Pharmaceutical care practice : drug-related problems and opportunities for new services

Within the last decades, the role of the pharmacist and of pharmacy practice have moved from that of drug manufacturing and technical dispensing to a more cognitive role with patient orientation. The concept of pharmaceutical care focuses on the process of ‘using a drug’, bearing in mind that the dispensing of a drug is neither the beginning nor the end of this process. Pharmaceutical care is based on a relationship between the patient and the pharmacist who accepts responsibility for the patient. However, much of the impetus for pharmaceutical care provision has been driven by academics, and only limited published data on the extent to which pharmaceutical care has been adopted and implemented are available. The aim of project A was to evaluate the current provision of pharmaceutical care by European community pharmacists and the impact of a range of factors that could affect its implementation. For this study, the behavioural pharmaceutical care scale (BPCS) was used. A total of 4,696 questionnaires were obtained. The mean total BPCS scores ranged from 50.6 (Denmark; DK) to 83.5 (Ireland). The results of project A suggest that the provision of pharmaceutical care in a comprehensive fashion is still limited within Europe. Pharmacists rarely documented activities related to patient care and did not often engaged in implementing therapeutic objectives and monitoring plans. With project B, we aimed to explore differences between standard pharmacists, pharmacists participating in quality circles, and Danish pharmacists. Moreover, discussion of the BPCS’ reliability and applicability as a research tool for pharmacy practice was of interest. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6% (DK) to 45.8% (CH). The specialised QC and Danish pharmacists reached significantly lower scores than Swiss and German pharmacists. Our results show that pharmacies in all regions are adequately equipped to provide pharmaceutical care. However, the provision of pharmaceutical care mainly occured when pharmacists were supported by their computer system. The findings cast doubt on the results of the whole BPCS study, and the question arises if the BPCS is a sensitive scale to enable a conclusion about the extent to which pharmaceutical care is provided to patients. To evaluate the benefit of pharmaceutical care, we need tools to describe and document drug-related problems (DRPs) and to measure their impact on patient outcomes. However, no accepted standard tool for classification of DRPs has been made available so far. The aims of project C were to explore the occurrence of DRPs with new prescriptions and to analyse differences between primary care and hospital discharge. Furthermore, we aimed to evaluate the applicability of a modified classification system. Prescriptions of 616 patients were analysed. In 19.6% of all prescriptions, 141 clinical DRPs were detected. The most frequent clinical DRPs were potential drug-drug interactions (37.6%), drug choice (24.8%), and drug use problems (15.6%). There were 222 prescriptions (36.0%) that contained 278 technical DRPs. The most frequent technical DRPs were unclear package size or therapy duration (32.7%) and unclear dosing instructions (30.9%). The results of this study showed that clinical and technical DRPs were frequently observed and that the number of prescribed drugs was the only factor with an influence on the frequency. The modified classification system, especially the amendment with a technical DRP category, proved to be useful and allowed the classification of all DRPs, but remained rather complicated to apply in pharmacy practice. To get insight into the patients’ medication management, it may be useful to visit patients at home. Although recent studies indicated that pharmacist-led medication reviews and home visits are potentially beneficial, it is still an open question if tailored medication reviews are needed. With project D – a pilot study – we set the goal to explore patients’ knowledge about newly prescribed medication and to gain first experiences in performing home visits. We conducted 70 phone interviews with patients who received newly prescribed medications some days ago. Only 35% of drug names could be given by patients. However, 92% of all stated purposes of drugs were correct. Out of 70 interviewed patients, 20 agreed to be visited at their home. Two (10.0%) patients had drug use problems, seven (35.0%) suffered from adverse drug events. The patients’ knowledge a few days after receiving newly prescribed drugs was rather good. Home visits of such patients showed to be a feasible service for community pharmacists. In project E, we aimed to analyse the number and pattern of DRPs at patients’ home. Two investigators visited 54 diabetes type 2 (DM) and 22 solid organ transplant (Tx) patients in their homes, using a structured interview guide. The mean number of drugs was 12.5 ± 4.4 (Tx) and 13.9 ± 5.4 (DM). We identified significant differences between the number of DRPs of Tx and DM patients (6.3 ± 1.7 vs. 7.8 ± 2.5; p=0.010). The most relevant DRPs in Tx and DM patients were uncertainty about one or multiple purposes or justification of drugs (36.4%; 48.1%), no basic knowledge about potential interactions (18.2%; 61.1%), confusion of generic and trade names (27.3%; 74.1%), and risk for non-adherence (77.3% and 61.1%). Among all patients, 11 (14.5%) reported to have problems with their drugs. If interviews had been conducted at the pharmacies rather than the patient homes, we most probably would have detected only 48.6% of DRPs. The results of this study indicated that more tailored interview guides for different diseases would enable more efficient home visits. The most frequently observed DRPs are important shortcomings which easily can be solved by pharmacists

Multi-species integrative biclustering

We describe an algorithm, multi-species cMonkey, for the simultaneous biclustering of heterogeneous multiple-species data collections and apply the algorithm to a group of bacteria containing Bacillus subtilis, Bacillus anthracis, and Listeria monocytogenes. The algorithm reveals evolutionary insights into the surprisingly high degree of conservation of regulatory modules across these three species and allows data and insights from well-studied organisms to complement the analysis of related but less well studied organisms

A Distance-Weighted Interaction Map Reveals a Previously Uncharacterized Layer of the Bacillus subtilis Spore Coat

SummaryBacillus subtilis spores are encased in a protein assembly called the spore coat that is made up of at least 70 different proteins. Conventional electron microscopy shows the coat to be organized into two distinct layers. Because the coat is about as wide as the theoretical limit of light microscopy, quantitatively measuring the localization of individual coat proteins within the coat is challenging. We used fusions of coat proteins to green fluorescent protein to map genetic dependencies for coat assembly and to define three independent subnetworks of coat proteins. To complement the genetic data, we measured coat protein localization at subpixel resolution and integrated these two data sets to produce a distance-weighted genetic interaction map. Using these data, we predict that the coat comprises at least four spatially distinct layers, including a previously uncharacterized glycoprotein outermost layer that we name the spore crust. We found that crust assembly depends on proteins we predicted to localize to the crust. The crust may be conserved in all Bacillus spores and may play critical functions in the environment

The Program of Gene Transcription for a Single Differentiating Cell Type During Sporulation in \u3cem\u3eBacillus subtilis\u3c/em\u3e

Asymmetric division during sporulation by Bacillus subtilis generates a mother cell that undergoes a 5-h program of differentiation. The program is governed by a hierarchical cascade consisting of the transcription factors: σE, σK, GerE, GerR, and SpoIIID. The program consists of the activation and repression of 383 genes. The σE factor turns on 262 genes, including those for GerR and SpoIIID. These DNA-binding proteins downregulate almost half of the genes in the σE regulon. In addition, SpoIIID turns on ten genes, including genes involved in the appearance of σK. Next, σK activates 75 additional genes, including that for GerE. This DNA-binding protein, in turn, represses half of the genes that had been activated by σK while switching on a final set of 36 genes. Evidence is presented that repression and activation contribute to proper morphogenesis. The program of gene expression is driven forward by its hierarchical organization and by the repressive effects of the DNA-binding proteins. The logic of the program is that of a linked series of feed-forward loops, which generate successive pulses of gene transcription. Similar regulatory circuits could be a common feature of other systems of cellular differentiation

The Program of Gene Transcription for a Single Differentiating Cell Type during Sporulation in Bacillus subtilis

Asymmetric division during sporulation by Bacillus subtilis generates a mother cell that undergoes a 5-h program of differentiation. The program is governed by a hierarchical cascade consisting of the transcription factors: σ(E), σ(K), GerE, GerR, and SpoIIID. The program consists of the activation and repression of 383 genes. The σ(E) factor turns on 262 genes, including those for GerR and SpoIIID. These DNA-binding proteins downregulate almost half of the genes in the σ(E) regulon. In addition, SpoIIID turns on ten genes, including genes involved in the appearance of σ(K) (.) Next, σ(K) activates 75 additional genes, including that for GerE. This DNA-binding protein, in turn, represses half of the genes that had been activated by σ(K) while switching on a final set of 36 genes. Evidence is presented that repression and activation contribute to proper morphogenesis. The program of gene expression is driven forward by its hierarchical organization and by the repressive effects of the DNA-binding proteins. The logic of the program is that of a linked series of feed-forward loops, which generate successive pulses of gene transcription. Similar regulatory circuits could be a common feature of other systems of cellular differentiation

Characterization of a Bacillus anthracis spore coat-surface protein that influences coat-surface morphology

Bacterial spores are encased in a multilayered proteinaceous shell, called the coat. In many Bacillus spp., the coat protects against environmental assault and facilitates germination. In Bacillus anthracis , the spore is the etiological agent of anthrax, and the functions of the coat likely contribute to virulence. Here, we characterize a B. anthracis spore protein, called CotΒ, which is encoded only in the genomes of the Bacillus cereus group. We found that CotΒ is synthesized specifically during sporulation and is assembled onto the spore coat surface. Our analysis of a cotΒ null mutant in the Sterne strain reveals that CotΒ has a role in determining coat-surface morphology but does not detectably affect germination. In the fully virulent Ames strain, a cotΒ null mutation has no effect on virulence in a murine model of B. anthracis infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72138/1/j.1574-6968.2008.01380.x.pd

Bacillus subtilis Spore Resistance to Simulated Mars Surface Conditions

In a Mars exploration scenario, knowing if and how highly resistant Bacillus subtilis spores would survive on the Martian surface is crucial to design planetary protection measures and avoid false positives in life-detection experiments. Therefore, in this study a systematic screening was performed to determine whether B. subtilis spores could survive an average day on Mars. For that, spores from two comprehensive sets of isogenic B. subtilis mutant strains, defective in DNA protection or repair genes, were exposed to 24 h of simulated Martian atmospheric environment with or without 8 h of Martian UV radiation [M(+)UV and M(-)UV, respectively]. When exposed to M(+)UV, spore survival was dependent on: (1) core dehydration maintenance, (2) protection of DNA by α/β-type small acid soluble proteins (SASP), and (3) removal and repair of the major UV photoproduct (SP) in spore DNA. In turn, when exposed to M(-)UV, spore survival was mainly dependent on protection by the multilayered spore coat, and DNA double-strand breaks represent the main lesion accumulated. Bacillus subtilis spores were able to survive for at least a limited time in a simulated Martian environment, both with or without solar UV radiation. Moreover, M(-)UV-treated spores exhibited survival rates significantly higher than the M(+)UV-treated spores. This suggests that on a real Martian surface, radiation shielding of spores (e.g., by dust, rocks, or spacecraft surface irregularities) might significantly extend survival rates. Mutagenesis were strongly dependent on the functionality of all structural components with small acid-soluble spore proteins, coat layers and dipicolinic acid as key protectants and efficiency DNA damage removal by AP endonucleases (ExoA and Nfo), non-homologous end joining (NHEJ), mismatch repair (MMR) and error-prone translesion synthesis (TLS). Thus, future efforts should focus on: (1) determining the DNA damage in wild-type spores exposed to M(+/-)UV and (2) assessing spore survival and viability with shielding of spores via Mars regolith and other relevant materials

An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network

Organisms from all domains of life use gene regulation networks to control cell growth, identity, function, and responses to environmental challenges. Although accurate global regulatory models would provide critical evolutionary and functional insights, they remain incomplete, even for the best studied organisms. Efforts to build comprehensive networks are confounded by challenges including network scale, degree of connectivity, complexity of organism–environment interactions, and difficulty of estimating the activity of regulatory factors. Taking advantage of the large number of known regulatory interactions in Bacillus subtilis and two transcriptomics datasets (including one with 38 separate experiments collected specifically for this study), we use a new combination of network component analysis and model selection to simultaneously estimate transcription factor activities and learn a substantially expanded transcriptional regulatory network for this bacterium. In total, we predict 2,258 novel regulatory interactions and recall 74% of the previously known interactions. We obtained experimental support for 391 (out of 635 evaluated) novel regulatory edges (62% accuracy), thus significantly increasing our understanding of various cell processes, such as spore formation

Comparative Microbial Modules Resource: Generation and Visualization of Multi-species Biclusters

The increasing abundance of large-scale, high-throughput datasets for many closely related organisms provides opportunities for comparative analysis via the simultaneous biclustering of datasets from multiple species. These analyses require a reformulation of how to organize multi-species datasets and visualize comparative genomics data analyses results. Recently, we developed a method, multi-species cMonkey, which integrates heterogeneous high-throughput datatypes from multiple species to identify conserved regulatory modules. Here we present an integrated data visualization system, built upon the Gaggle, enabling exploration of our method's results (available at http://meatwad.bio.nyu.edu/cmmr.html). The system can also be used to explore other comparative genomics datasets and outputs from other data analysis procedures – results from other multiple-species clustering programs or from independent clustering of different single-species datasets. We provide an example use of our system for two bacteria, Escherichia coli and Salmonella Typhimurium. We illustrate the use of our system by exploring conserved biclusters involved in nitrogen metabolism, uncovering a putative function for yjjI, a currently uncharacterized gene that we predict to be involved in nitrogen assimilation