Transcriptomic landscape of granulosa cells and peripheral blood mononuclear cells in women with PCOS compared to young poor responders and women with normal response.

STUDY QUESTION: Are transcriptomic profiles altered in ovarian granulosa cells (GCs) and peripheral blood mononuclear cells (PBMNCs) of women with polycystic ovary syndrome (PCOS) compared to young poor responders (YPR) and women with normal response to ovarian stimulation? SUMMARY ANSWER: RNA expression profiles in ovarian GCs and PBMNCs were significantly altered in patients with PCOS compared with normoresponder controls (CONT) and YPR. WHAT IS KNOWN ALREADY: PCOS is characterised by a higher number of follicles at all developmental stages. During controlled ovarian hyperstimulation, PCOS women develop a larger number of follicles as a result of an exacerbated response, with an increased risk of ovarian hyperstimulation syndrome. Despite the number of developing follicles, they are often heterogeneous in both size and maturation stage, with compromised quality and retrieval of immature oocytes. Women with PCOS appear to have a longer reproductive lifespan, with a slightly higher menopausal age than the general population, in addition to having a higher antral follicular count. As a result, the ovarian follicular dynamics appear to differ significantly from those observed in women with poor ovarian response (POR) or diminished ovarian reserve. STUDY DESIGN, SIZE, DURATION: Transcriptomic profiling with RNA-sequencing and validation using quantitative reverse transcription PCR (qRT-PCR). Women with PCOS (N = 20), YPR (N = 20) and CONT (N = 20). Five patients for each group were used for sequencing and 15 samples per group were used for validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was defined using the revised Rotterdam diagnostic criteria for PCOS. The YPR group included women <35 years old with <4 mature follicles (at least 15 mm) on the day of the trigger. According to internal data, this group represented the bottom 15th percentile of patients' responses in this age group. It was consistent with Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) criteria for POR (Group 3). The young CONT group included women <35 years without PCOS or anovulation, who developed >14 mature follicles (at least 15 mm on transvaginal ultrasound). According to internal data, a threshold of >14 mature follicles was established to represent the top 25% of patients in this age group in this clinic.Overall, n = 60 GCs and PBMNCs samples were collected and processed for total RNA extraction. To define the transcriptomic cargo of GCs and PBMNCs, RNA-seq libraries were successfully prepared from samples and analysed by RNA-seq analysis. Differential gene expression analysis was used to compare RNA-seq results between different groups of samples. Ingenuity pathway analysis was used to perform Gene Ontology and pathways analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In PBMNCs of PCOS, there were 65 differentially expressed genes (DEGs) compared to CONT, and 16 compared to YPR. In GCs of PCOS, 4 genes showed decreased expression compared to CONT, while 58 genes were differentially expressed compared to YPR. qRT-PCR analysis confirmed the findings of the RNA-seq. The functional enrichment analysis performed revealed that DEGs in GCs of PCOS compared to CONT and YPR were prevalently involved in protein ubiquitination, oxidative phosphorylation, mitochondrial dysfunction and sirtuin signaling pathways. LARGE SCALE DATA: The data used in this study is partially available at Gene Ontology database. LIMITATIONS, REASONS FOR CAUTION: The analysis in PBMNCs could be uninformative due to inter-individual variability among patients in the same study groups. Despite the fact that we considered this was the best approach for our study's novel, exploratory nature. WIDER IMPLICATIONS OF THE FINDINGS: RNA expression profiles in ovarian GCs and PBMNCs were altered in patients with PCOS compared with CONT and YPR. GCs of PCOS patients showed altered expression of several genes involved in oxidative phosphorylation, mitochondrial function and sirtuin signaling pathways. This is the first study to show that the transcriptomic landscape in GCs is altered in PCOS compared to CONT and YPR. STUDY FUNDING/COMPETING INTEREST(S): This study was partially supported by grant PI18/00322 from Instituto de Salud Carlos III, and European Regional Development Fund (FEDER), 'A way to make Europe' awarded to S.H. M.C., S.H., S.T., L.R., M.R., I.R., A.P. and R.C. declare no conflict of interests concerning this research. E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence. TRIAL REGISTRATION NUMBER: N/A.

Potential Development of Vitrified Immature Human Oocytes: Influence of the Culture Medium and the Timing of Vitrification.

How does the in vitro maturation (IVM) medium and the vitrification procedure affect the survival of germinal vesicle (GV) oocytes obtained from stimulated cycles and their development to the blastocyst stage? In total, 1085 GV human oocytes were obtained after women underwent a cycle of controlled ovarian stimulation, and these oocytes were subjected to IVM before or after their vitrification. IVM was carried out in two commercial culture media not specifically designed for maturation. MII oocytes were then activated and embryo development until day 6 was evaluated. According to the results, a higher percentage of oocytes reach the MII stage if they are vitrified before they undergo IVM. Nevertheless, the medium used and the sample size determine whether these differences become significant or not. Similar survival rates and development to blastocysts were observed in all the conditions studied.

Potentially inappropriate medication in acute hospitalized elderly patients with polypharmacy: an observational study comparing PRISCUS, STOPP, and Beers criteria.

PURPOSE: To compare the prevalence of potentially inappropriate medication (PIM) in the elderly according to the PRISCUS list, STOPP criteria, and Beers criteria. Secondary, to describe the differences using the three criteria focused on the inappropriate prescription of psychotropic drugs in the elderly. METHODS: A retrospective study was performed at Severo Ochoa University Hospital. The study included 365 patients, aged 80 years and older, living in Madrid, Spain. RESULTS: 93.42% of patients received at least one PIM during hospitalization. Using the PRISCUS list, this changed from 32.6 to 2.7% at discharge. Applying STOPP criteria lowered the percentage from 65.20 to 10.95%, and with Beers criteria from 80.27 to 10.13. Lower Barthel index at admission was associated with an increased relative risk for receiving at least one PIM (OR 1.79, 95% CI 1.15-2.80, p = 0.024) using PRISCUS list as a tool in conjunction with STOPP criteria (OR 1.44, 95% CI 0.89-2.33, p = 0.037). Polypharmacy at admission predicted the presence of PIMs with STOPP criteria (OR 1.74, 95% CI 1.07-2.84, p = 0.001). Regarding psychotropic medicines, 208 patients (56.98%) received at least one psychotropic medicine during hospitalization. A total of 26.30% of patients were treated with psychotropic medicines, detected by the PRISCUS list, and 53.97% and 29.85% with STOPP and Beers, respectively. CONCLUSIONS: Explicit criteria are a useful tool for identifying during hospitalization of the elderly patients. As indicated by the results, new research is needed to carry out an adaptation in our country that includes an evaluation of the strengths of the three tools to decrease PIMs and improve prescription in the elderly.

Impact of Maturation and Vitrification Time of Human GV Oocytes on the Metaphase Plate Configuration.

The combination of in vitro maturation (IVM) techniques and oocyte vitrification (OV) could increase the number of useful oocytes in different types of patients. IVM and subsequent OV is the most widely used clinical strategy. Would the results improve if we reverse the order of the techniques? Here, we evaluated survival, in vitro maturation, time to extrude the first polar body (PB), and the metaphase plate configuration of human prophase I (GV) oocytes before or after their vitrification. Specific, 195 GV oocytes from 104 patients subjected to controlled ovarian stimulation cycles were included. We stablished three experimental groups: GV oocytes vitrified and IVM (Group GV-Vit), GV oocytes IVM and vitrified at MII stage (Group MII-Vit), and GV oocytes IVM (Group not-Vit). All of them were in vitro matured for a maximum of 48 h and fixed to study the metaphase plate by confocal microscopy. According to our results, the vitrification of immature oocytes and their subsequent maturation presented similar survival, maturation, and metaphase plate conformation rates, but a significantly higher percentage of normal spindle than the standard strategy. Additionally, the extension of IVM time to 48 h did not seem to negatively affect the oocyte metaphase plate configuration.

Hyphenation of proton transfer reaction mass spectrometry with thermal analysis for monitoring the thermal degradation of retinyl acetate.

RATIONALE: The processing of retinyl acetate, a vitamin and biomarker, at high temperatures causes significant decomposition of the compound and thus loss of its activity. The rate of mass loss can be conveniently studied by thermogravimetry (TG). However, this technique generally fails to reveal which compounds have evolved from the compound. In this work we propose a new hyphenation approach to continuously monitor the thermal decomposition of retinyl acetate and follow the evolution of specific volatile organic compounds (VOCs). METHODS: Thermal degradation of retinyl acetate was followed by TG coupled to a direct injection mass spectrometer based on proton transfer reaction mass spectrometry (PTR-MS) to follow continuously the thermal decomposition of retinyl acetate. The results were also compared with those obtained by a second evolved gas analysis system based on the coupling of TG with FTIR. RESULTS: The TG results showed two main mass losses, at 180°C and 350°C. When the PTR-MS instrument was connected to the outlet of the TG instrument, specific fragment ions (m/z 43, 61, 75, 85 and 97) showed characteristic evolution profiles. The first mass loss was mainly associated with the release of acetic acid (m/z 43 and 61), whereas the second mass loss was connected with the degradation of the molecule backbone (m/z 43, 61, 75, 85 and 97). These results were substantially correlated with those achieved by TG coupled with FTIR, although PTR-MS showed superior performance in terms of the qualitative identification of specific fragments and better sensitivity toward complex organic VOCs. CONCLUSIONS: The proposed TG-PTR-MS technique shows a great potential for following in real time the thermal degradation of ingredients such as retinyl acetate and identifying compounds evolved at specific temperatures.

Ultrastructural characteristics of human oocytes vitrified before and after in vitro maturation.

The development of an effective program that combines in vitro maturation (IVM) and cryopreservation for immature oocytes would represent a novel advance for in vitro fertilization (IVF), especially as a means to preserve the fertility of women in unique situations. The aim of this study was to analyze the ultrastructural characteristics of human oocytes, obtained after controlled ovarian stimulation, to determine whether IVM is best performed before or after vitrification. To this end, we analyzed the following features in a total of 22 MII oocytes: size, zona pellucida and perivitelline space, mitochondria number, M-SER (mitochondria-smooth endoplasmic reticulum) aggregates and M-V (mitochondria-vesicle) complexes, the number of cortical granules and microvilli, and the presence of vacuolization using transmission electron microscopy (TEM). Each oocyte presented a rounded shape, with an intact oolemma, and was surrounded by a continuous zona pellucida and perivitelline space. Statistical analysis comparing oocytes vitrified before or after IVM indicated that there were no significant differences between examined characteristics.

Improving pharmacotherapy outcomes in patients with hepatitis C virus infection treated with direct-acting antivirals: The GRUviC project.

BACKGROUND/OBJECTIVE: Pharmaceutical care is needed in hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAA). We describe the implementation of a comprehensive pharmaceutical care programme (CPCP) for HCV-infected patients treated with DAA in a tertiary-care hospital and provide data about health outcomes and costs. METHODS: Quasi-experimental study between 1 April 2015 and 30 June 2016. A group of hospital pharmacists collaborating on HCV infection implemented interventional measures for validation of drug prescriptions, detection of clinically relevant drug-drug interactions and adverse drug events (ADEs), and patient education. Quality, health and cost-effectiveness outcomes were evaluated. RESULTS: A total of 1070 patients were enrolled. Pharmacists made 327 interventions that led to the prevention of 299 (91.4%) medication errors, 16 of which were grade G-H (NCC MERP classification). The main reasons for the pharmacist's intervention were management of 143 drug-drug interactions. The overall sustained virologic response at week 12 posttreatment (SVR12) rate was 93.0% (95% CI 91.4-94.6). The SVR12 was higher than 90.0% in all populations, except in genotype 3 patients (86.0%, 95% CI 78.7-93.9), decompensated cirrhotic patients (81.1%, 95% CI 69.7-92.6) and transplant recipients (86.8%, 95% CI 76.7-96.9). ADEs occurred in 85.5% of the study patients, but only 1.0% (11 patients) experienced an ADE that led to premature discontinuation. The total cost of treatment was €18 279 225 (€17 083 per patient). The most cost-effective treatment was selected in 93.1% of patients. CONCLUSIONS: The implementation of a CPCP developed by hospital pharmacists in patients treated with DAAs for HCV infection is an effective approach that improves patient safety and education. The active involvement of the pharmacist in improving adherence to local guidelines promoted the selection of the most cost-effective treatment in the majority of cases.

Risks in the implementation and use of smart pumps in a pediatric intensive care unit: application of the failure mode and effects analysis.

OBJECTIVES: The aim of this study was to identify risk points in the different stages of the smart infusion pump implementation process to prioritize improvement measures. METHODS: Failure modes and effects analysis (FMEA) in the pediatric intensive care unit (PICU) of a General and Teaching Hospital. A multidisciplinary team was comprised of two intensive care pediatricians, two clinical pharmacists and the PICU nurse manager. FMEA was carried out before implementing CareFusion infusion smart pumps and eighteen months after to identify risk points during three different stages of the implementation process: creating a drug library; using the technology during clinical practice and analyzing the data stored using Guardrails® CQI v4.1 Event Reporter software. RESULTS: Several actions for improvement were taken. These included carrying out periodical reviews of the drug library, developing support documents, and including a training profile in the system so that alarms set off by real programming errors could be distinguished from those caused by incorrect use of the system. Eighteen months after the implementation, these measures had helped to reduce the likelihood of each risk point occurring and increase the likelihood of their detection. CONCLUSIONS: Carrying out an FMEA made it possible to detect risk points in the use of smart pumps, take action to improve the tool, and adapt it to the PICU. Providing user training and support tools and continuously monitoring results helped to improve the usefulness of the drug library, increased users' compliance with the drug library, and decreased the number of unnecessary alarms.

Effects of a Pharmacist-Designed Clinical Decision Support System on Antimicrobial Stewardship.

BACKGROUND: Clinical decision support systems (CDSSs) are computer applications, which can be applied to give guidance to practitioners in antimicrobial stewardship (AS) activities; however, further information is needed for their optimal use. OBJECTIVES: Our objective was to analyze the implementation of a CDSS program in a second-level hospital, describing alerts, recommendations, and the effects on consumption and clinical outcomes. METHODS: In October 2020, a pharmacist-driven CDSS designed for AS was implemented in a second-level hospital. The program provides a list of alerts related to antimicrobial treatment and microbiology, which were automatized for revision by the AS professionals. To analyze the implementation of the CDSS, a pre-post-intervention, retrospective study was designed. AS-triggered alerts and recommendations (total number and rate of acceptance) were compiled. The effect of the CDSS was measured using antimicrobial consumption, duration of antimicrobial treatments, in-hospital mortality, and length of stay (LOS) for patients admitted for infectious causes. RESULTS: The AS team revised a total of 7,543 alerts and 772 patients had at least one recommendation, with an acceptance rate of 79.3%. Antimicrobial consumption decreased from 691.1 to 656.8 defined daily doses (DDD)/1,000 beds-month (p = 0.04) and the duration of antimicrobial treatment from 3.6 to 3.3 days (p < 0.01). In-hospital mortality decreased from 6.6 to 6.2% (p = 0.46) and mean LOS from 7.2 to 6.2 days (p < 0.01). CONCLUSION: The implementation of a CDSS resulted in a significant reduction of antimicrobial DDD, duration of antimicrobial treatments, and hospital LOS. There was no significant difference in mortality.

Haemorrhagic complications in patients with renal insufficiency during treatment or prophylaxis with dalteparin.

OBJECTIVES: Low-molecular-weight heparins are widely used in clinical practice for the treatment or prophylaxis of venous thromboembolism (VTE). As these drugs are eliminated mainly by renal means, any renal function impairment may lead to higher plasma concentrations and increase the risk of bleeding. This study aims to evaluate whether in clinical practice there is an increase in the occurrence of bleeding in patients with renal insufficiency (RI) during treatment or prophylaxis with dalteparin, and to analyse the risk factors potentially influencing the appearance of such bleeding events. METHODS: Patients were sampled from the Universitary Severo Ochoa Hospital, Leganés, Spain. This was a retrospective cohort study with a 1 year inclusion period, conducted at a Spanish university hospital with 400 beds, on patients undergoing treatment or prophylaxis for VTE with dalteparin for a minimum of 3 days. The main outcome measure was the number of patients who had bleeding events, independently of their severity, during dalteparin administration in patients with RI. RESULTS: 367 patients were included in the study. Bleeding occurred in 17.9% of patients in the group with RI and in 7.3% of patients with normal renal function (NRF). Most haemorrhages in both cohorts were grade 2 on the WHO scale (64.7% in the RI group and 69.2% in the NRF group). Logistic regression analysis allowed the presence of RI (MDRD-4 (Modification of Diet in Renal Disease) <50 mL/min) to be identified as a risk factor. CONCLUSION: Patients with RI treated with dalteparin face a higher risk of bleeding than those with NRF, which seems to make it necessary to monitor and seek new dosage adjustments for these patients.Impact on practice statements: This study yields new data on dalteparin in RI, which has not been widely studied before.

Error Detection and Cost Savings With an Image-Based Workflow Management System Connected to a Computerized Prescription Order Entry Program for Antineoplastic Compounding.

OBJECTIVE: The aim of the study was to analyze both the prevalence of errors with the implementation of an image-based workflow management system during the antineoplastic compounding process, and the estimated costs associated with the negative clinical outcome if the errors had not been intercepted. METHODS: Three months after the implementation of Phocus Rx system at a hospital pharmacy department, the identification, classification (type, preparation stage, and cause), and potential severity degree (from negligible to catastrophic) of the errors intercepted were determined. The probability of an error causing an adverse event if it had reached the patient (from nil [0] to high [0.6]) and its consequences was estimated by a team of clinical pharmacists and physicians. Cost-effectiveness analysis from the hospital's perspective was performed. RESULTS: Overall, 9872 antineoplastic medications were prepared using Phocus Rx. The total compounding error rate was 0.8% (n = 78, 56 [69.2%] were related to incorrect dose, 20 [28.2%] to incorrect drug preparation or conditioning technique, and 2 [2.6%] were wrong drugs). Approximately 70% of the detected errors were classified as undetectable via the previous verification practice, with 11.55% judged to be potentially severe (n = 9) and 51.3% moderate (n = 29). Likelihood of occurrence of an adverse event was medium (0.4) to high (0.6) for 37.2% of the errors. Estimated cost ratio and return on investment were €4.21 and 321%, respectively. CONCLUSIONS: The implementation of Phocus Rx prevented antineoplastic preparation errors that would have reached the patient otherwise. In addition, acquisition of this technology was estimated to be cost-effective.

Assessment of exposure-response relationship for bevacizumab in patients with metastatic colorectal cancer.

Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI: 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI: 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.

Fabrication and morphological characterization of biopolymer particles formed by electrostatic complexation of heat treated lactoferrin and anionic polysaccharides.

Biopolymer particles fabricated from proteins and/or polysaccharides can be used to encapsulate functional components or to modify various functional properties of materials. In this study, sub-micrometer biopolymer particles were fabricated by electrostatic complexation of heat-denatured protein (lactoferrin, LF) particles with anionic polysaccharides (alginate, carrageenan, or pectin). The aim of the study was to exploit macromolecular electrostatic interactions to form sub-micrometer sized particles and study their stability and morphological characteristics. Initially, protein particles were formed by heat treatment (91 degrees C, 20 min) of a lactoferrin solution (0.2% LF, pH 7), which led to a suspension of protein particles with mean diameter of 200-400 nm and isoelectric point of pI approximately 8.5. Biopolymer particles were then formed by mixing the protein particles with anionic polysaccharides at pH 8 and then lowering the pH to promote electrostatic deposition of polysaccharides onto the protein particle surfaces. The influence of pH (2-11) and ionic strength (0-200 mM NaCl) on the properties and stability of the complexes was studied using turbidity, dynamic light scattering, and electrophoresis measurements. Relatively stable particles could be formed from pH 5 to 8, but appreciable aggregation occurred at lower pH which was attributed to charge neutralization and bridging effects. LF-pectin complexes were relatively stable to salt addition, but LF-carrageenan and LF-alginate complexes exhibited aggregation at higher salt concentrations. These results have important implications for the application of lactoferrin-polysaccharide complexes as functional components in commercial products, such as pharmaceuticals, personal care products, and foods.

Novel mobile application for direct communication between pharmacists and patients treated with oral antineoplastic agents.

PURPOSE: Initial experience with use of a smartphone application to enhance communication with and home monitoring of hematology/oncology patients under treatment with oral antineoplastic agents (OAAs) is described. SUMMARY: Broad use of OAAs is changing the landscape of hematology/oncology patient care, with this form of therapy giving patients greater autonomy but also raising concerns about correct OAA administration and management of adverse effects (AEs) or interactions. Information and communication technologies, specifically mobile health technologies, are ideal tools in this new environment. A multidisciplinary team at a large hospital in Spain developed a smartphone application for patients receiving OAA therapy that consists of 5 modules or functionalities: (1) a treatment agenda, or electronic journal of patient activity, including medication use; (2) a treatment record; (3) continuous recording of vital signs (blood pressure and temperature), health-related quality of life, and AEs, with management of AEs based on an algorithm that displays different recommendations according to AE severity; (4) 2-way messaging capability; and (5) information and links to websites of interest. From June through November 2017, 37 patients downloaded and used the application. About two-thirds (68%) of the patients sent a total of 182 messages to the pharmacist on duty; 58% of the patients registered at least 1 AE. The mean time of registration of the first AE after initiation of OAA therapy was 8 days. As a result of patient use of the application, 2 emergency room visits were avoided and 3 patients were referred to a general practitioner. CONCLUSION: The application has allowed real-time monitoring of patients treated with OAAs. This new patient-pharmacist communication channel has facilitated the early detection of AEs, contributing to the safety of treatment and patient satisfaction with healthcare.

Social and health care needs in patients with hereditary fructose intolerance in Spain. / Necesidades sociosanitarias en pacientes con intolerancia hereditaria a la fructosa en España.

INTRODUCTION: Hereditary fructose intolerance is a metabolic disease due to an aldolase B deficiency. Our objective was to ascertain the social and health care needs of those with this deficiency. MATERIAL AND METHODS: A prospective, observational study was performed. A survey of social and health care needs was conducted to hereditary fructose intolerance patients living in Spain. RESULTS: Most patients had been diagnosed, mainly by genetic analysis in children and based on fructose overload in adults. Population surveyed had no sequelae (72.34%) or disability (64%), and 83.33% of children and 52.38% of adults were taking drugs (p <.05) (2.06 drugs on average). Most patients had attended medical visits in the past two years, mainly in metabolic disease units (42.5%) and/or nutrition units (42.5%), but less than a half attended reference centers (mostly children [p <0.05]). Although 48% were satisfied with health care, they felt discriminated in recreational activities, school, health and/or daily activities. The most reliable sources of information were the specialized care physician (69.39%) and patients' association (59.18%). Fifty-five percent reported no problem in any quality of life dimension, although some had problems in daily activities, pain, and anxiety. CONCLUSIONS: Although hereditary fructose intolerance is less disabling than other rare diseases, it is important to know the needs of those who suffer from it. Although time to diagnosis has shortened, the poorer health care and satisfaction with it perceived in adults makes it necessary to emphasize the needs of this population, and the critical need of training and information of health care professionals.

Risks and medication errors analysis to evaluate the impact of a chemotherapy compounding workflow management system on cancer patients' safety.

A failure modes, effects and criticality analysis was supported by an observational medication error rate study to analyze the impact of Phocus Rx®, a new image-based workflow software system, on chemotherapy compounding error rates. Residual risks that should be a target for additional action were identified and prioritized and pharmacy staff satisfaction with the new system was evaluated. In total, 16 potential failure modes were recognized in the pre-implementation phase and 21 after Phocus Rx® implementation. The total reduction of the criticality index was 67 percent, with a reduction of 46 percent in material preparation, 76 percent in drug production and 48 percent in quality control subprocesses. The relative risk reduction of compounding error rate was 63 percent after the implementation of Phocus Rx®, from 0.045 to 0.017 percent. The high-priority recommendations defined were identification of the product with batch and expiration date from scanned bidimensional barcodes on drug vials and process improvements in image-based quality control. Overall satisfaction index was 8.30 (SD 1.06) for technicians and 8.56 (SD 1.42) for pharmacists (p = 0.655). The introduction of a new workflow management software system was an effective approach to increasing safety in the compounding procedures in the pharmacy department, according to the failure modes, effects and criticality analysis method.

Effect of a Mobile App for the Pharmacotherapeutic Follow-Up of Patients With Cancer on Their Health Outcomes: Quasi-Experimental Study.

BACKGROUND: Oral antineoplastic agents (OAAs) have revolutionized cancer management. However, they have been reported with adverse side effects and drug-drug interactions. Moreover, patient adherence to OAA treatment is critical. Mobile apps can enable remote and real-time pharmacotherapeutic monitoring of patients, while also promoting patient autonomy in their health care. OBJECTIVE: The primary objective was to analyze the effect of using a mobile app for the follow-up of patients with oncohematological malignancies undergoing treatment with OAAs on their health outcomes. The secondary objectives were to analyze the role of the app in communication with health care professionals and patient satisfaction with the app. METHODS: We performed a comparative, quasi-experimental study based on a prepost intervention with 101 patients (control group, n=51, traditional pharmacotherapeutic follow-up vs intervention group, n=50, follow-up through e-OncoSalud, a custom-designed app that promotes follow-up at home and the safety of patients receiving OAAs). The effect of this app on drug safety, adherence to treatment, and quality of life was evaluated. RESULTS: With regard to drug safety, 73% (37/51) of the patients in the control group and 70% (35/50) of the patients in the intervention group (P=.01) presented with drug-related problems. The probability of detecting an insufficiently treated health problem in the intervention group was significantly higher than that in the control group (P=.04). The proportion of patients who presented with side effects in the intervention group was significantly lower than that in the control group (P>.99). In the control group, 49% (25/51) of the patients consumed some health resources during the first 6 months of treatment compared with 36% (18/50) of the patients in the intervention group (P=.76). Adherence to treatment was 97.6% (SD 7.9) in the intervention group, which was significantly higher than that in the control group (92.9% [SD 10.0]; P=.02). The EuroQol-5D in the intervention group yielded a mean (SD) index of 0.875 (0.156), which was significantly higher than that in the control group (0.741 [0.177]; P<.001). Approximately 60% (29/50) of the patients used the messaging module to communicate with pharmacists. The most frequent types of messages were acknowledgments (77/283, 27.2%), doubts about contraindications and interactions with OAAs (70/283, 24.7%), and consultations for adverse reactions to treatment (39/283, 13.8%). The satisfaction with the app survey conducted in the intervention group yielded an overall mean (SD) score of 9.1 (0.4) out of 10. CONCLUSIONS: Use of e-OncoSalud for the real-time follow-up of patients receiving OAAs facilitated the optimization of some health outcomes. The intervention group had significantly higher health-related quality of life and adherence to treatment than the control group. Further, the probability of the intervention group presenting with side effects was significantly lower than that of the control group.

Influence of particle size and intestinal conditions on in vitro lipid and protein digestibility of walnuts and peanuts.

A static in vitro model was used to assess walnuts and peanuts macronutrient digestion of with two different particle size. Nuts were digested under different intestinal conditions of pH (6 or 7), bile concentration (1-10 mM) and pancreatic concentration (1000 to 4000 LU/g fat) the matrix degradation index (MDI), proteolysis and lipolysis were analyzed. Results showed that nuts particle size affects proteolysis and MDI the most; intestinal pH was more relevant in free fatty acids release. Lipolysis extent was lower under suboptimal intestinal conditions of pH 6 and bile salts 1 mM, and in peanuts it was lower than walnuts (567, 585, 134 and 398 mg FFA/g fat in large and small walnuts, and large and small peanuts, respectively). The higher the pancreatic concentration the higher the proteolysis extent in walnuts; in peanuts, protein digestibility was limited even at high pancreatic concentration at pH 6 and bile concentration 1 mM.

A first approach for an evidence-based in vitro digestion method to adjust pancreatic enzyme replacement therapy in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis have to take enzymatic supplements to allow for food digestion. However, an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy (PERT) is inexistent, and lipid content of meals is used as a rough criterion. OBJECTIVE: In this study, an in vitro digestion model was set up to determine the theoretical optimal dose (TOD) of enzymatic supplement for a selection of foods, which is the dose that allows for maximum lipolysis extent. METHODS: A static in vitro digestion model was applied to simulate digestion of eight foods covering a wide range of lipid contents. First, the dose of the enzymatic supplement was fixed at 2000 lipase units per gram of fat (LU/g fat) using intestinal pH and bile salt concentration as variables. Second, intestinal pH and bile salt concentrations were fixed and the variable was the dose of the enzymatic supplement. Lipolysis extent was determined by measuring the free fatty acids released from initial triglycerides content of foods after digestion. Results in terms of percentage of lipolysis extent were fitted into a linear-mixed segmented model and the deducted equations were used to predict the TOD to reach 90% of lipolysis in every food. In addition, the effect of intestinal pH and bile salt concentration were investigated. RESULTS: The predictive equations obtained for the assessed foods showed that lipolysis was not only dependent on the dose of the enzyme supplement or the lipid content. Moreover, intestinal pH and bile salt concentration had significant effects on lipolysis. Therefore an evidence-based model can be developed taking into account these variables. CONCLUSIONS: Depending on food characteristics, a specific TOD should be assigned to achieve an optimal digestion extent. This work represents a first step towards an evidence-based method for PERT dosing, which will be applied in an in vivo setting to validate its efficacy.