approach to characterize arabica and robusta varieties by structural analysis of the triacylglycerol (TAG) fraction is reported. The lipids were Soxhlet extracted from ground roasted coffee beans with petroleum ether, and the fatty acids (FA) were determined as their corresponding methyl esters. The results of a chemical-enzymatic-chromatographic method were elaborated by a chemometric procedure, Linear Discriminant Analysis (LDA). According to the total and intrapositional FA composition of TAG fraction, the obtained results were able to characterize roasted pure coffee samples and coffee mixtures with 10% robusta coffee added to arabica coffee. Totally correct classified samples were obtained when the TAG stereospecific results of the considered coffee mixture (90 : 10 arabica/robusta) were elaborated by LDA procedure.

Relationship between chromosome 9 of maize and wheat homeologous group 7 chromosomes.

Comparison of the genetic map of maize chromosome 9 with maps of wheat chromosomes has revealed a high degree of colinearity between maize chromosome 9 and the group 4 and 7 chromosomes of wheat. The order of DNA markers on the short arm and a proximal region of the long arm of the genetic map of maize chromosome 9 is highly conserved with the marker order on the short arm and proximal region of the long arm of the genetic map of the wheat homeologous group 7 chromosomes. A major part of the long arm of the genetic map of maize chromosome 9 is homeologous with a short segment in the proximal region of the long arm of the genetic map of the wheat group 4 chromosomes. Evidence is also presented that maize chromosome 9 has diverged from the wheat group 7 chromosomes by both a pericentric and a paracentric inversion. The paracentric inversion is probably unique to maize among the major cereal genomes.

Carbon-Nanohorn Based Nanofluids for a Direct Absorption Solar Collector for Civil Application.

Direct solar absorption has been often considered in the past as a possible solution for solar thermal collectors for residential and small commercial applications. A direct absorption could indeed improve the performance of solar collectors by skipping one step of the heat transfer mechanism in standard devices and having a more convenient temperature distribution inside the collector. Classical solar thermal collectors have a metal sheet as absorber, designed such that water has the minimum temperature in each transversal section, in order to collect as much solar thermal energy as possible. On the other hand, in a direct configuration, the hottest part of the system is the operating fluid and this allows to have a more efficient conversion. Nanofluids, i.e., fluids with a suspension of nanoparticles, such as carbon nanohorns, could be a good and innovative family of absorbing fluids owing to their higher absorption coefficient compared to the base fluid and stability under moderate temperature gradients. Moreover, carbon nanohorns offer the remarkable advantage of a reduced toxicity over other carbon nanoparticles. In this work, a three-dimensional model of the absorption phenomena in nanofluids within a cylindrical tube is coupled with a computational fluid dynamics (CFD) analysis of the flow and temperature field. Measured optical properties of nanofluids at different concentrations have been implemented in the model. Heat losses due to conduction, convection and radiation at the boundaries are considered as well.

Cultural studies on two isolates of "Mycobacterium genavense" from patients with acquired immunodeficiency syndrome.

Two strains of the newly proposed species "Mycobacterium genavense" have been isolated, using the radiometric system (Bactec, Becton Dickinson), from the blood of two HIV-infected patients. Disseminated infections due to the new organism closely resemble those of the Mycobacterium avium complex, with prevalently intestinal symptomatology. We report here on the cultural behavior of the isolates, which are enhanced at pH 6, are inhibited by NAP, do not require supplements, and grow best at 37 degrees C. We also report on the antibiotic susceptibility of the isolates.

Dobutamine as palliative drug in home-care advanced cancer patients.

We describe a patient with advanced cancer whose severe symptoms of congestive heart failure were successfully treated with dobutamine. The intermittent intravenous administration of dobutamine 5 micrograms/kg/min for 3 hr per day at home enabled control of dyspnea, leg edema, and pain, and increased urine output after 1 day. An improvement in renal function was observed in the following days. The mechanism and the utility of a palliative approach with dobutamine are discussed.

Home palliative care: results in 1991 versus 1988.

Home care is greatly expanding because of the savings it offers by avoiding unnecessary hospitalization and also because patients benefit from being in their own home environments. Since 1988, Societa Assistenza Malato Oncologico Terminale (SAMOT) has organized a pain relief and home palliative care unit for terminal cancer patients. Objectives, difficulties, protocols, and achievements of 4 years of experience were examined, and the findings of the various years were compared. Our results suggest that considerable progress has been made in home palliative care. There are still social and cultural difficulties to overcome, however.

Biocatalyzed acidolysis of soybean oil triacylglycerols to increase oleic acid content.

Lipase catalyzed acidolysis of triacylglycerols (TAG) of soybean oil with oleic acid in organic solvent was studied; immobilized lipase from Rhizomucor miehei was used and the effects of reaction time, incubation temperature and enzyme load on TAG total and positional fatty acid (FA) percentage compositions were investigated. The results show that oleic acid incorporation was high after 24 and 48 h, while after 72 h a lower level of oleic acid in TAG was observed. Moreover, for the reactions carried out at 30 and 40 degrees C, it was observed that the oleic acid level was about 46.5% while ligtly higher values (about 49%) were observed at 50 degrees C; however, under this last condition, the modification of sn-2 position FA composition was higher. Finally, the variable enzyme load resulted also important on the incorporation of oleic acid; in particular, even if the value of 10% (w/w) of enzyme load resulted in a lightly lower incorporation of oleic acid in soybean oil TAG (about 45%), in this situation a minimal modification of sn-2 position FA composition was obtained.

HPLC does not differentiate Mycobacterium paratuberculosis from Mycobacterium avium.

HPLC, which is gaining its place as identification tool in mycobacteriology laboratories, has been proposed to distinguish Mycobacterium paratuberculosis from Mycobacterium avium. We had reported no significant difference between M. avium and M. paratuberculosis reference strain ATCC 19698. Because of the advantages offered by such a method, we enlarged our observations to include more isolates of M. paratuberculosis. Within the double cluster of peaks obtained by both M. avium and M. paratuberculosis, we could not find a consistent difference typical of M. paratuberculosis. Therefore, the present study confirmed that M. avium and M. paratuberculosis could not be distinguished by HPLC, raising doubts of a straightforward use of HPLC to identify M. paratuberculosis.

Identification of the newly described Mycobacterium poriferae from tuberculous lesions of snakehead fish (Channa striatus).

A mycobacterium isolated form a cultured snakehead with nodular lesions was identified on the basis of high performance liquid chromatography (HPLC) profile of cell wall mycolic acids, and confirmed by conventional tests, as Mycobacterium poriferae, a species previously isolated only from a marine sponge. The profiles of M. poriferae, Mycobacterium aurum and Mycobacterium parafortuitum are here reported for the first time.

Does alkalinization of 0.75% ropivacaine promote a lumbar peridural block of higher quality?

BACKGROUND AND OBJECTIVES: We did not find clinical studies of the alkalization of ropivacaine in the literature. The objectives of this study were: (1) to determine the quantity of sodium bicarbonate (NaHCO(3)), which alkalinizes 0.75% ropivacaine (with and without adrenaline); (2) to verify the physico-chemical alterations arising from this alkalization; and (3) to determine whether alkalinized ropivacaine produces a higher-quality epidural block measured via sensory-motor onset, block spread and anesthesia duration. METHODS: It was determined in the laboratory that 0.012 and 0.015 mEq of NaHCO(3), respectively, alkalinized 10 mL of the 0.75% ropivacaine solutions without and with adrenaline (1:200,000). In the second phase, the study was random and double-blind and involved 60 patients divided into 3 groups of 20 (G1, G2, and G3). Via epidural lumbar blocks, these groups received, respectively, 10 mL of 0.75% ropivacaine plus 0.5 mL of 0.9% NaCl (solution A), 10 mL of 0.75% ropivacaine plus 0.0012 mEq of NaHCO(3) (solution B), and 10 mL of 0.75% ropivacaine (with adrenaline) plus 0.015 mEq of NaHCO(3) (solution C). The pH, PCO(2) (partial CO(2) pressure), and the nonionized fractions of the 0.75% ropivacaine solutions were compared before and after the addition of 0.9% NaCl or NaHCO(3) or adrenaline plus NaHCO(3). The motor and sensory onsets, block spread, and the duration of the block were evaluated. RESULTS: The values of the pH, PCO(2), and nonionized fractions increased significantly in solutions B and C in relation to solution A. No differences among the groups were observed in relation to block spread and sensory-motor onset. The duration of the sensory blocks was significantly greater in the patients in groups G2 and G3. CONCLUSION: This study indicates that the quantity of NaHCO(3) needed to alkalize 10 mL of 0.75% ropivacaine at room temperature is 0.012 mEq. When the solution contains adrenaline 1:200,000 (mg.mL(-1)), up to 0.015 mEq of NaHCO(3) may be added. The alkalization of the 0.75% ropivacaine solution did not cause a reduction of sensory-motor onset, but did provide a significant increase in the duration of the epidural block with no significant differences between the solutions with and without adrenaline.