Vitamin d deficiency with high parathyroid hormone levels is related to late onset SEPSIS among preterm infants.

Preterm infants (PTs) are at greater risk for vitamin D deficiency, which relates to the possibility of a higher incidence of comorbidities. Our goal was twofold, 1) to monitor vitamin D, calcium, phosphorus, parathyroid hormone (PTH), matrix metalloproteinase-8 (MMP-8) serum levels at three-time points during hospitalization, and 2) to assess the association between 25-hydroxyvitamin D (25OHD) levels and outcomes in PTs. METHODS: We carried out a follow-up on 50 Caucasian PTs ≤ 32 weeks of gestational age (GA) and/or ≤ 1500 g birth weight at 28 days and at 4 months. PTs were divided into two subgroups for tests of association with clinical outcomes based on vitamin D deficient infants 25(OH) D cord blood levels: ≤ 20 ng/ml). At an initial stage, 25(OH) D levels were determined in maternal/preterm blood samples and were compared to full term delivery infants. RESULTS: There were no differences in 25(OH) D serum levels at birth when comparing PTs to term infants, or regarding maternal levels. A strong positive correlation was detected between maternal and neonatal 25(OH) D serum levels among PTs and term infants (r: 0.466; p < 0.001). Neonates with vitamin D deficiency did not present a higher incidence of comorbidities. PTs were classified in two subgroups based on vitamin D and PTH (group 1: vitamin D < 20 ng/mL and PTH > 60 pg/mL; group 2: vitamin D > 20 and PTH < 60 pg/mL). The PTs in group 1 showed a higher incidence of LOS (RR: 2; 95% CI: 1.31-3.55). No relationship was observed between MMP-8 serum levels and the incidence of sepsis. CONCLUSIONS: This study did not find any evidence of an increase in preterm birth risk related to vitamin D level at birth. Vitamin D deficiency by itself is not associated with a higher incidence of comorbidities. However, the binomial vitamin D-PTH must be taken into consideration.

Farmers' perceptions and acceptance of crossbred guinea pigs in Mantaro Valley, Peru.

This study aimed at assessing farmers' perceptions and acceptance of the proposed breeding strategy of Instituto Veterinario de Investigaciones Tropicales y de Altura (IVITA), located in the Central Andes of Peru. A total of 34 farmers, who had received guinea pigs from IVITA, were interviewed. The questionnaire was performed in Spanish language and covered topics about the guinea pig production, feeding, mating system, training, the main products, perception and acceptance of crossbred lines ("cuy RG"), and the farmers' comment about the terminal crossbred animal ("cuy G"). The preferred feeding strategy was a combination of forage and supplement. All farmers implemented a controlled mating system. Most farmers had received training on feeding, reproduction, management, equipment, and facilities. The main product is animals for slaughter. The 82.40% of farmers reported that they do not purchase guinea pigs from IVITA anymore, because they are highly susceptibility to lymphadenitis, which is a highly contagious disease and causes swollen lymph nodes and affects the meat quality. Most of the respondents classified the "cuy RG" and "cuy G" as suitable for meat production and were satisfied with the performance of the animals. Therefore, 58.80% of respondents already recommended "cuy RG" to other farmers. However, 17.70% of the respondents would not recommend these animals because they are susceptible to disease, especially lymphadenitis. Therefore, IVITA should engage in more structured dialogue with farmers and regularly include their opinion in future improvement of its breeding strategies. This could help to reach higher acceptance rates by farmers.

Biologically synthesized silver nanoparticles as potent antibacterial effective against multidrug-resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.

Manufacture of magnesium-fortified Chihuahua cheese.

The aim of this study was to manufacture magnesium-fortified Chihuahua cheese and to evaluate the effect of magnesium fortification on quality parameters. Addition of magnesium chloride to milk during pasteurization (5.44, 10.80, 16.40, 22.00, and 25.20 g of MgCl2·6H2O/L of milk) resulted in cheese with increased magnesium content, proportional to the amount of magnesium added (up to 2,957.13 mg of Mg/kg of cheese). As magnesium content increased, coagulation time and moisture content also increased, whereas calcium content decreased. Higher levels of magnesium fortification (16.40 g of MgCl2·6H2O/L of milk or more) induced the development of bitter-acid flavors and softer texture. Addition of 10.80 g of MgCl2·6H2O/L to milk resulted in Chihuahua cheese that meets regulatory standards and possesses physicochemical and sensory characteristics similar to those of nonfortified Chihuahua cheese. Under this milk fortification level, the manufactured cheese is able to provide 148.4 mg of magnesium per day (35% of the recommended daily intake of magnesium for adult males and 46% for adult females) assuming 3 portions (28 g each) are consumed.

Breathing variability during propofol/remifentanil procedural sedation with a single additional dose of midazolam or s-ketamine: a prospective observational study.

PURPOSE: Regulation of spontaneous breathing is highly complex and may be influenced by drugs administered during the perioperative period. Because of their different pharmacological properties we hypothesized that midazolam and s-ketamine exert different effects on the variability of minute ventilation (MV), tidal volume (TV) and respiratory rate (RR). METHODS: Patients undergoing procedural sedation (PSA) with propofol and remifentanil received a single dose of midazolam (1-3 mg, n = 10) or s-ketamine (10-25 mg, n = 10). We used non-invasive impedance-based respiratory volume monitoring to record RR as well as changes in TV and MV. Variability of these three parameters was calculated as coefficients of variation. RESULTS: TV and MV decreased during PSA to a comparable extent in both groups, whereas there was no significant change in RR. In line with our hypothesis we observed marked differences in breathing variability. The variability of MV (- 47.5% ± 24.8%, p = 0.011), TV (- 42.1% ± 30.2%, p = 0.003), and RR (- 28.5% ± 29.3%, p = 0.011) was significantly reduced in patients receiving midazolam. In contrast, variability remained unchanged in patients receiving s-ketamine (MV + 16% ± 45.2%, p = 0.182; TV +12% ± 47.7%, p = 0.390; RR +39% ± 65.2%, p = 0.129). After termination of PSA breathing variables returned to baseline values. CONCLUSIONS: While midazolam reduces respiratory variability in spontaneously breathing patients undergoing procedural sedation, s-ketamine preserves variability suggesting different effects on the regulation of spontaneous breathing.

Effectiveness of a decision aid for patients with knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To assess the effectiveness of a Patient Decision Aid (PtDA) for knee osteoarthritis. METHOD: Randomized controlled trial, in which 193 patients were allocated to the PtDA or usual care. Outcome measures were the Decisional Conflict Scale (DCS), knowledge of osteoarthritis and arthroplasty, satisfaction with the decision-making process (SDMP) and treatment preference, assessed immediately after the intervention. At 6 months, the same measures were applied in non-operated patients, whereas those who underwent arthroplasty completed the SDMP and the Decisional Regret Scale (DRS). RESULTS: The PtDA produced a significant immediate improvement of decisional conflict (MD = -11.65, 95%CI: -14.93, -8.37), objective knowledge (MD = 10.37, 99%IC: 3.15, 17.70) and satisfaction (MD = 6.77, 99%CI: 1.19, 12.34), and a different distribution of preferences (χ2 = 8.74, p = 0.033). Patients with less than secondary education obtained a stronger effect on decisional conflict (p = 0.015 for the interaction) but weaker for knowledge (p = 0.051). At 6 months, there were no significant differences in any variable, including the rate of total knee replacement. Operated patients showed a low level of regret, which was not affected by the intervention. CONCLUSION: The PtDA is effective immediately after its application, but it shows no effects in the medium-term. Future research should investigate which subgroups of patients could benefit more from this intervention, as well as the longitudinal evolution of decision-related psychological variables.

Variations in respiratory rate do not reflect changes in tidal volume or minute ventilation after major abdominal surgery.

Monitoring of postoperative pulmonary function usually includes respiratory rate and oxygen saturation measurements. We hypothesized that changes in postoperative respiratory rate do not correlate with changes in tidal volume or minute ventilation. In addition, we hypothesized that variability of minute ventilation and tidal volume is larger than variability of respiratory rate. Respiratory rate and changes in tidal volume and in minute ventilation were continuously measured in 27 patients during 24 h following elective abdominal surgery, using an impedance-based non-invasive respiratory volume monitor (ExSpiron, Respiratory Motion, Waltham, MA, US). Coefficients of variation were used as a measure for variability of respiratory rate, tidal volume and minute ventilation. Data of 38,149 measurements were analyzed. We found no correlation between respiratory rate and tidal volume or minute ventilation (r2 = 0.02 and 0.01). Mean respiratory rate increased within the first 24 h after abdominal surgery from 13.9 ± 2.5 to 16.2 ± 2.4 breaths/min (p = 0.008), while tidal volume and minute ventilation remained unchanged (p = 0.90 and p = 0.18). Of interest, variability of respiratory rate (0.21 ± 0.06) was significantly smaller than variability of tidal volume (0.37 ± 0.12, p < 0.001) and minute ventilation (0.41 ± 0.12, p < 0.001). Changes in postoperative respiratory rate do not allow conclusions about changes in tidal volume or minute ventilation. We suggest that postoperative alveolar hypoventilation may not be recognized by monitoring respiratory rate alone. Variability of respiratory rate is smaller than variability in tidal volume and minute ventilation, suggesting that adaptations of alveolar ventilation to metabolic needs may be predominately achieved by variations in tidal volume.

Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

Estimation of genetic parameters for four Peruvian guinea pig lines.

This study aimed to estimate genetic parameters for four guinea pig lines of a crossbreeding scheme. Two paternal lines are selected for growth rate (P1) and feed conversion rate (P2), whereas two maternal lines are selected for growth rate of litter (M1) and litter size at birth (M2). The heritabilities and genetic correlations were estimated with animal linear models employing multivariate analyses with REML. The heritabilities for birth weight (BW) were 0.21±0.02 and 0.23±0.03 for P1 and P2, respectively, and for weaning weight (WW), the heritability was 0.28±0.03 for P2. The estimates for weight at 60 days of age (W60) were 0.34±0.01 and 0.47±0.04 for P1 and P2, respectively, and for partial feed conversion rate was 0.46±0.03 for P2. Heritabilities for litter weight at birth (LW) were 0.09±0.03 and 0.10±0.03 for P1 and M1, respectively. For litter weight at 10 days of age (LW10), the heritability was 0.15±0.03 for M1. Heritabilities for litter size (LS) were 0.17±0.03, 0.20±0.03 and 0.11±0.03, and for number of pups born alive (BA) were 0.09±0.03, 0.14±0.03 and 0.09±0.03 for P1, M1 and M2, respectively. Similarly, high genetic correlations were found between BW, WW and W60 and between LW, LS, LW10 and BA. The genetic correlation between BW direct and maternal was moderately negative (- 0.24 ± 0.10) for P1. These results show the genetic status for all four guinea pig lines, which is essential for the further improvement of the currently implemented breeding programme and also indicate an opportunity for genetic improvement.

Anxiety levels among social work students during the COVID-19 lockdown in Spain.

The COVID-19 pandemic has compelled university students to adapt to remote learning modalities resulting in increased of anxiety symptoms. This study explores levels of anxiety, and risk and protection factors among Social Work students at two universities in southern Spain. Thirty four percent were experiencing severe anxiety, and 28.5% mild to moderate, revealing that anxiety levels had increased significantly. Greater concern about academic situation and future economic scenario, living in an urban area and leave the habitual residence increased anxiety symptoms. By contrast, family income stability and higher social support from relatives reduced anxiety symptoms. These results support the planning of emotional support services for college students, as well as the incorporation in the study plans the acquisition of skills to live better in these conditions.

Electron versus Muon Neutrino Induced Cross Sections in Charged Current Quasielastic Processes.

Differences between ν_{e} and ν_{µ} quasielastic cross sections are essential in neutrino oscillation analyses and CP violation searches for experiments such as DUNE and T2HK. The ratio of these is however poorly known experimentally and for certain kinematic regions theoretical models give contradictory answers. We use two independent mean-field based models to investigate this ratio using ^{40}Ar and ^{12}C targets. We demonstrate that a proper treatment of the final nucleon's wave function confirms the dominance of ν_{µ} over ν_{e} induced cross sections at forward lepton scattering.

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.

Differences in the regulation of inflammatory pathways in adolescent- and adult-onset first-episode psychosis.

A precise description of the inflammatory response in first-episode psychosis (FEP) by age of onset does not exist. We explored baseline and 6-month follow-up differences in the pro/anti-inflammatory balance in plasma and peripheral blood mononuclear cells in adolescent-onset FEP (≤ 18 y.o., N = 27) and adult-onset FEP (≥ 25 y.o., N = 43) using non-parametric 1-category ANCOVA, with age group as an independent variable and values of pro- and anti-inflammatory markers at baseline and at follow-up as dependent variables. We used a non-parametric repeated-measures mixed-effects model to explore the baseline/6-month change in pro- and anti-inflammatory markers within adolescent- and adult-onset groups, exploring differential trajectories of change by means of the interaction of time by age-of-onset group. Levels of the nuclear transcription factor (NFκB), a master regulator of the inflammatory and oxido/nitrosative status of cells, were higher in adolescent-onset FEP both at baseline and after 6 months. During follow-up, we found further increases in levels of soluble inflammatory markers (PGE2 and NO2-) only in adolescent-onset FEP. In contrast, in adult-onset FEP, the expression of inducible NO synthase (iNOS), which is also pro-inflammatory, tended to decrease, with no further increase in other pro-inflammatory markers. Significant differences in the direction of change by age-of-onset cohort exist only for NFκB (F = 4.165, df = 2, 70.95, p = 0.019). Our results support the existence of changes in the pro/anti-inflammatory balance in FEP depending on the neurodevelopmental stage at illness onset. These results also suggest that inflammation may be a potential therapeutic target in adolescent-onset FEP.

A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate-prednisone.

Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods: In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.

Emotion processing and psychosocial functioning in euthymic bipolar disorder.

OBJECTIVE: To examine emotion processing in euthymic bipolar patients (EBP) compared to healthy controls. In addition, to determine whether or not there is an association between emotion processing and psychosocial functioning. MATERIAL AND METHODS: A sample of 60 EBP and 60 healthy controls matched for age, gender, education level, and premorbid intelligence were studied. All subjects were assessed using the MATRICS Consensus Cognitive Battery (MCCB) and two additional executive function measures: the Trail Making Test-Part B and the Stroop Test. Emotion processing was examined using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Psychosocial functioning was assessed using the Functional Assessment Short Test (FAST). RESULTS: Euthymic bipolar patients obtained lower scores than controls in all MSCEIT measures except for the using emotions branch. Likewise, EBP obtained a worse performance than healthy controls in all neurocognitive domains. Correlation between MSCEIT strategic area measures and FAST total score was found (r = -0.311; P < 0.016). Regression analysis showed that residual depressive symptomatology explains a 9.1% of the variance in functional outcome. MSCEIT strategic area score explained an additional 8.6%. Neurocognition did not increase the percentage of the variance explained by emotion processing. CONCLUSIONS: Euthymic bipolar patients exhibit deficits in emotion processing. Emotion processing is associated with social functioning in these patients.

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.

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review. / Síndrome ROHHAD (obesidad de rápida progresión, disfunción hipotalámica, hipoventilación y disregulación autonómica). Presentación de un caso y revisión de la literatura.

INTRODUCTION: ROHHAD syndrome (rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation) is a rare and complex disease, presenting in previously healthy children at the age of 2-4 years. Up to 40% of cases are associated with neural crest tumours. DEVELOPMENT: We present the case of a 2-year-old girl with symptoms of rapidly progressing obesity, who a few months later developed hypothalamic dysfunction with severe electrolyte imbalance, behaviour disorder, hypoventilation, and severe autonomic dysregulation, among other symptoms. Although the pathophysiology of this syndrome remains unclear, an autoimmune hypothesis has been proposed for ROHHAD. Therefore, after obtaining a limited response to intravenous immunoglobulins, we decided to test the response to a high dose cyclophosphamide (low dose was not effective either). Unfortunately our patient experienced many severe complications (among them central pontine myelinolysis, from which the patient recovered, and failure to wean from the ventilator requiring tracheostomy and long term ventilation) that required a prolonged ICU stay. Although her behaviour improved, our patient unfortunately died suddenly at home at the age of 5 due to respiratory pathology. CONCLUSIONS: ROHHAD syndrome is a rare and little-known disease which requires a multidisciplinary approach because it involves complex symptoms and multiple organ system involvement. Alveolar hypoventilation should be identified early and appropriate treatment should be started promptly for the best possible outcome. Immunomodulatory treatment with immunoglobulins, cyclophosphamide, or rituximab has previously resulted in symptom improvement in some cases. Because of the low incidence of the syndrome, multi-centre studies must be carried out in order to gather more accurate information about ROHHAD pathophysiology and design an appropriate therapeutic approach.

The role of selection and historical factors in driving population differentiation along an elevational gradient in an island bird.

Adaptation to local environmental conditions and the range dynamics of populations can influence evolutionary divergence along environmental gradients. Thus, it is important to investigate patterns of both phenotypic and genetic variations among populations to reveal the respective roles of these two types of factors in driving population differentiation. Here, we test for evidence of phenotypic and genetic structure across populations of a passerine bird (Zosterops borbonicus) distributed along a steep elevational gradient on the island of Réunion. Using 11 microsatellite loci screened in 401 individuals from 18 localities distributed along the gradient, we found that genetic differentiation occurred at two spatial levels: (i) between two main population groups corresponding to highland and lowland areas, respectively, and (ii) within each of these two groups. In contrast, several morphological traits varied gradually along the gradient. Comparison of neutral genetic differentiation (FST ) and phenotypic differentiation (PST ) showed that PST largely exceeds FST at several morphological traits, which is consistent with a role for local adaptation in driving morphological divergence along the gradient. Overall, our results revealed an area of secondary contact midway up the gradient between two major, cryptic, population groups likely diverged in allopatry. Remarkably, local adaptation has shaped phenotypic differentiation irrespective of population history, resulting in different patterns of variation along the elevational gradient. Our findings underscore the importance of understanding both historical and selective factors when trying to explain variation along environmental gradients.

Impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome.

WHAT IS KNOWN AND OBJECTIVE: Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. METHODS: A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. RESULTS: Thirty-five patients were included in the study. Median SF at baseline was 1636 µg/L, and it decreased to 1399 µg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF (r = -0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient's death (25%). WHAT IS NEW AND CONCLUSION: Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care.