Hjärtsvikt är en folksjukdom där prevalensen har uppskattats till cirka 2 %. Sjukdomen innebär att hjärtats funktion är försämrad. Idag behandlas hjärtsvikt vanligtvis med ACE-hämmare, betablockerare och ibland spironolakton. Spironolakton är en mineralkortikoidreceptorantagonist, som i RALES-studien (1999) har visat goda effekter på mortalitets- och morbiditetsreduktion hos hjärtsviktspatienter när den gavs som tillägg till ACE-hämmare. Idag är det ännu inte helt känt hur läkemedlet utövar sin effekt. Syftet med detta arbete är att undersöka vad spironolakton har för effekt på hjärta, blodkärl samt det sympatiska nervsystemet hos hjärtsviktspatienter. En litteraturstudie gjordes där sju studier utvärderades. Två av de utvalda studierna behandlade spironolaktons effekt på blodkärlen, två på hjärtremodelleringen, två på hjärtfibrosen och en på det sympatiska nervsystemet. Resultaten från studierna visade att spironolakton har goda effekter på kärlen bland annat genom att öka biotillgängligheten av kväveoxid. Läkemedlet har också goda effekter på hjärtremodelleringen, troligtvis framförallt genom att minska fibrosbildningen. Dessutom har spironolakton fördelaktiga effekter på det sympatiska nervsystemet. Många av spironolaktons effekter beror troligtvis på dess förmåga att blockera aldosterons effekt. De fysiologiska effekter som visades i detta arbete kan sannolikt ge mortalitets- och morbiditetsreduktion hos verklighetens hjärtsviktspatienter då läkemedlet adderas till modern basbehandling. I RALES var betablockeraranvändning ovanlig och klinikens patienter motsvarade inte verklighetens patienter. Därför kan en modern studie liknande RALES, men på verklighetens hjärtsviktspatienter, ge svar på frågan om spironolakton idag är ett effektivt läkemedel för behandling av hjärtsvikt.

Bakgrund: Menopaus definieras som tidpunkten för en kvinnans sista spontana menstruationsblödning. Cirka 65 000 svenska kvinnor passerar varje år sin menopaus och genomsnittsåldern för menopaus i Sverige och i övriga västvärden är 51-52 år. Substitutionsbehandling med östrogen och progesteron har länge använts för att lindra typiska menopausala symptom som värmevallningar och svettningar. Nyare studier visar att substitutionsbehandling med östrogen och progesteron ökar risken för att drabbas av kardiovaskulära sjukdomar och bröstcancer. Oro kring biverkningar liksom att kvinnor av annan anledning inte kan använda östrogen, har medfört ett ökat intresse för alternativbehandlingar som kan lindra menopausala symptom. En ny studie visar att mer än 50 % av kvinnor med menopausala symptom använder sig av någon sorts alternativbehandling för att lindra sina besvär. Extrakt av jordstam från silverax (Cimicifuga racemosa) har använts i Europa i mer än 40 år för att behandla klimakteriebesvär, och är idag den mest använda alternativbehandlingen. Syfte: I föreliggande litteraturstudie har syftet varit att undersöka om silverax kan minska upplevda vasomotoriska besvär, under perioden kring menopaus. Metod: Undersökningen är en litteraturstudie baserad på 5 randomiserade kliniska studier, hämtade från databaserna PubMed och Medline. Resultat: Silverax tycks vara ett effektivt behandlingsalternativ för att minska vasomotoriska symptom hos kvinnor som befinner sig i tidigt stadium av menopausen. Studierna visar en bra tolerans till extraktet utan allvarliga biverkningar. Diskussion: Fler stora randomiserade, kontrollerade och framförallt längre studier behövs för att man ska kunna dra slutsatser om effekten och säkerheten av silverax, och därmed visa om extraktet kan vara en effektiv behandlingsmetod vid menopausala symptom.

<p> The purpose of this pilot protocol was to examine the process of instillation of a bladder cancer optical imaging agent for blue light cystoscopy (BLC) procedures in a preoperative area in Bronx, NY with registered nurses (RNs). The RNs followed a process flowchart and completed a checklist. </p><p> A retrospective review was completed by the Assistant Director of Research for Urology and the Study Principal Investigator on 20 charts with four time stamps. The time stamps included the &ldquo;Scheduled Time of Surgery&rdquo;, &ldquo;In Pre Procedure&rdquo;, &ldquo;Medication Administration Record (MAR)&rdquo;, and &ldquo;In Room&rdquo;. The prospective review was completed on 10 BLC procedures by the preoperative RNs. In addition to the time stamps, there were three other questions descriptively examined on consent completion, an instill catheter order, and catheter placement at the bedside. </p><p> The Wilcoxon Test Statistic was utilized to determine whether there was a significant difference between prospective and retrospective timeframes upon implementation of a standardized protocol for a preoperative procedure. The Chi-square test was performed to determine whether there was a significant difference between retrospective and prospective information on &ldquo;MAR&rdquo; documentation. </p><p> There is no standard protocol for the BLC procedure at this hospital. Inconsistent processes with instillation of the optical imaging agent can result in negative outcomes, delays, and unsafe environments. This pilot protocol for the BLC procedure is important to develop a standard protocol for all preoperative areas that utilize this technology across the United States. </p><p>

<p> The purpose of a clinical trial is to demonstrate safety, tolerability and efficacy of investigational medications before receiving FDA approval for medical use. The success of clinical trials heavily relies on quick patient recruitment as well as long-term patient retention throughout the duration of the study. Recruitment and retention have been identified as the most expensive components of research, in some instances consisting of up to 33% of the designated budget spanning from phase I to III trials. In light of the rising costs of pharmaceutical research, it is important to investigate factors implicated in patient recruitment and retention throughout a clinical trial. Focusing on a Major Depressive Disorder study, an analysis of the following factors determining patient involvement in clinical trials was proposed: sex, age, weight, distance from site, marital status, concomitant medications, comorbid diseases, and work status, among others. Using logistical regression model, a retrospective study was conducted in order to characterize a profile of an optimized patient. Logistic regression analysis of data revealed that the most significant determinant of patient enrollment into a Major Depressive Disorder study is the use of an antidepressant treatment (ADT) at the time of pre-screening consultation. A closer look revealed that a potential patient was three times more likely to enroll in the study if he or she was on an ADT than an individual without the treatment. Further analysis confirmed model significance and result validity, as well as prompted ideas for further research. </p><p>

Background: Medication related admissions (MRAs) account for a substantial amount of all hospital admissions and most MRAs are considered preventable. In order to reduce the amount of MRAs, comprehensive medication reviews performed by clinical pharmacists on hospitalised patients could be a viable strategy. To study the effect of these reviews on the incidence of MRAs, a method of assessing whether an admission is an MRA or not is required. Two such methods will be compared in this study. Aim: The aim of this study was to assess hospitalisations using AT-HARM10 and the OPERAM DRA Adjudication Guide (OPERAM tool) and compare the results. Method: The OPERAM tool and AT-HARM10 were used to assess hospitalisations.  Assessments yielding different results were discussed in a review panel and the reasons for the differences were determined. Cases where the assessments provided different results due to an error made by the assessor were changed. Trends in the reasons for deviation as well as statistics on the agreements of the tools were produced. Results: The initial agreements between the tools was 76%. After adjustment from the review panel discussion the agreement was 95%. A few cases where the OPERAM tool did not follow current evidence-based recommendations were identified. Discussion: Though the tools showed a high level of agreement, a few strengths and limitations of both designs could be identified. The main limitation of the OPERAM tool was the trigger tool which contained some outdated information while in AT-HARM10 the competence of the assessor could impact the results. Conclusion: Both tools showed a high level of agreement and seem to be a viable option for determining whether a hospital admission is possibly or unlikely to be an MRA.

The purpose of this study was to examine the influence of content of a copovidone binder (0%, 5% and 10% w/w) and its addition method on compression and compaction properties of six MCCformulations following dry granulation. Briquetting was used to form dry granules for furthercharacterization. The mean yield pressure and fracture strength of granules were assessed at 300MPa on the basis of “in-die” Heckel and Adams model respectively. Then tablet tensile strengthof manufactured tablets was determined at 100 and 300 MPa. The results demonstrated thatintragranular addition of further binder (10%) to MCC could increase plasticity. However, therewas a drastic reduction in compactibility of dry granules mostly impacted by binding capacity ofthe binder. Generally, 5% intragranular:5% extragranular binder under a compaction pressure of300 MPa had the greatest binder efficacy on strength of pure MCC tablets while 10%extragranular binder improved tensile strength significantly at 100 MPa. PVP in a level of 5%w/w had no significant impact on tensile strength of tablets compacted at 100 and 300 MPa.

Mastocytos är en ovanlig myeloproliferativ neoplasi där en klonal ackumulation av mastceller påverkar olika organ. Hos mastocytospatienter ses vanligen en mutation i Kit-genen (Kit D816V) som kodar för tyrosinkinasreceptor Kit, receptorn får därav basaktivitet vilket leder till att mastcellerna kan proliferera, överleva samt ha sekretorisk aktivitet utan att aktiveras av sin ligand. Mastcellen har en hög koncentration proinflammatoriska mediatorer som vid stimuli frisätts och orsakar besvär som urticaria, diarré och anafylaxi. Prognosen för mastocytospatienter är god men ofta ses en påverkad livskvalitet och sällsynt även en förkortad livslängd. Behandling består dels av att undvika utlösande faktorer som värme, kyla, alkohol och insektsbett men även läkemedelsbehandlingar som påverkar symtom från mediatorerna som t.ex. antihistaminer och leukotrienhämmare. Vid aggressiv sjukdom används olika cytoreduktiva behandlingar, i första hand interferon-a med kladribin eller kortikosteroider men även allogen stamcellstransplantation utförs. Tyrosinkinashämmare är också cytoreduktiva genom att hämma tyrosinkinasreceptorer som har en tillväxtstimulerande effekt. Den enda godkända tyrosinkinashämmaren för mastocytos i Sverige är midostaurin som har en bred kinasprofil men studier pågår på mer selektiva hämmare som t.ex. avapritinib. Studiens syfte var att undersöka om dessa tyrosinkinashämmare är effektiva och säkra som behandling för patienter med mastocytos genom att analysera vetenskapliga artiklar från databasen Pubmed. Midostaurin visade en signifikant svarsfrekvens hos lite mer än hälften av patienterna och hade effekt i samtliga subtyper, i studierna sågs också en reduktion av mastceller i benmärg hos ungefär hälften av populationerna och en övergripande medianöverlevnad på 28,7 månader. Dock besvärades patienterna av biverkningar, vanligast illamående och kräkningar varpå en stor andel avslutade studien i förtid. I de två studierna där masitinib undersöktes sågs signifikanta resultat vad gällde förbättring i symtom som klåda, flush och depression, även serumtryptasnivåer och livskvalitet förbättrades med en varaktig respons. En stor andel biverkningar rapporterades även med masitinib med illamående och kräkningar hos över hälften av patienterna i den ena studien, dock registrerades inte så stor andel avhopp vilken kan bero på att patienterna behandlades med 5-HT3 receptorantagonister. I de sista två studierna undersöktes avapritinib in vitro ocn in vivo. Resultaten visade att avapritinib hade en överlägsen effekt jämfört med midostaurin in vitro där endast 10 % av kolonierna uppvisade Kit D816V positiv mutation efter behandling. En övergripande respons på 83 % samt antineoplastisk aktivitet sågs också hos samtliga subtyper. Biverkningar rapporterades från en stor andel av patienterna och de allvarligaste var neutropeni och anemi. Inga generella slutsatser kan dras av denna studie, dock pekar resultaten på att tyrosinkinashämmare har effekt hos patienter med systemisk mastocytos. Samtliga hämmare följs tyvärr av många och endel allvarliga biverkningar och det finns endast ett fåtal studier varav flera saknar både randomisering och kontrollgrupp för att styrka resultaten. Svarsmekanismen är också mycket komplicerad med många obesvarade frågor som vilken patient som svarar på vilken behandling och om respons beror på Kit mutation och eventuellt andra somatisk mutationer. / Mastocytosis is a rare myeloproliferative neoplasia in which a clonal accumulation of mast cells affects different organs. In mastocytosis patients a mutation is usually seen in the Kit gene (Kit D816V) encoding receptor tyrosine kinase Kit. The receptor thereby gain basal activity which allows the mast cells to proliferate, survive and have secretory activity without being activated by it’s ligand. The mast cell has a high concentration of proinflammatory mediators that are released during stimuli and cause symptoms such as urticaria, diarrhea, abdominal pain and anaphylaxis. The prognosis for mastocytosis patients is good but often affects quality of life and for some there is a shortened life expectancy. Treatment consists partly of avoiding environmental triggers such as heat, cold, alcohol and insect bites, but also drug treatments that affect the symptoms from the mediators such as antihistamines and leukotriene inhibitors. In aggressive systemic mastocytosis, various cytoreductive treatments are used, primarily interferon-a with cladribine or corticosteroids, but also allogeneic stem cell transplantation is performed. Tyrosine kinase inhibitors are also cytoreductive by inhibiting tyrosine kinase receptors that have a growth-stimulating effect. The only approved tyrosine kinase inhibitor for mastocytosis in Sweden is midostaurine, which has a broad kinase profile but studies are ongoing on more selective inhibitors such as avapritinib. The purpose of the study was to investigate whether these tyrosine kinase inhibitors are effective and safe as treatment for patients with mastocytosis by analyzing scientific articles from the database Pubmed. Midostaurine showed a significant response rate in slightly more than half of the patients and had efficacy in all subtypes, it also showed a reduction in bone marrow mast cells in about half of the populations and an overall median survival of 28.7 months. However, patients were bothered by side effects, most commonly nausea and vomiting, with a large amount completing the study prematurely. In the two studies in which masitinib was studied, significant results were seen in terms of improvement in symptoms such as pruritus, flushing and depression, also serum tryptase levels and quality of life were improved with a sustained response. A large proportion of adverse events were also reported with masitinib, nausea and vomiting were seen in more than half of the patients in one of the studies, however, not as large a proportion of dropouts was recorded. In the last two studies, avapritinib was studied in vitro and in vivo. The results showed that avapritinib had a superior effect compared to midostaurine in vitro where only 10% of the colonies had an Kit D816V positive mutation after treatment. An overall response of 83% and antineoplastic activity was also seen in all subtypes. Side effects were reported from a large proportion of patients and the most serious were neutropenia and anemia. No general conclusions can be drawn from this study; however, the results indicate that tyrosine kinase inhibitors have an effect in patients with systemic mastocytosis. Unfortunately, all inhibitors are followed by many and some serious side effects and there are only a few studies out of which several lack both randomization and control groups to confirm the results. The response mechanism is also very complicated with many unanswered questions such as which patient responds to which treatment and whether response is due to Kit mutation and other somatic mutations.

Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines.

Local transcutaneous delivery of non-steroidal anti-inflammatory drugs avoids gastrointestinal side effects and concentrates drugs in the intended tissues. An extraction and HPLC method was developed for ketoprofen in skin, fascia and muscle. Tissue samples were homogenized in NaHCO3. After methylene chloride removal of lipids, the aqueous layer was acidified with HCl and back extracted into isooctane/isopropanol. Ketoprofen was derivatized with ethylchloroformate/S-(-)-α-phenylethylamine in triethylamine, then detected by HPLC. Ketoprofen recovery was linear (1-33 μg/g) and was detected in these tissues following in vivo cathodic iontophoresis (160 mA*min). This represents the first non-radioactive method for determination of ketoprofen in tissues following transcutaneous iontophoresis.

BACKGROUND AND OBJECTIVES: Interprofessional education (IPE) is recommended by many as a means by which to prepare clinicians for collaborative practice and a mechanism by which to improve the overall quality of health care. The objective of this study was to determine the impact of an interprofessional medicine-pharmacy student home visit experience on students' self-assessments of skills and abilities related to team-based care and identification of medication-related problems METHODS: Third-year medical and fourth-year pharmacy students completed an interprofessional home visit centered on identification of medication-related problems. Students were surveyed before and after the IPE assignment to assess changes in self-assessed skills and abilities. Survey items consisted of Likert-type statements on a 5-point scale (1=strongly disagree, 5=strongly agree) and free-text responses. Students also completed reflection papers regarding their experiences RESULTS: Twenty-two medical and 20 pharmacy students conducted medication-focused interviews of 22 patients at home as interprofessional teams. Medical and pharmacy student self-assessments of skills and abilities related to team-based care and identification of medication-related problems improved after completion of the assignment. Both groups of students perceived an improvement in confidence regarding communication skills, both with patients and with other health professions students. Changes were reported on 12 survey items. Student feedback on the IPE experience was positive CONCLUSIONS: Students' self-perception of skills and abilities related to interprofessional team-based care and identification of medication-related problems are improved after IPE medication-focused home visit assignment. Student feedback supports the value of interprofessional patient care clinical experiences.