Differentiation of Sialyl Linkages Using a Combination of Alkyl Esterification and Phenylhydrazine Derivatization: Application for N-Glycan Profiling in the Sera of Patients with Lung Cancer.

Alterations in oligosaccharides and types of sialic acid (SA) attachments have been associated with different pathological states. Matrix-assisted laser desorption mass spectrometry (MS) is commonly used for glycosylation studies. However, native sialylated glycans are suppressed or not detected during MS experiments. Consequently, different approaches have been employed to neutralize the negative charge of the carboxyl group. In this study, we present the advantage of phenylhydrazine (PHN) labeling for the detection and efficient discrimination of SA linkages when this derivatization follows alkyl esterification. As expected, PHN-labeled sialylated oligosaccharides with the 2,6-linkage type can be easily recognized according to the additional shift in mass corresponding to the presence of a methyl or ethyl group. Surprisingly, oligosaccharides with the 2,3-linked SA residue instead of a lactone were detected carrying the second PHN unit. This was beneficial as no further processing after esterification was needed to stabilize the lactone form. Moreover, during tandem mass experiments, all modified glycans produced favorable fragmentation patterns with a coherent recognition of SA linkages. Although both types of esterification, herein called the EST-PHN approach, provided comparable results, methylation exhibited marginally higher linkage specificity than ethyl esterification. The simplicity and effectiveness of the methodology are demonstrated on the model compound, sialyllactose, and its applicability for biological studies is presented on N-glycan profiling in the sera of lung cancer patients.

Patient-related characteristics associated with non-persistence with statin therapy in elderly patients following an ischemic stroke.

PURPOSE: This study was aimed at evaluating the extent of non-persistence with statin therapy in elderly patients after an ischemic stroke and identifying patient-related characteristics that are risk factors for non-persistence. METHODS: The evaluable study cohort (n = 2748) was derived from the database of the largest health insurance provider in the Slovak Republic. Patients aged ≥65 years who were initiated on statin therapy following the diagnosis of an ischemic stroke during one full year (1 January 2010 to 31 December 2010) constituted this cohort. Each patient was followed for a period of 3 years from the date of the first statin prescription. Patients with a continuous treatment gap of 6 months without statin prescription were designated as non-persistent. The Cox proportional hazard model was applied to determine patient-associated characteristics that influenced the likelihood of non-persistence. RESULTS: During the 3-year follow-up period, 39.7% of patients in the study cohort became non-persistent. Factors associated with decreased probability of a patient becoming non-persistent were age ≥75 years (hazard ratio (HR) 0.75), polypharmacy (concurrent use of ≥6 drugs) (HR 0.79), diabetes mellitus (HR 0.80), dementia (HR 0.81) and hypercholesterolemia (HR 0.50). On the other hand, the presence of anxiety disorders (HR 1.33) predicted an increased likelihood of a patient being non-persistent. CONCLUSIONS: Our findings suggest that patients aged ≥75 years or those with the presence of diabetes mellitus, dementia, hypercholesterolemia or polypharmacy were likely to be persistent with statin therapy, whereas those with anxiety disorders may need greater assistance with persistence of statin therapy. Copyright © 2016 John Wiley & Sons, Ltd.

Non-persistence with antiplatelet therapy in elderly patients after a transient ischemic attack.

BACKGROUND: Antiplatelet therapy following a transient ischemic attack (TIA) constitutes an important secondary prevention measure. AIMS: The study was aimed at evaluating the development of non-persistence with antiplatelet therapy in elderly patients after a TIA and identifying patient-related characteristics associated with the probability of non-persistence during the follow-up period. METHODS: The study cohort (n = 854) was selected from the database of the largest health insurance provider of the Slovak Republic. It included patients aged ≥65 years, in whom antiplatelet medication was initiated following a TIA diagnosis during the period between 1 January 2010 and 31 December 2010. Each patient was followed for a period of 3 years from the date of the first antiplatelet medication prescription associated with TIA diagnosis. Patients in whom there was a treatment gap of at least 6 months without antiplatelet medication prescription were defined as "non-persistent". The factors predicting non-persistence were identified in the Cox proportional hazards model. RESULTS: At the end of the follow-up period, 345 (40.4%) patients were non-persistent with antiplatelet medication. Protective factors decreasing a patient´s likelihood of becoming non-persistent were age ≥75 years [hazard ratio (HR) = 0.75], polypharmacy (concurrent use of ≥6 drugs) (HR = 0.79), arterial hypertension (HR = 0.68), diabetes mellitus (HR = 0.74), hypercholesterolemia (HR = 0.75), and antiplatelet medication switching during the follow-up period (HR = 0.73). CONCLUSIONS: It is concluded that following a TIA, elderly patients aged <75 years or those with normal serum cholesterol levels, without certain comorbid conditions and polypharmacy may benefit from special counselling to encourage persistence with secondary preventive medication.

Non-Adherence to Statin Treatment in Older Patients with Peripheral Arterial Disease Depending on Persistence Status.

The effectiveness of statins in secondary prevention of peripheral arterial disease (PAD) largely depends on patients' adherence to treatment. The aims of our study were: (a) to analyze non-adherence during the whole follow-up in persistent patients, and only during persistence for non-persistent patients; (b) to identify factors associated with non-adherence separately among persistent and non-persistent patients. A cohort of 8330 statin users aged ≥65 years, in whom PAD was newly diagnosed between January 2012-December 2012, included 5353 patients persistent with statin treatment, and 2977 subjects who became non-persistent during the 5-year follow-up. Non-adherence was defined using the proportion of days covered <80%. Patient- and statin-related characteristics associated with non-adherence were identified with binary logistic regression. A significantly higher proportion of non-adherent patients was found among non-persistent patients compared to persistent subjects (43.6% vs. 29.6%; p < 0.001). Associated with non-adherence in both persistent and non-persistent patients was high intensity statin treatment, while in non-persistent patients, it was employment and increasing number of medications. In patients with a poor adherence during their persistent period, an increased risk for discontinuation may be expected. However, there is also non-adherence among persistent patients. There are differences in factors associated with non-adherence depending on patients' persistence.

Factors Associated with Reinitiation of Statin Treatment in Older Patients with Peripheral Arterial Disease.

BACKGROUND: Long-term persistence represents a basic precondition of successful statin treatment in patients with peripheral arterial disease (PAD). OBJECTIVES: The aims of our study were evaluation of reinitiation in older PAD patients who were non-persistent with statin treatment, and identification of patient-related characteristics associated with the patient's probability of reinitiation. METHODS: Our study cohort included 2977 older patients (≥ 65 years) who were non-persistent with statin treatment in whom PAD was newly diagnosed in 2012. Reinitiation was defined as the first statin prescription recorded after discontinuation. To analyze factors associated with the patient´s probability of reinitiation, Cox regression with time-dependent covariates was applied. RESULTS: After post-discontinuation follow-up of a mean of 27 months, reinitiation of statin treatment was recorded for 1244 (41.8%) patients. Increasing age, Parkinson's disease, being a new statin user (patient in whom statin treatment was initiated in association with PAD diagnosis), general practitioner as the index prescriber who prescribed a statin for the first time after diagnosis of PAD, coadministration of loop diuretics, and longer persistence before discontinuation decreased the patient's likelihood of reinitiation, whereas myocardial infarction during non-persistence, high-intensity statin treatment, and increasing number of medications increased the patient's probability of reinitiation. CONCLUSIONS: In patients with characteristics associated with a lower probability of reinitiation, more concentrated outreach and further evaluation of these groups to identify interventions that might be helpful to encourage reinitiation are needed.

The effect of selected patient's characteristics on the choice of antihypertensive medication in the elderly in Slovakia.

PURPOSE: The aim of the present study was to determine which patient-related characteristics influence the selection of the antihypertensive drug class in elderly patients in Slovakia. METHODS: The sample for our study (n = 401) was selected from 1045 patients admitted to the Department of Internal Medicine of a general hospital during the period of 1 December 2003-31 March 2005. Patients aged 65 or more with documented arterial hypertension and treated with at least one antihypertensive drug were enrolled in our retrospective study. Specific socio-demographic and clinical characteristics as well as cardiovascular comorbid conditions were evaluated as potential factors that could have influenced the choice of antihypertensive drug class. RESULTS: The most frequently prescribed antihypertensive drugs were angiotensin-converting enzyme (ACE) inhibitors and diuretics (61.8% and 60.1% of patients, respectively). Patients aged >/= 85 years had lower probability of ACE inhibitors prescription (OR = 0.49). Females had higher chance of calcium channel blockers use (OR = 3.84) and lower odds of diuretics administration (OR = 0.50). In patients living alone, ACE inhibitors were preferred (OR = 2.16). The use of diuretics was more frequent in polymorbid patients (OR = 1.95). Immobile patients had lower chance of being prescribed beta-blockers and calcium channel blockers (OR = 0.25 and OR = 0.39, respectively). CONCLUSION: The present study revealed that the selection of the antihypertensive drug class in elderly patients is influenced not only by comorbid conditions present but also by socio-demographic and clinical characteristics, such as age, sex, living alone, polymorbidity and immobilization. These characteristics reflect the doctor's perception of risk from pharmacotherapy of hypertension in elderly patients.

Patient-Associated Characteristics Influencing the Risk for Non-Persistence with Statins in Older Patients with Peripheral Arterial Disease.

BACKGROUND AND OBJECTIVES: Secondary prevention of peripheral arterial disease includes administration of statins regardless of the patient's serum cholesterol level. Our study aimed to identify patient-associated risk factors for statin non-persistence and comparison of the explanatory power of models based on clusters of patient-associated characteristics. METHODS: Our study cohort (n = 8330) was assembled from the database of the largest health insurance provider in the Slovak Republic. Statin users aged ≥ 65 years in whom peripheral arterial disease was diagnosed during 2012 were included. Patients were followed for 5 years; those with a treatment gap period of at least 6 months without statin prescription were classified as "non-persistent". The risk factors for non-persistence were identified within six models (sociodemographic, cardiovascular events, comorbid conditions, statin-related characteristics, cardiovascular co-medication and full model) using Cox regression. The explanatory power of models was assessed using Harrell's C-index. RESULTS: At the end of the follow-up, 35.7% of patients were found to be non-persistent. The full model had the highest explanatory power (C = 0.632). Female sex, atorvastatin and rosuvastatin as initially administered statins, being a new statin user and an increasing co-payment were associated with an increased risk for non-persistence. Increasing age, history of ischaemic stroke, diabetes mellitus, general practitioner as index prescriber, increasing overall number of medications and co-administration of certain cardiovascular co-medications were associated with a lower likelihood for non-persistence. CONCLUSIONS: Patients identified as high risk for non-persistence require special attention aimed at the improvement of their persistence with statin treatment.

Age-Related Differences in Non-Persistence with Statin Treatment in Patients after a Transient Ischaemic Attack.

BACKGROUND AND OBJECTIVE: Non-persistence with secondary preventive measures, including medications such as statins, adversely affects the prospects of successful outcomes. This study was aimed at evaluating non-persistence with statin therapy in cohorts of young and elderly patients after a transient ischaemic attack (TIA) and identifying patient-associated characteristics that influence the risk for non-persistence. METHODS: The study cohorts included 797 adult patients who were initiated on statin therapy following a TIA diagnosis between 1 January 2010 and 31 December 2010. Patients were followed up for 3 years and those with a treatment gap of at least a 6-month period were considered 'non-persistent'. In order to identify any age-related differences, all analyses were conducted in the entire study cohort (n = 797) as well as separately in the 'younger' (aged <65 years, n = 267) and the 'older' (aged ≥65 years, n = 530) patients. RESULTS: Non-persistence was significantly more common in younger patients compared to older patients (67.8% vs. 49.1%; p < 0.001). Factors that decreased the probability of non-persistence in younger and older patients included diabetes mellitus (hazard ratio [HR] = 0.72 and HR = 0.64, respectively) and hypercholesterolaemia (HR = 0.43 and HR = 0.62, respectively). Female gender (HR = 1.42) was associated with a higher and increasing number of medications taken (HR = 0.93), with lower probability for non-persistence in younger patients but not in the older patients. CONCLUSIONS: Our results indicate that certain patients with TIA require special counselling to improve persistence with statin therapy. These include younger patients, especially females and those not on polypharmacy, and both younger and older patients without diabetes mellitus or hypercholesterolaemia.

Factors Influencing Non-Persistence with Antiplatelet Medications in Elderly Patients After Ischaemic Stroke.

OBJECTIVES: This study investigated the extent of, and patient-related characteristics for, non-persistence with antiplatelet therapy during follow-up in elderly patients after their first ischaemic non-cardioembolic stroke. METHODS: A database of the largest health insurance provider in the Slovak Republic was used to assemble the study cohort of 4319 patients (56.8% were women) aged ≥65 years in whom antiplatelet therapy was initiated following a hospital-based diagnosis of stroke during the period 1 January 2010 to 31 December 2010. Patients were followed for 3 years from the date on which the first prescription of antiplatelet medication was recorded. Patients with a 6-month treatment gap without antiplatelet medication prescription were designated as non-persistent, and the Cox proportional hazards model was used to identify predictors of non-persistence. RESULTS: At the end of the 3-year follow-up period, 1184 (27.4%) patients were considered non-persistent with antiplatelet medication. In 1244 (28.8%) patients, a switch in the use of a particular antiplatelet drug was registered during this follow-up period. Female sex (hazard ratio [HR] 1.25) was associated with increased risk of non-persistence. In contrast, factors associated with lower probability of non-persistence were age ≥75 years (HR 0.72), switch in antiplatelet medication use (HR 0.76), diabetes mellitus (HR 0.81), dementia (HR 0.69) and epilepsy (HR 0.69). CONCLUSIONS: Our results suggest that women, patients aged <75 years, and patients without certain comorbid conditions may need improved assistance in secondary prevention management after an ischaemic stroke.

Variability issues in determining the concentration of isoprene in human breath by PTR-MS.

This paper deals with variability issues connected with the proton transfer reaction-mass spectrometry (PTR-MS) measurements of isoprene concentration. We focus on isoprene as an abundant and widely studied compound in human breath. The variability caused by the measurement process is described by the within-sample distribution. Thus, based on the formula for computing isoprene concentration that reflects the principle of the PTR-MS, a theoretical model for the within-sample distribution of isoprene concentration is suggested. This model, which assumes that the distribution is proportional to a quotient of two independent Poisson-distributed random variables, is then confronted with empirical distributions obtained from 17 breath samples collected from a healthy individual within a month. (In each sample, isoprene concentration was determined 97 times.) The empirical within-sample distributions are also compared to normal and log-normal distributions. While those seem to be satisfactory approximations, the theoretical model is found suitable only in 10 out of 17 breath samples. We also comment on the stability of samples during the measurement process in the PTR-MS instrument and, for the sake of comparison, determine the within-sample and the within-subject variability of isoprene concentrations in our data. The respective geometric standard deviations are 1.01 and 1.29.