Applying Data Science methods and tools to unveil healthcare use of lung cancer patients in a teaching hospital in Spain.

PURPOSE: Our primary goal was to study the use of outpatient attendances by lung cancer patients in Hospital Universitario Puerta de Hierro Majadahonda (HUPHM), Spain, by leveraging our Electronic Patient Record (EPR) and structured clinical registry of lung cancer cases as well as assessing current Data Science methods and tools. METHODS/PATIENTS: We applied the Cross-Industry Standard Process for Data Mining (CRISP-DM) to integrate and analyze activity data extracted from the EPR (9.3 million records) and clinical data of lung cancer patients from a previous registry that was curated into a new, structured database based on REDCap. We have described and quantified factors with an influence in outpatient care use from univariate and multivariate points of view (through Poisson and negative binomial regression). RESULTS: Three cycles of CRISP-DM were performed resulting in a curated database of 522 lung cancer patients with 133 variables which generated 43,197 outpatient visits and tests, 1538 ER visits and 753 inpatient admissions. Stage and ECOG-PS at diagnosis and Charlson Comorbidity Index were major contributors to healthcare use. We also found that the patients' pattern of healthcare use (even before diagnosis), the existence of a history of cancer in first-grade relatives, smoking habits, or even age at diagnosis, could play a relevant role. CONCLUSIONS: Integrating activity data from EPR and clinical structured data from lung cancer patients and applying CRISP-DM has allowed us to describe healthcare use in connection with clinical variables that could be used to plan resources and improve quality of care.

Monitoring ibuprofen enantiomers released from polymeric systems.

Two methacrylic derivatives of ibuprofen (N-[4-[2-(4-isobutylphenyl)propionyloxy]phenyl] methacrylamide (MAI) and 2-[(4-isobutylphenyl)propionyloxy]ethyl methacrylate (MEI)) were used together with 2-hydroxyethyl methacrylate (HEMA) to synthesize four polymeric materials: two hydrophobic homopolymers, PMAI and PMEI, and two hydrophilic copolymers containing 70% (w/w) HEMA, MAI-HEMA 30 and MEI-HEMA 30. The enantiomeric determination of R- and S-IBU released from these four systems has been carried out by capillary electrophoresis. Release of R- and S-IBU was monitored during in vitro assays done at 37 degrees C at pH 7.4 and 10 in buffered solutions and rat plasma. There is a hydrolytical activation in plasma and at pH 10 compared to pH 7.4; moreover, the release rate from the copolymers is much higher than from the homopolymers as a consequence of the greater hydrophilic character. A slight excess of the S-enantiomer of IBU is observed in all the experiments, being more relevant at higher release rates, i.e. copolymers at pH 10.

NSAIDs bound to methacrylic carriers: microstructural characterization and in vitro release analysis.

Chemically controlled drug delivery systems or 'polymeric drugs' based on copolymers of 2-hydroxyethyl methacrylate, HEMA, and five methacrylic derivatives which incorporate ibuprofen or ketoprofen in their chemical structure by means of labile ester bonds, MAI, MAK, MAEK, MEI and MEK, have been prepared by free radical polymerization in solution at 50 degrees C. Three different spacers have been incorporated to the monomer structure: an aromatic amide, an aliphatic ester and a combined aromatic amide/aliphatic ester. Copolymerization reactions of the methacrylamide derivatives with HEMA follow the terminal model with reactivity ratio values, determined by the Tidwell and Mortimer (J. Polym. Sci. A 1965;3:369-378) non-linear least-squares treatment, of r(MAI)=0.38, r(HEMA)=1.69; r(MAK)=0.30, r(HEMA)=0.48; and r(MAEK)=0.66, r(HEMA)=2.85. From these values and considering that the methacrylates MEI and MEK are structurally related to HEMA, the microstructural analysis give us a random distribution of the monomeric units. The HEMA-rich copolymers, used for the in vitro experiments, showed a very high population of sequences with the active residue isolated by HEMA units. The in vitro release experiments were carried out at pH 7.4 and 9, using six different compositions for each copolymer system (1, 2.5, 5, 10, 20 and 30 wt% of the active acrylic monomer). The results show a controlled release in terms of weeks with very different profiles which depend on the type of spacer (the aromatic ester is more susceptible to hydrolysis than the aliphatic one), drug (ketoprofen release rate is higher than the ibuprofen one), composition of the copolymer (as a general rule, the release rate increases with the content of the attached drug until some composition where this effect is reverted because of the global increase in hydrophobicity) and pH (the release rate is noticeably higher in a strong basic medium, pH 9).

HEMA-based methacrylic carriers incorporating ketoprofen: chain flexibility and swelling behaviour.

The chain flexibility, swelling and release behaviour of several copolymer systems of pharmacological interest have been studied. The systems are copolymers of 2-hydroxyethyl methacrylate with two support comonomers, i.e. N-(4-hydroxyphenyl) methacrylamide and N-[4-(2-hydroxy)ethoxyphenyl] methacrylamide and copolymers of 2-hydroxyethyl methacrylate with these carrier structures bearing ketoprofen (N-(4-[2-(3-benzoylphenyl)propionyloxy]phenyl methacrylamide and N-(4-[2-(3-benzoylphenyl)propionyloxy]2-ethoxyphenyl methacrylamide). In these copolymers ketoprofen was attached via different spacer groups, i.e. 4-aminophenoxy and 4-aminoethoxyphenyl. The chain structures are discussed on the basis of reactivity ratios. The properties of the polymeric drugs and of the parent carriers were studied comparatively by DSC and through the swelling of films from DMF solutions in pH 7.4 buffers. Data are discussed in terms of chain flexibility and swelling.

Controlled release of NSAIDs bound to polyacrylic carrier systems.

The synthesis, characterization and properties of new acrylic "polymeric drugs" derived from the NSAIDs agents ibuprofen and ketoprofen are described. The swelling behavior in hydrated medium and the controlled release from hydrophilic copolymers of the NSAIDs derivatives and 2-hydroxyethylmethacrylate, HEMA, are discussed, considering the hydrolytical reactivity of the acrylamide or acrylic ester functional groups, the aromatic or aliphatic structure of the spacer side groups, and the hydrophilic character of the copolymer systems. The results obtained demonstrated that the swelling degree of copolymers depends on the average composition of copolymers, decreasing with the increase of the average fraction of the corresponding acrylic derivative of ibuprofen or ketoprofen in the copolymer system. In addition, polymers which support the NSAIDs active component through aromatic amide links, are more sensitive to hydrolytical processes than those of alkyl ester functions. The results obtained demonstrate that these supports could be applied for direct administration, transdermal, systemic or intra-articular injection, as well as in the form of films on wounds.