Risk of Drug-Drug Interactions in Out-Hospital Drug Dispensings in France: Results From the DRUG-Drug Interaction Prevalence Study

Introduction: Drug interactions could account for 1% of hospitalizations in the general population and 2-5% of hospital admissions in the elderly. However, few data are available on the drugs concerned and the potential severity of the interactions encountered. We thus first aimed to estimate the prevalence of dispensings including drugs Contraindicated or Discommended because of Interactions (CDI codispensings) and to identify the most frequently involved drug pairs. Second, we aimed to investigate whether the frequency of CDI codispensings appeared higher or lower than the expected for the drugs involved. Methods: We carried out a study using a random sample of all drugs dispensings registered in a database of the French Health Insurance System between 2010 and 2015. The distribution of the drugs involved was described considering active principles, detailing the 20 most frequent ones for both contraindicated or discommended codispensings (DCs). To investigate whether the frequency of CDI codispensings appeared higher or lower than the expected for the drugs involved, we developed a specific indicator, the Drug-drug interaction prevalence study-score (DIPS-score), that compares for each drug pair the observed frequency of codispensing to its expected probability. The latter is determined considering the frequencies of dispensings of the individual drugs constituting a pair of interest. Results: We analyzed 6,908,910 dispensings: 13,196 (0.2%) involved contraindicated codispensings (CCs), and 95,410 (1.4%) DCs. For CCS, the most frequently involved drug pair was "bisoprolol+flecainide" = 5,036); four out of five of the most represented pairs involved cardiovascular drugs. For DCS, the most frequently involved drug pair was "ramipril+spironolactone" = 4,741); all of the five most represented pairs involved cardiovascular drugs. The drug pair involved in the CC with the highest score value was "citalopram+hydroxyzine" (DIPS-score: 3.7; 2.9-4.6); that with the lowest score was "clarithromycin+simvastatin" (DIPS-score: 0.2; 0.2-0.3). DIPS-score median value was 0.4 for CCs and 0.6 for DCs. Conclusion: This high prevalence of CDI codispensings enforces the need for further risk-prevention actions regarding drug-drug interactions (DDIs), especially for arrhythmogenic or anti-arrhythmic drugs. In this perspective, the DIPS-score we develop could ease identifying the interactions that are poorly considered by clinicians/pharmacists and targeting interventions

Assessment of pre- and post-harvest anti-sprouting treatments to replace CIPC for potato storage

To avoid losses from sprouting during potato storage, the anti-sprouting agent chlorpropham [CIPC] has been widely used over the past few decades. However, the European Union recently decided not to authorize the renewal of CIPC, prompting the value chain to find alternative treatments. We assessed for three years the potential of pre- and post-harvest anti-sprouting treatments to replace CIPC using four potato-processing varieties. Pre-harvest application of maleic hydrazide [MH] and post-harvest applications of 3-decen-2-one, 1,4-dimethylnapthalene [1,4-DMN] and CIPC were performed following supplier’s recommendations. In addition, we evaluated the potential of 3-decen-2-one and 1,4-DMN to prolong the efficacy of pre-harvest MH treatment anti-sprouting activity during storage. All molecules significantly reduced sprouting after seven months of storage compared with the untreated control group. MH, 3-decen-2-one, 1,4-DMN and CIPC displayed respectively 86.9 %; 77.9 %, 73.6 % and 99.8 % of efficacy to control sprout weight and 79.4 %; 73.4 %, 68.4 % and 96.9 % of efficacy to control sprout length. Our results suggest that using 3-decen-2-one and 1,4-DMN in combination with MH do not bring additional benefit to control sprouting. Because differences in dormancies could be observed between varieties, we also showed that the efficacy of post-harvest treatments is genotype-dependent, while MH pre-harvest treatment is effective equally for all varieties. Applications of CIPC and MH led to detectable residues in tubers, while no residue of 1,4-DMN has been detected in tubers treated with this molecule (< LOQ). We concluded that treatments with MH, 1,4-DMN and 3-decen-2-one are valuable alternatives to CIPC to control sprouting of processing potatoes

Prédiction de la dormance des pommes de terre pendant le stockage

Potato sprouting during storage occurs after a break in dormancy, leading to a decrease in quality and consequently economic losses. We used 3379 records from multi-year and multi-environment trials of 537 potato varieties to identify the main factors driving potato dormancy and to develop predictive models for an efficient sprouting forecast. The variety explained the majority of the dormancy variability (60.3%), followed by the year (13.9%) and the location (5.4%). About 250 predictors were considered to develop a predictive model of potato dormancy. The selected model had a validation precision of 14.59 days; it used the variety class and the sum of the daily maximum temperatures in the air during the period from planting to harvest as predictors. The predictions of the selected model were supported by results of the in vivo trial using dormancy measurements from potato varieties grown under different temperature regimes in greenhouse conditions. With the growing impact of climate change on crop production, predictive models as developed here can provide an efficient and cost-effective tool to optimize the control of potato sprouting during storage.2. Zero hunge

Identification of potato varieties suitable for cold storage and reconditioning: A safer alternative to anti-sprouting chemicals for potato sprouting control.

peer reviewedLow temperature storage as an alternative to anti-sprouting chemicals in potato storage may induce reducing sugars (RS) accumulation (i.e. glucose and fructose) in potato tubers. This phenomenon is called "cold induced sweetening" (CIS) and occurs in certain varieties. CIS leads to a decrease in the organoleptic qualities and darkening of processed potato and the accumulation of toxic molecules such as acrylamide. To identify potato varieties suitable for storage at low temperatures, we screened six commercial processing varieties: Lady Claire (LC), Verdi, Kiebitz (KB), Pirol, Agria and Markies for their CIS characteristics and sprout-forming potential after storage at 4 °C and 8 °C. Our findings reveal that 4 °C storage allows for efficient sprout reduction in all six tested varieties for up to 4.5 months of storage. Three CIS-resistant varieties, namely Verdi, Lady Claire and Kiebitz, were identified as able to be stored for up to four months at 4 °C with limited increase in glucose content. Conversely, Pirol, Agria and Markies showed an increase in glucose content with a decrease in storage temperature and can be considered as CIS-susceptible varieties. After processing into crisps, the CIS-susceptible varieties displayed poor crisp color quality (brown to black color crisps) after storage for two months at 4 °C compared to the storage at 8 °C, whereas the CIS-resistant varieties had good crisp color quality (pale yellow color crisps) after storage at both 4 and 8 °C. Interestingly, the trends of total RS and/or glucose content in the CIS-resistant and in the CIS-susceptible varieties were correlated with the trends in Vacuolar Invertase (VInv) gene expression for most varieties, as well as with the trends in acrylamide content after processing. In addition, reconditioning of Markies variety after storage at 4 °C by gradually increasing the temperature to 15 °C resulted in a significant decrease of VInv transcript levels (reduction of 80 %), acrylamide content (reduction of 75 %) and glucose content when compared to a storage at 4 °C without reconditioning. Those results demonstrate that the reconditioning technique is a key factor for a sustainable potato storage and for improving the quality of processed potatoes

Risk of Drug-Drug Interactions in Out-Hospital Drug Dispensings in France: Results From the DRUG-Drug Interaction Prevalence Study

Introduction: Drug interactions could account for 1% of hospitalizations in the general population and 2–5% of hospital admissions in the elderly. However, few data are available on the drugs concerned and the potential severity of the interactions encountered. We thus first aimed to estimate the prevalence of dispensings including drugs Contraindicated or Discommended because of Interactions (CDI codispensings) and to identify the most frequently involved drug pairs. Second, we aimed to investigate whether the frequency of CDI codispensings appeared higher or lower than the expected for the drugs involved.Methods: We carried out a study using a random sample of all drugs dispensings registered in a database of the French Health Insurance System between 2010 and 2015. The distribution of the drugs involved was described considering active principles, detailing the 20 most frequent ones for both contraindicated or discommended codispensings (DCs). To investigate whether the frequency of CDI codispensings appeared higher or lower than the expected for the drugs involved, we developed a specific indicator, the Drug-drug interaction prevalence study-score (DIPS-score), that compares for each drug pair the observed frequency of codispensing to its expected probability. The latter is determined considering the frequencies of dispensings of the individual drugs constituting a pair of interest.Results: We analyzed 6,908,910 dispensings: 13,196 (0.2%) involved contraindicated codispensings (CCs), and 95,410 (1.4%) DCs. For CCS, the most frequently involved drug pair was “bisoprolol+flecainide” (n = 5,036); four out of five of the most represented pairs involved cardiovascular drugs. For DCS, the most frequently involved drug pair was “ramipril+spironolactone” (n = 4,741); all of the five most represented pairs involved cardiovascular drugs. The drug pair involved in the CC with the highest score value was “citalopram+hydroxyzine” (DIPS-score: 3.7; 2.9–4.6); that with the lowest score was “clarithromycin+simvastatin” (DIPS-score: 0.2; 0.2–0.3). DIPS-score median value was 0.4 for CCs and 0.6 for DCs.Conclusion: This high prevalence of CDI codispensings enforces the need for further risk-prevention actions regarding drug-drug interactions (DDIs), especially for arrhythmogenic or anti-arrhythmic drugs. In this perspective, the DIPS-score we develop could ease identifying the interactions that are poorly considered by clinicians/pharmacists and targeting interventions

Assignment of PolyProline II Conformation and Analysis of Sequence – Structure Relationship

International audienceBACKGROUND: Secondary structures are elements of great importance in structural biology, biochemistry and bioinformatics. They are broadly composed of two repetitive structures namely α-helices and β-sheets, apart from turns, and the rest is associated to coil. These repetitive secondary structures have specific and conserved biophysical and geometric properties. PolyProline II (PPII) helix is yet another interesting repetitive structure which is less frequent and not usually associated with stabilizing interactions. Recent studies have shown that PPII frequency is higher than expected, and they could have an important role in protein - protein interactions. METHODOLOGY/PRINCIPAL FINDINGS: A major factor that limits the study of PPII is that its assignment cannot be carried out with the most commonly used secondary structure assignment methods (SSAMs). The purpose of this work is to propose a PPII assignment methodology that can be defined in the frame of DSSP secondary structure assignment. Considering the ambiguity in PPII assignments by different methods, a consensus assignment strategy was utilized. To define the most consensual rule of PPII assignment, three SSAMs that can assign PPII, were compared and analyzed. The assignment rule was defined to have a maximum coverage of all assignments made by these SSAMs. Not many constraints were added to the assignment and only PPII helices of at least 2 residues length are defined. CONCLUSIONS/SIGNIFICANCE: The simple rules designed in this study for characterizing PPII conformation, lead to the assignment of 5% of all amino as PPII. Sequence - structure relationships associated with PPII, defined by the different SSAMs, underline few striking differences. A specific study of amino acid preferences in their N and C-cap regions was carried out as their solvent accessibility and contact patterns. Thus the assignment of PPII can be coupled with DSSP and thus opens a simple way for further analysis in this field