Seasonal influenza vaccination among people with diabetes: influence of patients' characteristics and healthcare use on behavioral changes.

Annual seasonal influenza vaccination (SIV) is recommended for people with diabetes, but vaccine coverage remains low. We estimated the probabilities of stopping or starting SIV, their correlates, and the expected time spent in the vaccinated state over 10 seasons for different patient profiles. We set up a retrospective cohort study of patients with diabetes in 2006 (n = 16,026), identified in a representative sample of beneficiaries of the French National Health Insurance Fund. We followed them up over 10 seasons (2005/06-2015/16). We used a Markov model to estimate transition probabilities and a proportional hazards model to study covariates. Between two consecutive seasons, the probabilities of starting (0.17) or stopping (0.09) SIV were lower than those of remaining vaccinated (0.91) or unvaccinated (0.83). Men, older patients, those with type 1 diabetes, treated diabetes or more comorbidities, frequent contacts with doctors, and with any hospital stay for diabetes or influenza during the last year were more likely to start and/or less likely to stop SIV. The mean expected number of seasons with SIV uptake over 10 seasons (range: 2.6-7.9) was lowest for women <65 years with untreated diabetes and highest for men ≥65 years with type 1 diabetes. Contacts with doctors and some clinical events may play a key role in SIV adoption. Healthcare workers have a crucial role in reducing missed opportunities for SIV. The existence of empirical patient profiles with different patterns of SIV uptake should encourage their use of tailored educational approaches about SIV to address patients' vaccine hesitancy.

[Relevance of the health insurance databases to study spatial disparities in asthma prevalence: A study in southeastern France]. / Intérêt des données de remboursement de l'assurance-maladie pour l'étude des disparités territoriales de la prévalence de l'asthme : une étude en Provence-Alpes-Côte d'Azur.

BACKGROUND: Data on asthma prevalence at a small-area level would be useful to set up and monitor French local public health policies. This study, based on drug reimbursement databases in southeastern France, aimed to (1) compare asthma-like disorders prevalence estimated by using three different indicators; (2) study sociodemographic characteristics associated with these indicators; (3) verify whether these indicators are equivalent to study geographical disparities of the asthma-like disorders prevalence at a small-area level. METHODS: The study was conducted among the beneficiaries of the National Health Insurance Fund aged 18-44 years residing in southeastern France in 2010 (n=1,371,816). Using data on asthma drugs reimbursements (therapeutic class R03), we built three indicators to assess asthma-like disorders prevalence: at least 1, 2 or 3 purchase(s) in 2010. We analyzed sociodemographic characteristics associated with these indicators, and their geographical disparities at a small-area level using multilevel logistic regression models. RESULTS: The crude asthma-like disorders prevalence varied between 2.6 % and 8.4 % depending on the indicator. It increased with age, was higher for women than for men, and among low-income people for all three indicators. We measured significant geographical disparities. Areas with high prevalence rates were the same regardless of the indicator. CONCLUSION: The indicators built in this study can be useful to identify high prevalence areas. They could contribute to launch discussion on environmental health issues at the local level.

Is exposure to night-time traffic noise a risk factor for purchase of anxiolytic-hypnotic medication? A cohort study.

BACKGROUND: Studies suggest that road traffic noise increases risks of sleep disturbances, anxiety and depressive symptoms, but few have focused on psychotropic drug use. We examined whether exposure to night-time road traffic noise in Marseilles (France) is associated with an increased risk of purchasing anxiolytic or hypnotic medications. METHODS: Cohort of 190,617 inhabitants of Marseilles (aged 18-64 years) covered by the National Health Insurance Fund. We used the CadnaA noise propagation prediction model to calculate a potential road noise exposure indicator at dwellings for the night-period: Ln. Association between the number of purchases of anxiolytics-hypnotics in 2008-9 and the Ln was analysed with a zero-inflated negative binomial (ZINB) model adjusted for characteristics of individuals (sociodemographic, consultations with general practitioners, presence of chronic psychiatric disorder), prescribers (demographic, specialty, workload) and neighbourhoods (medical density, complaints filed for environmental noise). Analyses were stratified by the deprivation level of the census block of residence to control for the confounding effects of neighbourhood socio-economic status. RESULTS: The ZINB model showed a small but significant increase in the risk of purchasing higher numbers of anxiolytics-hypnotics for Ln greater than 55 dB(A) only in the low deprivation stratum. CONCLUSION: We found some evidence that potential exposure to night-time road traffic noise might affect individual use of anxiolytics-hypnotics. Further research based on strictly individual approaches is warranted to assess exposure to road traffic noise more precisely and reliably than allowed by noise propagation prediction models.

[Potentially inappropriate prescriptions for the elderly: a study of health insurance reimbursements in Southeastern France]. / Prescriptions médicamenteuses potentiellement inadaptées chez les personnes âgées : une étude en Provence-Alpes-Côte d'Azur à partir des données de remboursements de l'Assurance maladie.

BACKGROUND: This study conducted in the region of Provence-Alpes-Côte d'Azur (PACA) sought to assess the feasibility of constructing and using indicators of potentially inappropriate prescriptions for the elderly from health insurance reimbursement data. We present and discuss different indicators of inappropriate prescriptions for people aged 70 years or older (at-risk prescriptions, dangerous or at-risk coprescriptions, absence of necessary coprescriptions) and reports their prevalence in PACA. METHODS: The indicators were constructed from the French list of inappropriate prescriptions, national agency guidelines, and the advice of experts in the field. The indicators selected were applied to the databases of the PACA Salaried Workers' Health Insurance Fund for 2008 for all recipients aged 70 years or older and compared according to age, sex, chronic disease status, and, after standardization for age and sex, according to district of residence. RESULTS: In January 2009, 500,904 recipients aged 70 years or older were identified in the data base of the Salaried Workers' Health Insurance Fund, 60.8% of whom were women and 52.1% of whom had approved coverage for a chronic disease. The potentially inappropriate prescriptions most frequently observed here, in decreasing order, were: prescription of an NSAID without the coprescription of gastric protection (28.1%); long-term benzodiazepine treatment (21.5%); prescription of long half-life benzodiazepine (14.9%), and long-term treatment with NSAIDs (11.6%). Overall, the prevalence of each increased significantly with age and was higher among women and people with chronic diseases. Significant variations were also observed between the different districts of PACA. CONCLUSION: Our results confirm that a substantial proportion of elderly people receive potentially inappropriate prescriptions. They also suggest that health insurance reimbursement data could be used in some prescription domains for monitoring trends in the potentially inappropriate prescriptions in the populations of various territories, provided that specific limitations are considered.

[Evaluation of hospital stays linkage quality to study health spatial variation. a feasibility study in three French regions]. / Évaluation de la qualité du chaînage des séjours hospitaliers pour l'étude des variations spatiales de santé à partir des données du PMSI. Étude de faisabilité dans trois régions françaises.

BACKGROUND: Since 2001, the French hospital stay databases (Programme de médicalisation des systèmes d'information, PMSI) have included a unique and anonymous identifier in order to cross-link discharge abstracts from a given patient, within and across hospitals. These data could be used to estimate prevalence for some diseases at a territorial level provided that linkage quality is good enough. Few morbidity data are available at this scale. This study analyzes the link between linkage quality and hospitalization rates in three French regions (Picardy, Brittany and Provence-Alpes-Côte d'Azur-Paca). METHODS: We studied short stays in medicine-chirurgical-obstetrical units for the 2004-2005 period (all stays, and stays with mention of cancer or asthma). To study linkage quality, the percentage of linkable stays (no error during the production of the anonymous identifier) was calculated at regional and territorial levels (areas used by regional health authorities). The interquartile range (IQR=third quartile-first quartile) of the percentage of linkable stays was calculated and the link between this percentage and standardized rates of people hospitalized at least once in 2004 or 2005 tested by Spearman correlation coefficients. RESULTS: For all stays, percentages of linkable stays were 94.4%, 96.6% and 97.0% in Picardy, Paca and Brittany respectively in 2004-2005. Geographical variation at the territorial level was higher in Picardy (IQR between 4 and 6) than in the two other regions (IQR between 1 and 2). The percentage of linkable stays was positively and significantly associated with the hospitalization rate for all stays and those with mention of cancer in Picardy only. CONCLUSION: According to these results, PMSI data earlier than 2006 should be used with precaution; linkage quality should be analyzed before making geographical or time comparisons of hospitalization rates. Comparisons cannot always be made. Other studies should be carried out in other regions, and to analyze recent trends in linkage quality.

Feedback and lessons from the prescription of rimonabant, a drug to be used under strict guidelines, in southeastern France, March 2007 through June 2008.

BACKGROUND: To provide feedback on the initial market authorization of rimonabant, a drug to be used under strict guidelines, we conducted a study with information from the National health insurance reimbursements database for southeastern France. The aims of this study were to: (1) describe the characteristics of subjects who have had one rimonabant prescription reimbursed; (2) study the frequency of prescriptions that did not comply with reimbursement criteria; (3) study the frequency of prescriptions for patients simultaneously treated with antidepressants; and (4) analyse the factors associated with both types of prescription (patient and prescriber characteristics). METHODS: Using the database of drug reimbursements maintained by the southeastern France general health insurance fund, we studied the characteristics of outpatients with at least one reimbursement for rimonabant, compared them to the rest of the population, and analysed compliance with the indications, contraindications, and regulations for rimonabant prescription with multivariate logistic regressions. RESULTS: A total of 10,510 beneficiaries (0.28%) had at least one rimonabant reimbursement. Among them, 55.7% were treated for diabetes. For at least 62.4% of rimonabant beneficiaries, the reimbursement regulations were not respected: this was significantly more frequent among women less than 57 years old, subjects with no chronic diseases, and when the prescriber was not an endocrinologist; 11.4% of rimonabant beneficiaries also received an antidepressant treatment. CONCLUSION: Despite the specific status of rimonabant regarding its reimbursement modalities, these results suggest that some prescribers get around reimbursement instructions and that a significant percentage of prescriptions did not respect an important contraindication. Tools to follow up the prescriptions of new drugs with strict guidelines for use should be developed and physicians should be better informed and trained regarding specific prescription regulations.

Prevalence of treated diabetes: Geographical variations at the small-area level and their association with area-level characteristics. A multilevel analysis in Southeastern France.

AIM: This study estimated geographical variations in the prevalence of treated diabetes (TD) at the small-area level in Southeastern France to determine whether or not the characteristics of these areas (in particular, socioeconomic status or "SES") are associated with TD independent of person-level factors. METHODS: The study used drug reimbursement data for 2008 from the General Health Insurance Scheme in Southeastern France for beneficiaries aged 18 years or over. TD patients were defined as those to whom oral antidiabetic drugs or insulin had been dispensed at least three times within the year. Area (canton) characteristics associated with the prevalence of TD were studied using multilevel Poisson regression. RESULTS: In 2008, the crude prevalence of TD in adults in Southeastern France was 5.14%. In addition, TD prevalence was significantly higher in the more deprived and population-dense cantons independent of person-level factors (age, gender, low SES). CONCLUSION: This study found a positive association between area deprivation and TD, and adds further evidence to the scanty data so far available on this topic. This finding should contribute to pinpointing priority action areas for programmes of diabetes prevention. However, more research is needed to further elucidate the mechanism(s) linking area deprivation and diabetes.

[Impact of the estimation of the medically insured population on the pharmacological prevalence of diabetes at the regional and small area level]. / Impact de l'estimation de la population affiliée à l'assurance-maladie sur le calcul de la prévalence pharmacologique du diabète à l'échelle régionale et territoriale.

BACKGROUND: Data derived from Health Insurance databases are very useful for health observation. These data are however still underused, particularly for small local areas. This may be partly explained by the lack of reliable data on the number of insured people. Recent simplification of the Répertoire national interrégimes de l'assurance-maladie (RNIAM) indicator (French register of health insurance) gives the opportunity to improve the usefulness of these databases. This indicator specifies the beneficiaries' status towards the General Health Insurance Fund. This study aimed to select the population of beneficiaries, which could be most adequately used to calculate health indicators based on these data. METHODS: Data were collected from the outpatient database of the Southeastern France General Health Fund. We compared beneficiaries' characteristics according to the RNIAM indicator, calculated the annual unadjusted and age-adjusted regional and local prevalence of diabetes mellitus in two different populations: the whole initial beneficiaries database, and the population of "effective" beneficiaries (persons whose reimbursements were effectively managed by the General Health Insurance). RESULTS: The initial database included 4,817,871 beneficiaries. Almost 80% were in the "effective" population, 14% had left the General Health Insurance, or Southeastern France, and 4% were doubles. The annual unadjusted prevalence of diabetes mellitus was 3.31% in the initial database, and more than 20% higher when calculated among "effective" beneficiaries. Impact on aged-adjusted prevalence was less important (+9% at regional level), but the increase varied from 6 to 42% for the small local areas. Impact was much higher on age and gender specific rates. CONCLUSION: When Health Insurance databases are used to calculate health indicators at various geographical levels, only "effective" beneficiaries should be selected. The methodology for determining health indicators might be improved by updating databases (e.g. the date of the RNIAM indicator last update should be added).

[Corticotropic axis and chronic stress in abdominal obesity and metabolic syndrome]. / Axe corticotrope et stress chronique dans l'obésité abdominale et le syndrome métabolique.

Several indicators of corticotropic axis hyperactivity have been observed in common abdominal obesity, which is clinically similar to the obesity found in Cushing's syndrome. Corticotropic axis hyperactivity may be involved in the development and metabolic and cardiovascular complications of abdominal obesity. Several mechanisms may be responsible for this hormonal dysregulation: genetic, lifestyle, and nutritional factors, and chronic stress. We note the necessity of methodologically-impeccable clinical studies for an objective evaluation of the role of stress in obesity.

The archaeal DNA primase: biochemical characterization of the p41-p46 complex from Pyrococcus furiosus.

We characterized the primase complex of the hyperthermophilic archaeon, Pyrococcus furiosus. The two proteins, Pfup41 and Pfup46, have similar sequences to the p48 and p58 subunits, respectively, of the eukaryotic DNA polymerase alpha-primase complex. Unlike previously reported primases, the Pfup41 preferentially utilizes deoxyribonucleotides for its de novo synthesis, and moreover, it synthesizes up to several kilobases in length in a template-dependent manner (Bocquier, A., Liu, L., Cann, I., Komori, K., Kohda, D., and Ishino, Y. (2001) Curr. Biol. 11, 452-456). The p41-p46 complex showed higher DNA binding activity than the catalytic p41 subunit alone. In addition, the amount of DNA synthesized by the p41-p46 complex was much more abundant and shorter in length than that by Pfup41 alone. The activity for RNA primer synthesis, which was not detected with Pfup41, was observed from the reaction using the p41-p46 complex in vitro. The in vitro replication of M13 single-stranded DNA by the P. furiosus proteins was stimulated by ATP. Observation of the labeled primers by using [gamma-(32)P]ATP in the substrates suggests ATP as the preferable initiating nucleotide for the p41-p46 complex. These results show that the primer synthesis activity of Pfup41 is regulated by Pfup46, and the p41-p46 complex may function as the primase in the DNA replication machinery of P. furiosus, in a similar fashion to the eukaryotic polymerase alpha-primase complex.

Archaeal primase: bridging the gap between RNA and DNA polymerases.

In the evolution of life, DNA replication is a fundamental process, by which species transfer their genetic information to their offspring. DNA polymerases, including bacterial and eukaryotic replicases, are incapable of de novo DNA synthesis. DNA primases are required for this function, which is sine qua non to DNA replication. In Escherichia coli, the DNA primase (DnaG) exists as a monomer and synthesizes a short RNA primer. In Eukarya, however, the primase activity resides within the DNA polymerase alpha-primase complex (Pol alpha-pri) on the p48 subunit, which synthesizes the short RNA segment of a hybrid RNA-DNA primer. To date, very little information is available regarding the priming of DNA replication in organisms in Archaea. Available sequenced genomes indicate that the archaeal DNA primase is a homolog of the eukaryotic p48 subunit. Here, we report investigations of a p48-like DNA primase from Pyrococcus furiosus, a hyperthermophilic euryarchaeote. P. furiosus p48-like protein (Pfup41), unlike hitherto-reported primases, does not catalyze by itself the synthesis of short RNA primers but preferentially utilizes deoxynucleotides to synthesize DNA fragments up to several kilobases in length. Pfup41 is the first DNA polymerase that does not require primers for the synthesis of long DNA strands.

The relative orientation of the fibronectin 6F1(1)F2 module pair: a 15N NMR relaxation study.

The structure of a pair of modules (6F1(1)F2), that forms part of the collagen-binding region of fibronectin, is refined using heteronuclear relaxation data. A structure of the pair was previously derived from 1H-1H NOE and 3J(HalphaHN) data [Bocquier et al. (1999) Structure, 7, 1451-1460] and a weak module-module interface, comprising Leu19 and Leu28, in 6F1, and Tyr68 in 2F1, was identified. In this study, the definition of the average relative orientation of the two modules is improved using the dependence of 15N relaxation on rotational diffusion anisotropy. This structure refinement is based on the selection of a subset of structures from sets calculated with NOE and 3J(HalphaHN) data alone, using the quality of the fits to the relaxation data as the selection criterion. This simple approach is compared to a refinement strategy where 15N relaxation data are included in the force field as additional restraints [Tjandra et al. (1997) Nat. Struct. Biol., 4, 443-449].

Solution structure of a pair of modules from the gelatin-binding domain of fibronectin.

BACKGROUND: Fibronectin has a role in vital physiological processes such as cell migration during embryogenesis and wound healing. It mediates the attachment of cells to extracellular matrices that contain fibrous collagens. The affinity of fibronectin for native collagen and denatured collagen (gelatin) is located within a 42 kDa domain that contains four type 1 (F1) and two type 2 (F2) modules. A putative ligand-binding site has been located on an isolated F2 module, but the accessibility of this site in the intact domain is unknown. Thus, structural studies of module pairs and larger fragments are required for a better understanding of the interaction between fibronectin and collagen. RESULTS: The solution structure of the 101-residue 6F1 1F2 module pair, which has a weak affinity for gelatin, has been determined by multidimensional NMR spectroscopy. The tertiary structures determined for each module conform to the F1 and F2 consensus folds established previously. The experimental data suggest that the two modules interact via a small hydrophobic interface but may not be tightly associated. Near-random-coil 1H NMR chemical shifts and fast dynamics for backbone atoms in the linker indicate that this region is unlikely to be involved in the overall stabilisation of the module pair. CONCLUSIONS: The modules in the 6F1 1F2 module pair interact with each other via a flexible linker and a hydrophobic patch, which lies on the opposite side of the 1F2 module to the putative collagen-binding site. The intermodule interaction is relatively weak and transient.