Bone scan index and progression-free survival data for progressive metastatic castration-resistant prostate cancer patients who received ODM-201 in the ARADES multicentre study

Background: ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. Objective: To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. Design, setting, and participants: From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n = 47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. Outcome measurements and statistical analysis: We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). Results and limitations: In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07–0.58; p = 0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17–0.74; p = 0.006) than those who had a BSI increase >20% during treatment. Conclusions: The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. Patient summary: An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer

Deposition and absorption of inhaled drugs

Main objectives of this thesis were to evaluate a gamma scintigraphic method used to quantify drug aerosol deposition in the lung, to investigate the influence of two aerosol inhalation parameters on the distribution of inhaled dry powder within the airways, to assess pulmonary absorption kinetics and bioavailability of an inhaled hydrophilic solute in relation to site of deposition, and to assess the influence of a surface active agent (sodium taurocholate, a bile salt) on the deposition and absorption of an inhaled hydrophilic solute. Repeated planar gamma scintigraphy was found to provide the same information on total pulmonary drug deposition as an independent method that involved assessments of urinary drug recovery after blockage of gastrointestinal drug absorption when all of the critical parts of the methodological procedures were accurately and meticulously executed. In this work, the inhalation flow used at dry powder aerosol inhalation did not appear to influence intrapulmonary deposition pattern or total pulmonary deposition. On the other hand, dose delivery late in the breath was observed to increase dry powder aerosol penetration into the lung as a consequence of the greater lung volume and, thus, larger airway dimensions that the aerosol particles encountered. The main pulmonary elimination pathway for the inhaled hydrophilic drug solute was found to be trans-epithelial absorption, whereas mucociliary clearance was less important. Independent of intrapulmonary aerosol deposition pattern, absorption of was rapid and extensive. Both rate and extent of absorption increased by the surface active agent

Exhaled breath condensate-site and mechanisms of formation

Exhaled breath condensate (EBC) analysis is a promising tool for diagnosis and management of pulmonary diseases. Its clinical usefulness is still limited however due to unresolved issues around e. g. reproducibility, anatomical site of origin of EBC solutes and mechanisms of EBC formation. To gain some knowledge on these issues, three different airway deposition patterns of an aqueous aerosol containing technetium-99m were studied in eight healthy non-smoking subjects. EBC was collected 20 min after each radioaerosol administration and analyzed for gamma radiation and electrolytes. Radioaerosol deposition in preferentially central lung compared with preferentially peripheral lung resulted in 3.8 times higher EBC radioactivity. EBC concentrations of Na+ and K+ correlated significantly indicating dilution by water vapor to be a major source of variability. Since Na+/K+- and Na+/S2--concentration ratios, but not Na+/Cl--or Na+/Ca2+-, were comparable to those previously reported for alveolar lining fluid (ALF), some mechanisms other than dilution are likely also to be involved. In conclusion, our findings indicate that EBC derives mainly from the central airways, that the electrolyte composition of EBC does not consistently reflect that of ALF, and that EBC concentrations of electrolytes are determined not only by ALF dilution with water vapor but also by other mechanisms

In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol.

Pulmonary delivery of pharmaceutical aerosols can be quantified using gamma scintigraphy. Technetium-99m, the most commonly used radionuclide in scintigraphic studies, cannot be incorporated into the drug molecule and, therefore, may be distributed differently from the drug itself, particularly if the drug is presented as a solid in a liquid suspension or as a dry powder formulation. This study demonstrated the importance of using conditions relevant to the in vivo situation in the in vitro characterisation of a dry powder aerosol of 99mTc-labelled lactose. The influence of inspiratory flow on the distribution of aerosol within the lungs was investigated in eight healthy subjects who inhaled the 99mTc-labelled lactose at four flows (30,40,60 and 80 l/min). No differences in penetration index (PI) or count density distribution of radioactivity were seen, indicating that regional distribution of aerosol in healthy airways was insensitive to differences in the inspiratory effort exerted by the subject while inhaling the experimental dry powder radioaerosol

An advanced and detailed in vitro validation procedure for the radiolabeling of carrier-free terbutaline sulphate dry powder

The aerodynamic properties of 99mTc radiolabeled carrier-free terbutaline sulphate (TBS) have been thoroughly investigated following delivery by Turbuhaler® (AstraZeneca Lund, Sweden). A full and detailed radiolabeling procedure is also reported. The in vitro radiolabel validation was performed to determine whether TBS radiolabeled in this way would be representative of the commercially available product Bricanyl® Turbuhaler during clinical trials. The results indicated that variations in aerodynamic properties had been introduced and that the radiolabel would slightly underestimate the fine particle fraction of Bricanyl, but would nonetheless act as a suitable marker in vivo. Assumptions regarding the aerodynamic properties of doses likely to be received by clinical trial subjects were also examined. This has been achieved by extending the validation procedures beyond those usually reported to include dose number, time, and homogeneity dependent studies. It was found that doses extracted for testing purposes and simulated patient doses extracted shortly afterward had similar properties. Doses extracted 2 h after initial testing also had similar properties to the test doses. These results suggested that data from the test doses could be used for quality control purposes, would be representative of the doses to be received by clinical trial subjects, and that a short delay between initial testing and trial subject inhalation would be acceptable

Drugs, distrust and dialogue : - a focus group study with Swedish GPs on discharge summary use in primary care

BACKGROUND: Discharge summary with medication report effectively counteracts drug-related problems due to insufficient information transfer in care transitions. The benefits of the discharge summary may be lost if it is not adequately used, and factors affecting optimal use by the GP are of interest. Since the views of Swedish GPs are unexplored, this study aimed to explore and understand GPs experiences, perceptions and feelings regarding the use of the discharge summary with medication report.METHOD: This qualitative study was based on four focus group discussion with 18 GPs and resident physicians in family medicine which were performed in 2016 and 2017. A semi-structured interview guide was used. The interviews were transcribed verbatim and analysed using qualitative content analysis.RESULTS: The analysis resulted in three final main themes: "Importance of the discharge summary", "Role of the GP" and "Create dialogue" with six categories; "Benefits for the GP and perceived benefits for the patient", "GP use of the information", "Significance of different documents", "Spider in the web", "Terminus/End station" and "Improved information transfer in care transitions". Overall, the participants described clear benefits with the discharge summary when accurate although perceived deficiencies were also quite rife.CONCLUSION: The GPs experiences and views of the discharge summary revealed clear benefits regarding mainly medication information, awareness of any plans as well as shared knowledge with the patient. However, perceived deficiencies of the discharge summary affected its use by the GP and enhanced communication was called for

"Nu sätter vi ord på det, ryggraden har flyttat till huvudet" : kollegialt lärande och ett språkutvecklande förhållningssätt som beprövad erfarenhet i fritidshemsverksamheten

Artikeln beskriver ett utvecklingsarbete bedrivet i fritidshemsverksamhet. Syftet var att genom kollegialt lärande utveckla ett språkutvecklande förhållningssätt i verksamheten. Arbetet genomfördes under tre terminer och dokumentationen utgörs av anteckningar från observationer och samtalsträffar samt ljudinspelning från ett återkopplande samtal inspirerat av ”stimulated recall”. Resultatet bekräftar tidigare forsknings beskrivningar av fritidsverksamhet som en verksamhet som under senare år påverkats av organisatoriska förändringar och som en miljö för informellt lärande och processinriktad didaktik. Resultatet visar också på möjligheter att utveckla fritidshemsverksamhetens särskilda karaktär genom kollegialt lärande och strävan efter vetenskaplig grund. Utvecklingsarbetet bidrog till att stärka fritidslärarnas yrkesroll och öka deras medvetenhet om språkets betydelse för lärande

Pulmonary clearance rate of two chemically different forms of inhaled pertechnetate

Attempts to image the pulmonary deposition site of radiolabeled aerosols delivered by dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs) using single photon emission computed tomography (SPECT) have been limited by the rapid pulmonary clearance of radiolabel. To determine whether aqueous solubility of the radiolabel is a significant factor, the pulmonary clearance rates of two chemically different forms of Tc-99m were calculated. A dry powder formulation of terbutaline sulphate was radiolabeled for inhalation by Turbuhaler (AstraZeneca) using the water-soluble salt sodium pertechnetate and the water-insoluble salt tetraphenylarsonium pertechnetate. A pilot study was conducted during which two control subjects each inhaled the two radiolabeled aerosols on separate days. Intrasubject clearance rates for the two species were very similar. It was therefore concluded that water insolubility of the pertechnetate salt alone was not enough to extend the lung residency time of the radiolabel