Spatiotemporal variability in socioeconomic inequalities in COVID-19 vaccination in Catalonia, Spain.

OBJECTIVES: Socioeconomic inequalities have played a significant role in the unequal coverage of the COVID-19 vaccine. The objectives of this study were to (1) assess the socioeconomic inequalities in COVID-19 vaccination coverage in Catalonia, Spain; (2) analyse the spatial variation over time of these inequalities; and (3) assess variations in time and space in the effect of vaccination on inequalities in COVID-19 outcomes. STUDY DESIGN: A mixed longitudinal ecological study design was used. METHODS: Catalonia is divided in to 373 Basic Health Areas. Weekly data from these Basic Health Areas were obtained from the last week of December 2020 until the first week of March of 2022. A joint spatio-temporal model was used with the dependent variables of vaccination and COVID-19 outcomes, which were estimated using a Bayesian approach. The study controlled for observed confounders, unobserved heterogeneity, and spatial and temporal dependencies. The study allowed the effect of the explanatory variables on the dependent variables to vary in space and in time. RESULTS: Areas with lower socioeconomic level were those with the lowest vaccination rates and the highest risk of COVID-19 outcomes. In general, individuals in areas that were located in the upper two quartiles of average net income per person and in the lower two quartiles of unemployment rate (i.e., the least economically disadvantaged) had a higher propensity to be vaccinated than those in the most economically disadvantaged areas. In the same sense, the greater the percentage of the population aged ≥65 years, the higher the propensity to be vaccinated, while areas located in the two upper quartiles of population density and areas with a high percentage of poor housing had a lower propensity to be vaccinated. Higher vaccination rates reduced the risk of COVID-19 outcomes, while COVID-19 outcomes did not influence the propensity to be vaccinated. The effects of the explanatory variables were not the same in all areas or between the different waves of the pandemic, and clusters of excess risk of low vaccination in the most disadvantaged areas were detected. CONCLUSIONS: COVID-19 vaccination inequalities in the most disadvantaged areas could be a result of structural barriers, such as the lack of access to information about the vaccination process, and/or logistical challenges, such as the lack of transportation, limited Internet access or difficulty in scheduling appointments. Public health strategies should be developed to mitigate these barriers and reduce vaccination inequalities.

Short-term effects of air pollution and noise on emergency hospital admissions in Madrid and economic assessment.

INTRODUCTION: The aim of this study was to study the effect of air pollution and noise has on the population in Madrid Community (MAR) in the period 2013-2018, and its economic impact. METHODS: Time series study analysing emergency hospital admissions in the MAR due to all causes (ICD-10: A00-R99), respiratory causes (ICD-10: J00-J99) and circulatory causes (ICD-10: I00-I99) across the period 2013-2018. The main independent variables were mean daily PM2.5, PM10, NO2, 8-h ozone concentrations, and noise. We controlled for meteorological variables, Public Holidays, seasonality, and the trend and autoregressive nature of the series, and fitted generalised linear models with a Poisson regression link to ascertain the relative risks and attributable risks. In addition, we made an economic assessment of these hospitalisations. RESULTS: The following associations were found: NO2 with admissions due to natural (RR: 1.007, 95% CI: 1.004-1.011) and respiratory causes (RR: 1.012, 95% CI: 1.005-1.019); 8-h ozone with admissions due to natural (RR: 1.049, 95% CI: 1.014-1.046) and circulatory causes (RR: 1.088, 95% CI: 1.039-1.140); and diurnal noise (LAeq7-23h) with admissions due to natural (RR: 1.001, 95% CI: 1.001-1.002), respiratory (RR: 1.002, 95% CI: 1.001-1.003) and circulatory causes (RR: 1.003, 95% CI: 1.002-1.005). Every year, a total of 8246 (95% CI: 4580-11,905) natural-cause admissions are attributable to NO2, with an estimated cost of close on €120 million and 5685 (95% CI: 2533-8835) attributed to LAeq7-23h with an estimated cost of close on €82 million. CONCLUSIONS: Nitrogen dioxide, ozone and noise are the main pollutants to which a large number of hospitalisations in the MAR are attributed, and are thus responsible for a marked deterioration in population health and high related economic impact.

[Mechanical thrombectomy in a Chilean public hospital. Experience in 149 patients]. / Manejo avanzado del infarto cerebral en un hospital público chileno: trombectomía mecánica en el Hospital Barros Luco Trudeau.

BACKGROUND: Mechanical thrombectomy is the accepted treatment for acute ischemic stroke in Large Vessel Occlusion. The Barros Luco Trudeau hospital developed endovenous thrombolysis in 2010, and since 2012, implemented endovascular management, becoming the neurovascular center in the southern area of the metropolitan region. AIM: To describe endovascular management of acute ischemic stroke in a Chilean public hospital. MATERIAL AND METHODS: Analysis of patients with acute ischemic stroke that were treated with mechanical throm-bectomy from 2012 to 2019 in the Barros Luco Hospital. RESULTS: In the study period, a mechanical thrombectomy was carried out in 149 patients aged 61 ± 15 years (46% females). The average National institute of Health Stroke Scale (NIHSS) at presentation was 19 ± 4-5. Anterior or posterior circulation involvement was present in 89.9 and 10.1 % of patients. Twenty-five percent of patients were referred from other public centers. The mean lapse between onset of symptoms and thrombectomy was 266 ± 178 in. Ninety days after the procedure, 58% of patients had minimal or absent disability (Modified Ranson score of 0-2), and 19,2% died. CONCLUSIONS: Mechanical thrombectomy, according to this experience, has favorable clinical outcomes in patients with high NIHSS scores at entry.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Partial contributions and temporal trends of leading causes of death during the last four decades in Spain.

OBJECTIVES: The study was conducted to assess time trend shifts of leading causes of death and their partial contributions over the years 1975-2016 in Spain. STUDY DESIGN: A longitudinal ecological epidemiologic design was conducted to analyse linear trend period shifts using joinpoint regression as the annual percentage of change (APC) in the period 1975-2016. The partial contributions were illustrated as the rate ratio of a singular-cause to their major-cause shift periods. RESULTS: HIV/AIDS shaped the increasing trend period of infectious diseases in 1989-1995 (APC = 25.3, P < 0.05) and the decreasing trend in 1995-1999 and 1999-2016. Lung cancer fell gradually from 1994 in men (-0.4, P < 0.05); however, in women, the condition continued increasing from 1990 (P < 0.05). Dementia types influenced mental and neurological disease drifts. The recent trend for circulatory periods (1980-2016) was mainly modulated by cardiac ischaemia, with increased partial contributions (25%, 32% and 30%). Traffic accidents defined the descending tendency of external causes. CONCLUSIONS: Spain showed a Western pattern in descended rates, including non-decreasing trends in mental and neurological diseases, pancreatic cancer, drug abuse and suicide. Trend shifts and partial contributions illustrated targets for further mortality reduction.

A novel mobile application to determine mandibular and tongue laterality discrimination in women with chronic temporomandibular disorder.

BACKGROUND: Chronic pain from temporomandibular disorders (TMDs) is caused by a somatosensory disturbance due to sustained activation of central nervous system nociceptive pathways, which can induce changes in neuroplasticity in the thalamus, basal ganglia and limbic system, as well as disturbances in the somatosensory, prefrontal and orbitofrontal cortex and cognitive impairment. The main objective of this study was to determine the discrimination capacity of mandibular and tongue laterality between women with chronic TMDs and asymptomatic women. MATERIAL AND METHODS: This descriptive-comparative study examined 2 groups with a total of 30 women. All participants were between the ages of 23 and 66 years and were assigned to the chronic TMD group or the asymptomatic group according to the inclusion criteria. We employed a mobile application developed specifically for this study to measure the accuracy and reaction time (RT) of mandibular and tongue laterality discrimination. RESULTS: The chronic TMD group had a lower success rate in laterality discrimination (mean mandibular accuracy of 40% and mean tongue accuracy of 67%) than the asymptomatic group (mean mandibular accuracy of 61% and mean tongue accuracy of 90%). These results showed statistically significant differences between the groups for mandibular laterality discrimination (d, 1.14; p<0.01) and tongue laterality discrimination (d, 0.79; p=0.03). The asymptomatic group had faster RTs than the chronic TMD group. The data revealed statistically significant differences for the right mandibular RT (d, 0.89; p=0.02) and right tongue RT (d, 0.83; p=0.03). However, there were no significant differences for left mandibular and left tongue RT. CONCLUSIONS: We found that the women with chronic TMDs had a lower success rate and slower RTs in the discrimination of mandibular laterality when compared with the asymptomatic women.

Mortality attributable to high temperatures over the 2021-2050 and 2051-2100 time horizons in Spain: Adaptation and economic estimate.

BACKGROUND: In recent years, a number of studies have been conducted with the aim of analysing the impact that high temperatures will have on mortality over different time horizons under different climate scenarios. Very few of these studies take into account the fact that the threshold temperature used to define a heat wave will vary over time, and there are practically none which calculate this threshold temperature for each geographical area on the assumption that there will be variations at a country level. OBJECTIVE: To analyse the impact that high temperatures will have on mortality across the periods 2021-2050 and 2051-2100 under a high-emission climate scenario (RCP8.5), in a case: (a) where adaptation processes are not taken into account; and (b) where complete adaptation processes are taken into account. MATERIAL AND METHODS: Based on heat-wave definition temperature (Tthreshold) values previously calculated for the reference period, 2000-2009, for each Spanish provincial capital, and their impact on daily mortality as measured by population attributable risk (PAR), the impact of high temperatures on mortality will be calculated for the above-mentioned future periods. Two hypotheses will be considered, namely: (a) that Tthreshold does not vary over time (scenario without adaptation to heat); and, (b) that Tthreshold does vary over time, with the percentile to which said Tthreshold corresponds being assumed to remain constant (complete adaptation to heat). The temperature data were sourced from projections generated by Coupled Model Intercomparison Project (CMIP5) climate models adapted to each region's local characteristics by the State Meteorological Agency (Agencia Estatal de Meteorología/AEMET). Population-growth projections were obtained from the National Statistics Institute (Instituto Nacional de Estadística/INE). In addition, an economic estimate of the resulting impact will be drawn up. RESULTS: The mean value of maximum daily temperatures will rise, in relation to those of the reference period (2000-2009), by 1.6°C across the period 2021-2050 and by 3.3°C across the period 2051-2100. In a case where there is no heat-adaptation process, overall annual mortality attributable to high temperatures in Spain would amount to 1414 deaths/year (95% CI: 1089-1771) in the period 2021-2050, rising to 12,896 deaths/year (95% CI: 9852-15,976) in the period 2051-2100. In a case where there is a heat-adaptation process, annual mortality would be 651 deaths/year (95% CI: 500-807) in the period 2021-2050, and 931 deaths per year (95% CI: 770-1081) in the period 2051-2100. These results display a high degree of heterogeneity. The savings between a situation that does envisage and one that does not envisage an adaptive process is €49,100 million/year over the 2051-2100 time horizon. CONCLUSION: A non-linear increase in maximum daily temperatures was observed, which varies widely from some regions to others, with an increase in mean values for Spain as a whole that is not linear over time. The high degree of heterogeneity found in heat-related mortality by region and the great differences observed on considering an adaptive versus a non-adaptive process render it necessary for adaptation plans to be implemented at a regional level.

Will there be cold-related mortality in Spain over the 2021-2050 and 2051-2100 time horizons despite the increase in temperatures as a consequence of climate change?

INTRODUCTION: Global warming is resulting in an increase in temperatures which is set to become more marked by the end of the century and depends on the accelerating pace of greenhouse gas emissions into the atmosphere. Yet even in this scenario, so-called "cold waves" will continue to be generated and have an impact on health. OBJECTIVES: This study sought to analyse the impact of cold waves on daily mortality at a provincial level in Spain over the 2021-2050 and 2051-2100 time horizons under RCP4.5 and RCP 8.5 emission scenarios, on the basis of two hypotheses: (1) that the cold-wave definition temperature (T threshold) would not vary over time; and, (2) that there would be a variation in T threshold. MATERIAL AND METHODS: The results of a retrospective study undertaken for Spain as a whole across the period 2000-2009 enabled us to ascertain the cold-wave definition temperature at a provincial level and its impact on health, measured by reference to population attributable risk (PAR). The minimum daily temperatures projected for each provincial capital considering the above time horizons and emission scenarios were provided by the State Meteorological Agency. On the basis of the T threshold definition values and minimum daily temperatures projected for each province, we calculated the expected impact of low temperatures on mortality under the above two hypotheses. Keeping the PAR values constant, it was assumed that the mortality rate would vary in accordance with the available data. RESULTS: If T threshold remained constant over the above time horizons under both emission scenarios, there would be no cold-related mortality. If T threshold were assumed to vary over time, however, then cold-related mortality would not disappear: it would instead remain practically constant over time and give rise to an estimated overall figure of around 250 deaths per year, equivalent to close on a quarter of Spain's current annual cold-related mortality and entailing a cost of approximately €1000 million per year. CONCLUSION: Given that cold waves are not going to disappear and that their impact on mortality is far from negligible and is likely to remain so, public health prevention measures must be implemented to minimise these effects as far as possible.

Drug cost avoidance in clinical trials of breast cancer.

BACKGROUND: The objectives of this study were to determine if clinical trials in breast cancer, with an investigational drug, created direct drug cost savings for the healthcare system related to cost avoidance of the best standard of care treatments used in these studies. The aim was to quantify this potential drug cost avoidance. METHODS: We conducted a retrospective observational study of the drug cost avoidance during the study period (2014-2016). We included clinical trials with investigational drug, managed by pharmacy department and provided by the sponsor. The patients included had a therapeutic alternative defined as standard treatment that should have been received in case of not participating in the clinical trial. Direct cost savings, to national healthcare system, associated to clinical trials were calculated. RESULTS: Thirty-seven clinical trials with a total of 89 breast cancer patients were included in the study. A total of 62.2% were phase III and 75.7% belonged to the pharmaceutical industry. They provided a total cost avoidance of 957,246€ (1,130,028$), an average cost avoidance per patient of 10,756€ (12,697$). CONCLUSIONS: Our study suggests that those clinical trials in which investigational drug are provided or refunded by the sponsor provide substantial cost savings. Due to the shortage of published articles that calculate the cost avoided in medication, we cannot compare directly the results obtained in the different institutions.

Feed pellets containing chitosan nanoparticles as plasmid DNA oral delivery system for fish: In vivo assessment in gilthead sea bream (Sparus aurata) juveniles.

The aim of this study was the assessment of preloaded feed pellets as a delivery system for plasmid DNA (pDNA), with the purpose of evaluating the potential administration of DNA vaccines orally in aquacultured fish. Pellets were made up by usual feed ingredients, which were mixed with chitosan nanoparticles entrapping a model plasmid (pCMVß) expressible in eukaryotic cells before being elaborated. The plasmid is characterized by the insertion of the reporter gene lacZ, encoding for the bacterial enzyme ß-galactosidase (ß-gal). The possible in vivo expression of the exogenous gene was measured in different fish tissues of gilthead sea bream (Sparus aurata) juveniles by two different procedures. On the one hand, the activity of the enzyme ß-gal was detected and quantified in muscle, liver and intestine; on the other, specific IgM against ß-gal antigen was titrated in blood samples. Intramuscular (i.m.) injection of equal amounts of plasmid was also carried out for the purpose of comparison with oral administration. The expression of the reporter gene was detected in fish tissues following both oral and i. m. administration of pDNA up to 60 days. However, organ distribution of the gene expression was more evident after oral (ß-gal activity measured in gut, liver and muscle) than after parenteral administration (restricted to adjacent muscle tissues). In agreement, specific IgM titration indicated that humoral immune response was more intense and sustained throughout the experimental period after oral than after i. m. delivery of equal amounts of pDNA. These results suggest that feed pellets containing chitosan nanoparticles might enable efficient oral delivery of pDNA, a fact that might imply valuable applications in terms of on-farm mass immunization purposes, especially with regard to DNA-based vaccines and small size fish, in which i. m. administration remains unfeasible.

Eosinophilia secondary to lenalidomide therapy.

WHAT IS KNOWN AND OBJECTIVE: Limited data are available on eosinophilia as a drug adverse event. We describe a case of eosinophilia from lenalidomide therapy. CASE DESCRIPTION: A 50-year-old woman received lenalidomide, dexamethasone and cyclophosphamide as POEMS syndrome treatment. Eosinophil count rose during lenalidomide treatment and decreased in the periods off treatment. Naranjo nomogram suggested a probable association between the use of lenalidomide and eosinophilia. WHAT IS NEW AND CONCLUSION: Eosinophilia has rarely been described with lenalidomide. This case shows a clear temporal relationship between lenalidomide and eosinophilia.

Concomitant use of sorafenib with ombitasvir/paritaprevir/ritonavir and dasabuvir: Effectiveness and safety in clinical practice.

WHAT IS KNOWN AND OBJECTIVE: No studies have evaluated the use of sorafenib with the direct-acting antiviral ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV). CASE SUMMARY: Three hepatitis C virus genotype 1b-infected patients with well-preserved liver function were included in this prospective case series. The patients were taking sorafenib for advanced hepatocellular carcinoma and received OBV/PTV/r+DSV for 12 weeks. One patient discontinued sorafenib while concomitant treatment due to grade 2 fatigue and muscular pain. The other two patients reported only grade 1 adverse effects. Sustained virologic response at 24 weeks was achieved, and no tumour recurrences were found. WHAT IS NEW AND CONCLUSION: The concurrent use of OBV/PTV/r+DSV with sorafenib was considered safe and effective.

Growth performance, body composition, and digestive functionality of Senegalese sole (Solea senegalensis Kaup, 1858) juveniles fed diets including microalgae freeze-dried biomass.

Senegalese sole is one of the most promising fish species cultivated in the Southern European countries. This study was aimed at assessing the effects of microalgae biomass added to diets for Senegalese sole juveniles on fish growing and condition status. Three isoproteic (52%) and isolipidic (10%) were formulated containing 15% Tisochrysis lutea (TISO), Nannochloropsis gaditana (NAN), or Scenedesmus almeriensis (SCE) biomass, respectively. An experimental microalgae-free diet (CT) and a commercial diet (COM) were used as controls. Fish were fed at 3% of their body weight for 85 days. Final body weight of fish fed microalgae-supplemented diets did not differ from group fed CT diet. Fish-fed CT, TISO, NAN, and SCE showed higher growth performance and nutrient utilization figures than specimen-fed COM diet. The highest carcass lipid content was found in COM group (141 g kg-1), and no differences were observed in body protein content. Ash was significantly higher in TISO, NAN, and SCE groups compared to fish-fed CT. Muscle EPA and DHA contents were not modified owing to the different dietary treatments. The n3/n6 and EPA/DHA ratios in muscle were similar in all the experimental groups. The quantification of digestive proteolytic activities did not differ among experimental groups, although differences in the protease pattern in digestive extracts by zymography were revealed in those fish fed on COM diet. Both α-amylase activity in the intestinal lumen and leucine aminopeptidase in the intestinal tissue were significantly lower in COM fish. Specimens fed on SCE diet showed a higher leucine aminopeptidase activity associated to the intestinal tissue compared to NAN-fed fish (0.40 and 0.25 U g tissue-1, respectively). The ultrastructural study revealed that the dietary inclusion of algal biomass, especially T. lutea and N. gaditana, had a positive impact on the absorptive capacity of the intestinal mucosa. The highest values for the parameters microvilli length and microvilli absorption surface were observed in fish fed on NAN diet (1.99 µm and 45.93 µm2, respectively). Even though further studies aimed at optimizing commercial formulas for Senegalese sole are required prior to any large-scale practical utilization, the results obtained clearly suggest the potential of microalgae as dietary ingredients for this fish species.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

Bone density, microarchitecture, and material strength in chronic kidney disease patients at the time of kidney transplantation.

Bone health is assessed by bone mineral density (BMD). Other techniques such as trabecular bone score and microindentation could improve the risk of fracture's estimation. Our chronic kidney disease (CKD) patients presented worse bone health (density, microarchitecture, mechanical properties) than controls. More than BMD should be done to evaluate patients at risk of fracture. INTRODUCTION: BMD measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health in end-stage renal disease (ESRD) patients. Recently, trabecular bone score (TBS) and microindentation that can measure microarchitectural and mechanical properties of bone have demonstrated better correlation with fractures than DXA in different populations. We aimed to characterize bone health (BMD, TBS, and strength) and calcium/phosphate metabolism in a cohort of 53 ESRD patients undergoing kidney transplantation (KT) and 94 controls with normal renal function. METHODS: Laboratory workout, lumbar spine/hip BMD measurements (using DXA), lumbar spine TBS, and bone strength were carried out. The latter was assessed with an impact microindentation device, standardized as percentage of a reference value, and expressed as bone material strength index (BMSi) units. Multivariable linear regression was used to study differences between cases and controls adjusted by age, gender, and body mass index. RESULTS: Among cases, serum calcium was 9.6 ± 0.7 mg/dl, phosphorus 4.4 ± 1.2 mg/dl, and intact parathyroid hormone 214 pg/ml [102-390]. Fourteen patients (26.4%) had prevalent asymptomatic fractures in spinal X-ray. BMD was significantly lower among ESRD patients compared to controls: lumbar 0.966 ± 0.15 vs 0.982 ± 0.15 (adjusted p = 0.037), total hip 0.852 ± 0.15 vs 0.902 ± 0.13 (adjusted p < 0.001), and femoral neck 0.733 ± 0.15 vs 0.775 ± 0.12 (adjusted p < 0.001), as were TBS (1.20 [1.11-1.30] vs 1.31 [1.19-1.43] (adjusted p < 0.001)) and BMSi (79 [71.8-84.2] vs 82. [77.5-88.9] (adjusted p = 0.005)). CONCLUSIONS: ESRD patients undergoing transplant surgery have damaged bone health parameters (density, microarchitecture, and mechanical properties) despite acceptably controlled hyperparathyroidism. Detecting these abnormalities may assist in identifying patients at high risk of post-transplantation fractures.

Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents.

We assessed the impact of a pharmacotherapy follow-up programme on key safety points [adverse events (AE) and drug administration] in outpatients treated with oral antineoplastic agents (OAA). We performed a comparative, interventional, quasi-experimental study of outpatients treated with OAA in a Spanish hospital to compare pre-intervention group patients (not monitored by pharmacists during 2011) with intervention group patients (prospectively monitored by pharmacists during 2013). AE data were collected from medical records. Follow-up was 6 months, and 249 patients were included (pre-intervention, 115; intervention, 134). After the first month, AE were detected in 86.5% of patients in the pre-intervention group and 80.6% of patients in the intervention group, P = 0.096. During the remaining months, 79.0% patients had at least one AE in the pre-intervention group compared with 78.0% in the intervention group, P = 0.431. AE were more prevalent with sorafenib and sunitinib. In total, 173 drug interactions were recorded (pre-intervention, 80; intervention, 93; P = 0.045). Drug interactions were more frequent with erlotinib and gefitinib; food interactions were more common with sorafenib and pazopanib. Our follow-up of cancer outpatients revealed a reduction in severe AE and major drug interactions, thus helping health professionals to monitor the safety of OAA.

Survival Benefit From Kidney Transplantation Using Kidneys From Deceased Donors Aged ≥75 Years: A Time-Dependent Analysis.

Patients with end-stage renal disease have longer survival after kidney transplantation than they would by remaining on dialysis; however, outcome with kidneys from donors aged ≥75 years and the survival of recipients of these organs compared with their dialysis counterparts with the same probability of obtaining an organ is unknown. In a longitudinal mortality study, 2040 patients on dialysis were placed on a waiting list, and 389 of them received a first transplant from a deceased donor aged ≥75 years. The adjusted risk of death and survival were calculated by non-proportional hazards analysis with being transplanted as a time-dependent effect. Projected years of life since placement on the waiting list was almost twofold higher for transplanted patients. Nonproportional adjusted risk of death after transplantation was 0.44 (95% confidence interval [CI] 0.61-0.32; p < 0.001) in comparison with those that remained on dialysis. Stratifying by age, adjusted hazard ratios for death were 0.17 (95% CI 0.47-0.06; p = 0.001) for those aged <65 years, 0.56 (95% CI 0.92-0.34; p = 0.022) for those aged 65-69 years and 0.82 (95% CI 1.28-0.52; p = 0.389) for those aged ≥70 years. Although kidney transplantation from elderly deceased donors is associated with reduced graft survival, transplanted patients have lower mortality than those remaining on dialysis.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.