The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in Barcelona (Spain): A long-term, clinical, epidemiologic and economic study.

BACKGROUND: Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. METHODS: From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. RESULTS: A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. CONCLUSIONS: Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods.

Comparing the first and second waves of COVID-19 in a tertiary university hospital in Barcelona.

BACKGROUND: Hospitals have constituted the limiting resource of the healthcare systems for the management of the COVID-19 pandemic. As the pandemic progressed, knowledge of the disease improved, and healthcare systems were expected to be more adapted to provide a more efficient response. The objective of this research was to compare the flow of COVID-19 patients in emergency rooms and hospital wards, between the pandemic's first and second waves at the University Hospital of Vall d'Hebron (Barcelona, Spain), and to compare the profiles, severity and mortality of COVID-19 patients between the two waves. METHODS: A retrospective observational analysis of COVID-19 patients attending the hospital from February 24 to April 26, 2020 (first wave) and from July 24, 2020, to May 18, 2021 (second wave) was carried out. We analysed the data of the electronic medical records on patient demographics, comorbidity, severity, and mortality. RESULTS: The daily number of COVID-19 patients entering the emergency rooms (ER) dropped by 65% during the second wave compared to the first wave. During the second wave, patients entering the ER were significantly younger (61 against 63 years old p<0.001) and less severely affected (39% against 48% with a triage level of resuscitation or emergency; p<0.001). ER mortality declined during the second wave (1% against 2%; p<0.000). The daily number of hospitalised COVID-19 patients dropped by 75% during the second wave. Those hospitalised during the second wave were more severely affected (20% against 10%; p<0.001) and were referred to the intensive care unit (ICU) more frequently (21% against 15%; p<0.001). Inpatient mortality showed no significant difference between the two waves. CONCLUSIONS: Changes in the flow, severity and mortality of COVID-19 patients entering this tertiary hospital during the two waves may reflect a better adaptation of the health care system and the improvement of knowledge on the disease.

Withdrawal of hospital outpatient treatments in severe diseases due to unacceptable toxicity: A retrospective study from the register of patients and treatments.

AIM: To retrospectively analyse hospital outpatient treatment (HOT) withdrawal due to unacceptable toxicity at our hospital. Information regarding unacceptable toxicity leading to treatment withdrawal was recorded. METHODS: HOT interruptions because of unacceptable toxicity were identified from the Register of Patients and Treatments (RPT) (January 2014 to December 2017). Information regarding the demographic and clinical characteristics of patients, adverse drug reactions (ADRs) and drug treatments was retrieved from electronic health records. Causality and previous knowledge of ADRs were assessed according to the Spanish Pharmacovigilance System algorithm. Information regarding HOT risk management plans (RMPs) and their classification as inverted black triangle medicines was obtained from the European Medicines Agency (EMA). RESULTS: HOTs were withdrawn due to unacceptable toxicity in 136 (1.5%) registries corresponding to 135 (1.7%) patients. Fifty-one different HOTs (38.6% of those registered) were involved in 240 ADR/HOT pairs: 24 (47%) were additional monitoring medicines and 37 (72.5%) were EMA RMPs. The most frequent medicines involved in ADRs were lenalidomide (30, 12.5%) (mainly neutropenia, thrombocytopenia and bicytopenia), bevacizumab (19, 7.9%) (mainly venous and pulmonary thromboembolism) and sunitinib (13, 5.4%) (mainly thromboembolic events, diarrhoea and worsening of chronic renal failure). Cytopenia (40, 17.3%), diarrhoea (15, 6.5%), asthenia (9, 3.9%) and neuropathy (6, 2.6%) were the most frequent ADRs. All ADRs were severe, 10 (6 patients) had been poorly described or were unknown and only 9 (5 patients) had been reported by spontaneous notification. CONCLUSIONS: Valuable information regarding severe and unknown ADRs was obtained from the RPT. Such registers are useful tools to complement spontaneous ADR notifications.

Determinantes sociales y clínicos del uso de servicios sanitarios en mujeres con cáncer de mama (Cohorte DAMA) / Social and clinical determinants of the use of health services in women with breast cancer (Cohort DAMA)

Objetivo: Describir y analizar los factores asociados al uso de los servicios sanitarios (urgencias, ingresos y atención primaria) en mujeres supervivientes de cáncer de mama diagnosticadas o tratadas en cuatro hospitales universitarios de Barcelona entre 2003 y 2013, en el marco del proyecto Cohorte DAMA. Método: Diseño descriptivo anidado en una cohorte mixta (Cohorte Dama). Se obtuvo la información sociodemográfica y del uso de servicios sanitarios a través de cuestionario, y del tumor a partir de la historia clínica. Se efectuaron modelos de regresión logística, calculando la odds ratio del uso de servicios sanitarios (urgencias, ingresos hospitalarios y atención primaria) cruda y ajustada (ORa) por método diagnóstico, características del tumor y de la mujer, y sus intervalos de confianza del 95%. Resultados: La presencia de enfermedades crónicas se asoció a mayor uso de los tres niveles asistenciales (ORa: 3,53 urgencias, 1,67 ingresos, 3,89 atención primaria) y a complicaciones derivadas del tratamiento (ORa: 1,35 urgencias, 1,43 atención primaria). Un nivel económico desfavorecido incrementó el riesgo de uso de urgencias y de atención primaria, pero no el de los ingresos hospitalarios. Un estadio tumoral avanzado se asoció a un mayor riesgo de ingreso. Por edad, las menores de 50 años presentaron más riesgo de uso de urgencias e ingresos. Conclusiones: Los factores asociados al uso de servicios de salud difieren según el nivel asistencial. La presencia de trastornos crónicos, la menor edad y la clase social desfavorecida incrementan el riesgo del uso de servicios más que el estadio tumoral y las complicaciones derivadas del tratamiento. El método diagnóstico, el tiempo de supervivencia y el uso de terapias no convencionales no influyeron en ello

Objective: To describe and analyse the factors associated with the use of health services (emergency departments, admissions and primary care) in women survivors of breast cancer diagnosed or treated in four university hospitals of Barcelona (Spain) between 2003 and 2013, within the framework of the Cohort DAMA project. Method: Descriptive design nested in a mixed cohort (Cohort Dama). We obtained sociodemographic information and information on the use of health services through a questionnaire, and on the tumour from the clinical history. Logistic regression models were performed, calculating the odds ratio of the use of health services (emergency departments, hospital admissions and primary care) raw and adjusted (aOR) by diagnostic method, the characteristics of the tumour and of the women and their 95% confidence intervals. Results: The presence of chronic diseases was associated with greater use of the three levels of care. A disadvantaged economic level increases the risk of use of emergency departments and primary care but not of hospital admissions, while a higher tumour stage is associated with a greater risk of admission. By age, those under 50 had a higher risk of using emergency departments and admissions. Conclusions: The factors associated with the use of health services differ according to the level of care (aOR: 3.53 emergency departments, 1.67 admissions, 3.89 primary care) and treatment-derived complications (aOR: 1.35 emergency departments, 1.43 primary care). The presence of chronic disorders, younger age, disadvantaged social class, increases the risk of using services more than the tumour stage and treatment-derived complications. Neither the diagnostic method nor the survival time, nor the use of non-conventional therapies influence this

Doctors' opinions on clinical coordination between primary and secondary care in the Catalan healthcare system / Opinión de los médicos sobre coordinación entre atención primaria y especializada en el sistema de salud catalán

Objective: To analyse doctors' opinions on clinical coordination between primary and secondary care in different healthcare networks and on the factors influencing it. Methods: A qualitative descriptive-interpretative study was conducted, based on semi-structured interviews. A two-stage theoretical sample was designed: 1) healthcare networks with different management models; 2) primary care and secondary care doctors in each network. Final sample size (n = 50) was reached by saturation. A thematic content analysis was conducted. Results: In all networks doctors perceived that primary and secondary care given to patients was coordinated in terms of information transfer, consistency and accessibility to SC following a referral. However, some problems emerged, related to difficulties in acceding non-urgent secondary care changes in prescriptions and the inadequacy of some referrals across care levels. Doctors identified the following factors: 1) organizational influencing factors: coordination is facilitated by mechanisms that facilitate information transfer, communication, rapid access and physical proximity that fosters positive attitudes towards collaboration; coordination is hindered by the insufficient time to use mechanisms, unshared incentives in prescription and, in two networks, the change in the organizational model; 2) professional factors: clinical skills and attitudes towards coordination. Conclusions: Although doctors perceive that primary and secondary care is coordinated, they also highlighted problems. Identified factors offer valuable insights on where to direct organizational efforts to improve coordination

Objetivo: Analizar la opinión de los médicos sobre la coordinación entre la atención primaria (AP) y la atención especializada (AE) en diferentes redes de servicios de salud, e identificar los factores relacionados. Método: Estudio cualitativo descriptivo-interpretativo basado en entrevistas semiestructuradas. Se diseñó una muestra teórica en dos etapas: 1) redes de servicios de salud con diferentes modelos de gestión; 2) en cada red, médicos de AP y AE. El tamaño muestral se alcanzó por saturación (n = 50). Se realizó un análisis temático de contenido. Resultados: En las tres redes, los médicos expresaron que la atención está coordinada en términos de intercambio de información, consistencia y accesibilidad de AE tras derivación urgente. Sin embargo, emergieron problemas relacionados con el acceso no urgente y cambios en prescripciones, y en dos redes la inadecuación clínica de las derivaciones entre ambos niveles. Se identificaron los siguientes factores relacionados: 1) organizativos: facilitan la coordinación, la existencia de mecanismos de transferencia de información, de comunicación y de acceso rápido, y la proximidad física que promueve actitudes positivas a la colaboración; la obstaculizan el tiempo insuficiente para el uso de mecanismos, incentivos no compartidos en la prescripción y, en dos redes, un cambio del modelo organizativo; 2) relacionados con los profesionales: habilidades clínicas y actitudes frente a la coordinación. Conclusiones: Aunque los médicos perciben que la atención entre niveles está coordinada, también señalan problemas. Los factores identificados muestran hacia dónde dirigir los esfuerzos organizativos para su mejora

[Social and clinical determinants of the use of health services in women with breast cancer (Cohort DAMA)]. / Determinantes sociales y clínicos del uso de servicios sanitarios en mujeres con cáncer de mama (Cohorte DAMA).

OBJECTIVE: To describe and analyse the factors associated with the use of health services (emergency departments, admissions and primary care) in women survivors of breast cancer diagnosed or treated in four university hospitals of Barcelona (Spain) between 2003 and 2013, within the framework of the Cohort DAMA project. METHOD: Descriptive design nested in a mixed cohort (Cohort Dama). We obtained sociodemographic information and information on the use of health services through a questionnaire, and on the tumour from the clinical history. Logistic regression models were performed, calculating the odds ratio of the use of health services (emergency departments, hospital admissions and primary care) raw and adjusted (aOR) by diagnostic method, the characteristics of the tumour and of the women and their 95% confidence intervals. RESULTS: The presence of chronic diseases was associated with greater use of the three levels of care. A disadvantaged economic level increases the risk of use of emergency departments and primary care but not of hospital admissions, while a higher tumour stage is associated with a greater risk of admission. By age, those under 50 had a higher risk of using emergency departments and admissions. CONCLUSIONS: The factors associated with the use of health services differ according to the level of care (aOR: 3.53 emergency departments, 1.67 admissions, 3.89 primary care) and treatment-derived complications (aOR: 1.35 emergency departments, 1.43 primary care). The presence of chronic disorders, younger age, disadvantaged social class, increases the risk of using services more than the tumour stage and treatment-derived complications. Neither the diagnostic method nor the survival time, nor the use of non-conventional therapies influence this.

Doctors' opinions on clinical coordination between primary and secondary care in the Catalan healthcare system.

OBJECTIVE: To analyse doctors' opinions on clinical coordination between primary and secondary care in different healthcare networks and on the factors influencing it. METHODS: A qualitative descriptive-interpretative study was conducted, based on semi-structured interviews. A two-stage theoretical sample was designed: 1) healthcare networks with different management models; 2) primary care and secondary care doctors in each network. Final sample size (n = 50) was reached by saturation. A thematic content analysis was conducted. RESULTS: In all networks doctors perceived that primary and secondary care given to patients was coordinated in terms of information transfer, consistency and accessibility to SC following a referral. However, some problems emerged, related to difficulties in acceding non-urgent secondary care changes in prescriptions and the inadequacy of some referrals across care levels. Doctors identified the following factors: 1) organizational influencing factors: coordination is facilitated by mechanisms that facilitate information transfer, communication, rapid access and physical proximity that fosters positive attitudes towards collaboration; coordination is hindered by the insufficient time to use mechanisms, unshared incentives in prescription and, in two networks, the change in the organizational model; 2) professional factors: clinical skills and attitudes towards coordination. CONCLUSIONS: Although doctors perceive that primary and secondary care is coordinated, they also highlighted problems. Identified factors offer valuable insights on where to direct organizational efforts to improve coordination.

Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis.

In the present study, tissue distribution and the therapeutic effect of topically applied cyclosporine A (CsA)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly(lactic acid) (mPEGhexPLA) nanocarriers (ApidSOL) on experimental autoimmune uveitis (EAU) were investigated. The CsA-loaded mPEGhexPLA nanocarrier was tolerated well locally and showed no signs of immediate toxicity after repeated topical application in mice with EAU. Upon unilateral CsA treatment, CsA accumulated predominantly in the corneal and sclera-choroidal tissue of the treated eye and in lymph nodes (LN). This regimen reduced EAU severity in treated eyes compared to PBS-treated controls. This improvement was accompanied by reduced T-cell count, T-cell proliferation, and IL-2 secretion of cells from ipsilateral LN. In conclusion, topical treatment with CsA-loaded mPEGhexPLA nanocarriers significantly improves the outcome of EAU.

Doctors' opinion on the contribution of coordination mechanisms to improving clinical coordination between primary and outpatient secondary care in the Catalan national health system.

BACKGROUND: Clinical coordination is considered a health policy priority as its absence can lead to poor quality of care and inefficiency. A key challenge is to identify which strategies should be implemented to improve coordination. The aim is to analyse doctors' opinions on the contribution of mechanisms to improving clinical coordination between primary and outpatient secondary care and the factors influencing their use. METHODS: A qualitative descriptive study in three healthcare networks of the Catalan national health system. A two-stage theoretical sample was designed: in the first stage, networks with different management models were selected; in the second, primary care (n = 26) and secondary care (n = 24) doctors. Data were collected using semi-structured interviews. Final sample size was reached by saturation. A thematic content analysis was conducted, segmented by network and care level. RESULTS: With few differences across networks, doctors identified similar mechanisms contributing to clinical coordination: 1) shared EMR facilitating clinical information transfer and uptake; 2) mechanisms enabling problem-solving communication and agreement on clinical approaches, which varied across networks (joint clinical case conferences, which also promote mutual knowledge and training of primary care doctors; virtual consultations through EMR and email); and 3) referral protocols and use of the telephone facilitating access to secondary care after referrals. Doctors identified organizational (insufficient time, incompatible timetables, design of mechanisms) and professional factors (knowing each other, attitude towards collaboration, concerns over misdiagnosis) that influence the use of mechanisms. DISCUSSION: Mechanisms that most contribute to clinical coordination are feedback mechanisms, that is those based on mutual adjustment, that allow doctors to exchange information and communicate. Their use might be enhanced by focusing on adequate working conditions, mechanism design and creating conditions that promote mutual knowledge and positive attitudes towards collaboration.

Continuity of clinical management and information across care levels: perceptions of users of different healthcare areas in the Catalan national health system.

BACKGROUND: The integration of health care has become a priority in most health systems, as patients increasingly receive care from several professionals in various different settings and institutions, particularly those with chronic conditions and multi-morbidities. Continuity of care is defined as one patient experiencing care over time as connected and coherent with his or her health needs and personal circumstances. The objective is to analyse perceptions of continuity of clinical management and information across care levels and the factors influencing it, from the viewpoint of users of the Catalan national health system. METHODS: A descriptive-interpretative qualitative study was conducted using a phenomenological approach. A two-stage theoretical sample was selected: (i) the study contexts: healthcare areas in Catalonia with different services management models; (ii) users ≥ 18 years of age who were attended to at both care levels for the same health problem. Data were collected by means of individual semi-structured interviews with patients (n = 49). All interviews were recorded and transcribed. A thematic content analysis was conducted segmented by study area, with a mixed generation of categories and triangulation of analysts. RESULTS: Patients in all three areas generally perceived that continuity of clinical management across levels existed, on referring to consistent care (same diagnosis and treatment by doctors of both care levels, no incompatibilities of prescribed medications, referrals across levels when needed) and accessibility across levels (timeliness of appointments). In terms of continuity of information, patients in most areas mentioned the existence of information sharing via computer and its adequate usage. Only a few discontinuity elements were reported such as long waiting times for specific tests performed in secondary care or insufficient use of electronic medical records by locum doctors. Different factors influencing continuity were identified by patients, relating to the health system itself (clear distribution of roles between primary and secondary care), health services organizations (care coordination mechanisms, co-location, insufficient resources) and physicians (willingness to collaborate, commitment to patient care, the primary care physician's technical competence). CONCLUSIONS: Care continuity across care levels is experienced by patients in the areas studied, with certain exceptions that highlight where there is room for improvement. Influencing factors offer valuable insights on where to direct coordination efforts.

Importance of vial shape and type on the reproducibility of size exclusion chromatography measurement of monoclonal antibodies.

The goal of this work is to understand the phenomenon behind the poor injection repeatability often observed with protein biopharmaceuticals. All the measurements were carried out in size exclusion chromatography (SEC) mode, using fifteen commercially available therapeutic monoclonal antibodies (mAbs). First of all, we proved that the variation of peak areas between consecutive injections was much more critical with highly concentrated mAb samples (up to 80mg/mL), while the SEC measurements of commercial mAbs having concentrations below 5mg/mL were reliable. Second, we emphasized that the shapes, volumes and materials of the sample vial insert also contribute to the change of peak areas observed during consecutive injections. In this study, six different insert models were studied and the most critical were the ones possessing the narrowest conical shape at the bottom. Furthermore, the homogenization of samples (with pipette mixing rather than vortex) prior to analysis was of great interest and allows a significant improvement in injection repeatability. Finally, because the on-wall (on-insert) adsorption of mAbs reaches its equilibrium in around 50min, it is advised to add a specified residence time prior to injection to achieve repeatable injection.

Prototype sphere-on-sphere silica particles for the separation of large biomolecules.

The goal of this study was to evaluate the possibilities offered by a prototype HPLC column packed with ∼2.5µm narrow size distribution sphere-on-sphere (SOS) silica particles bonded with C4 alkyl chains, for the analytical characterization of large biomolecules. The kinetic performance of this material was evaluated in both isocratic and gradient modes using various model analytes. The data were compared to those obtained on other widepore state-of-the-art fully core-shell and fully porous materials commonly employed to separate proteins moreover to a reference 5µm wide pore material that is still often used in QC labs. In isocratic mode, minimum reduced plate height values of hmin=2.6, 3.3 and 3.3 were observed on butylparaben, decapeptide and glucagon, respectively. In gradient elution mode, the SOS column performs very high efficiency when working with fast gradients. This prototype column was also comparable (and sometimes superior) to other widepore stationary phases, whatever the gradient time and flow rate, when analyzing the largest model protein, namely BSA. These benefits may be attributed to the SOS particle morphology, minimizing the intra-particle mass transfer resistance. Finally, the SOS column was also applied for the analytical characterization of commercial monoclonal antibody (mAb) and antibody-drug conjugate (ADC) samples. With these classes of proteins, the performance of SOS column was similar to the best widepore stationary phases available on the market.

Practical method development for the separation of monoclonal antibodies and antibody-drug-conjugate species in hydrophobic interaction chromatography, part 1: optimization of the mobile phase.

The goal of this work is to provide some recommendations for method development in HIC using monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) as model drug candidates. The effects of gradient steepness, mobile phase pH, salt concentration and type, as well as organic modifier were evaluated for tuning selectivity and retention in HIC. Except the nature of the stationary phase, which was not discussed in this study, the most important parameter for modifying selectivity was the gradient steepness. The addition of organic solvent (up to 15% isopropanol) in the mobile phase was also found to be useful for mAbs analysis, since it could provide some changes in elution order, in some cases. On the contrary, isopropanol was not beneficial with ADCs, since the most hydrophobic DAR species (DAR6 and DAR8) cannot be eluted from the stationary phase under these conditions. This study also illustrates the possibility to perform HIC method development using optimization software, such as Drylab. The optimum conditions suggested by the software were tested using therapeutic mAbs and commercial cysteine linked ADC (brentuximab-vedotin) and the average retention time errors between predicted and experimental retention times were ∼ 1%.

Development and testing of indicators to measure coordination of clinical information and management across levels of care.

BACKGROUND: Coordination across levels of care is becoming increasingly important due to rapid advances in technology, high specialisation and changes in the organization of healthcare services; to date, however, the development of indicators to evaluate coordination has been limited. The aim of this study is to develop and test a set of indicators to comprehensively evaluate clinical coordination across levels of care. METHODS: A systematic review of literature was conducted to identify indicators of clinical coordination across levels of care. These indicators were analysed to identify attributes of coordination and classified accordingly. They were then discussed within an expert team and adapted or newly developed, and their relevance, scientific soundness and feasibility were examined. The indicators were tested in three healthcare areas of the Catalan health system. RESULTS: 52 indicators were identified addressing 11 attributes of clinical coordination across levels of care. The final set consisted of 21 output indicators. Clinical information transfer is evaluated based on information flow (4) and the adequacy of shared information (3). Clinical management coordination indicators evaluate care coherence through diagnostic testing (2) and medication (1), provision of care at the most appropriate level (2), completion of diagnostic process (1), follow-up after hospital discharge (4) and accessibility across levels of care (4). The application of indicators showed differences in the degree of clinical coordination depending on the attribute and area. CONCLUSION: A set of rigorous and scientifically sound measures of clinical coordination across levels of care were developed based on a literature review and discussion with experts. This set of indicators comprehensively address the different attributes of clinical coordination in main transitions across levels of care. It could be employed to identify areas in which health services can be improved, as well as to measure the effect of efforts to improve clinical coordination in healthcare organizations.

The performance of integrated health care networks in continuity of care: a qualitative multiple case study of COPD patients.

BACKGROUND: Integrated health care networks (IHN) are promoted in numerous countries as a response to fragmented care delivery by providing a coordinated continuum of services to a defined population. However, evidence on their effectiveness and outcome is scarce, particularly considering continuity across levels of care; that is the patient's experience of connected and coherent care received from professionals of the different care levels over time. The objective was to analyse the chronic obstructive pulmonary disease (COPD) patients' perceptions of continuity of clinical management and information across care levels and continuity of relation in IHN of the public health care system of Catalonia. METHODS: A qualitative multiple case study was conducted, where the cases are COPD patients. A theoretical sample was selected in two stages: (1) study contexts: IHN and (2) study cases consisting of COPD patients. Data were collected by means of individual, semi-structured interviews to the patients, their general practitioners and pulmonologists and review of records. A thematic content analysis segmented by IHN and cases with a triangulation of sources and analysists was carried out. RESULTS: COPD patients of all networks perceived that continuity of clinical management was existent due to clear distribution of roles for COPD care across levels, rapid access to care during exacerbations and referrals to secondary care when needed; nevertheless, patients of some networks highlighted too long waiting times to non-urgent secondary care. Physicians generally agreed with patients, however, also indicated unclear distribution of roles, some inadequate referrals and long waiting times to primary care in some networks. Concerning continuity of information, patients across networks considered that their clinical information was transferred across levels via computer and that physicians also used informal communication mechanisms (e-mail, telephone); whereas physicians highlighted numerous problems of the information system, thus the need to use informal communication channels. Finally, regarding continuity of relation, patients of some networks pointed out high turnover of personnel - being frequently seen by locum doctors or assigned to new physicians - which hindered the development of a trusting relationship. CONCLUSION: Study findings suggest a generally perceived adequate performance of IHN in continuity of care but also the existence of a series of difficulties related to all continuity types. Results can provide opportunities to improving the care process of COPD patients but also of patients with other conditions who receive care across the primary and secondary care level.

New prostaglandin analog formulation for glaucoma treatment containing cyclodextrins for improved stability, solubility and ocular tolerance.

Latanoprost is a practically insoluble prostaglandin F2α analog considered a first-line agent for glaucoma treatment. From a pharmaceutical point of view, latanoprost is challenging to be formulated as an eye drop due to its poor water solubility and the presence of an ester bond that needs to be cleaved in vivo but maintained unchanged during storage. Cyclodextrins (CDs) are known to form complexes with hydrophobic drugs, influencing their stability, availability, solubility, and tolerance in a non-predictable manner. A variety of CDs including native α, ß, and γCDs as well as substituted hydroxypropylßCD, hydroxypropylγCD, dimethylßCD, sulphatedßCD, and propylaminoßCD were screened and the most appropriate CD for the formulation of latanoprost for an ocular topical application was selected. Among the tested CDs, propylaminoßCD had the best trade-off between latanoprost stability and availability, which was confirmed by its complex constant value of 3129M(-1). Phase-solubility and NMR investigations demonstrated that the propylaminoßCD effectively formed a complex involving the ester group of latanoprost providing protection to its ester bond, while ensuring proper latanoprost solubilization. Furthermore, in vivo experiments demonstrated that the latanoprost-propylaminoßCD formulation led to lower ocular irritation than the commercial latanoprost formulation used as a reference. The latanoprost-propylaminoßCD formulation was demonstrated to successfully address the main stability, solubility, and tolerance limitations of topical ocular latanoprost therapy for glaucoma.

Adaptación y validación de la escala CCAENA(R) para evaluar la continuidad asistencial entre niveles de atención en Colombia y Brasil / Adaptation and validation of the CCAENA(R) scale for the measurement of continuity of care between healthcare levels in Colombia and Brazil

Objetivo: Adaptar y validar la escala del Cuestionario de Continuidad Asistencial Entre Niveles de Atención (CCAENA©) en el contexto de los sistemas de salud colombiano y brasileño. Métodos: El estudio consistió en dos fases: 1) adaptación de la escala CCAENA© al contexto de cada país mediante dos pretests y una prueba piloto; y 2) validación mediante la aplicación de la escala en una encuesta poblacional en Colombia y Brasil. Se analizaron las siguientes propiedades psicométricas: validez de constructo (análisis factorial), consistencia interna (alfa de Cronbach; correlaciones ítem-resto), multidimensionalidad de las escalas (coeficientes de correlación de Spearman) y análisis de grupos conocidos (test de ji al cuadrado). Resultados: Se seleccionaron 14 de los 21 ítems de la escala original y se reformularon pasando de una afirmación con opciones de respuesta de acuerdo a una pregunta con opciones de respuesta de frecuencia. El análisis factorial mostró que los ítems se agrupan en tres factores: continuidad entre niveles asistenciales, continuidad de relación con el proveedor de atención primaria y continuidad de relación con el proveedor de atención especializada. El alfa de Cronbach indicó una buena concordancia interna (>0,80 en todas las escalas). Los coeficientes de correlación indican que los tres factores pueden interpretarse como escalas separadas (<0,70) y presentan una adecuada capacidad de diferenciar entre grupos. Conclusiones: La versión adaptada del CCAENA© muestra adecuadas validez y fiabilidad en ambos países, manteniendo una alta equivalencia con la versión original. Es una herramienta útil y viable para evaluar la continuidad asistencial entre niveles asistenciales desde la perspectiva del usuario en ambos contextos (AU)

Objective: To adapt and to validate the scale of the questionnaire Continuity of Care between Care Levels (CCAENA©) in the context of the Colombian and Brazilian health systems. Methods: The study consisted of two phases: 1) adaptation of the CCAENA© scale to the context of each country, which was tested by two pretests and a pilot test, and 2) validation by means of application of the scale in a population survey in Colombia and Brazil. The following psychometric properties were analyzed: construct validity (exploratory factor analysis), internal consistency (Cronbach's alpha and item-rest correlations), the multidimensionality of the scales (Spearman correlation coefficients), and known group validity (chi-square test). Results: Of the 21 items of the original scale, 14 were selected and reformulated based on a statement with response options of agreement to a question with frequency response options. Factor analysis showed that items could be grouped into three factors: continuity across healthcare levels, the patient-primary care provider relationship, and the patient-secondary care provider relationship. Cronbach's alpha indicated good internal consistency (>0.80 in all the scales). The correlation coefficients suggest that the three factors could be interpreted as separated scales (<0.70) and had adequate ability to differentiate between groups. Conclusion: The adapted version of the CCAENA© shows adequate validity and reliability in both countries, maintaining a high equivalence with the original version. It is a useful and feasible tool to assess the continuity of care between healthcare levels from the users’ perspective in both contexts (AU)

[Adaptation and validation of the CCAENA(©) scale for the measurement of continuity of care between healthcare levels in Colombia and Brazil]. / Adaptación y validación de la escala CCAENA(©) para evaluar la continuidad asistencial entre niveles de atención en Colombia y Brasil.

OBJECTIVE: To adapt and to validate the scale of the questionnaire Continuity of Care between Care Levels (CCAENA(©)) in the context of the Colombian and Brazilian health systems. METHODS: The study consisted of two phases: 1) adaptation of the CCAENA(©) scale to the context of each country, which was tested by two pretests and a pilot test, and 2) validation by means of application of the scale in a population survey in Colombia and Brazil. The following psychometric properties were analyzed: construct validity (exploratory factor analysis), internal consistency (Cronbach's alpha and item-rest correlations), the multidimensionality of the scales (Spearman correlation coefficients), and known group validity (chi-square test). RESULTS: Of the 21 items of the original scale, 14 were selected and reformulated based on a statement with response options of agreement to a question with frequency response options. Factor analysis showed that items could be grouped into three factors: continuity across healthcare levels, the patient-primary care provider relationship, and the patient-secondary care provider relationship. Cronbach's alpha indicated good internal consistency (>0.80 in all the scales). The correlation coefficients suggest that the three factors could be interpreted as separated scales (<0.70) and had adequate ability to differentiate between groups. CONCLUSION: The adapted version of the CCAENA(©) shows adequate validity and reliability in both countries, maintaining a high equivalence with the original version. It is a useful and feasible tool to assess the continuity of care between healthcare levels from the users' perspective in both contexts.

Acceso a los servicios de salud de la población inmigrante en España / Immmigrant´s access to health care in Spain: a review

Fundamentos: Una importante proporción de población en España es inmigrante y la evidencia internacional señala su acceso inadecuado a los servicios de salud. El objetivo es conocer el acceso a la atención de la población inmigrante en España. Métodos: Revisión bibliográfica de los artículos originales (1998- 2012) sobre acceso y utilización de los servicios de la población inmigrante en España registrados en Medline y MEDES. Se identificaron 319 artículos de los que se seleccionaron 20. Se utilizó el modelo de Aday y Andersen para el análisis. Resultados: Entre los artículos seleccionados, 13 estudios cuantitativos analizaron diferencias en la utilización de los servicios entre inmigrantes y autóctonos y 7 determinantes del acceso en inmigrantes. En líneas generales estos muestran menor utilización de la atención especializada, mayor de las urgencias y no se observaron diferencias entre grupos en atención primaria. Los 5 estudios cuantitativos sobre determinantes se centraron en las características de la población (sexo, edad, nivel de estudios y posesión de seguro privado) sin observarse un patrón claro. Los 2 estudios cualitativos analizaron factores relacionados con los servicios de salud y encontraron barreras en el acceso, como la provisión de información o los requisitos para obtener la tarjeta sanitaria. Conclusiones: El acceso a la atención en inmigrantes ha sido limitadamente abordado, con aproximaciones diferentes y los factores relacionados con la oferta, escasamente analizados. No se observa un patrón de utilización, las diferencias dependen de la clasificación de los inmigrante según origen y nivel asistencial. No obstante, en inmigrantes se observa menor utilización de la atención especializada y mayor de las urgencias, así como determinantes del acceso distintos a la necesidad (AU)

Background: An important proportion of the population in Spain is immigrant and the international literature indicates their inadequate access to health services. The objective is to contribute to improving the knowledge on access to health care of the immigrant population in Spain. Methods: Review of original papers published (1998-2012) on access to health services of the immigrant population in Spain published in Medline and MEDES. Out of 319 studies, 20 were selected, applying predefined criteria. The results were analyzed using the Aday and Andersen framework. Results:Among the publications, 13 quantitative studies analysed differences in health care use between the immigrant and the native population, and 7 studied determinants of access of immigrants. Studies showed less use of specialized care by immigrants, higher use of emergency care and no differences in the use of primary care between groups. Five quantitative articles on determinants of access focused on factors related to the immigrant population (sex, age, educational level and holding private health insurance), but without observing clear patterns. The two qualitative studies analyzed factors related to health services, describing access to healthcare barriers such as the limited provision of information or the requirements for personal health card. Conclusion: Access to health care in immigrants has been scarcely studied, using different approaches and the barely analysed factors related to the services. No clear patterns were observed, as differences depend on the classification of migrants according to country of origin and the level of care. However, studies showed less use of specialized care by immigrants, higher use of emergency care and the existence of determinants of access different to their needs (AU)

[Immigrants' access to health care in Spain: a review]. / Acceso a los servicios de salud de la población inmigrante en España.

BACKGROUND: An important proportion of the population in Spain is immigrant and the international literature indicates their inadequate access to health services. The objective is to contribute to improving the knowledge on access to health care of the immigrant population in Spain. METHODS: Review of original papers published (1998-2012) on access to health services of the immigrant population in Spain published in Medline and MEDES. Out of 319 studies, 20 were selected, applying predefined criteria. The results were analyzed using the Aday and Andersen framework. RESULTS: Among the publications, 13 quantitative studies analysed differences in health care use between the immigrant and the native population, and 7 studied determinants of access of immigrants. Studies showed less use of specialized care by immigrants, higher use of emergency care and no differences in the use of primary care between groups. Five quantitative articles on determinants of access focused on factors related to the immigrant population (sex, age, educational level and holding private health insurance), but without observing clear patterns. The two qualitative studies analyzed factors related to health services, describing access to healthcare barriers such as the limited provision of information or the requirements for personal health card. CONCLUSION: Access to health care in immigrants has been scarcely studied, using different approaches and the barely analysed factors related to the services. No clear patterns were observed, as differences depend on the classification of migrants according to country of origin and the level of care. However, studies showed less use of specialized care by immigrants, higher use of emergency care and the existence of determinants of access different to their needs.