Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. METHODS: Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. RESULTS: All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. CONCLUSIONS: Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma.

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG). STUDY DESIGN AND METHODS: Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases. RESULTS: Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized enzyme-linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B, and anti-D) were reduced to minimal levels. CONCLUSIONS: Multiple batches of anti-SARS-CoV-2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].

Effect of comorbidities on survival in patients >80 years of age at onset of renal replacement therapy: data from the ERA-EDTA Registry.

BACKGROUND: The number of elderly patients on renal replacement therapy (RRT) is increasing. The survival and quality of life of these patients may be lower if they have multiple comorbidities at the onset of RRT. The aim of this study was to explore whether the effect of comorbidities on survival is similar in elderly RRT patients compared with younger ones. METHODS: Included were 9333 patients ≥80 years of age and 48 352 patients 20-79 years of age starting RRT between 2010 and 2015 from 15 national or regional registries submitting data to the European Renal Association-European Dialysis and Transplantation Association Registry. Patients were followed until death or the end of 2016. Survival was assessed by Kaplan-Meier curves and the relative risk of death associated with comorbidities was assessed by Cox regression analysis. RESULTS: Patients ≥80 years of age had a greater comorbidity burden than younger patients. However, relative risks of death associated with all studied comorbidities (diabetes, ischaemic heart disease, chronic heart failure, cerebrovascular disease, peripheral vascular disease and malignancy) were significantly lower in elderly patients compared with younger patients. Also, the increase in absolute mortality rates associated with an increasing number of comorbidities was smaller in elderly patients. CONCLUSIONS: Comorbidities are common in elderly patients who enter RRT, but the risk of death associated with comorbidities is less than in younger patients. This should be taken into account when assessing the prognosis of elderly RRT patients.

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study.

In this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living-related donor (LRD) or living-unrelated donor (LUD). Adult patients in the ERA-EDTA Registry who received their first kidney transplant in 1998-2017 were included. Ten-year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five-year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7-4.6) and 10.8% (95% CI: 10.1-11.5) versus 6.5% (95% CI: 5.7-7.4) and 12.2% (95% CI: 11.2-13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87-1.13) for patient survival and 1.03 (95% CI: 0.94-1.14) for graft survival. Unadjusted risk of death-censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04-1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death-censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.

[Health care for patients with multimorbidity. The perception of professionals]. / La atención sanitaria a pacientes con multimorbilidad. La percepción de los profesionales.

OBJECTIVE: To explore the perceptions of health professionals about the characteristics of health care for patients with multimorbidity. DESIGN: Qualitative study of phenomenological trajectory made between January and September 2015 through 3 group interviews and 15 individual interviews. LOCATION: Aragonese Health Service. PARTICIPANTS: Medical and nursing professionals of the Aragon Health Service belonging to various services: Internal Medicine, Primary Care, Emergency and Management. A pharmacist was also included. METHODS: A non-probabilistic intentional sampling was carried out that allowed for the selection of professionals in terms of discourse representation criteria, allowing to know and interpret the phenomenon studied in depth, in its different visions. We interviewed health professionals with different profiles who knew in depth the characteristics of care provided to patients with multimorbidity. The interviews were recorded, transcribed literally and interpreted, through the social analysis of the discourse. RESULTS: Professional culture oriented to individual pathologies, lack of coordination among professionals, high prevalence of multi-prescriptions, Clinical Practice Guidelines oriented to individual pathologies and specialist training focused on individual diseases. CONCLUSIONS: Both the professional culture and the organization of the healthcare system have been oriented towards the attention to individual pathologies, which results in the difficulty to offer a more integrated care to patients with multimorbidity.

Performance of an easy-to-use prediction model for renal patient survival: an external validation study using data from the ERA-EDTA Registry.

Background: An easy-to-use prediction model for long-term renal patient survival based on only four predictors [age, primary renal disease, sex and therapy at 90 days after the start of renal replacement therapy (RRT)] has been developed in The Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in 10 European countries. Methods: Data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period 1995-2005 were included. Patients <16 years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10- (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes. Results: We used a data set of 136 304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with some small variation on the country level. The concordance index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75. Conclusions: A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.

[Perceptions of patients and health professionals about the quality of care provided to chronic obstructive pulmonary disease patients]. / Percepciones de pacientes y profesionales sobre la calidad de la atención a personas con enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To explore the understanding and knowledge of patients and health professionals about factors that influence the quality of care provided in Primary Care to people with Chronic Obstructive Pulmonary Disease (COPD). DESIGN: Qualitative study performed between February and March 2010. LOCATION: Primary Care Centers. PARTICIPANTS: Medical and nursing professionals and patients with COPD. METHODS: Non-probabilistic intentional sampling with representation criterion of the discourse. Two group (focus group) and 6 individual interviews were performed. The interviews were recorded, literally transcribed and interpreted by social discourse analysis. RESULTS: Patients neither identify properly the symptomatology nor they assume the COPD importance until advanced states. The lacks of knowledge about the evolution of the disease and the impact on quality of life hinders the necessary changes. Professionals reports problems with performing spirometry. Among doctors, scepticism regarding to the effectiveness of the interventions aimed at change of behaviour is identified. The existence of Clinical Guides, the improvement of the coordination between professionals and the alignment of priorities between managers and professionals stand out as organizational factors. CONCLUSIONS: The identified factors suggest the possibility of improving the health care through improved communication to motivate them to take the recommended changes and to increase the adherence to treatments. To this effect, the awareness and training of professionals, the healthcare coordination, the implementation of Clinical Guides and the use of indicators in a process of quality assessment.

Age and gender differences in the prevalence and patterns of multimorbidity in the older population.

BACKGROUND: The coexistence of several chronic diseases in one same individual, known as multimorbidity, is an important challenge facing health care systems in developed countries. Recent studies have revealed the existence of multimorbidity patterns clustering systematically associated distinct clinical entities. We sought to describe age and gender differences in the prevalence and patterns of multimorbidity in men and women over 65 years. METHODS: Observational retrospective multicentre study based on diagnostic information gathered from electronic medical records of 19 primary care centres in Aragon and Catalonia. Multimorbidity patterns were identified through exploratory factor analysis. We performed a descriptive analysis of previously obtained patterns (i.e. cardiometabolic (CM), mechanical (MEC) and psychogeriatric (PG)) and the diseases included in the patterns stratifying by sex and age group. RESULTS: 67.5% of the aged population suffered two or more chronic diseases. 32.2% of men and 45.3% of women were assigned to at least one specific pattern of multimorbidity, and 4.6% of men and 8% of women presented more than one pattern simultaneously. Among women over 65 years the most frequent pattern was the MEC pattern (33.3%), whereas among men it was the CM pattern (21.2%). While the prevalence of the CM and MEC patterns decreased with age, the PG pattern showed a higher prevalence in the older age groups. CONCLUSIONS: Significant gender differences were observed in the prevalence of multimorbidity patterns, women showing a higher prevalence of the MEC and PG patterns, as well as a higher degree of pattern overlapping, probably due to a higher life expectancy and/or worse health. Future studies on multimorbidity patterns should take into account these differences and, therefore, the study of multimorbidity and its impact should be stratified by age and sex.

Effective presence of antibodies against common human coronaviruses in immunoglobulin medicinal products.

BACKGROUND: Immunoglobulin products (for intravenous, intramuscular and subcutaneous administration) prepared from geographically diverse plasma pools were tested for activity against common human coronaviruses (HCoVs). Products from plasma obtained from Germany, Czech Republic, Slovak Republic, USA and Spain were tested for antibodies to common HCoVs: 229E, OC43, NL63 and HKU1. As these products are manufactured from pooled plasma from thousands of donors, the antibodies therein are representative of HCoV exposure in the population at large. METHODS: Immunoglobulin products were tested for antibodies to four common HCoVs by enzyme-linked immunosorbent assays (ELISAs). Neutralization assays were conducted using HCoV-229E cultured on to MRC5 cells. RESULTS: ELISAs showed that when expressed as specific activity (anti-HCoV activity/mg immunoglobulin), similar activity against the four common HCoVs was seen across the immunoglobulin products regardless of concentration or geographic origin. Highest anti-HCoV activity was seen against HCoV-229E, followed by HCoV-OC43, HCoV-NL63 and HCoV-HKU1. The neutralization assays showed similar potency for two immunoglobulin products prepared by different processes. CONCLUSIONS: To the authors' knowledge, this is the first demonstration of antibodies to common HCoVs in immunoglobulin products. These results may explain the cross-reactivity seen with pre-pandemic immunoglobulin products and severe acute respiratory syndrome coronavirus-2, and contribute to differences in severity of illness between patients.

Medicinal Immunoglobulin G Products (2020) Show High Infectivity Neutralizing Activity Against Seasonal Influenza Virus Strains Selected for Future Vaccines (2020-2022).

Immunoglobulin (Ig)G medicinal products manufactured in 2020 were tested for infectivity neutralization and hemagglutination inhibition against World Health Organization-selected influenza strains included in worldwide vaccines 2020-2022. The IgG batches (from US plasma) showed potent activity. Intravenous immunoglobulin could potentially add to therapies for serious influenza cases in immunocompromised patients. Further study is warranted.

Does the pharmacy expenditure of patients always correspond with their morbidity burden? Exploring new approaches in the interpretation of pharmacy expenditure.

BACKGROUND: The computerisation of primary health care (PHC) records offers the opportunity to focus on pharmacy expenditure from the perspective of the morbidity of individuals. The objective of the present study was to analyse the behaviour of pharmacy expenditure within different morbidity groups. We paid special attention to the identification of individuals who had higher values of pharmacy expenditure than their morbidity would otherwise suggest (i.e. outliers). METHODS: Observational study consisting of 75,574 patients seen at PHC centres in Zaragoza, Spain, at least once in 2005. Demographic and disease variables were analysed (ACG 8.1), together with a response variable that we termed 'total pharmacy expenditure per patient'. Outlier patients were identified based on boxplot methods, adjusted boxplot for asymmetric distributions, and by analysing standardised residuals of tobit regression models. RESULTS: The pharmacy expenditure of up to 7% of attendees in the studied PHC centres during one year exceeded expectations given their morbidity burden. This group of patients was responsible for up to 24% of the total annual pharmacy expenditure. There was a significantly higher number of outlier patients within the low-morbidity band which matched up with the higher variation coefficient observed in this group (3.2 vs. 2.0 and 1.3 in the moderate- and high-morbidity bands, respectively). CONCLUSIONS: With appropriate validation, the methodologies of the present study could be incorporated in the routine monitoring of the prescribing profile of general practitioners. This could not only enable evaluation of their performance, but also target groups of outlier patients and foster analyses of the causes of unusually high pharmacy expenditures among them. This interpretation of pharmacy expenditure gives new clues for the efficiency in utilisation of healthcare resources, and could be complementary to management interventions focused on individuals with a high morbidity burden.

Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens.

Aim: There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. Material & methods: Gamunex®-C and Flebogamma® DIF (Grifols) intravenous immunoglobulin (IVIG) products were tested using ELISA techniques for antibodies against several antigens of human common betacoronaviruses that may crossreact with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Results: Both IVIGs showed consistent reactivity to components of the tested viruses. Positive crossreactivity was seen in SARS-CoV, middle east respiratory syndrome-CoV and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 µg/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. Conclusion: Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted.

Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins.

Background: Cross-reactivity against human coronaviruses with Flebogamma® DIF and Gamunex®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.

New Male Users of Lipid-Lowering Drugs for Primary Prevention of Cardiovascular Disease: The Impact of Treatment Persistence on Morbimortality. A Longitudinal Study.

The objective of this study was to analyse persistence to lipid-lowering drug use for primary prevention of cardiovascular disease (CVD) in a new users cohort, to explore all-cause and cardiovascular related morbidity, comorbidity and mortality in this group and, finally, to study the relationship between persistence and morbimortality. We selected subjects who started lipid-lowering treatment for primary prevention of CVD between 1 January 2010 and 31 December 2017 (N = 1424), and classified them as treatment-persistent or -nonpersistent. Bivariate analyses were performed to compare sociodemographic and clinical variables, morbimortality and time to event between groups. The association between morbidities was explored using comorbidity network analysis. The effect of persistence was analysed using logistic regression and Cox survival analyses. Only 38.7% of users were persistent with treatment. Persistent and nonpersistent users had similar sociodemographic and clinical profiles, although differed in age, smoking status, and glycemia. Comorbidity networks revealed that the number of co-occurring diagnoses was higher in nonpersistent than persistent users. Adjusted analyses indicated a protective effect of treatment persistence, especially against major adverse cardiovascular events (MACE), but this effect was not statistically significant. Observational studies are crucial to characterize real-world effectiveness.

Human mesenchymal stem cells maintain their phenotype, multipotentiality, and genetic stability when cultured using a defined xeno-free human plasma fraction.

BACKGROUND: Mesenchymal stem cells (MSCs) show promising characteristics for their use in advanced therapy medicinal products. However, there are some unresolved concerns, such as the use of animal components for their expansion. In this study we assessed the suitability of a xeno-free supplement for cell culture (SCC) derived from human plasma, to culture and expand human MSCs (hMSCs) from different origins. Characteristics of viable cultured hMSCs such as genetic stability, phenotype and multipotentiality were qualitatively evaluated. METHODS: hMSCs from adipose tissue (AT), bone marrow (BM) and umbilical cord (UC) and supplier sources (commercial/non-commercial) were used. After hMSCs expansion in a xeno-free medium, classical hMSCs markers were studied by immunocytochemistry, and genetic stability was tested by classic karyotyping. The capacity of hMSCs to differentiate into adipogenic, osteogenic, and chondrogenic cells in differentiation media was assessed using different staining. Different lots of SCC were used to assure consistency between batches. RESULTS: All hMSCs tested maintained their morphology and adherence to plastic during their expansion, and preserved their genetic stability, phenotype and differentiation potential. No differences were observed when using different lots of SCC. Moreover, the proliferation rate, evaluated as population doubling time (PDT) of commercial BM and AT hMSCs, was higher in the xeno-free medium than in the control media provided by the suppliers of the cells (PDT of 4.6 for BM-hMSC and 6.4 for AT-hMSC in xeno-free medium, and 7.0 and 14.7 respectively in the commercial media). UC-hMSCs PDT was similar in all the media tested. When using non-commercial BM-hMSCs, PDT was lower in the xeno-free medium, but reverted to the control level with the addition of growth factors. CONCLUSIONS: SCC-containing medium can be a feasible xeno-free alternative to expand hMSCs for advanced therapies.

Brachytherapy in lip cancer.

Lip cancer is one of the most prevalent skin tumours of the head and neck. The characteristics of the tumour relate to their exophyitic growth in an area of easy visual acces which allows their diagnosis in early stages. As a result, there is a better prognosis with the present treatments. In early stages the treatment can be performed by surgery or by brachytherapy, and the results are similar on local control; nevertheless brachytherapy offers the best functional and esthetic results. We are reporting on a review of the literature in relation to indications, techniques and results of brachytherapy for lip cancer.

La atención sanitaria a pacientes con multimorbilidad. La percepción de los profesionales / Health care for patients with multimorbidity. The perception of professionals

OBJETIVO: Explorar las percepciones de los profesionales sanitarios sobre las características de la atención sanitaria a pacientes con multimorbilidad. DISEÑO: Estudio cualitativo de trayectoria fenomenológica realizado entre enero y septiembre de 2015 mediante 3 entrevistas grupales (grupos de discusión) y 15 individuales. Emplazamiento: Servicio Aragonés de Salud. PARTICIPANTES: Profesionales médicos y de enfermería del Servicio Aragonés de Salud pertenecientes a distintos servicios: Medicina Interna, Atención Primaria, Urgencias y Gestión. También se incluyó un farmacéutico. MÉTODOS: Se realizó un muestreo intencional no probabilístico que permitiese configurar las unidades muestrales buscando criterios de representatividad del discurso, permitiendo conocer e interpretar el fenómeno estudiado en profundidad, en sus diferentes visiones. Se entrevistó a profesionales sanitarios con perfiles diferentes que conociesen en profundidad la atención a pacientes con multimorbilidad. Las entrevistas fueron grabadas, transcritas literalmente e interpretadas, mediante el análisis social del discurso. RESULTADOS: Se identifica una cultura profesional orientada a la atención de enfermedades individuales, falta de coordinación entre especialidades, pacientes sometidos a numerosas prescripciones, Guías de Práctica Clínica y formación especialmente centradas en enfermedades individuales. CONCLUSIONES: Tanto la cultura profesional como la organización del sistema sanitario se encuentran orientadas a la atención de enfermedades individuales, lo que redunda en dificultades para ofrecer una atención más integral a los pacientes con multimorbilidad

OBJECTIVE: To explore the perceptions of health professionals about the characteristics of health care for patients with multimorbidity. DESIGN: Qualitative study of phenomenological trajectory made between January and September 2015 through 3 group interviews and 15 individual interviews. LOCATION: Aragonese Health Service. PARTICIPANTS: Medical and nursing professionals of the Aragon Health Service belonging to various services: Internal Medicine, Primary Care, Emergency and Management. A pharmacist was also included. METHODS: A non-probabilistic intentional sampling was carried out that allowed for the selection of professionals in terms of discourse representation criteria, allowing to know and interpret the phenomenon studied in depth, in its different visions. We interviewed health professionals with different profiles who knew in depth the characteristics of care provided to patients with multimorbidity. The interviews were recorded, transcribed literally and interpreted, through the social analysis of the discourse. RESULTS: Professional culture oriented to individual pathologies, lack of coordination among professionals, high prevalence of multi-prescriptions, Clinical Practice Guidelines oriented to individual pathologies and specialist training focused on individual diseases. CONCLUSIONS: Both the professional culture and the organization of the healthcare system have been oriented towards the attention to individual pathologies, which results in the difficulty to offer a more integrated care to patients with multimorbidity

Non-adherence to antihypertensive medication: The role of mental and physical comorbidity.

BACKGROUND: Multiple parameters influence adherence to drug treatment, including socio-economic, healthcare, condition, therapy, and patient-related factors. However, studies of the impact of patient-related factors, particularly regarding comorbid conditions, have produced conflicting results. OBJECTIVES: To analyse the association between mental and physical comorbidity and non-adherence to antihypertensive medication in patients attending primary care, after including a comprehensive range of chronic comorbidities and potential confounders. METHODS: Cross-sectional study of 113,397 adults with a diagnosis of hypertension in 2010 assigned to the public health service of a region in northeastern Spain. Pharmacy billing records were linked to data from electronic health records at individual level. Non-adherence was defined as an antihypertensive medication possession ratio (MPR) <80%. Multivariable logistic regression models were used to estimate the odds ratio for non-adherence. Potential predictors included mental and physical comorbidity, age, sex, blood pressure level, nationality, rurality, polypharmacy, and number of visits to the GP and to different specialties. RESULTS: One fifth of the study population showed poor adherence levels. Female sex, younger age, foreign nationality, living in a rural area, low blood pressure levels, polypharmacy, and mental comorbidity were positively and significantly associated with non-adherence. Conversely, non-adherence was negatively and significantly associated with the presence of cardiovascular risk factors and higher annual rates of GP visits. CONCLUSION: The majority of patient-related determinants identified here (e.g., the presence of mental comorbidity, polypharmacy, foreign nationality) underscores the need for a patient- rather than a disease-centred care approach, as well as adequate physician-patient communication.