1B). Based

on these TEER values, RL-65 cell layers were further characterised at the AL interface after 8 days in SFM and 8 and 21 days in SCM. Immunocytochemistry experiment on RL-65 layers cultured at the AL interface for 8 days in both media showed a positive staining for the zo-1 protein along the cell perimeter, in agreement with the location of tight junction proteins (Fig. 2). 14C-mannitol permeability studies resulted in Papp values ranging from 0.54 ± 0.11 to 3.09 ± 0.36 × 10−6 cm/s, depending on the conditions and length in culture ( Table 1). Those were in the same http://www.selleckchem.com/products/gsk126.html range as in-house and published Papp obtained in existing human bronchial epithelial cell culture models ( Table 1). After 8 days at an AL interface, 14C-mannitol Papp values were significantly lower in RL-65 layers grown in SCM than in layers maintained in SFM, in agreement with the higher TEER achieved in SCM. As previously reported for the Calu-3 and 16HBE14o- cell lines ( Forbes et al., 2003 and Sakagami, 2006), a strong inverse correlation (R = 0.9658) with power regression was indeed found between TEER and 14C-mannitol Papp

values in RL-65 layers ( Fig. 3). The morphology of RL-65 layers was characterised using histological and SEM examinations. Cross-sections of RL-65 cell layers cultured in SFM for 8 days depicted Z-VAD-FMK order 2–3 layers of cuboidal cells similar to that observed for sections of NHBE cells maintained at an AL interface for 21 days (Fig. 4A and D). In contrast, RL-65 cells cultured in SCM for 8 days formed a viable layer 1–3 cells thick adjacent to the filter underneath a ∼5 μm thick layer of pink/purple eosin stained

material containing no viable cells (Fig. 4B). After 21 days, the non-viable apical substance had extended to a ∼30 μm thick stratum and viable RL-65 cells formed a flatter single layer adjacent to the filter (Fig. 4C). Alcian blue staining failed to show the presence of mucopolysaccharides at the surface of RL-65 cell layers while positive staining was observed apically in Calu-3 and NHBE cell layers (data not shown). SEM images of the RL-65 apical surface revealed a heterogeneous cell population (Fig. 5A). At closer magnification, small cylindrical appendages, ∼2 μm in length and <0.5 μm in diameter before were observed protruding from the apical cell surface of RL-65 cells cultured in SFM, suggesting the presence of microvilli or immature cilia (Fig. 5B). This assumption was supported by a localised positive immunohistochemical staining for the cilia marker β-tubulin at the surface of the layers (Fig. 5C). Gene expression analysis of selected transporters revealed similar relative mRNA levels in RL-65 cells cultured for 8 days in either SFM or SCM. Expression levels were negligible (<0.001) for abcb1a (mdr1a), abcc2 (mrp2), slc22a1-3 (oct1-3) whilst a low (0.001–0.02) or moderate (0.02–0.

4f) compared to just a few hours at 37 °C for MVeGFP. The difference in thermal stability may be attributed to the presence (measles) or absence (adenovirus) of a viral envelope as the enveloped viruses are noted for greater temperature sensitivity than non-enveloped viruses [39]. Maintenance of vaccine efficacy in the absence of a cold chain has the potential to extend GDC 0449 immunity against deadly diseases into the world’s poorest communities and thereby save tens of thousands of lives

each year. Although alternative approaches for MV stabilization are being explored [26] and [40], the reformulation of existing LAVs is a promising approach towards eliminating the need for refrigeration during their storage, distribution, and use while not requiring major modifications to the existing manufacturing process. This screening platform allows for

reformulation of existing vaccines and could also be integrated into the formulation design process in the developmental stage of new vaccines. Although in Antidiabetic Compound Library the present work, the screening process was applied towards increasing LAV resistance to higher temperatures, an analogous process could be applied for addressing sensitivity to cold or freezing, or towards optimization against performance metrics other than infectivity. As a proof-of-concept, we applied the screening platform to MV, and several formulations were validated with vaccine strain virus that suffer <1.0 log loss after 8 h at 40 °C in the liquid state. This is a significant gain in thermal stability relative to two representative commercial vaccines (Attenuvax® and M-VAC™) and would allow the reconstituted multi-dose vials of vaccine to be used for a full working day in a health clinic without access to refrigeration.

This dataset represents the most comprehensive information to date on the thermal stability of MV in liquid formulation, and therefore may be of broad interest to the MV and vaccine development communities. We acknowledge that thermal stability in the reconstituted (liquid) state must be paired with stability in the lyophilized state. The HT screening platform described here has been extended to address the more technically challenging problem of evaluating diverse lyophilized formulations, from and we will report those results separately (High throughput screening of lyophilization conditions: application to the monovalent measles vaccine; manuscript in preparation). Also, the underlying biophysical effect of excipients on virus has not been explored during this project; however, this topic is being rigorously pursued by other groups [41]. In order for a reformulation to be implemented, the change must be attractive for the vaccine producer. We recognize that a firmly entrenched manufacturing process is a high barrier to adoption.

Le diagnostic repose sur la détection de cette population lymphocytaire au sein des organes atteints. Une parotidomégalie s’observe dans 88 % des cas avec ou sans syndrome sec qui reste toutefois rare. L’atteinte pulmonaire se caractérise par une infiltration interstitielle lymphocytaire et l’atteinte rénale par une néphromégalie, une néphropathie tubulo-interstitielle, une acidose tubulaire distale de type IV et une protéinurie modérée. Dans ces cas, l’infiltration interstitielle est composée de lymphocytes majoritairement T CD8+, de monocytes et de plasmocytes [27]. Parmi les autres

manifestations rapportées au cours de ce syndrome figurent une méningite lymphocytaire aseptique (4 % à 11 % des cas) ou une paralysie faciale (2 à 7 % des cas). Une gastrite, une hépatite ou une myosite lymphocytaire selleck screening library sont plus rares. De manière intéressante, une infiltration des muscles par des lymphocytes CD8+/CD28− a également été rapportée au cours des myosites chez le sujet négatif pour le VIH [33]. Les patients atteints de DILS ont une fréquence accrue de certains allèles du

complexe majeur d’histocompatibilité (CMH) de classe II comme l’allèle HLA-DRB1 × 1301 chez INCB28060 ic50 les sujets issus de population noires et caucasiennes et l’allèle HLA-DRB1 × 1102 surtout chez les sujets issus de population noires [32] and [34]. De plus, certains allèles du CMH présentent des peptides du VIH au TCR, suggérant un processus médié par des antigènes. Les mécanismes par lesquels ces lymphocytes infiltrent les viscères restent mal compris. Les lymphocytes T CD8+ pourraient exprimer des molécules d’adhésion, reconnaissant des ligands spécifiques, au

sein des tissus infiltrés. Une autre hypothèse stipule l’expression par certains tissus, comme les glandes parotides, d’antigènes viraux que reconnaîtraient spécifiquement ces lymphocytes. L’infiltration viscérale justifie parfois un traitement qui associe alors corticoïdes et antirétroviraux. La réponse au traitement nearly peut être excellente, mais une corticodépendance peut s’observer [27]. La population T CD8+/CD57+ a été incriminée dans différents processus pathologiques au cours des allogreffes de cellules souches hématopoïétiques comme l’inhibition de la granulopoïése (voire de l’ensemble de l’hématopoïèse) ou l’induction d’une réaction du greffon contre l’hôte. Cette expansion au cours de la réaction du greffon contre l’hôte (aiguë ou chronique) est oligoclonale [35] and [36] et marquée par une restriction des gènes Vβ utilisés, suggérant une stimulation antigénique chronique à son origine, possiblement de nature infectieuse [35]. Cette expansion, qui peut persister jusqu’à six ans après la greffe, a été associée à une incidence plus faible de rechute chez les patients atteints de leucémie, évoquant son implication dans l’effet anti-leucémique du greffon (effet GVL) [37], [38] and [39].

1B) are characterized by positive responses for both directions of the grating reversals for several grating positions, in particular when positive and negative contrast are balanced over the receptive field. These response characteristics cannot be explained by a model with linear integration of light signals over space. More formally, the distinction between linear X cells and nonlinear Y cells is often based on computing the amplitudes of the first

and the second harmonic of the firing rate in response to the periodic grating reversals (Hochstein and Shapley, 1976). X cell responses are dominated by the first harmonic (Fig. 1C), whereas the fact that Y cells can respond to both grating reversals leads to frequency doubling and an often dominant second harmonic in the firing rate profile (Fig. 1D). Note that the linear spatial integration in X cells does not imply that these cells respond to the two opposite grating reversals with firing rate profiles that are ATM Kinase Inhibitor price equal in magnitude with opposite signs, as would be expected for a completely linear system. In fact, retinal ganglion cells, like most other neurons in the nervous system, display a nonlinear dependence of the firing rate on stimulus strength simply because the spiking itself is subject to a threshold and potentially saturation. Thus, positive responses upon grating reversals are typically more pronounced than the amount of suppression observed for

the opposing reversal. This can www.selleckchem.com/JNK.html be viewed as a nonlinear transformation of the integrated activation signal. This nonlinearity, however, does not affect how signals are integrated over space prior to this output transformation. We will return to this distinction between different nonlinear stages in the stimulus–response relation of ganglion cells below. The separation between X cells and Y cells does

not always appear clear-cut and may in some systems rather represent the extremes of a continuum with different degrees of nonlinear integration, as reported, for example, for mouse retina (Carcieri et al., 2003). Moreover, and the fact that anatomical investigations typically distinguish around ten to twenty different types of ganglion cells (Masland, 2001, Rockhill et al., 2002, Dacey, 2004, Kong et al., 2005, Coombs et al., 2006, Field and Chichilnisky, 2007 and Masland, 2012) suggests that the classification of X and Y cells represents only a coarse categorization, which might allow further division into subtypes, for example, by refined measurements of the spatial integration characteristics. The finding of nonlinearly integrating ganglion cells has led to the development of subfield models, which describe the receptive field structure of Y cells as composed of spatial subfields whose signals are nonlinearly combined (Fig. 2). These model efforts were initiated by measurements of Y cell responses to sinusoidal temporal modulations of different spatial patterns (Hochstein and Shapley, 1976).

4C), amygdala (F(3–16) = 2.451; selleckchem p = 0.10 Fig. 4C) and hippocampus (F(3–16) = 1.519; p = 0,24 Fig. 4C). The chronic treatment increased the mitochondrial complex II-III activity in the prefrontal cortex (F(3–15) = 4.175; p = 0,03 Fig. 4C) and hippocampus (F(3–13) = 10.168; p = 0.001 Fig. 4C) with imipramine at the dose of 30 mg/kg and in the amygdala (F(3–14) = 10.512; p = 0.001 Fig. 4C) with all treatments, but did not alter in the prefrontal cortex (F(3–15) = 4.175; p > 0.05 Fig. 4C) and in the hippocampus

(F(3–13) = 10.168; p > 0.05 Fig. 4C). The acute administration increased Selleckchem Crizotinib the mitochondrial complex IV activity in the hippocampus (F(3–13) = 18.471; p < 0,001 Fig. 4D) with all treatments, compared with saline, but did not alter in the prefrontal cortex (F(3–12) = 0.828; p = 0.50 Fig. 4D) and amygdala (F(3–11) = 4,514; p = 0,27 Fig. 4D). The chronic treatment did not alter the mitochondrial complex IV activity in the prefrontal cortex (F(3–13) = 0.689; p = 0.57 Fig. 4D), amygdala (F(3–16) = 3.666; p = 0.35 Fig. 4D) or hippocampus (F(3–11) = 2.317; p = 0.13 Fig. 4D). The acute treatment decreased the Bcl-2 protein levels in the

prefrontal cortex (F(3–12) = 106.818; p < 0,001 Fig. 5A) and in the hippocampus (F(3–12) = 265,226; p < 0,001 Fig. 5A) with imipramine at the dose of 30 mg/kg and lamotrigine at the dose of 20 mg/kg, and also in the amygdala (F(3–12) = 87.304; p < 0.001 Fig. 5A) with all treatments, compared with saline. The chronic treatment decreased the Bcl-2 protein levels in the prefrontal cortex (F(3–12) = 310.093; p < 0.001 Fig. 5A), amygdala (F(3–12) = 238.818; p < 0.001

Fig. 5A) and hippocampus (F(3–12) = 557.669; p < 0.001 Fig. 5A) with all treatments. The acute treatment second increased the AKT protein levels in the prefrontal cortex (F(3–12) = 49.088; p = 0.000 Fig. 5B) with imipramine at the dose of 30 mg/kg, in the amygdala (F(3–12) = 70.335; p < 0.001 Fig. 5B) with lamotrigine at the dose of 20 mg/kg and in the hippocampus (F(3–12) = 21.011; p = 0.009 Fig. 5B), with imipramine at the dose of 30 mg/kg and with lamotrigine at the dose of 20 mg/kg, compared with saline. The acute treatment also decreased the AKT protein levels in the amygdala with imipramine at the dose of 30 mg/kg (F(3–12) = 70.335; p = 0.04 Fig. 5B) and in the hippocampus with lamotrigine at the dose of 10 mg/kg (F(3–12) = 21.011; p = 0.04 Fig. 5B). The chronic treatment increased the AKT protein levels in the prefrontal cortex (F(3–12) = 121.938; p < 0,001 Fig. 5B), amygdala (F(3–12) = 83.853; p < 0.001 Fig. 5A) and hippocampus (F(3–12) = 58.262; p < 0,001 Fig. 5B) after all treatments.

A recent study of children with severe influenza disease suggested that anti-influenza mucosal antibody

may be particularly important in children [33]. There is also evidence that IgA may be more cross-reactive against antigenically drifted influenza viruses than IgG [34]. Although a previous study demonstrated IgA responses following Autophagy Compound Library nmr LAIV, the relationship between IgA responses and the incidence of influenza illness was not evaluated [27]. Three previous randomized, placebo-controlled clinical studies of LAIV efficacy in young children prospectively evaluated postvaccination IgA responses in a subset of study subjects [14], [20] and [35]. This analysis describes the strain-specific IgA responses observed in these 3 studies and examines the relationship between IgA and the incidence of influenza illness. Nasal IgA responses were evaluated using data from 3 prospective, 2-year, randomized, placebo-controlled studies of LAIV in children. The detailed methods and inclusion/exclusion criteria for each study have been previously published. Study 1 was a 2-year study conducted in influenza vaccine-naive children 12 to <36 months of age selleckchem from 2000 to 2002 in Asia [20]. Study 2 [35] was conducted

in influenza vaccine-naive children 6 to <36 months of age attending day care in several European countries and Israel from 2000 to 2002. Study 3 [14] was conducted in influenza vaccine-naive children 6 to <36 months of age in South America and South Bay 11-7085 Africa in 2001–2002. In studies 1 and 2, children were randomized to 2 doses of vaccine or placebo approximately 1 month apart in year 1. In study 3, there were 3 randomized treatment groups in year 1:2 doses of vaccine approximately 1 month apart, 1 dose of vaccine followed by 1 dose of placebo approximately 1 month later, and 2 doses of placebo approximately 1 month apart. In all 3 studies, subjects received a single dose of vaccine or placebo

in year 2 [14]. The vaccines and placebos used in each study are described in Supplementary Text 1. In all studies, nasal IgA and serum HAI antibody titers were evaluated in a subset of subjects enrolled. A separate population was defined each year. Nasal wash and serum samples were collected from subjects on 4 occasions over the 2 years: immediately before the first dose in year 1, approximately 1 month after the second dose in year 1, immediately before the year 2 dose, and approximately 1 month after the year 2 dose. In study 3, due to the randomization of subjects to 1 versus 2 doses of vaccine in the first year, additional samples were collected from subjects immediately before the second dose in year 1.

Consistent with our original conclusion, laser therapy would appear to show some promise as a treatment for neck pain. We were not, however, able to explain the conflicting

results regarding the efficacy of laser therapy, nor the reasons for medium- but not short-term benefits. Thus, the Abstract to the original paper should be revised to note that: ‘Treatment with laser therapy resulted in better pain and disability outcomes at medium-term follow-up but not at short-term follow-up. “
“Physiotherapists commonly assess and treat patients with lower extremity joint disorders. Despite varying levels of evidence, a growing number of studies have shown that manual joint Pexidartinib order mobilisations or manipulations are effective in certain disorders such as hip and knee osteoarthritis, patellofemoral pain syndrome, ankle inversion sprain, plantar fasciitis, metatarsalgia, and hallux limitus/rigidus (Brantingham et al 2009). Measurement of passive movement is indicated in order to assess joint restrictions and to help diagnose these disorders. Passive movement, either physiological or accessory, can be reported as range of

motion, end-feel, or pain and is an indication of the integrity of joint structures (Cyriax 1982, Hengeveld and Banks 2005, Kaltenborn 2002). Passive physiological range of motion may be measured using vision or instruments Imatinib solubility dmso such as goniometers or inclinometers. An essential requirement of clinical measures is that they are valid and reliable so that they can be used to discriminate between individuals (Streiner and Norman 2008). Inter-rater reliability is a component of reproducibility along with agreement

and refers to the relative measurement error, ie, the variation between patients as measured by different raters in relation to the total variance of the measurements (De Vet et al 2006, Streiner and Norman 2008). High inter-rater reliability for measurements of lower extremity joints is a prerequisite for valid and uniform clinical decisions about joint restrictions and related disorders (Bartko and Carpenter 1976). Several reviews have systematically summarised and appraised the evidence with to respect to the inter-rater reliability of passive movements of human joints. Seven systematic reviews have been published on passive spinal and pelvic movement including segmental intervertebral motion assessment (Haneline et al 2008, Hestbæk and Leboeuf-Yde 2000, May et al 2006, Seffinger et al 2004, Stochkendahl et al 2006, Van Trijffel et al 2005, Van der Wurff et al 2000). In general, inter-rater reliability was found to be poor and studies were of low methodological quality. A recent systematic review showed better inter-rater reliability for measurements of passive physiological range of motion in upper extremity joints using instruments compared to measurements using vision and compared to measurements of end-feel or accessory range of motion (Van de Pol et al 2010).

Positive change in health-related behaviour was defined as a positive change in any of: parent-reported diet, physical activity, screen-time behaviour, or health or leisure services use between baseline and one or six month follow-up. An individual with data at both one and six month follow-ups was categorised as having changed their behaviour if an improvement was observed at either time point. Positive change in diet was defined as an increase in healthy eating score between baseline and follow-up. The healthy eating score was derived from the frequency of consumption of fruits,

vegetables, sugary drinks, and snacks (Croker et al., 2012). For each food category, a score ranging from 1 to 7 was generated according to the frequency VX-770 cost Anti-cancer Compound Library cell assay of consumption (higher score for increasing consumption of fruit and vegetables, the reverse for other food categories); the healthy eating score was derived as a mean of these

scores, with a higher score indicating healthier eating behaviours. Improvement in physical activity was defined as a change from a child not meeting the national physical activity recommendation of 1 h per day at baseline (Department of Health, 2011), to achieving this level at follow-up. Improvement in screen-time behaviours was similarly defined as a change from not meeting screen-time recommendations of up to two hours per day at baseline (American Academy of Paediatrics, 2012), to meeting this level at follow-up. Positive change in the 3-mercaptopyruvate sulfurtransferase use of health or leisure services was defined as a change from not accessing any of these services for their child’s weight at baseline, to accessing one or more of these at follow-up. Predictor variables for intention to change health-related behaviour were: 1) parental recognition of their child’s overweight status (parents described their child as overweight or very overweight; parents of obese children that described their child as overweight were considered to recognise

their child’s overweight status because they acknowledged an issue with excess weight), and 2) parental recognition of the health risks associated with their child’s overweight status (parents answered Yes to the question, Do you think your child’s current weight puts their health at risk?), at one month. The predictor variable for change in health-related behaviour was intention to change behaviour. Other predictors for both outcomes were ethnicity of child (white or non-white, from PCT records), child’s sex, child’s school year, child overweight status (overweight or obese, from NCMP), deprivation tertiles (using the Index of Multiple Deprivation IMD score, a measure of local area deprivation based on postal code), and PCT (an indicator of area level differences). The characteristics of the cohort were described using frequencies and percentages.

Fecal samples were immediately frozen at home by the subjects; mTOR inhibitor fecal extracts were subsequently prepared and stored at −70 °C [11]. Antibody levels in ALS specimens, fecal extracts and sera were analyzed by ELISA using plates coated with CFA/I, CS3, CS5, CS6, GM1 plus LTB or O78 LPS [9] and [11]. Fecal antibody levels were determined as the antigen-specific SIgA titer divided

by the total SIgA concentration of each sample [15]. LT toxin neutralization titers were determined using the Y1 adrenal cell assay [16]. Safety endpoints were defined as absence of any vaccine-related serious AEs and not significantly higher frequencies of vaccine-related severe AEs in each of the vaccine groups than in the placebo group. Primary immunogenicity endpoints

were defined as induction of immune responses in any of the vaccine groups in either of the primary assays proposed (fecal SIgA or ALS IgA) to at least four of the five primary vaccine components (CFA/I, CS3, CS5, CS6 and LTB). The magnitudes of immune responses (fold rises) were calculated as the post-immunization divided by pre-immunization antibody levels. Statistical differences were evaluated using t-test (magnitudes, ELISA results), Mann–Whitney test (magnitudes, toxin neutralization results) and Fisher’s exact test (frequencies) with Holm’s correction for multiple testing [17]. Differences between vaccine groups and the placebo group were evaluated using one-tailed statistical tests; all other statistical tests were two-tailed. P-values <0.05 were Proteasome inhibitor considered significant. Of 161 subjects screened, 129 were enrolled with 30–35 subjects in each of the four study groups (Table 1 and Supplementary material; Fig. 1). The age and gender distributions were comparable in Groups A, B and C, but more males

were randomized to Group D (Table 1). Overall, MEV administered alone and in Isotretinoin combination with dmLT was safe and well tolerated. No serious AEs were reported and the recorded AEs were mainly mild and not significantly different among any of the vaccine groups (B, C, D) and the placebo group (A). The addition of dmLT did not alter the safety profile. Altogether 89 solicited symptoms, deemed to be possibly or probably related to treatment, were recorded (Table 2); these AEs did not differ in either frequency or intensity between the different study groups. No significant changes of other clinical parameters, including serum chemistry and hematology, were observed in any of the volunteers. ASC responses against the primary vaccine antigens were studied by counting IgA ASCs by the ELISPOT method as well as by measuring antibody levels in lymphocyte secretions by the ALS method in the initial 43 randomized subjects. Since the frequencies of responses against all antigens were comparable using the two methods (data not shown), the ALS method was used in all subsequent study subjects as the sole measure of ASC responses.

All statistical analyses were performed using Stata 12.0 (StataCorp, College Station, TX, USA) statistical software. The study was conducted according to Ethical Principles for Medical Research Involving Human Participants of the World Medical Association, the Declaration of Helsinki, and the International Ethical Guidelines for Epidemiological Studies. The Ethic Research

Committee of the Directorate of Public Health and Public Health Research Center of Valencia approved the study protocol and provided the exemption from obtaining individual informed consent to obtain and merge individual data from the different registries. Overall, 438,024 adults aged 65 years and older on 1 October 2011 were vaccinated against influenza during the 2011–2012 season (51% of MEK inhibitor the total population ≥65 years PI3K inhibitor old in Valencia region). We excluded 252,372 who resided outside the nine HSAs under study, 5593 that were institutionalized, and 16,038 who had received a different vaccine to those being compared. This left 164,021 (19% of the total population ≥65 years old in Valencia region) subjects for the analysis (Fig. 1). The cohort mean age was 76.7 (standard deviation: 7.2) years, and 55.3% were female. A total of 49.7% of cohort members were recorded as suffering from “chronic cardio-respiratory conditions” in the Vaccine Information

System database, but only 8% were on chronic cardiovascular and respiratory medication. A total of 62,058 (37.8%) people were vaccinated with virosomal-TIV and 101,963 (62.2%) were vaccinated with intradermal-TIV (Fig. 1, Table 1). The age and sex distribution of patients vaccinated with each vaccine were similar (Table 1). Subjects vaccinated with virosomal-TIV were more likely to be reported as belonging to the “cardio-respiratory risk group” (59.3% for virosomal versus 43.8% for intradermal TIV; P < .001). However, pharmaceutical claim distributions were similar between both groups of vaccinees ( Table 1). During the time influenza

was circulating in the community, we identified 127 hospitalizations related to Tryptophan synthase influenza among subjects vaccinated with virosomal-TIV, out of 914,740 total person-weeks at risk. We also identified 133 hospitalizations related to influenza among subjects vaccinated with intradermal-TIV, out of 1,504,570 total person-weeks at risk (Fig. 1, Table 2). From the total of 260 cases, 241 were identified through the VAHNSI scheme, 12 were reported to the Microbiological Surveillance Network (RedMIVA) and 15 (0.6%) patients were ascertained from the CMBD because of a discharge diagnosis for influenza (ICD9-CM 487–488.89), seven of these (five virosomal-TIV and two intradermal-TIV vaccinees) lacked a laboratory result for the confirmation of influenza virus infection. The most frequent primary diagnosis among those with a positive laboratory result for influenza was chronic obstructive pulmonary disease (COPD) (24.5%), followed by pneumonia (21.3%). A total of 24.