Systematic review of pragmatic randomised control trials assessing the effectiveness of professional pharmacy services in community pharmacies.

BACKGROUND: Implementation of Professional Pharmacy Services (PPSs) requires a demonstration of the service's impact (efficacy) and its effectiveness. Several systematic reviews and randomised controlled trials (RCT) have shown the efficacy of PPSs in patient's outcomes in community pharmacy. There is, however, a need to determine the level of evidence on the effectiveness of PPSs in daily practice by means of pragmatic trials. To identify and analyse pragmatic RCTs that measure the effectiveness of PPSs in clinical, economic and humanistic outcomes in the community pharmacy setting. METHODS: A systematic search was undertaken in MEDLINE, EMBASE, the Cochrane Library and SCIELO. The search was performed on January 31, 2020. Papers were assessed against the following inclusion criteria (1) The intervention could be defined as a PPS; (2) Undertaken in a community pharmacy setting; (3) Was an original paper; (4) Reported quantitative measures of at least one health outcome indicator (ECHO model); (5) The design was considered as a pragmatic RCT, that is, it fulfilled 3 predefined attributes. External validity was analyzed with PRECIS- 2 tool. RESULTS: The search strategy retrieved 1,587 papers. A total of 12 pragmatic RCTs assessing 5 different types of PPSs were included. Nine out of the 12 papers showed positive statistically significant differences in one or more of the primary outcomes (clinical, economic or humanistic) that could be associated with the following PPS: Smoking cessation, Dispensing/Adherence service, Independent prescribing and MTM. No paper reported on cost-effectiveness outcomes. CONCLUSIONS: There is limited available evidence on the effectiveness of community-based PPS. Pragmatic RCTs to evaluate clinical, humanistic and economic outcomes of PPS are needed.

Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues.

This paper presents a novel methodology to in-vivo estimate the elastic constants of a constitutive model proposed to characterize the mechanical behavior of the breast tissues. An iterative search algorithm based on genetic heuristics was constructed to in-vivo estimate these parameters using only medical images, thus avoiding invasive measurements of the mechanical response of the breast tissues. For the first time, a combination of overlap and distance coefficients were used for the evaluation of the similarity between a deformed MRI of the breast and a simulation of that deformation. The methodology was validated using breast software phantoms for virtual clinical trials, compressed to mimic MRI-guided biopsies. The biomechanical model chosen to characterize the breast tissues was an anisotropic neo-Hookean hyperelastic model. Results from this analysis showed that the algorithm is able to find the elastic constants of the constitutive equations of the proposed model with a mean relative error of about 10%. Furthermore, the overlap between the reference deformation and the simulated deformation was of around 95% showing the good performance of the proposed methodology. This methodology can be easily extended to characterize the real biomechanical behavior of the breast tissues, which means a great novelty in the field of the simulation of the breast behavior for applications such as surgical planing, surgical guidance or cancer diagnosis. This reveals the impact and relevance of the presented work.

Randomized clinical trial on the usefulness of 3D printing in intra-articular fractures of the distal radius. / Ensayo clínico aleatorizado sobre la utilidad de la impresión 3D en las fracturas intraarticulares de radio distal.

OBJECTIVES: We evaluated the utility of 3D printing technology for preoperative planning in the treatment of intra-articular fractures of the distal radius in relation to the improvement of surgical technique, radiological and clinical results. MATERIAL AND METHODS: A total of 30 patients with 2B and C fractures of the AO classification were operated on by a single surgeon with a volar plate, randomly divided into two groups, 15 of them with conventional planning (Rx and CT) and 15 adding a 3D model of the fracture and the previous simulation of the intervention. Simulation time, surgical time in minutes, radioscopy time in minutes, loss of material expressed in lost screws were recorded. Clinical evaluation based PRWE questionnaire and full radiographic analysis was done for all patients with a mean follow-up of 6 months by an independent, blinded observed. RESULTS: No statistically significant differences were observed in the PRWE questionnaire (p=0.22), nor were we observed differences in the radiological values, except in relation to the articular step (p=0.028), which represents statistical significance, but in both groups the median was of 0.0 (0.0-0.0). We also did not see statistically significant differences in surgical times (p=0.745), radioscopy (p=0.819) or in the loss of synthesis material (p=0.779). CONCLUSIONS: 3D printing has not improved the parameters studied in relation to routinely operated patients.

A study about coefficients to estimate the error in biomechanical models used to virtually simulate the organ behaviors.

In this paper, a set of coefficients commonly used in Medical Image to estimate the committed error comparing two images is presented, which, combined together, allow to determine the similarity between volumes. Furthermore, an analysis of the behavior of these coefficients is performed to determine those coefficients that better discriminate the fit error, proving that these are Jaccard coefficient and a modification of Hausdorff coefficient. In addition, the combination of both coefficients is applied to compare two given biomechanical models of the lamb liver.

Pneumoperitoneum technique simulation in laparoscopic surgery on lamb liver samples and 3D reconstruction.

In this paper, a procedure to experimentally simulate the behavior of the liver when the pneumoperitoneum technique is applied in laparoscopic surgery is presented, as well as methodology to make the comparison of each sample before and after insufflating the gas. This comparison is carried out using the 3D reconstruction of the volume from the CT images when either pneumoperitoneum is applied and when it is not. This methodology has showed that there are perceptible changes of volume when the pneumoperitoneum is applied.

Role of CYP450 in pharmacokinetics and pharmacogenetics of antihypertensive drugs.

INTRODUCTION: Antihypertensive drugs are principally metabolised by enzymes of the P450 (CYP450) cytochrome family. Response to hypertensive treatment whose genetic basis is beginning to be known presents inter-individual differences among patients. OBJECTIVE: The aim of this review is to document the role of cytochrome enzymes P450 in the metabolising process of antihypertensive drugs, and to identify the most relevant polymorphisms in genes that code for these enzymes in order to facilitate future studies in hypertension pharmacogenetics. METHODS: A keyword search was performed in the following literature databases: Pubmed, Rxlist and Medscape. Genetic polymorphism public databases were also consulted (PharmGKB, NCBI and the CYP450 allele nomenclature committee web page. RESULTS: Enzymes CYP2D6, CYP2C9, CYP2D19 and CYP3A4 participate in the metabolising process of most antihypertensive drugs. Considering the allelic frequency in the population and the variability in the clinical response associated with genetic polymorphism, we find the study of the following alleles CYP2D6 *2, *4, deletion and duplication; CYP2C9*2 and *3, CYP2C19 *2 and CYP3A4*1B to be of crucial importance. CONCLUSIONS: The study of polymorphisms in P450 cytochrome genes may contribute to an individualised therapy in the treatment against hypertension.

Hospitalization budget impact during the COVID-19 pandemic in Spain.

OBJECTIVES: The aim was to determine the direct impact of the COVID-19 pandemic on Spain's health budget. METHODS: Budget impact analyses based on retrospective data from patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) admitted to a Spanish hospital between February 26 and May 21, 2020. Direct medical costs from the perspective of the hospital were calculated. We analyzed diagnostic tests, drugs, medical and nursing care, and isolation ward and ICU stays for three cohorts: patients seen in the emergency room only, hospitalized patients who tested positive for SARS-CoV-2, and patients who tested negative. RESULTS: The impact on the hospital's budget for the 3 months was calculated at €15,633,180, 97.4% of which was related to health care and hospitalization. ICU stays accounted for 5.3% of the total costs. The mean cost per patient was €10,744. The main costs were staffing costs (10,131 to 11,357 €/patient for physicians and 10,274 to 11,215 €/patient for nurses). Scenario analysis showed that the range of hospital expenditure was between €14,693,256 and €16,524,924. The median impact of the pandemic on the Spanish health budget in the sensitivity analysis using bootstrapped individual data was €9357 million (interquartile range [IQR], 9071 to 9689) for the conservative scenario (113,588 hospital admissions and 11,664 ICU admissions) and €10,385 million (IQR, 110,030 to 10,758) for the worst-case scenario (including suspected cases). CONCLUSION: The impact of COVID-19 on the Spanish public health budget (12.3% of total public health expenditure) is greater than multiple sclerosis, cancer and diabetes cost.

Collaborative health service planning: A stakeholder analysis with social network analysis to develop a community pharmacy service.

BACKGROUND: Stakeholder participation optimizes health planning, fostering the acceptability and integration of new health services. Collaborative approaches may help overcome existing challenges in the development, implementation and evaluation of community pharmacy services (CPSs). Stakeholder analyses lay the foundation for building collaboration in the integrated delivery of health care. OBJECTIVES: This stakeholder analysis was performed to organize a collaborative initiative to develop a CPS aimed at preventing cardiovascular diseases in Andalucía (Spain). It aimed to identify stakeholders, differentiate/categorize them, and analyze stakeholder relationships. METHOD: Stakeholders were identified using the snowballing technique. To differentiate/categorize stakeholders and analyze the relationships (i.e., collaboration) an online web-based questionnaire was sent to 186 stakeholders. Stakeholders were asked for: (1) their influence, interest and attitude toward the initiative; (2) stakes/interests; (3) capacity to contribute to the initiative; (4) desire for involvement; (5) concerns; (6) whom they considered a key stakeholder; and (7) the level of collaboration they had with other stakeholders. Data analysis combined descriptive qualitative content analysis, descriptive quantitative analysis and social network analysis. RESULTS: Of the 186 stakeholders approached, 96 (51.6%) participated. The identification process yielded 217 stakeholders (individuals, organizations or collectives), classified into 10 groups. Fifty-seven stakeholders were considered critical to the intended initiative. Most participant stakeholders supported the initiative and were willing to collaborate in the development of the CPS. Public health and science were the main driving interests. A collaboration network existed between the 96 stakeholders. CONCLUSION: This study revealed the magnitude of the social system surrounding the development of a CPS aimed at preventing cardiovascular disease. A large array of stakeholders was identified and analyzed, and a group of critical stakeholders selected. Stakeholder characteristics such as attitude toward the initiative, potential contribution, desire for involvement, and the existing collaboration network, provided complementary information that was helpful for planning the process and stakeholder engagement.

Stakeholder analysis in health innovation planning processes: A systematic scoping review.

Integrating health innovations into the health system is a complex endeavour that requires a well-designed planning process engaging key stakeholders. Stakeholder analyses lay the foundations to inform appropriate planning processes and undertake strategic actions. A systematic scoping review was performed to explore how stakeholder analyses are applied in health innovation planning processes and a guideline to report stakeholder analyses was developed. The literature search was conducted in PubMed, Scopus and DOAJ; grey literature was sought using Google. Articles reporting stakeholder analyses during the planning process of health policies, systems, products and technologies, and services and delivery methods were included. Fifty-one records were incorporated in the qualitative synthesis. Stakeholder analyses were conducted worldwide, used in all types of health innovations, applied in all phases of the planning process and conducted both prospectively and retrospectively. The steps followed to perform stakeholder analysis, the methods used, the stakeholder attributes analysed and how authors reported the analyses were heterogeneous. Forty-one studies reported the identification of stakeholders, 50 differentiated/categorised them and 25 analysed stakeholder relationships. Only some authors proposed future actions based on the results obtained in their stakeholder analysis. A list of Reporting Items for Stakeholder Analysis (i.e., the RISA tool) is proposed to contribute to the reporting guidelines to enhancing the quality and transparency of health research.

Application of the SCORE and Wilson-Grundy methods for the assessment of cardiovascular risk in community pharmacies.

BACKGROUND: The assessment and follow-up of patients with risk factors, or with cardiovascular disease (CVD), involves estimating and monitoring their CVD risk (CVDR). There are different opinions about the most appropriate method for this. OBJECTIVE: To compare the SCORE system and the Wilson-Grundy system (based on Framingham's study). METHODS: A descriptive, observational study over 15 days in six pharmacies, with patients aged between 25 and 74 years, and with a prescription for medications related to hypertension, dyslipidaemia, CVD prevention or type-2 diabetes. Results of patients' absolute CVDR were assessed and compared using the SCORE system and the Wilson-Grundy method, adapted for Spain. The Chi-square test was used to compare proportions, and the Student t-test was used to compare mean values, including odds ratios (OR) and 95% confidence intervals (95%CI). RESULT: A total of 257 patients [165 women, 92 men; mean (SD) age, 60.9 (10.8) years; percentage of previous medical history of hypertension (70.0%), dyslipidaemia (42.4%), type-2 diabetes (19.5%) and CVD (22.6%)] participated. With the CVDR assessed with SCORE, the distribution was as follows: low 35.8%, intermediate 21.0% and high 43.2%. The corresponding values using the Wilson-Grundy system was low 60.7%, intermediate 8.2% and high 31.1%. CONCLUSION: The cardiovascular risk of patients that attend community pharmacies with prescriptions for cardiovascular medications is significantly higher when assessed using the SCORE system than with the Wilson-Grundy method.

A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time.

This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 mm, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (<0.2 s).

Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial.

AIMS: The purpose of this study was to identify the effect of pentoxifylline on the urinary protein excretion profile in type 2 diabetic patients. METHODS: 40 type 2 nonhypertensive diabetic patients were randomly allocated to receive either pentoxifylline 400 mg t.i.d. or placebo daily for 16 weeks. Eligible subjects were those with urinary albumin excretion between 20 and 200 microg/min. Subjects receiving angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium antagonists, and diuretics as well as those with reduced renal function, pregnancy, urinary tract infection, and smoking were not included. A 6-month pretreatment stabilization phase aimed to reduce and stabilize fasting serum glucose levels was carried out. Urinary proteins were identified by electrophoresis, and immunodetection was identified by Western blot. Electrophoretic analysis was performed using molecular weight markers of 150, 132, 77, and 66 kDa to identify high-weight proteins, and 54, 41, 36, 27, 21, 14.3, and 12 kDa to identify low-weight proteins. RESULTS: At baseline, subjects in both groups who showed a glomerular tubular pattern did not differ in their urinary excretion profile. The urinary proteins identified were immunoglobulin G, ceruloplasmin, transferrin, and albumin (glomerular pattern) as well as alpha1-antitrypsin, alpha1-acid glycoprotein, collagenase inhibitor, alpha1-microglobulin, trypsin inhibitor, lysozyme, and beta2-microglobulin (tubular pattern). Subjects who received pentoxifylline had reduced urinary excretion of high- and low-molecular weight proteins. CONCLUSIONS: Urinary protein excretion in type 2 diabetic subjects shows a mixed, glomerular and tubular, pattern. Pentoxifylline reduces the excretion of both high and low molecular-weight urinary proteins.

[Nutritional assessment of a university population]. / Evaluación nutricional de una población universitaria.

In this work, we have planned to perform a nutritional assessment of a group of 50 students from the University of Granada, to which questionnaires have been administered relating to 24-hour remembrance of type and frequency of food consumption, for 30 days. In order to know macro- and micronutrients intake, the results have been analyzed with DietSource software. At the same time, anthropometrical measurements have been taken to verify their possible change during the study period. We have been able to observe a protein intake slightly higher than the recommended intake, similarly to what occurs with lipids. The studied group positively values menus with high content in meat, whereas deficiencies in fruit and vegetable intake are observed. In addition, there is a variation of anthropometrical measurements of these individuals during the study period. We also noticed a deficiency in some micronutrients such as iron, zinc, calcium, iodine, cupper, selenium, vitamin E, and folic acid in all the studied population. However, vitamin C and thiamine levels in both groups and riboflavin levels in women may be considered adequate. From these results, we may highlight a nutrition unbalance in this population group since we have observed some deficiencies in the intake of important micronutrients for health maintenance and promotion, and macronutrient consumption that diverges from the established recommendations.

[Comparative clinical study of 2 surgical techniques for trapeziometacarpal osteoarthritis]. / Estudio clínico comparativo de 2 técnicas quirúrgicas de rizartrosis del pulgar.

OBJECTIVE: In trapeziometacarpal osteoarthritis (or rhizarthrosis), there is great controversy over the surgical technique to choose: simple trapeziectomy, resection-interposition arthroplasty, interposition arthroplasty suspension-or arthroplasty with implant or prosthesis. These latter 2 are the most used without consensus in the literature on the technique to choose and without sufficient comparative studies. The objective is to compare the 2 techniques most used today: suspension-interposition arthroplasty and arthroplasty with prosthesis. MATERIAL AND METHOD: A prospective study was conducted on 15 patients diagnosed with grade 2-3 rhizarthrosis treated with interposition arthroplasty-suspension (group 1) and 15 with prosthesis (group 2) showing clinical outcomes, advantages and disadvantages of each. The study variables were the visual analogue scale (VAS), the DASH questionnaire, the grip strength, the strength of end to end and end-lateral clamp, the joint balance adduction-abduction and preemption-retropositioning, and the opposition. The 2 groups are from 2 different hospitals operated on by a hand surgeon from the Hand Unit. The follow-up time for all patients included in the study was 12 months. RESULTS: The VAS, DASH and grip strength at 12 months did not show significant differences. As regards the strength of end to end and end-lateral clamp, group 2 showed the highest values in all follow-up periods with statistically significant differences. CONCLUSIONS: Patient selection and surgical experience is essential, given the satisfactory results of both techniques. Arthroplasty prosthesis is reserved for grades 2 and 3, middle-aged patients, good trapezium architecture, and experienced surgeons.

Patient-specific simulation of the intrastromal ring segment implantation in corneas with keratoconus.

PURPOSE: The purpose of this study was the simulation of the implantation of intrastromal corneal-ring segments for patients with keratoconus. The aim of the study was the prediction of the corneal curvature recovery after this intervention. METHODS: Seven patients with keratoconus diagnosed and treated by implantation of intrastromal corneal-ring segments were enrolled in the study. The 3D geometry of the cornea of each patient was obtained from its specific topography and a hyperelastic model was assumed to characterize its mechanical behavior. To simulate the intervention, the intrastromal corneal-ring segments were modeled and placed at the same location at which they were placed in the surgery. The finite element method was then used to obtain a simulation of the deformation of the cornea after the ring segment insertion. Finally, the predicted curvature was compared with the real curvature after the intervention. RESULTS: The simulation of the ring segment insertion was validated comparing the curvature change with the data after the surgery. Results showed a flattening of the cornea which was in consonance with the real improvement of the corneal curvature. The mean difference obtained was of 0.74 mm using properties of healthy corneas. CONCLUSIONS: For the first time, a patient-specific model of the cornea has been used to predict the outcomes of the surgery after the intrastromal corneal-ring segments implantation in real patients.

A new methodology for the in vivo estimation of the elastic constants that characterize the patient-specific biomechanical behavior of the human cornea.

This work presents a methodology for the in vivo characterization of the complete biomechanical behavior of the human cornea of each patient. Specifically, the elastic constants of a hyperelastic, second-order Ogden model were estimated for 24 corneas corresponding to 12 patients. The finite element method was applied to simulate the deformation of human corneas due to non-contact tonometry, and an iterative search controlled by a genetic heuristic was used to estimate the elastic parameters that most closely approximates the simulated deformation to the real one. The results from a synthetic experiment showed that these parameters can be estimated with an error of about 5%. The results of 24 in vivo corneas showed an overlap of about 90% between simulation and real deformed cornea and a modified Hausdorff distance of 25 µm, which indicates the great accuracy of the proposed methodology.

[Treatment of proximal radioulnar synostosis using a posterior interosseous antegrade flow pedicled flap]. / Tratamiento de la sinostosis radiocubital proximal mediante la interposición de colgajo interóseo posterior de flujo anterógrado.

The aim of this study is to determine the different therapeutic options described for the treatment of radioulnar synostosis, and report our experience with posterior interosseous antegrade flow pedicled flap with technical amendments. Two patients, who were treated with the designed flap, and with more than one year of follow-up, were reviewed. The technical innovations, end result and complications are described. In the two cases described, there was no recurrence of synostosis, which is the most frequent complication described in this condition, and no postoperative complications were observed. In the literature, many filler materials, from artificial to biological free or vascularized, have been used the radioulnar space after excision of synostosis. The technique that provides the best results is the interposition of muscle or vascularized adipofascial flaps. The Interosseous posterior antegrade flow pedicled flap is reliable, with a low morbidity, and is an effective alternative for the treatment of proximal radioulnar synostosis.

Analysis of several biomechanical models for the simulation of lamb liver behaviour using similarity coefficients from medical image.

In this study, six biomechanical models for simulating lamb liver behaviour are presented. They are validated using similarity coefficients from Medical Image on reconstructed volumes from computerised tomography images. In particular, the Jaccard and Hausdorff coefficients are used. Loads of 20 and 40 g are applied to the livers and their deformation is simulated by means of the finite element method. The models used are a linear elastic model, a neo-Hookean model, a Mooney-Rivlin model, an Ogden model, a linear viscoelastic model and a viscohyperelastic model. The model that provided a behaviour that is closest to reality was the viscohyperelastic model, where the hyperelastic part was modelled with an Ogden model.