The Doctrine of Equivalents after Hilton Davis and Markman, and a Proposal for Further Clarification

In March 1997, the United States Supreme Court issued its decision in Warner-Jenkinson Co. v. Hilton Davis Chemical Co. ( Hilton Davis I/,)\u27 which had been eagerly anticipated in the intellectual property community

Renal clinical pharmacy services

Klinisch-pharmazeutische Dienstleistungen im Bereich Nephrologie befassen sich unter anderem mit speziellen Arzneimittel- und Arzneimitteltherapie-assoziierten Problemen in Patienten mit eingeschränkter Nierenfunktion bei chronischer Niereninsuffizienz, terminalem Nierenversagen oder nach Nierentransplantation. Charakteristische Begleiterkrankungen in dieser Patientenpopulation sind häufig. Für den Klinischen Pharmazeuten bieten sich in diesem komplexen Umfeld viele Möglichkeiten einen Beitrag zu leisten und es gibt umfangreiche wissenschaftliche Literatur hierfür. Möglichkeiten umfassen u.a. das Management von Risikofaktoren (z.B. Hypertonie, kardiovaskuläre Erkrankungen und Diabetes), das Management von Begleiterkrankungen (z.B. Anämie, Störungen im Calcium-, Phosphat- und Vitamin-D-Haushalt), sowie die Prävention und das Management von Arzneimittel-assoziierten Problemen. Patienten mit eingeschränkter Nierenfunktion sind besonders empfindlich für Arzneimittel-assoziierte Probleme. Die fehlende Berücksichtigung von Dosierungsempfehlungen bedingt häufig eigentlich verhinderbare Arzneimittelnebenwirkungen. Die Beurteilung der Nierenfunktion und korrekte, an diese angepasste Arzneimitteldosierungen sind unerlässlich, um unerwünschte Arzneimittelwirkungen zu vermeiden und letztendlich eine optimale Patientenversorung zu gewährleisten. Die Existenz von Begleiterkrankungen, deren Schweregrad und verschiedene Verfahren (z.B. Dialyse) beeinflussen die Pharmakokinetik und die Pharmakodynamik von Arzneimitteln und können so zum Auftreten von Arzneimittel-assoziierten Problemen beitragen. Auf der nephrologischen Normalpflegestation einer großen österreichischen Universitätsklinik wurden erfolgreich klinisch-pharmazeutische Dienstleistungen implementiert und durch Beschreibung und Auswertung der klinisch-pharmazeutischen Interventionen und anderen Beiträgen während der Stationsvisiten evaluiert. Häufige Arzneimittel-assoziierte Probleme (z.B. Dosierungsfehler, Gebrauch nicht indizierter Arzneimittel, Fehler in der Dokumentation), häufig betroffene Arzneistoffe (z.B. Antibiotika, Protonenpumpenhemmer, Virustatika), die Akzeptanzrate der vorgeschlagenen Interventionen seitens des ärztlichen Personals und die Beurteilung der Signifikanz wurden erhoben. Die Ergebnisse müssen unter Berücksichtigung methodischer und systematischer Grenzen interpretiert werden. Die vorliegende Arbeit stellt die erste wissenschaftliche Arbeit im Bereich angewandter klinisch-pharmazeutischer Forschung auf nationaler österreichischer Ebene dar. Sie liefert Ergebnisse zur Implementierung klinisch-pharmazeutischer Dienstleistungen und unterstreicht den Beitrag des Klinischen Pharmazeuten in einem diesbezüglich noch in den Kinderschuhen steckenden Umfeld.Renal clinical pharmacy services focus on special drug- and pharmacotherapy-related issues in patients with renal impairment (e.g., chronic kidney disease patients, end-stage renal disease patients, kidney transplantation patients). Patients with renal insufficiency are characterised by several different comorbidities that affect many organ systems. Opportunities for the clinical pharmacist to contribute to the complex care of these patients at various stages and in the aforementioned patient groups are described. Possible areas in which the clinical pharmacist can contribute are risk factor management (e.g., hypertension, cardiovascular disease, and diabetes), management of comorbidities (e.g., anaemia, metabolic bone disease), and prevention and management of drug-related problems (DRPs). Patients with renal impairment are especially susceptible to DRPs. Non-adherence to dosing guidelines often leads to the occurrence of preventable adverse drug events. Accurate assessment of kidney function and assurance of dosage adaptation is key to avoid unwanted drug effects and, ultimately, to ensure optimal patient outcomes. Factors including the severity and prevalence of coexistent medical conditions and different procedures (e.g., form of dialysis) may influence the pharmacokinetics and pharmacodynamics of the drugs used and, therefore, contribute to the occurrence of DRPs. Successful implementation of clinical pharmacy services on an internal nephrology ward was evaluated by describing and evaluating the impact of a clinical pharmacist’s participation during ward rounds. Data on commonly detected DRPs (e.g., dosing issues, use of unindicated drugs, inaccuracies in medical records), performed interventions, affected drugs (e.g., antibiotics, proton pump inhibitors, antivirals), the physicians’ acceptance rate of the suggested interventions, and the significance assessment of the interventions are reported. Limitations to the results and their impact are mainly due to issues in study methodology. This thesis represents the first scientific thesis in the area of applied clinical pharmacy research on a national level in Austria and yields data on its implementation in the renal setting and the clinical pharmacist’s role in the evolving system of clinical pharmacy services

Atorvastatin in stroke: a review of SPARCL and subgroup analysis

Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA) reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention

Influência da compactação no crescimento e na nutrição de Eucalyptus badjensis.

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Self-reported clinical pharmacy service provision in Austria: an analysis of both the community and hospital pharmacy sector: a national study.

Background: With expansion of more advanced clinical roles for pharmacists we need to be mindful that the extent to which clinical pharmacy services (CPS) are implemented varies from one country to another. To date no comprehensive assessment of number and types of CPS provided by either community or hospital pharmacies in Austria exists. Objective: To analyse and describe the number and types of CPS provided in both community and hospital pharmacies, as well as the level of clinical pharmacy education of pharmacists across Austria. Setting: Austrian community and hospital pharmacies. Method: An electronic questionnaire to determine number and types of CPS provided was issued to all chief pharmacists at all community (n=1365) and hospital pharmacies (n=40) across Austria. Besides current and future CPS provision, education and training provision were determined. Main outcome measure: Extent of and attitude towards CPS in Austria. Results: Response rates to the surveys were 19.1% (n=261/1365) in community and 92.5% (n=37/40) in hospital pharmacies. 59.0% and 89.2% of community and hospital pharmacies, respectively, indicated that CPS provision has increased substantially in the past 10 years. 51.0% of community pharmacies reported to provide a medication review service, while 97.3% of hospitals provide a range of CPS. Only 18.0% of community pharmacies offer services other than medication review services at dispensing. Binary regressions show that provision of already established medication management is a predictor for the willingness of community pharmacists to extend the range of CPS (p [less than] 0.01), while completed training in the area of clinical pharmacy is not (p [greater than] 0.05). More hospital than community pharmacists have postgraduate education in clinical pharmacy (17.4% vs 6.5%). A desire to complete postgraduate education was shown by 28.3% of community and 14.7% of hospital pharmacists. Lack of time, inadequate remuneration, lack of resources and poor relationship between pharmacists and physicians were highlighted as barriers. Conclusion: Both community and hospital pharmacists show strong willingness to expand their CPS provision and will need continued support, such as improved legislative structures, more supportive resources and practice focused training opportunities, to further these services

Observation of Intermolecular Coulombic Decay and Shake-up Satellites in Liquid Ammonia

We report the first nitrogen 1s Auger–Meitner electron spectrum from a liquid ammonia microjet at a temperature of ~223 K (–50 °C) and compare it with the simultaneously measured spectrum for gas-phase ammonia. The spectra from both phases are interpreted with the assis- tance of high-level electronic structure and ab initio molecular dynamics calculations. In addition to the regular Auger–Meitner-electron features, we observe electron emission at kinetic energies of 374–388 eV, above the leading Auger–Meitner peak (3a12). Based on the electronic structure calculations, we assign this peak to a shake-up satellite in the gas phase, i.e., Auger–Meitner emission from an intermediate state with additional valence excitation present. The high-energy contribution is significantly enhanced in the liquid phase. We consider various mechanisms contributing to this feature. First, in analogy with other hydrogen-bonded liquids (noticeably water), the high-energy signal may be a signature for an ultrafast proton transfer taking place before the electronic decay (proton transfer mediated charge separation). The ab initio dynamical calculations show, however, that such a process is much slower than electronic decay and is, thus, very unlikely. Next, we consider a non-local version of the Auger–Meitner decay, the Intermolecular Coulombic Decay. The electronic structure calculations support an important contribution of this purely electronic mechanism. Finally, we discuss a non-local enhancement of the shake-up processes

Lymphoid aggregates in the bone marrow biopsies of patients with myelodysplastic syndromes – A potential prognostic marker?

BackgroundLymphoid aggregates (LA) are occasionally seen in bone marrow biopsies (BMB) of myelodysplastic syndromes (MDS) patients. Our aim was to evaluate their incidence and association with prognosis.MethodsWe compared BMB reports of MDS patients treated at the Tel Aviv Sourasky Medical Center (2011-2018), and controls (2015-2017, normal BMB), and examined the charts of the MDS patients (LA+ and LA-). Categorical, normally and non-normally distributed continuous variables were compared using Fisher’s exact, independent t and Mann-Whitney tests respectively. Adjusted [age, gender, lymphocytes, white blood cells (WBC) and diabetes mellitus (DM)] Cox proportional hazard model examined survival at 12 and 24 months.ResultsMDS patients (N=140) were older than controls (N=38; 74.1 vs 69.2 years, p=0.005); 34 MDS (24.3%) and 5 controls (13.2%) had LA+ (P=0.141). CD20/CD3 staining suggested LA polyclonality. MDS/LA+ (vs MDS/LA-) patients were younger, with a trend (not statistically significant) towards poor prognostic parameters: lower Hb, WBC, and platelets, higher LDH, BM cellularity, and IPSS-R score. The incidence of cardiovascular disease was similar, but MDS/LA+ had twice the incidence of DM (38.2% vs 19.0%, p=0.022). Similar trend for cancer (26.5% vs 14.3%, p=0.102). Twelve-month survival: 24/34 (70.6%) MDS/LA+; 88/106 (83.0%) MDS/LA- (p=0.140). This trend, seen in Kaplan-Meier curves, disappeared at 24 months. The hazard ratio for LA was 2.283 (p=0.055) for 12 months.ConclusionThese preliminary data suggest LA are relatively common (24%) in MDS BMB, and might indicate poor prognosis. This may reflect involvement of the immune system in MDS. Future studies will examine larger groups, to clarify the incidence, significance and the pathophysiology

How to measure work functions from aqueous solutions

The recent application of concepts from condensed-matter physics to photoelectron spectroscopy (PES) of volatile, liquid-phase systems has enabled the measurement of electronic energetics of liquids on an absolute scale. Particularly, vertical ionization energies, VIEs, of liquid water and aqueous solutions, both in the bulk and at associated interfaces, can now be routinely determined. These IEs are referenced to the local vacuum level, which is the appropriate quantity for condensed matter with associated surfaces, including liquids. Here, we connect this newly accessible energy level to another important surface property, namely, the solution work function, e$\Phi_{liq}$. We lay out the prerequisites for and unique challenges of determining e$\Phi$ of aqueous solutions and liquids in general. We demonstrate - for a model aqueous solution with a tetra-n-butylammonium iodide (TBAI) surfactant solute - that concentration-dependent work functions, associated with the surface dipoles generated by the segregated interfacial layer of TBA$^+$ and I$^-$ions, can be accurately measured under controlled conditions. We detail the nature of surface potentials, uniquely tied to the nature of the flowing-liquid sample, which must be eliminated or quantified to enable such measurements. This allows us to refer measured spectra of aqueous solutions to the Fermi level and quantitatively assign surfactant concentration-dependent spectral shifts to competing work function and electronic-structure effects, the latter determining, e.g., (electro)chemical reactivity. We describe the extension of liquid-jet PES to quantitatively access concentration-dependent surface descriptors that have so far been restricted to solid-phase measurements. These studies thus mark the beginning of a new era in the characterization of the interfacial electronic structure of aqueous solutions and liquids more generally.Comment: Main manuscript: 26 pages, 7 figures. Supporting information: 5 pages, 5 figure

Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations.</p> <p>Methods</p> <p>A literature search was conducted using the <it>Medline</it>, <it>Embase </it>and <it>International Pharmaceutical Abstracts </it>databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems.</p> <p>Results</p> <p>Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies.</p> <p>Conclusions</p> <p>Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.</p