Matrix Effects of Urine Marker Substances in LC-MS/MS Analysis of Drug of Abuse.

BACKGROUND: Analysis of drug abuse is frequently performed using high-performance liquid chromatography with an MS/MS detector and electrospray ionization. In this context, matrix effects, like signal reduction by ion suppression of individual analytes, play an important role. In this study, the authors evaluated the matrix effect caused by polyethylene glycol (PEG) with chain lengths ranging from 6 to 12 repeating units in drug analysis by LC-MS/MS. Selected chain lengths were used in the Ruma urine marker system. METHODS AND RESULTS: Amphetamines, opiates, opioids, antidepressants, psychotics, benzodiazepines, z-substances, and individual drugs, including THCCOOH, cocaine, LSD, and some of their metabolites were investigated. The matrix effect was investigated at PEG concentrations of 500 mcg/mL and 20 mcg/mL. The effect of each PEG molecule was determined. Furthermore, the effects of different common sample preparations on the PEG matrix effects were evaluated. There was a strong correlation between the retention time of PEG and the drug that was ion-suppressed by PEG. The matrix effect decreased to the point where it was within an acceptable range at the lower PEG concentrations investigated in this study. CONCLUSIONS: Matrix effects were observed for drugs with approximately the same retention times as the individual PEGs. The influence of the different workup methods was not as clear, which may be because of the similar solubilities of the PEGs and some analytes. At low PEG concentrations, the matrix effect was always below 60%, except for nortilidine. All the drugs were detectable. The effect on quantification was less than 15% for substances with deuterated analytes as internal standards and less than 32% for analytes without their own internal standards.

[Considerations on Excess Mortality in Germany in the year 2020 and 2021]. / Zur Übersterblichkeit in Deutschland in den Jahren 2020 und 2021.

At the end of 2020, in Germany a discussion broke out whether the past year was characterized by excess mortality. The opposite positions arose primarily from the way data was processed. In order to correct systematic trends of the last two decades, in the present study the annual death rates for Germany were calculated as the difference to those of the year 2000 and a polynomial fit of 2nd order was carried out for the total population and for the groups of people below and from 80 years of age. There were high coefficients of determination with R2 = 0.965, R2 = 0.982, and R2 = 0.991, respectively. The residuals of the individual years were interpreted as under or excess mortality. For the total population there were excess mortality rates for 2020 and 2021 with 11 500 and 10 468 deaths respectively, which in which in total is completely covered by the excess mortality of those aged 80 and over. In the age group below 80 years there was no excess mortality in the two years. For all age groups, excess mortality was most prominent in the year 2003.

Effect of Pulmonary Rehabilitation on Inspiratory Capacity During 6-min Walk Test in Patients With COPD: A PROSPECTIVE CONTROLLED STUDY.

PURPOSE: Purpose of this study was to analyze the impact of a pulmonary rehabilitation (PR) program on the measured inspiratory capacity (IC) in patients with chronic obstructive pulmonary disease (COPD) while performing a 6-min walk test (6MWT). METHODS: Before and after PR, IC was measured by spirometry both at the beginning and at the end of the 6MWT for 15 patients with COPD in the PR group (PRG) and compared with a similar calisthenics training group (CTG; n = 15). In addition, the COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ), and other lung function tests were recorded and compared. RESULTS: Both groups were not significantly different at baseline. Compared with the CTG, the PRG achieved a significant increase in the delta of IC measured during the 6MWT (0.5 ± 0.2 L [PRG] vs -0.2 + 0.2 L [CTG], P = .001). Significant differences were found for the 6MWT walking distance (PRG: 99 ± 36 m vs CTG: 5 ± 25 m, P = .001). No significant increase in dyspnea while performing the 6MWT was found in either group. The differences in the CAT score and the SGRQ Global score were significant only for the PRG in intragroup comparisons, whereas the intergroup comparison showed no significant differences. Except for residual volume, no significant changes in all parameters of the static lung function tests were observed in either group. CONCLUSION: Participation in a PR may lead to a significant and clinically relevant increase in IC and the walking distance. Additional research is necessary to define the effects of this increase in IC on exercise capacity.

Heart Rate and Oxygen Uptake Kinetics in Type 2 Diabetes Patients - A Pilot Study on the Influence of Cardiovascular Medication on Regulatory Processes.

The aim of this pilot study was to investigate whether there are differences in heart rate and oxygen uptake kinetics in type 2 diabetes patients, considering their cardiovascular medication. It was hypothesized that cardiovascular medication would affect heart rate and oxygen uptake kinetics and that this could be detected using a standardized exercise test. 18 subjects were tested for maximal oxygen uptake. Kinetics were measured in a single test session with standardized, randomized moderate-intensity work rate changes. Time series analysis was used to estimate kinetics. Greater maxima in cross-correlation functions indicate faster kinetics. 6 patients did not take any cardiovascular medication, 6 subjects took peripherally acting medication and 6 patients were treated with centrally acting medication. Maximum oxygen uptake was not significantly different between groups. Significant main effects were identified regarding differences in muscular oxygen uptake kinetics and heart rate kinetics. Muscular oxygen uptake kinetics were significantly faster than heart rate kinetics in the group with no cardiovascular medication (maximum in cross-correlation function of muscular oxygen uptake vs. heart rate; 0.32±0.08 vs. 0.25±0.06; p=0.001) and in the group taking peripherally acting medication (0.34±0.05 vs. 0.28±0.05; p=0.009) but not in the patients taking centrally acting medication (0.28±0.05 vs. 0.30±0.07; n.s.). It can be concluded that regulatory processes for the achievement of a similar maximal oxygen uptake are different between the groups. The used standardized test provided plausible results for heart rate and oxygen uptake kinetics in a single measurement session in this patient group.

Faster heart rate and muscular oxygen uptake kinetics in type 2 diabetes patients following endurance training.

Cardiorespiratory kinetics were analyzed in type 2 diabetes patients before and after a 12-week endurance exercise-training intervention. It was hypothesized that muscular oxygen uptake and heart rate (HR) kinetics would be faster after the training intervention and that this would be detectable using a standardized work rate protocol with pseudo-random binary sequences. The cardiorespiratory kinetics of 13 male sedentary, middle-aged, overweight type 2 diabetes patients (age, 60 ± 8 years; body mass index, 33 ± 4 kg·m-2) were tested before and after the 12-week exercise intervention. Subjects performed endurance training 3 times a week on nonconsecutive days. Pseudo-random binary sequences exercise protocols in combination with time series analysis were used to estimate kinetics. Greater maxima in cross-correlation functions (CCFmax) represent faster kinetics of the respective parameter. CCFmax of muscular oxygen uptake (pre-training: 0.31 ± 0.03; post-training: 0.37 ± 0.1, P = 0.024) and CCFmax of HR (pre-training: 0.25 ± 0.04; post-training: 0.29 ± 0.06, P = 0.007) as well as peak oxygen uptake (pre-training: 24.4 ± 4.7 mL·kg-1·min-1; post-training: 29.3 ± 6.5 mL·kg-1·min-1, P = 0.004) increased significantly over the course of the exercise intervention. In conclusion, kinetic responses to changing work rates in the moderate-intensity range are similar to metabolic demands occurring in everyday habitual activities. Moderate endurance training accelerated the kinetic responses of HR and muscular oxygen uptake. Furthermore, the applicability of the used method to detect these accelerations was demonstrated.

Effects of Oxygen Supply During Training on Subjects With COPD Who Are Normoxemic at Rest and During Exercise: A Blinded Randomized Controlled Trial.

BACKGROUND: It is well established that physical training enhances functionality and quality of life in patients with COPD. However, little data exist concerning the effects of the usefulness of oxygen supply during exercise training for > 3 months in patients with COPD who are normoxemic at rest and during exercise. We hypothesized that oxygen supply during training sessions enables higher training intensity and thus optimizes training results in patients with COPD. METHODS: In this blinded randomized controlled study, we carried out a 24-week training program with progressively increasing loads involving large muscle groups. In addition, we compared the influences of oxygen supplementation. Thirty-six subjects with moderate-to-severe COPD who were not dependent on long-term oxygen therapy trained under supervision for 24 weeks (3 times/week at 30 min/session). Subjects were randomized into 2 groups: oxygen supply via nasal cannula at a flow of 4 L/min and compressed air at the same flow throughout the training program. Lung function tests at rest (inspiratory vital capacity, FEV1, Tiffeneau index), cycle spiroergometry (peak ventilation, peak oxygen uptake, peak respiratory exchange rate, submaximal and peak lactic acid concentrations), 6-min walk tests, and quality-of-life assessments (Medical Outcomes Study 36-Item Short Form questionnaire) were conducted before and after 12 and 24 weeks. RESULTS: Independent of oxygen supplementation, statistically significant improvements occurred in quality of life, maximal tolerated load during cycling, peak oxygen uptake, and 6-min walk test after 12 weeks of training. Notably, there were no further improvements from 12 to 24 weeks despite progressively increased training loads. CONCLUSIONS: Endurance training 3 times/week resulted in significant improvements in quality of life and exercise capacity in subjects with moderate-to-severe COPD within the initial 12 weeks, followed by a stable period over the following 12 weeks with no further benefits of supplemental oxygen.

Marine oil dietary supplementation reduces delayed onset muscle soreness after a 30 km run.

OBJECTIVE: Runners are prone to delayed onset muscle soreness (DOMS) during long distance training. This especially holds for unaccustomed training volumes at moderate to high intensities. We investigated the effects of a marine oil complex, PCSO-524®, derived from the New Zealand green-lipped mussel (formulated as Lyprinol® and Omega XL®) on DOMS after a 30 km training run. METHODS: Initially, peak oxygen uptake of 32 distance runners (4 female, 28 male; median age 45 years, range 28-53) was measured on a treadmill with a 1.5 km hour(-1) increase every 4 minutes starting from 8.5 km hour(-1). At least 1-week after this initial test, they participated in a 30 km road run at a speed corresponding to about 70% of their individual peak oxygen uptake on a flat terrain. Before and after (0, 24, and 48 hours) the run, blood concentration of creatine kinase (CK) were measured and pain sensation was determined (pain scale from 0 = no pain to 10 = extremely painful). Runners were then matched in pairs based on maximal CK and peak oxygen uptake, and allocated randomly into two different groups. One group was supplemented with 400 mg per day of PCSO-524® for 11 weeks, the other group with an olive oil placebo. After that period, CK and pain sensations were remeasured following a second 30 km run at the same speed and on the same terrain. RESULTS: The general pattern of soreness in the PCSO-524® supplemented group was reduced by 1.1 units (standard error 0.41) compared to the placebo (P < 0.05), the effects being greater in lesser trained runners (P < 0.05). CK levels were positively associated with pain sensation (P < 0.05), but trends toward lower CK in the PCSO-524® group, which were also more pronounced in the lesser trained runners, were not statistically significant. CONCLUSION: Pain sensations experienced by distance runners following a 30 km run were reduced by supplementation with the marine oil complex PCSO-524®, an effect which was greater in lesser trained runners.

Efficiency of vibration exercise for glycemic control in type 2 diabetes patients.

Although it is well documented that persons suffering from diabetes type 2 profit from muscular activities, just a negligible amount of patients take advantage of physical exercises. During the last decade, vibration exercise (VE) could be established as an effective measure to prevent muscular atrophy and osteoporosis with low expenditure of overall exercise-time. Unfortunately, little is known about the metabolic effects of VE. In the present study we compared VE with the influence of strength training and a control group (flexibility training) on glycemic control in type 2 diabetes patients. Forty adult non-insulin dependent patients participated in the intervention. Fasting glucose concentration, an oral glucose tolerance test (OGTT), haemoglobin A1c (HbA1c), the isometric maximal torque of quadriceps muscles, and endurance capacity were evaluated at baseline and after 12 weeks of training with three training sessions per week. The main findings are: Fasting glucose concentrations remind unchanged after training. The area under curve and maximal glucose concentration of OGTT were reduced in the vibration and strength training group. HbA1c values tended to decrease below baseline date in the vibration training group while it increased in the two other intervention groups. Theses findings suggest that vibration exercise may be an effective and low time consuming tool to enhance glycemic control in type 2 diabetes patients.