Interventions to address deficits of pharmacological pain management in nursing home residents--A cluster-randomized trial.

BACKGROUND: To evaluate the effect of interventions for general practitioners and nursing home staff to improve pain severity and appropriateness of pain medication in nursing home residents (NHR). METHODS: This cluster-randomized controlled trial was conducted in six nursing homes in the intervention and control group, respectively. Pain management was analysed before (T0) and after (T1, T2) an educational intervention in 239 NHR, aged ≥65 years, without moderate or severe cognitive impairment. Primary and secondary outcomes were average pain severity and appropriateness of pain medication as determined with the Numeric Rating Scale and Pain Medication Appropriateness Scale (PMASD ), respectively. RESULTS: At T0, 72.2% and 73.7% of NHR (mean age 83 years) reported pain (average pain severity 2.4) in the intervention and control group, respectively. The PMASD at T0 was 53.9 in the intervention group and 60.8 in the control group (p = 0.12), while 20.6% compared to 6.9% (p = 0.009) received no pain medication in the two groups. At T2, non-significant improvements in the average pain severity (1.59) and PMASD (61.07) were observed in the intervention group. Moreover, the mean individual PMASD increased by 8.09 (p = 0.03) and the proportion of NHR without pain medication decreased by 50% (p = 0.03) in the intervention group. No appreciable changes were found in the control group at T2. CONCLUSIONS: NHR exhibited a high prevalence of pain with overall low severity, while a high proportion of individuals received inappropriate pain medications. Both findings were not significantly improved by the intervention, although some aspects of drug treatment were meaningful improved.

A parameter to quantify the degree of genetic mixing among individuals in hybrid populations.

Hybridization between genetically distinct taxa is a complex evolutionary process. One challenge to studying hybrid populations is quantifying the degree to which non-native genes have become evenly mixed among individuals in the population. In this paper, we present a variance-based parameter, md, that measures the degree to which non-native genes are evenly distributed among individuals in a population. The parameter has a minimum value of 0 for populations in which individuals from multiple taxa are present but have not interbred, and a maximum value of 1 for populations in which all individuals have the same amount of non-native ancestry. A recurrence equation showed that relatively few generations of random mating are required for md to approach 1 (indicating a well-mixed population), and that md is independent of initial amounts of non-native ancestry. The parameter is mathematically equivalent to FST and we show how existing formulae for FST can be used to estimate md when diagnostic loci are available. Computer simulations showed this estimator to have very little bias for realistic amounts of data.

[Quality and appropriateness of pain medication. Instrument for estimation in nursing home residents]. / Qualität und Angemessenheit der Schmerzmedikation. Instrument zur Einschätzung bei Pflegeheimbewohnern.

BACKGROUND: The pain medication appropriateness scale (PMASD) was developed in 2006 in the USA to evaluate the quality and appropriateness of pain treatment in nursing home residents (NHR). This tool can be used to identify potential problems with the pharmacological treatment of pain. METHODS: We developed a German version (PMASD) adapted to the German setting and applied it in Germany to NHR with and without cognitive impairment for the first time. In agreement with the original instrument a test result of >67 % was considered as appropriate pain treatment. RESULTS: For the 560 analyzed NHR the average SPMAS score was 39±1,7 (range from -67 to +100). Overall 72% of the study population did not achieve the defined threshold for appropriate pain management. CONCLUSIONS: An appropriate tool for quantitative evaluation of pain treatment was so far not available in Germany. The PMASD analysis showed deficits of pain management in NHR. This tool showed good practicability in Germany and could provide a valuable tool for pain treatment in clinical research and practice.

Application of the PEDD flow detector for analysis of natural dissolved organic substances in coloured water.

The automated techniques of measurement of water parameters are developed based on flow analysis (flow injection analysis, sequential injection analysis). PEDD detectors (paired emitter-detector diode), built with the use of two paired light-emitting diodes (LEDs) - emission and detection, can serve that purpose. The aim of the studies was to optimize the system for determination of the dissolved organic substances in coloured water with the use of PEDDs in the flowing-stream measurement system. The investigations were conducted for a number of concentrations of the humic, fulvic and tannic acids, which were measured as the dissolved organic carbon (DOC). Three arrangements of diodes (PEDD) with a selected emission spectrum and absorption characteristics were used. A two-beam flow cell was designed for the measurements. The signal from the detection diode was recorded and converted into absorbance through software written for that purpose. The results obtained showed a high sensitivity in relation to the concentration as well as the selectivity in the type of substances studied. A miniature and cheap photometric flow analysis set was proposed, adapted to work with one or several light wavelengths and steered by a microprocessor unit.

[Pain, fear of falling and functional performance in nursing home residents - a cross-sectional study]. / Schmerzen, Sturzangst und funktionelle Fähigkeiten von Menschen in Pflegeheimen - eine Querschnittsstudie.

Pain and fear of falling (FOF) are modifiable factors that might play an important role in functional performance of nursing homes residents (NHR). Both factors are characterised by deficits in research and provision of long-term care services. The purpose of this study was to examine the functional performance of NHR with and without pain or FOF. Quantitative data were collected on NHR in Berlin and Brandenburg using a cross-sectional design. The cognitive status was assessed using the Minimental state test. Existing pain and FOF were assessed as a question part of interview. Functional performance was examined using the Barthel Index (BI) the Timed «up & go¼-Test. Multiple linear regression analyses were performed to investigate the research question and the influence of additional explanatory variables (age, sex, relevant somatic morbidity). 217 NHR without considerable cognitive impairment (MMST >= 20) participated. 65 % of the NHR suffered from pain and 48 % had FOF. There was a statistically significant association between Pain or FOF und lower functional mobility. With respect to NHR able to walk, there was statistically significant association between Pain or FOF und lower performance in activities of daily living. Possibilities for interventions which might have positive effects on functional performance of NHR are an improved pain treatment and interventions to reduce FOF.

Antipsychotic drugs predominate in pharmacotherapy of nursing home residents with dementia.

INTRODUCTION: The aim of this study was to investigate the frequency of benzodiazepines, antidementia and antipsychotic drug prescriptions in nursing home residents (NHR).Data of a German health insurance company were retrospectively analyzed for the year 2008. METHODS: The study cohort comprised 13,042 NHR (82% women, mean age 83.6 ± 7 years). Following analgetics, antipsychotic drugs were the second most frequently prescribed drug group with 13.3% of all prescriptions. Dementia was diagnosed in 8 017 (61.5%) NHR. Thereof 51.6% received an antipsychotic, 17.3% a benzodiazepine and 15.2% an antidementia pharmaceutical, respectively. 18.1% of NHR with dementia and antipsychotic drug prescriptions were in combined treatment with antidementia pharmaceuticals. The rate of antipsychotic drug prescribing was significantly doubled in NHR with dementia compared to those without this diagnosis (p<0.01); the most frequently prescribed antipsychotics were melperone, risperidone and pipamperone. DISCUSSION: This study demonstrates the wide-spread use of psychotropic drugs in NHR. Moreover, dementia in NHR was associated with antipsychotic drug prescribing in every second patient. This highlights the need for further studies analyzing alternative treatments for dementia-related symptoms.

Deficits in pain treatment in nursing homes in Germany: a cross-sectional study.

BACKGROUND: Current knowledge about the quality and appropriateness of pharmacological pain treatment in nursing home residents (NHR), particularly in NHR with moderate to severe cognitive impairment, is poor. METHODS: This observational cross-sectional study assessed pain treatment in a random sample of NHR with or without cognitive impairment from nursing homes in Germany. Prescribed drugs, pain intensity and frequency, diagnoses, and surgical procedures and injuries during the last 4 weeks were documented. Quality and appropriateness of pain medication were assessed by analysis of pain medications and the Pain Medication Appropriateness Scale (PMAS) score (S(PMAS) ), with a cut-off value of >67% indicating appropriate pain treatment. RESULTS: A total of 321 residents (62% women) were studied, including 152 (47%) with severe cognitive impairment. The most frequently prescribed analgesics were dipyrone, fentanyl, tramadol and ibuprofen. The mean S(PMAS) was 48.5 ± 1.5 (range, -33 to +100). Residents with prescribed scheduled analgesics had a significantly better S(PMAS) than patients without such treatment (S(PMAS) 58 ± 1.5 vs. 37 ± 2.5, p < 0.01). NHR without current pain had significantly better S(PMAS) than residents suffering from pain (S(PMAS) 47 ± 1.9 vs. 59 ± 4.2, p = 0.01). With an S(PMAS) of 69 ± 1.5, residents (n = 106) with scheduled pain medication plus PRN analgesics achieved the highest scores in the population. Overall, similar results were found in NHR with and in NHR without cognitive impairment. CONCLUSION: Our study points to a significant deficit in pain treatment in German NHR, including NHR with or without cognitive impairment.

Active learning not associated with student learning in a random sample of college biology courses.

Previous research has suggested that adding active learning to traditional college science lectures substantially improves student learning. However, this research predominantly studied courses taught by science education researchers, who are likely to have exceptional teaching expertise. The present study investigated introductory biology courses randomly selected from a list of prominent colleges and universities to include instructors representing a broader population. We examined the relationship between active learning and student learning in the subject area of natural selection. We found no association between student learning gains and the use of active-learning instruction. Although active learning has the potential to substantially improve student learning, this research suggests that active learning, as used by typical college biology instructors, is not associated with greater learning gains. We contend that most instructors lack the rich and nuanced understanding of teaching and learning that science education researchers have developed. Therefore, active learning as designed and implemented by typical college biology instructors may superficially resemble active learning used by education researchers, but lacks the constructivist elements necessary for improving learning.

Diagnostic single nucleotide polymorphisms for identifying westslope cutthroat trout (Oncorhynchus clarki lewisi), Yellowstone cutthroat trout (Oncorhynchus clarkii bouvieri) and rainbow trout (Oncorhynchus mykiss).

We describe 12 diagnostic single nucleotide polymorphism (SNP) assays for use in species identification among rainbow and cutthroat trout: five of these loci have alleles unique to rainbow trout (Oncorhynchus mykiss), three unique to westslope cutthroat trout (O. clarkii lewisi) and four unique to Yellowstone cutthroat trout (O. clarkii bouvieri). These diagnostic assays were identified using a total of 489 individuals from 26 populations and five fish hatchery strains.

The computer program STRUCTURE does not reliably identify the main genetic clusters within species: simulations and implications for human population structure.

One of the primary goals of population genetics is to succinctly describe genetic relationships among populations, and the computer program STRUCTURE is one of the most frequently used tools for doing so. The mathematical model used by STRUCTURE was designed to sort individuals into Hardy-Weinberg populations, but the program is also frequently used to group individuals from a large number of populations into a small number of clusters that are supposed to represent the main genetic divisions within species. In this study, I used computer simulations to examine how well STRUCTURE accomplishes this latter task. Simulations of populations that had a simple hierarchical history of fragmentation showed that when there were relatively long divergence times within evolutionary lineages, the clusters created by STRUCTURE were frequently not consistent with the evolutionary history of the populations. These difficulties can be attributed to forcing STRUCTURE to place individuals into too few clusters. Simulations also showed that the clusters produced by STRUCTURE can be strongly influenced by variation in sample size. In some circumstances, STRUCTURE simply put all of the individuals from the largest sample in the same cluster. A reanalysis of human population structure suggests that the problems I identified with STRUCTURE in simulations may have obscured relationships among human populations-particularly genetic similarity between Europeans and some African populations.

How well do evolutionary trees describe genetic relationships among populations?

Bifurcating evolutionary trees are commonly used to describe genetic relationships between populations, but may not be appropriate for populations that did not evolve in a hierarchical manner. The degree to which bifurcating trees distort genetic relationships between populations can be quantified with R(2), the proportion the variation in a matrix of genetic distances between populations that is explained by a tree. Computer simulations were used to measure how well the unweighted pair group method with arithmetic mean (UPGMA) and neighbor-joining (NJ) trees depicted population structure for three evolutionary models: a hierarchical model of population fragmentation, a linear stepping-stone model of gene flow and a two-dimensional stepping-stone model of gene flow. These simulations showed that the UPGMA did an excellent job of describing population structure when populations had a bifurcating history of fragmentation, but severely distorted genetic relationships for the linear and two-dimensional stepping-stone models. The NJ algorithm worked well in a broader range of evolutionary histories, including the linear stepping-stone model. A computer program for performing the calculations described in this study is available for download at www.montana.edu/kalinowski.

Estimating relatedness and relationships using microsatellite loci with null alleles.

Relatedness is often estimated from microsatellite genotypes that include null alleles. When null alleles are present, observed genotypes represent one of several possible true genotypes. If null alleles are detected, but analyses do not adjust for their presence (ie, observed genotypes are treated as true genotypes), then estimates of relatedness and relationship can be incorrect. The number of loci available in many wildlife studies is limited, and loci with null alleles are commonly a large proportion of data that cannot be discarded without substantial loss of power. To resolve this problem, we present a new approach for estimating relatedness and relationships from data sets that include null alleles. Once it is recognized that the probability of the observed genotypes is dependent on the probabilities of a limited number of possible true genotypes, the required adjustments are straightforward. The concept can be applied to any existing estimators of relatedness and relationships. We review established maximum likelihood estimators and apply the correction in that setting. In an application of the corrected method to data from striped hyenas, we demonstrate that correcting for the presence of null alleles affect results substantially. Finally, we use simulated data to confirm that this method works better than two common approaches, namely ignoring the presence of null alleles or discarding affected loci.

Do polymorphic loci require large sample sizes to estimate genetic distances?

The coefficient of variation of estimates of three genetic distances (standard genetic distance of Nei, chord distance, FST) was examined with computer simulation to determine if large samples (per population) are necessary to precisely estimate genetic distances at loci with high levels of polymorphism. These simulations showed that loci with high mutation rates produce estimates of genetic distance with lower coefficients of variation than loci with lower mutation rates--without requiring larger sample sizes from each population. In addition, the rate at which increasing sample sizes decreases the coefficient of variation of estimates of genetic distances was shown to be approximately determined by the value of FST between the populations being sampled. When FST was greater than 0.05, sampling fewer than 20 individuals (per population) should be sufficient. When FST was less than 0.01, sampling 100 individuals (per population) or more will be useful.

How many alleles per locus should be used to estimate genetic distances?

As more microsatellite loci become available for use in genetic surveys of population structure, population geneticists are able to select loci to use in population structure surveys. This study used computer simulations to investigate how the number of alleles at loci affects the precision of estimates of four common genetic distances. This showed that equivalent results could be achieved by examining either a few loci with many alleles or many loci with a few alleles. More specifically, the total number of independent alleles appears to be a good indicator of how precise estimates of genetic distance will be.

Is the decline of desert bighorn sheep from infectious disease the result of low MHC variation?

Bighorn sheep populations have greatly declined in numbers and distribution since European settlement, primarily because of high susceptibility to infectious diseases transmitted to them from domestic livestock. It has been suggested that low variation at major histocompatibility complex (MHC) genes, the most important genetic aspect of the vertebrate immune system, may result in high susceptibility to infectious disease. Therefore, we examined genetic polymorphism at a MHC gene (Ovca-DRB) in a large sample, both numerically and geographically, of bighorn sheep. Strikingly, there were 21 different alleles that showed extensive nucleotide and amino acid sequence divergence. In other words, low MHC variation does not appear to be the basis of the high disease susceptibility and decline in bighorn sheep. On the other hand, analysis of the pattern of the MHC polymorphism suggested that nonsynonymous substitutions predominated, especially at amino acids in the antigen-binding site. The average overall heterozygosity for the 16 amino acid positions that are part of the antigen binding site is 0.389 whereas that for the 67 amino acid positions not involved with antigen binding is 0.076. These findings imply that the diversity present in this gene is functionally significant and is, or has been, maintained by balancing selection. To examine the evolution of DRB alleles in related species, a phylogenetic analysis including other published ruminant (Bovidae and Cervidae) species, was carried out. An intermixture of sequences from bighorn sheep, domestic sheep, goats, cattle, bison, and musk ox was observed supporting trans-species polymorphism for these species. To reconcile the species and gene trees for the 104 sequences examined, 95 'deep coalescent' events were necessary, illustrating the importance of balancing selection maintaining variation over speciation events.

Changes of structural and dynamic properties of model lipid membranes induced by alpha-tocopherol: implication to the membrane stabilization under external electric field.

The effects of alpha-tocopherol on electric properties of bilayer lipid membranes were investigated. Planar bilayer membranes formed by the Mueller-Rudin method were used. Voltammetric and chronopotentiometric measurements were performed using a four-electrode potentiostat-galvanostat. It was demonstrated that registration of membrane capacitance, resistance, and voltammetric characteristics provided information about the change in the structure and permeability of bilayer lipid membranes. The results suggested that incorporation of alpha-tocopherol into lipid membrane destabilized its structure and facilitated the electrogeneration of pores. The possible role of observed changes in physiological functions of alpha-tocopherol was discussed.

Population structure of Atlantic salmon (Salmo salar L.): a range-wide perspective from microsatellite DNA variation.

Atlantic salmon (n = 1682) from 27 anadromous river populations and two nonanadromous strains ranging from south-central Maine, USA to northern Spain were genotyped at 12 microsatellite DNA loci. This suite of moderate to highly polymorphic loci revealed 266 alleles (5-37/locus) range-wide. Statistically significant allelic and genotypic heterogeneity was observed across loci between all but one pairwise comparison. Significant isolation by distance was found within and between North American and European populations, indicating reduced gene flow at all geographical scales examined. North American Atlantic salmon populations had fewer alleles, fewer unique alleles (though at a higher frequency) and a shallower phylogenetic structure than European Atlantic salmon populations. We believe these characteristics result from the differing glacial histories of the two continents, as the North American range of Atlantic salmon was glaciated more recently and more uniformly than the European range. Genotypic assignment tests based on maximum-likelihood provided 100% correct classification to continent of origin and averaged nearly 83% correct classification to province of origin across continents. This multilocus method, which may be enhanced with additional polymorphic loci, provides fishery managers the highest degree of correct assignment to management unit of any technique currently available.

Estimation of linkage disequilibrium for loci with multiple alleles: basic approach and an application using data from bighorn sheep.

The great expansion of population genetic data using molecular techniques now allows examination of the extent of linkage disequilibrium for many pairs of loci, each locus often with multiple alleles. The expectation-maximization (EM) algorithm for generating maximum likelihood estimates of gametic frequencies from multiallelic genotypic data is described and applied. The EM algorithm is used in desert bighorn sheep where the population size, and consequently the sample size, is often small. We calculated haplotype frequencies for all pairwise combinations of five major histocompatibility loci and three microsatellite loci in 14 populations; the performance of the algorithm is discussed. Disequilibrium values are calculated and tested for statistical significance. High levels of disequilibrium are found between all pairs of major histocompatibility complex (MHC) loci and between MHC and a linked microsatellite locus.

Mechanism of inhibition of yeast squalene synthase by substrate analog inhibitors.

Squalene synthase catalyzes the reductive condensation of two identical substrate molecules, farnesyl diphosphate, to the hydrocarbon squalene via an obligatory intermediate, presqualene pyrophosphate. Since the kinetic mechanism of the transformation is sequential, two substrate binding pockets that recognize the same molecule must exist in the enzyme active site. This raises the possibility of a choice of binding pockets for inhibitors that are designed as substrate or reaction intermediate analogs and thus may provide some information on the mechanism of differentiation of the two identical molecules. In this report, we have investigated the mechanism of inhibition of a series of farnesyl diphosphate analog inhibitors. The inhibitors fall into two categories. One class of compounds binds to free enzyme as well as the enzyme substrate complex, and the binding is refractory to the concentration of the substrate. The second class binds only to the free enzyme, and its binding is significantly modulated by the substrate concentration. Very modest structural changes in the compounds appear to dictate which class of inhibitor any compound may fall into. The significance of these observations with respect to the mechanism of the enzyme are discussed.