Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

OBJECTIVE: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. METHODS: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. RESULTS: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. CONCLUSIONS: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

Effectiveness and safety profile of tofacitinib and baricitinib in rheumatoid arthritis patients: results from a 24-month real-life prospective study in Southern-Italy.

The primary objectives of the study were to evaluate the efficacy and safety of tofacitinib and baricitinib up to 24 months of follow-up in patients with rheumatoid arthritis (RA) treated in Southern Italy. Patients' data, activity index, and clinimetric scores were collected at baseline (T0), six (T6), twelve (T12), and twenty-four (T24) months following treatment initiation. At six, twelve, and twenty-four months, adverse events and treatment cessation were also recorded. Sixty-eight patients (mean age: 62.2±10.9 years; mean RA duration: 15±9.6 years) were enrolled over a period of 12 weeks. At baseline, twenty-four patients (35.3%) were treated with tofacitinib, and forty-four patients (64.7%) were treated with baricitinib. The baseline mean disease activity was moderate as measured by DAS28- ESR (5.0±1.0), DAS 28 CRP (4.69±0.94), and SDAI (26.87±10.73) score. Before beginning JAKinhibs therapy, thirty-two patients (61.8%) were taking bDMARDs, while the remaining thirty-six (38.2%) were bDMARDs-naïve. The 24-month retention rate for JAKinhibs was 91.1%. Six months after beginning treatment with JAKinhibs, a statistically significant improvement was observed in all evaluated activity indices and clinimetric scores. Improvement was confirmed during the 12- and 24-month follow-up evaluations. The positive correlation between baseline-T6 SDAI delta and discontinuation of JAKinhibs (p=0.02) suggests that RA worsening in the first six months may be a predictor of therapy withdrawal. Patients with RA responded favorably to tofacitinib and baricitinib in this prospective, real-world study from a single center in Southern Italy. Efficacy was observed despite an underlying persistent and treatment-resistant disease.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

PHYSIOPATHOLOGY OF OSTEOPOROSIS: FROM RISK FACTORS ANALYSIS TO TREATMENT.

Osteoporosis represents a relevant health issue, being the first cause of bone fractures in the elderly with subsequent implications in terms of survival and social costs. The improved knowledge about the physiopathology of this disease has led to a new definition of Osteoporosis, which shifts the attention from the “"decrease in bone mass"” to several elements related to what has globally been defined as bone quality. In fact, it has been shown that clinical risk factors affecting bone homeostasis coincide with osteoporosis risk factors. The evaluation of such clinical risk factors is an important element in the assessment of the global fracture risk. The availability of instruments for the assessment of the global fracture risk also suggests a change in the clinical perspective and raises new questions as yet unanswered.

Connectome-scale assessments of structural and functional connectivity in MCI.

Mild cognitive impairment (MCI) has received increasing attention not only because of its potential as a precursor for Alzheimer's disease but also as a predictor of conversion to other neurodegenerative diseases. Although MCI has been defined clinically, accurate and efficient diagnosis is still challenging. Although neuroimaging techniques hold promise, compared to commonly used biomarkers including amyloid plaques, tau protein levels and brain tissue atrophy, neuroimaging biomarkers are less well validated. In this article, we propose a connectomes-scale assessment of structural and functional connectivity in MCI via two independent multimodal DTI/fMRI datasets. We first used DTI-derived structural profiles to explore and tailor the most common and consistent landmarks, then applied them in a whole-brain functional connectivity analysis. The next step fused the results from two independent datasets together and resulted in a set of functional connectomes with the most differentiation power, hence named as "connectome signatures." Our results indicate that these "connectome signatures" have significantly high MCI-vs-controls classification accuracy, at more than 95%. Interestingly, through functional meta-analysis, we found that the majority of "connectome signatures" are mainly derived from the interactions among different functional networks, for example, cognition-perception and cognition-action domains, rather than from within a single network. Our work provides support for using functional "connectome signatures" as neuroimaging biomarkers of MCI.

Five-year economic evaluation of non-melanoma skin cancer surgery at the Costa del Sol Hospital (2006-2010).

BACKGROUND: The cost associated with treatment of non-melanoma skin cancer is expected to rise considerably over the coming decades. This important public health problem is therefore expected to have an enormous economic impact for the various public health services. OBJECTIVES: To estimate the cost of the surgical-care process of non-melanoma skin cancer at the Costa del Sol Hospital and seek areas to improve its efficiency, using the activity-based costing (ABC) method and the tools designed for decision analysis. SECONDARY OBJECTIVE: To compare the costs for hospitalized patients obtained using the ABC method with the data published by the Spanish Ministry of Health, using the diagnosis-related groups (DRG) classification system. MATERIAL AND METHODS: Retrospective analysis of the cost of non-melanoma skin cancer surgery at the Costa del Sol Hospital. RESULTS: The total estimated cost from 2006 to 2010 was 3 398 540€. Most of the episodes (47.3%) corresponded to minor outpatient surgery. The costs of the episodes varied greatly according to the type of admission: 423€ (minor outpatient surgery), 1267€ (major outpatient surgery), and 1832€ (inpatient surgery). The average cost of an inpatient episode varied significantly depending on the calculation system used (ABC: 2328€ vs. DRG: 5674€). CONCLUSIONS: The ABC cost analysis system favours standardization of the care process for these tumours and the detection of areas to improve efficiency. This would enable more reliable economic studies than those obtained using traditional methods, such as the DRG.

Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Cultural accommodations for cutoff scores of embedded performance validity tests in a Spanish college population.

OBJECTIVE: The objective of this study was to identify specific cutoff scores for three commonly used embedded performance validity tests (PVTs) for a Spanish speaking population. Culturally adapted cutoff scores for embedded PVTs were established using an analog study design. In addition, the psychometric properties of these measures when applying culturally adapted scores as compared to non-adapted scores were analyzed. METHOD: Participants (N = 114) were administered three embedded PVTs (Reliable Digit Span, Phonetic Fluency Test, and Animal Semantic Fluency Test) in a randomized order. Following an analog design, control participants were instructed to perform to the best of their abilities and the analog group was instructed to simulate cognitive impairment. RESULTS: In keeping with guidelines for specificity and sensitivity, the most culturally appropriate scores of ≤6, ≤27, and ≤16 were determined for the Reliable Digit Span, Phonetic Fluency Test, and the Semantic Fluency Test, respectively. CONCLUSIONS: This the first study addressing culturally sensitive cutoffs for commonly used embedded validity measures using a European Spanish population. While these findings cannot be generalized to forensic or clinical populations at the present time, they support the claim that specific cutoff scores that are sensitive to cultural variables are necessary in addressing embedded validity measures of the Reliable Digit Span, Phonetic Fluency Test, and Semantic Fluency Test.

Clinical characteristics and incidence of first fracture in a consecutive sample of post-menopausal women attending osteoporosis centers: The PROTEO-1 study.

BACKGROUND: Osteoporosis is a highly prevalent disease and fractures are a major cause of disability and morbidity. AIM: The purpose of this study was to characterize post-menopausal women attending osteoporosis centers in Italy, to evaluate physician management, and to determine the incidence of first osteoporotic fracture. SUBJECTS AND METHODS: PROTEO-1 was an observational longitudinal study with a 12-month follow-up. Data were collected from women attending osteoporosis centers. Women without prevalent fracture were eligible to enter the 1-yr follow-up phase: the clinical approach to patients according to their fracture risk profile and the incidence of fracture were recorded. RESULTS: 4269 patients were enrolled in 80 centers in the cross-sectional phase; 34.2% had an osteoporotic fracture at baseline. Patients with prevalent fractures were older and more likely to be treated compared with non-fractured patients. The incidence of vertebral or hip fracture after 1 yr was 3.84%, regardless of the calculated risk factor profile, and was significantly higher in patients with back pain at baseline (4.2%) compared with those without back pain (2.2%; p=0.023). Generally, physicians prescribed more blood exams and drugs to patients at higher risk of fracture. Among fractured patients only 24% were properly treated; the rate of non-responders to treatment was about 4%. CONCLUSIONS: In a large, unselected sample of post-menopausal women attending osteoporosis centers, those without previous fracture were at substantial risk of future fracture, regardless of their theoretical low 10-yr fracture risk. The presence of back pain in women without previous fracture warrants close attention.

The value of telephone consultations during COVID-19 pandemic. An observational study.

BACKGROUND: Many Spanish hospitals converted scheduled in-person visits to telephone visits during the COVID-19 lockdown. There is scarce information about the performance of those visits. AIM: To compare telephone visits during the COVID-19 lockdown period with previous in-person visits. DESIGN: Retrospective descriptive study. METHODS: Telephone visits from 15 March to 31 May 2020 were compared with in-person visits during the same period in 2019. MAIN MEASURES: The proportions of both groups were compared in term of failure to contact patient, requested diagnostic tests/referrals, discharges, admissions and emergency visits within 30-60 days. A sample of patients, and all participating physicians completed surveys. Z-score test was used (statistical significance P<0.05). RESULTS: A total of 5602 telephone visits were conducted. In comparison to in-person visits, telephone visits showed higher rates of visit compliance (95.9% vs. 85.2%, P<0.001) and discharges (22.12% vs. 11.82%; P<0.001), and lower number of ancillary tests and referrals. During the 30- and 60-day periods following the telephone visit, a reduction of 52% and 47% in the combined number of emergency department visits and hospital admissions was observed compared to in-person visits (P<0.01). Of the 120 patients surveyed, 95% were satisfied/very satisfied with the telephone visits. Of the 26 physicians, 84.6% considered telephone visits were useful to prioritize patients. CONCLUSIONS: During health emergencies, previously scheduled outpatient in-person visits can be converted to telephone visits, reducing absenteeism, increasing the rate of discharges and reducing ancillary tests and referrals without increasing the rate of hospital admissions or emergency department visits.

[Information systems for clinicians I. How to know what type of patients are attended in our hospitals]. / Sistemas de información para clínicos i. Cómo conocer qué tipo de pacientes se atienden en nuestros hospitales.

We describe a series of tools to study the types of patients treated in hospitals: the Minimum Basic Data Set (MBDS), International Classification of Diseases (ICD) and the more used patient classification system: Diagnosis Related Groups (DRG) and suggest their possible applications in the fields of management and clinical research.

[Information systems for clinicians II. How to analyze the efficiency and quality of in-hospital care]. / Sistemas de información para clínicos II. Cómo analizar la eficiencia y calidad de la asistencia intrahospitalaria.

We describe four possible readings of the analysis of case-mix in hospitals: variability of pathologies treated, assessment of the complexity of patients and efficiency in their care and analysis of quality of care in terms of clinical outcomes, as hospital mortality. We analyze the concept of risk adjustment, essential for comparison of results from different hospital services.

Epidemiology and clinical course of hepatitis A in Cantabria before and after the epidemic outbreak of June 2016. / Epidemiología y curso clínico de la hepatitis A en Cantabria antes y después del brote epidémico de junio 2016.

BACKGROUND AND OBJECTIVES: Since June 2016, there have been outbreaks of hepatitis A in various European countries, mainly affecting men who have sex with men (MSM). The aim of this study was to assess their clinical and epidemiological impact in Cantabria, Spain. MATERIAL AND METHODS: We retrospectively collected all cases of hepatitis A diagnosed in Cantabria between January 2013 and September 2018. We compared 2 periods: January 2013-May 2016 and June 2016-September 2018. RESULTS: A total of 156 cases were diagnosed, observing an increase in the incidence starting in October 2016. With regard to 2013-2016, we observed a higher proportion of men (50.0% vs. 84.5%; p=.012) with a predominance of the homosexual orientation (80.6%) and a higher rate of sexual transmission (0% vs. 48.3%; p=.061) for the patients in the 2016-2018 period. From the clinical standpoint, all cases of severe hepatitis occurred during this latter period. CONCLUSIONS: Our results reaffirm the high clinical and epidemiological impact of the epidemic outbreak in Cantabria and emphasizes the need for optimising the current prevention measures against hepatitis A.

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project.

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided.

Oil spill vulnerability assessment integrating physical, biological and socio-economical aspects: application to the Cantabrian coast (Bay of Biscay, Spain).

A methodology has been developed to carry out an integrated oil spill vulnerability index, V, for coastal environments. This index takes into account the main physical, biological and socio-economical characteristics by means of three intermediate indexes. Three different integration methods (worst-case, average and survey-based) along with ESI-based vulnerability scores, V(ESI), proposed for the Cantabrian coast during the Prestige oil spill, have been analyzed and compared in terms of agreement between the classifications obtained with each one for this coastal area. Results of this study indicate that the use of the worst-case index, V(R), leads to a conservative ranking, with a very poor discrimination which is not helpful in coastal oil spill risk management. Due to the homogeneity of this coastal stretch, the rest of the methods, V(I), V(M) and V(ESI), provide similar classifications. However, V(M) and V(I) give more flexibility allowing three indexes for each coastal segment and including socio-economic aspects. Finally, the V(I) procedure is proposed here as the more advisable as using this index promotes the public participation that is a key element in the implementation of Integrated Coastal Zone Management (IZCM).

Analysis of patients shared in consultations of internal medicine and other medical specialties. / Análisis de pacientes compartidos en consultas de medicina interna y otras especialidades médicas.

BACKGROUND AND OBJECTIVE: The aging population is resulting in an increasing number of patients with multiple diseases that require treatment by various specialties. We examined the evolution of consultations and of the percentage of patients treated by several medical specialties. METHODS: We analysed internal medicine (IM) consultations and those of other medical specialties in a hospital during 1997, 2007 and 2017 for the general population and for those older than 65 years. RESULTS: Over the course of 20 years, the rate of first IM consultations per 1000 inhabitants increased 44%, and that of other medical specialties increased 137%. The percentage of patients seen by more than one specialty went from 13.8% in 1997 to 32.6% in 2017 and reached 45.5% for those older than 65 years. CONCLUSIONS: The care for populations with growing comorbidity has a major impact on health systems and requires organisational changes for their care.

Validation of the PROFUND index to predict early post-hospital discharge mortality.

BACKGROUND: The PROFUND index (PI) is a prognostic scale for polypathological patients at 12 months. The objective of the study was to validate the PI as a predictor of 1-year mortality in a current cohort of polypathological patients and analyse its prognostic usefulness in the short-term (1 month and 3 months) after discharge from Internal Medicine. DESIGN: We conducted a prospective observational study and all polypathological patients discharged from an Internal Medicine Department between 01 March 2016 and 28 February 2017 were enrolled. METHODS: The variables recorded for each patient were age, sex, diseases and diagnostic categories defining patients as polypathological patients, PI at discharge, number of hospital admissions, length of stay, vital status at 1 year, and date and place of death if applicable. Follow-up lasted 1 year from the time of enrolment. RESULTS: Six hundred and ten polypathological patients were enrolled. Mortality was 41% and the patients who died were older, their length of stay was longer and their PI was higher compared with those who survived. The discrimination of the PI for predicting mortality was good, with a C-statistic of 0.718 [95% confidence interval (CI) 0.67-0.76]. In addition, a subgroup of patients with early mortality after discharge was identified, with a C-statistic of 0.74 (95% CI 0.67-0.80) at 30 days and 0.73 (95% CI 0.68-0.78) at 90 days. CONCLUSIONS: The PI is a valid tool for predicting early and 1-year mortality in polypathological patients after discharge from Internal Medicine.

[Influence of visual function on quality of life in patients with glaucoma]. / Influencia de la función visual en la calidad de vida de los pacientes con glaucoma.

OBJECTIVE: To determine the relationship between visual function objective measures and the perceived quality of life in patients with glaucoma and ocular hypertension. METHOD: This was a cross-sectional study of quality of life. Patients required knowledge to understand the questionnaire. PERIOD OF STUDY: April-May 2006. SETTING: third level hospital in Madrid. INSTRUMENT: Visual Function Index (VF-14). Visual acuity, computerized perimetry and ophthalmological examination were all performed. RESULTS: 120 questionnaires were distributed, 89.1% were returned completed. Cronbach's alpha was used for data validity and reliability (0.88). 49 patients had ocular hypertension (HTO) and 71 had glaucoma (52.1% men and 47.9% women). The mean health status was 73.9 (SD 24.13; range: 0-100); HTO: 81.4 (SD: 16.3) and glaucoma: 68.69 (SD:22) (p=0.001). These results were significantly correlated with the quality of life and visual acuity (r=0.51), mean deviation (MD) r=0.35, education level (p=0.024), and sex (p=0.031). No significant differences were found in the older groups or for evolution time. CONCLUSIONS: Quality of life measures can be useful in the management of patients with glaucoma, as a moderate relationship was found between quality of life, visual acuity and visual field loss in such patients. The VF-14 seems to discriminate between glaucoma and ocular hypertensive patients.

Geographical distribution and evolution of deaths in hospitals in Spain, 1996-2015. / Distribución geográfica y evolución de las muertes en hospitales en España, 1996-2015.

BACKGROUND AND OBJECTIVE: The location where death occurs varies widely among societies. The aim of this study was to describe the evolution in the hospital mortality rate (HMR) in Spain over the course of 20years and its distribution by province during a more recent period and to explore its relationship with potential explanatory variables. METHODS: This was an ecological study. The population mortality rates were obtained from the Natural Population Movement (Movimiento Natural de la Población), and the hospital mortality rates were obtained from the Specialised Care Information System (Sistema de Información en Atención Especializada), which includes information from all hospitals in Spain. We calculated the mortality rates for patients who were not surveyed and the HMR at the national level between 1996 and 2015 and for provinces between 2013 and 2015. The relationship between the provincial distribution of HMR and various demographic, socioeconomic and healthcare variables were analysed through simple and multiple linear regression. RESULTS: The HMR in Spain increased from 49% in 1996 to 56% in 2007, having remained stable from 1996 to 2015. The variation among provinces was 40% to 70%. The multivariate analysis showed a higher HMR in the less rural provinces and in those with a larger availability of hospital beds. CONCLUSIONS: There is considerable provincial heterogeneity in Spain in terms of the probability of dying in hospital or at home. This result could be partly explained by demographics (percentage of rural population) and the healthcare structure (number of hospital beds per population).