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Background: The elderly population deals with multimorbidity (three chronic conditions) and increasinged drug use with age. A comprehensive characterisation of the medication – including prescription and over-the-counter (OTC) drugs – of elderly patients in primary care is still insufficient.
Objectives: This study aims to characterise the medication (prescription and OTC) of multimorbid elderly patients in primary care and living at home by identifying drug patterns to evaluate the relationship between drugs and drug groups and reveal associations with recently published multimorbidity clusters of the same cohort.
Methods: MultiCare was a multicentre, prospective, observational cohort study of 3189 multimorbid patients aged 65 to 85 years in primary care in Germany. Patients and general practitioners were interviewed between 2008 and 2009. Drug patterns were identified using exploratory factor analysis. The relations between the drug patterns with the three multimorbidity clusters were analysed with Spearman-Rank-Correlation.
Results: Patients (59.3% female) used in mean 7.7 drugs; in total 24,535 drugs (23.7% OTC) were detected. Five drug patterns for men (drugs for obstructive pulmonary diseases (D-OPD), drugs for coronary heart diseases and hypertension (D-CHD), drugs for osteoporosis (D-Osteo), drugs for heart failure and drugs for pain) and four drug patterns for women (D-Osteo, D-CHD, D-OPD and drugs for diuretics and gout) were detected. Significant associations between multimorbidity clusters and drug patterns were detectable (D-CHD and CMD: male: ρ = 0.376, CI 0.322–0.430; female: ρ = 0.301, CI 0.624–0.340).
Conclusion: The drug patterns demonstrate non-random relations in drug use in multimorbid elderly patients and systematic associations between drug patterns and multimorbidity clusters were found in primary care.

Objectives Our study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use and cognitive function among participants in the MultiCare cohort. Design MultiCare is conducted as a longitudinal, multicentre, observational cohort study. Setting The MultiCare study is located in eight different study centres in Germany. Participants 3189 patients (59.3% female). Primary and secondary outcome measures The study had a cross-sectional design using baseline data from the German MultiCare study. Prescribed and over-the-counter drugs were classified using FORTA (Fit fOR The Aged), PRISCUS (Latin for ‘time-honoured’) and EU(7)-PIM lists. A mixed-effect multivariate linear regression was performed to calculate the association between PIM use patients’ cognitive function (measured with (LDST)). Results Patients (3189) used 2152 FORTA PIM (mean 0.9±1.03 per patient), 936 PRISCUS PIM (0.3±0.58) and 4311 EU(7)-PIM (1.4±1.29). The most common FORTA PIM was phenprocoumon (13.8%); the most prevalent PRISCUS PIM was amitriptyline (2.8%); the most common EU(7)-PIM was omeprazole (14.0%). The lists rate PIM differently, with an overall overlap of 6.6%. Increasing use of PIM is significantly associated with reduced cognitive function that was detected with a correlation coefficient of −0.60 for FORTA PIM (p=0.002), −0.72 for PRISCUS PIM (p=0.025) and −0.44 for EU(7)-PIM (p=0.005). Conclusion We identified PIM using FORTA, PRISCUS and EU(7)-PIM lists differently and found that PIM use is associated with cognitive impairment according to LDST, whereby the FORTA list best explained cognitive decline for the German population. These findings are consistent with a negative impact of PIM use on multimorbid elderly patient outcomes.

Objectives The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort.
Setting MultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany.
Participants 3189 patients (59.3% female).
Primary and secondary outcome measures Baseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function.
Results Patients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (−0.26; p=0.008 and −0.24; p=0.003, respectively).
Conclusion Multimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated.
Trial registration number ISRCTN89818205.

The role of nonequilibrium and quantal effects in fast nucleus-nucleus collisions is studied via the Vlasov-Uehling-Uhlenbeck theory which includes the nuclear mean field dynamics, two-body collisions, and Pauli blocking. The intranuclear cascade model, where the dynamics is governed by independent NN collisions, and the Vlasov equation, where the nuclear mean field determines the collision dynamics, are also studied as reference cases. The Vlasov equation (no collision term) yields single particle distribution functions which–after the reaction–are only slightly modified in momentum space; even in central collisions, transparency is predicted. This is in agreement with the predictions of the quantal time-dependent Hartree-Fock method. In contrast, large momentum transfer is obtained when the Uehling-Uhlenbeck collision term is incorporated; then the final momentum distribution is nearly spherically symmetric in the center of mass and a well-equilibrated nuclear system is formed: the nuclei stop each other; the translational kinetic energy is transformed into randomized microscopic motion. The Vlasov-Uehling-Uhlenbeck theory is supplemented with a phase space coalescence model of fragment formation. Calculated proton spectra compare well with recent data for Ar(42, 92, and 137 MeV/nucleon) + Ca. Also the total yields of medium mass fragments are well reproduced in the present approach. The mean field dynamics without two-body collisions, on the other hand, exhibits forward peaked proton distributions, in contrast to the data. The cascade approach underpredicts the yields of low energy protons by more than an order of magnitude.

Nuclear collisions from 0.3 to 2 GeV/nucleon are studied in a microscopic theory based on Vlasov's self-consistent mean field and Uehling-Uhlenbeck's two-body collision term which respects the Pauli principle. The theory explains simultaneously the observed collective flow and the pion multiplicity and gives their dependence on the nuclear equation of state.

Microscopic calculations of collective flow probing the short-range nature of the nuclear force
(1984)

Collisions between two nuclei have been modeled by numerical solution of classical approximations to the equations of motion of the constituent nucleons. For the reaction Nb(400 MeV/u)+Nb, a correlated sidewards emission of nucleons is observed. This is attributed to the repulsive short-range component of the nucleon-nucleon potential. A strong dependence of the flow angle on the impact parameter is observed, in accord with recent experimental results.

Within an extended semiquantal theory we perform large-sized coupled-channel calculations involving 260 collective levels for Coulomb fission of 238U. Differential Coulomb fission cross sections are studied as a function of bombarding energy and impact parameter for several projectiles. In the Xe + U case, total cross sections are also given. We find a strong dependence on projectile charge number, PCF(180°)∼(Zp)6 in the region 50≤Zp≤92 for a fixed ratio E/ECoul, which might be helpful to separate Coulomb fission experimentally from sequential fission following transfer reactions. Since the cross sections are sensitive to the moment of inertia ⊖ at the saddle point, Coulomb fission can serve as a tool to investigate the dependence of ⊖ on elongation. The fragment angular distribution exhibits deviations from 1/sinθf which are pronounced at low incident energies. Our theory indicates that the recently measured Xe + U fission cross sections contain a major fraction of Coulomb-induced fission at E≤0.85 ECoul. NUCLEAR REACTIONS, FISSION Calculated Coulomb fission cross sections σ(Ep,θp) for 54Xe, 67Ho, 82Pb, 92U→92238U, fragment angular distribution, fission energy spectrum, mean spin value 〈Jf〉.

The fluid dynamical model is used to study the reactions 20Ne+238U and 40Ar+40Ca at Elab=390 MeV/nucleon. The calculated double differential cross sections d²ð/dΩdE exhibit sidewards maxima in agreement with recent experimental data. The azimuthal dependence of the triple differential distributions, to be obtained from an event-by-event analysis of 4π; exclusive experiments, can yield deeper insight into the collision process: Jets of nuclear matter are predicted with a strongly impact-parameter-dependent thrust angle θjet(b). NUCLEAR REACTIONS Ar+Ca, Ne+U, Elab=393 MeV/nucleon, fluid dynamics with thermal breakup, double differential cross sections, azimuthal dependence of triple differential cross sections, event-by-event thrust analysis of 4π exclusive experiments.

Dynamics of Coulomb fission
(1980)

A general formalism is described for the treatment of Coulomb fission, within the framework of the semiquantal theory. We develop a model for the fission probabilities of levels excited in Coulomb excitation. This model contains penetration of the double-humped fission barrier, competition from gamma and neutron emission, and the spreading of the collective states into noncollective compound states. For 74184W + 92238U, the fission probability at θc.m.=180° is increased by a factor of 3.9, 3.3, and 2.0 at E/ECoul=0.77, 0.85, and 0.935, respectively, compared to the simplified sharp cutoff model used in earlier model calculations. The enhancement comes from barrier penetration. The damping of the fission probability due to spreading into noncollective compound states is small. Prompt Coulomb fission (near the distance of closest approach) is studied in a one-dimensional model. The results clearly imply that prompt fission is negligible. We have also studied the sudden approximation for collective rotational levels in connection with Coulomb fission. At high spins (I≈20), it leads to significant errors. Contrary to the basic assumption of the sudden approximation that the nuclear symmetry axis remains fixed during the collision, it is shown that Coulomb excitation results in a strong alignment of the nuclear symmetry axis perpendicular to the beam axis at small internuclear distances. NUCLEAR REACTIONS, FISSION Semiquantal theory of prompt and asymptotic Coulomb fission, study of double-humped barrier penetration, damping effects, neutron and γ emission. Calculated σ(Ep, θc.m.=180°).