The Effect of the Drug-Related Problems Prevention Bundle on Early Readmissions in Patients From the Emergency Department: A Randomized Clinical Trial.

BACKGROUND: Drug-related problems (DRPs) are prevalent and avoidable disease that patients experience due to drug use or nonuse. However, secondary prevention policies have not yet been systematized. OBJECTIVE: To assess the clinical impact of a secondary prevention bundle for DRPs in patients who visited the emergency department (ED) for medicine-related problems. METHODS: A single-center randomized clinical trial was conducted from August 28, 2019, to January 28, 2021, with 1-month follow-up. We included 769 adult patients who visited ED with a DRP associated with cardiovascular, alimentary tract, and metabolic system medications. For the intervention group, a DRP prevention bundle, consisting of a combined strategy initiated in the ED was applied. Patients in the control group received standard pharmaceutical care. Intervention was evaluated in terms of 30-day hospital readmission due to any cause. RESULTS: Final analysis included 769 patients, of which 68 (8.8%) were readmitted within 30 days (control group, 40 of 386 [cumulative incidence: 10.4%]; intervention group, 28 of 383 [cumulative incidence, 7.3%]). After adjustment of the model for chronic heart failure, there was a lower incidence of hospital readmission among patients in the intervention group compared with those in the control group, odds ratio: 0.59 [95% confidence interval: 0.37-0.97]; number needed to treat (NNT) = 32. No significant differences in other outcomes were observed. CONCLUSION AND RELEVANCE: In this clinical trial, DRP prevention bundle in adjusted analysis decreased the rate of 30-day hospital readmission for any cause in patients who visited ED for a DRP. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03607097).

Vitamin D, menopause, and aging: quo vadis?

Menopause and aging are associated with changes in circulating gonadal steroid hormones, insulin sensitivity, body composition, and also lifestyle and social coordinates. Vitamin D status influences different metabolic adjustments, aside from calcium-phosphorus and bone metabolism. The main blood marker used to measure endogenous vitamin D status is 25-hydroxyvitamin D. Aging is associated with increases in serum parathyroid hormone and alkaline phosphatase, and a decrease of serum calcium, phosphorus, and vitamin D metabolites. 25-Hydroxyvitamin D status is also influenced by the circannual rhythm of sun irradiation. Results of clinical association studies have not correlated with intervention trials, experimental studies, and/or meta-analyses regarding the role of vitamin D on different outcomes in women during their second half of life and the vitamin D supplementation dose needed to improve clinical endpoints. Discordant results have been related to the method used to measure vitamin D, the studied population (i.e., sociodemographics and ethnicity), study designs, and biases of analyses. Vitamin D supplementation with cholecalciferol or calcifediol may improve some metabolic variables and clinical outcomes in young postmenopausal and older women. Studies seem to suggest that calcifediol may have some advantages over other forms of vitamin D supplementation. Further studies are needed to define interventions with supplements and effective food fortification.

Association between depressed mood and sexual function among mid-aged Paraguayan women.

BACKGROUND: Depressive symptoms may affect female mid-life sexuality, whereas sexual problems tend to aggravate depression. Despite this, data assessing this association drawn from mid-aged Paraguayan women are scarce. OBJECTIVE: This study aimed to assess the association between depressed mood and the risk of sexual dysfunction during female mid-life. METHODS: Sexually active urban-living women from Asunción, Paraguay (n = 193, aged 40-60 years) were surveyed with the 6-item Female Sexual Function Index (FSFI-6), the 10-item Center for Epidemiological Studies Depression Scale (CESD-10), and a general questionnaire containing personal and partner information. Depressed mood was defined as a total CESD-10 score of 10 or more, and an increased risk for sexual dysfunction as an FSFI-6 total score of 19 or less. The association of depressed mood and an increased risk of sexual dysfunction was evaluated with multivariable Poisson regression. RESULTS: The mean age (±standard deviation) of surveyed woman was 48.3 ± 6.0 years and 61.1% (n = 118) were perimenopausal and postmenopausal. A total of 21.8% (n = 42) had depressed mood and 28.5% (n = 55) had an increased risk of sexual dysfunction. The final adjusted regression model determined that women with depressed mood were twice as likely to have an increased risk of sexual dysfunction, compared to women with normal mood (adjusted prevalence ratio = 2.14, 95% confidence interval 1.26-3.60). On the other hand, depressed mood was associated with a mean total FSFI-6 score that was 20% lower than that observed among women with normal mood (adjusted incidence rate ratio = 0.80, 95% confidence interval 0.68-0.93). CONCLUSION: In this mid-aged Paraguayan female sample there was a significant association between depressed mood and an increased risk of sexual dysfunction.

Genetic parameters for carcass traits and body weight using a Bayesian approach in the Canchim cattle.

Correlation between genetic parameters and factors such as backfat thickness (BFT), rib eye area (REA), and body weight (BW) were estimated for Canchim beef cattle raised in natural pastures of Brazil. Data from 1648 animals were analyzed using multi-trait (BFT, REA, and BW) animal models by the Bayesian approach. This model included the effects of contemporary group, age, and individual heterozygosity as covariates. In addition, direct additive genetic and random residual effects were also analyzed. Heritability estimated for BFT (0.16), REA (0.50), and BW (0.44) indicated their potential for genetic improvements and response to selection processes. Furthermore, genetic correlations between BW and the remaining traits were high (P > 0.50), suggesting that selection for BW could improve REA and BFT. On the other hand, genetic correlation between BFT and REA was low (P = 0.39 ± 0.17), and included considerable variations, suggesting that these traits can be jointly included as selection criteria without influencing each other. We found that REA and BFT responded to the selection processes, as measured by ultrasound. Therefore, selection for yearling weight results in changes in REA and BFT.

Psychological profiles and prescription opioid misuse, craving, and withdrawal in people with chronic pain.

BACKGROUND: The negative consequences of prescription opioid misuse and opioid use disorder make it relevant to identify factors associated with this problem in individuals with chronic pain. This cross-sectional study aimed at identifying subgroups of people with chronic pain based on their psychological profiles, prescription opioid misuse, craving, and withdrawal. METHODS: The sample comprised 185 individuals with chronic pain. We performed hierarchical cluster analysis on impulsivity, anxiety sensitivity, pain acceptance, pain intensity, opioid misuse, craving, and withdrawal. RESULTS: The four-cluster solution was the optimal one. Misuse, craving, and anxiety sensitivity were higher among people in the Severe-problems cluster than among people in the other three clusters. Withdrawal was the highest in the High-withdrawal cluster. Impulsivity was higher among people in the Severe-problems and High-withdrawal clusters than those in the Moderate-problems and Mild-problems clusters. Pain acceptance was higher among people in the Mild-problems cluster than among people in the other three clusters. Anxiety sensitivity and misuse were higher among people in the Moderate-problems cluster than among people in the Mild-problems cluster. CONCLUSIONS: These results support that impulsivity, anxiety sensitivity, and pain acceptance are useful constructs to identify subgroups of people with chronic pain according to their level of prescription opioid misuse, craving, and withdrawal. The results of this study may help in selecting the early intervention most suitable for each of the identified profiles. SIGNIFICANCE: The psychological profile of individuals with chronic pain, prescription opioid misuse, craving, and withdrawal is characterized by fearing anxiety-related symptoms due to the catastrophic interpretation of such symptoms and reacting impulsively to negative moods. In contrast, participants with high pain acceptance had less prescription opioid misuse, craving, and withdrawal. The profiles identified in this study could help clinicians select targets for intervention among profiles with similar needs and facilitate early interventions to prevent opioid misuse onset or aggravation.

F8 gene dosage defects in atypical patients with severe haemophilia A.

We performed molecular analysis of the factor 8 gene (F8) in 272 unrelated Spanish patients with haemophilia A (HA) and detected a mutation by routine analysis in 267 of them (98.1%). No mutation was detected in the remaining five patients despite clinical and laboratory confirmation of HA. The aim is to describe the molecular alterations in F8 discovered by gene dosage methodologies in three of these patients. For methodology, F8 sequencing, intragenic marker analysis, multiplex ligation-dependent probe amplification and quantitative real time-PCR were followed. One patient had Klinefelter syndrome (47,XXY) and a large deletion spanning exons 1-12 masked by the other F8 allele; the second patient showed a large duplication spanning exons 2-10 and the third patient revealed a non-contiguous double duplication of exons 14 and 23-25. The remaining two patients had mild HA and dosage results were normal. The application of gene dosage methods is useful to define haemophilic patients in whom mutations are not detected using other routine methods. Nevertheless, in a small percentage of patients (<1%), no molecular pathology can be identified after testing several genetic methodologies.

Photoisomerizable metallomesogens and soft crystals based on orthopalladated complexes.

With the aim of obtaining light-responsive liquid-crystalline palladium complexes, six palladium complexes derived from an orthometalated imine, bearing one or two azocarboxylato bridges, have been synthesized: [Pd(2)(µ-SC(10)H(21))(µ-O(2)CAzo)(L(1,2))(2)] (7 and 8), [Pd(2)(µ-SC(10)H(21))(µ-O(2)CAzo3C(10))(L(1,2))(2)] (9 and 10), [Pd(µ-O(2)CAzo)L(1)](2) (11), and [Pd(µ-O(2)CAzo3C(10))L(1)](2) (12), in which L(1) = p-H(21)C(10)OC(6)H(3)CH═NC(6)H(4)OC(10)H(21)-p, L(2) = p-H(21)C(10)OC(6)H(3)CH═NC(14)H(29), AzoCO(2)(-) = p-(phenylazo)benzoate, and Azo3C(10)CO(2)(-) = p-(2',3',4'-tris-n-decyloxyphenylazo)benzoate. Three of them (7-9), as well as the precursor Azo3C(10)CO(2)H (3), are thermotropic liquid crystals displaying nematic and smectic A mesophases, while 10-12 have been identified by X-ray diffraction to give rise to "soft" crystal phases. Electronic spectroscopy and (1)H NMR show that all of them undergo a trans-cis isomerization of the azobenzene moiety at λ = 365 nm. The molecular structure determines the photoresponse in solution, which is faster and more stable when the trisubstituted azocarboxylate is present and the motion of the azo group is not hindered by the orthometalated imine. The photoresponse has also been observed in the condensed phases, which change from the ordered phase to the isotropic liquid upon irradiation, except for compound 10, a soft crystal in which a permanent photoalignment highly sensitive to light polarization is produced. The latter is a behavior with potential applications, rather unusual in low-molecular-weight compounds.

Spontaneous spermatic vein thrombosis in pediatric patients: A condition to be considered. / Trombosis espontánea de la vena espermática en la edad pediátrica: una entidad a tener en cuenta.

Spermatic vein thrombosis is a very rare pathology, with 25 cases published only, 6 of which in patients under 15 years of age. We present the case of a male patient, as well as a review of the literature. A 12-year old boy presented at emergency with 3-day progressive testicular pain. Following abdominal Doppler ultrasound imaging, he was diagnosed with left spermatic vein thrombosis and nutcracker syndrome. Admission and enoxaparin treatment were decided upon. Patient evolution was satisfactory, with subsequent ultrasound imaging demonstrating the absence of thrombus. The patient is currently under follow-up and without treatment. Various treatments are mentioned in the literature, with conservative management being the treatment of choice.

La trombosis de la vena espermática es una patología muy poco frecuente, con solo 25 casos publicados, 6 de los cuales menores de 15 años. De esta manera presentamos el caso de un varón, así como la revisión de la literatura. Un paciente de 12 años de edad acudió a Urgencias por dolor testicular de aumento progresivo, de 3 días de evolución. Mediante ecografía doppler abdominal se diagnosticó de trombosis de la vena espermática izquierda y síndrome de cascanueces. Se decidió ingreso y tratamiento con enoxaparina. La evolución del paciente fue satisfactoria, en la ecografía posterior se observó la desaparición del trombo. El paciente se encuentra en seguimiento y sin tratamiento. Existen varios tratamientos reflejados en la literatura, siendo el de elección el manejo conservador.

[Negative results related to drugs required in hospitalisation]. / Resultados negativos asociados con medicamentos como causa de ingreso hospitalario.

OBJECTIVE: To assess the prevalence of negative clinical outcomes associated with medication as a cause of hospital admission and to determine their characteristics (types, categories, avoidability, severity and the drug groups involved.) To determine possible risk factors related to the appearance of this problem. METHOD: An observational study carried out over a three month period in a department of the university hospital, 163 patients were selected at random. The information obtained from the patient interview, the revision of clinical records and clinical sessions were used to then identify negative clinical outcomes using the Dader method. RESULTS: In 27 cases (16.6 %; 95 % confidence interval [CI], 1.6 to 23.0), negative clinical outcomes associated with medication were considered to be the main cause of hospital admission. The most frequent negative clinical outcomes associated with medication were untreated health problems, non-quantitative ineffectiveness and quantitative safety problems respectively. The overall prevalence of preventable admissions due to negative clinical outcomes associated with medication was 88.9 %; (95 % CI, 71.9 to 96.1 %.) With regards to severity, 74.1 % (95 % CI, 55.3 to 86.1 %) of the total admissions were moderate. The most common drugs implicated in hospital admissions were: antibacterial for systemic use, cardiovascular and non steroidal anti-inflammatory agents. Apart from age, no other factors were found for hospital admissions due to negative results associated with medication. CONCLUSIONS: Negative clinical outcomes associated with medication as cause of hospital admission are a prevalent problem and most of them are avoidable with pharmacotherapeutic follow-up.

Severe haemophilia A in a female resulting from an inherited gross deletion and a de novo codon deletion in the F8 gene.

Haemophillia A (HA) is an X-linked bleeding disorder caused by mutations in the F8 gene. While the disease affects 1 in 5000 males, phenotypic expression of haemophilia A is rare in females, similar to other X-linked recessive disorders. We describe a 5-year-old female with severe haemophilia A. We determined the underlying molecular defect in the F8 genes of the proband and her closest family members by direct DNA sequencing, marker analysis and quantitative real-time polymerase chain reaction. The patient showed two different mutations in the F8 gene: the paternal copy of the F8 gene had a de novo p.Phe652/653 deletion in exon 13 while the maternally inherited gene showed a large deletion encompassing exons 1 to 22. The structural analysis of residues Phe652/Phe653 based on a three-dimensional model of activated factor VIII provides evidence of the impact of the mutant factor VIII protein in the clinical manifestations of the patient. This unusual finding highlights the need to perform a thorough molecular analysis including sequencing, marker and quantitative analyses to identify compound heterozygous females with HA.

Application of intron 9 and intron 25 dinucleotide repeats of the factor VIII gene for carrier diagnosis in haemophilia A.

We describe the usefulness of two dinucleotide repeats located in intron 9 and in intron 25 of the factor VIII gene for carrier diagnosis of haemophilia A. We analyzed 100 unrelated Spanish women and 34 women from haemophilia A (HA) families in whom known intragenic markers were unhelpful in determining their carrier status. The heterozygosity rate of intron 9 and intron 25 markers in the 100 control women was lower (0.28 and 0.38, respectively) than the values obtained with common markers routinely used in our laboratory. However, the application of intron 9 and intron 25 markers was effective in identifying the at-risk X chromosome in 11 of 34 (32%) of the uninformative women from HA families. The combined use of these repeats with current markers may facilitate the identification of the X chromosome in HA families for application in carrier, prenatal and pre-implantation diagnoses.

Application of the SCORE and Wilson-Grundy methods for the assessment of cardiovascular risk in community pharmacies.

BACKGROUND: The assessment and follow-up of patients with risk factors, or with cardiovascular disease (CVD), involves estimating and monitoring their CVD risk (CVDR). There are different opinions about the most appropriate method for this. OBJECTIVE: To compare the SCORE system and the Wilson-Grundy system (based on Framingham's study). METHODS: A descriptive, observational study over 15 days in six pharmacies, with patients aged between 25 and 74 years, and with a prescription for medications related to hypertension, dyslipidaemia, CVD prevention or type-2 diabetes. Results of patients' absolute CVDR were assessed and compared using the SCORE system and the Wilson-Grundy method, adapted for Spain. The Chi-square test was used to compare proportions, and the Student t-test was used to compare mean values, including odds ratios (OR) and 95% confidence intervals (95%CI). RESULT: A total of 257 patients [165 women, 92 men; mean (SD) age, 60.9 (10.8) years; percentage of previous medical history of hypertension (70.0%), dyslipidaemia (42.4%), type-2 diabetes (19.5%) and CVD (22.6%)] participated. With the CVDR assessed with SCORE, the distribution was as follows: low 35.8%, intermediate 21.0% and high 43.2%. The corresponding values using the Wilson-Grundy system was low 60.7%, intermediate 8.2% and high 31.1%. CONCLUSION: The cardiovascular risk of patients that attend community pharmacies with prescriptions for cardiovascular medications is significantly higher when assessed using the SCORE system than with the Wilson-Grundy method.

[Negative results associated with medication in the emergency department of a hospital]. / Resultados negativos asociados con la medicación en un servicio de urgencias hospitalario.

OBJECTIVE: To find out the prevalence of negative results associated with medication (herein referred to as NRM) in patients attending the emergency department. To classify the results by severity, avoidability and cost, as well as to establish the factors associated with their appearance. METHOD: Observational, descriptive and cross-sectional study carried out in the emergency department of a tertiary hospital. Patient surveys and emergency department records were used as sources of information. The Dader Method and guidelines from the Third Consensus of Granada were used. Pearson's chi2 test was used to find the association between age, gender and number of drugs and showing signs of NRM. Avoidability was measured using Baena et al's criteria and severity was assessed according to whether or not the patient had been admitted into an observation stall or on to a hospital ward. RESULTS: 24.4% of patients visited the emergency department because of NRM. 16.1% needed to be hospitalised to solve their health issue. 83.9% of all patients with NRM and 77.3% of those hospitalised due to NRM could have been avoided. Statistically, there was a higher prevalence of NRM in patients taking 5 or more different drugs. An estimated euro 14,666,178 was spent on treating avoidable NRM cases in 2003. CONCLUSIONS: The prevalence of NRM in those who attended the emergency department, the high percentage of avoidability and the cost imposed on the Health Service seem to sufficiently argue a case for the consideration that NRM as a problem which requires the implementation of prevention programmes based on drug-treatment monitoring.

[References in articles published in Revista Española de anestesiología y reanimación: 1999-2003]. / Las referencias bibliográficas de los artículos publicados en la Revista Española de anestesiología y reanimación. Estudio del periodo 1999- 2003.

OBJECTIVE: To determine the characteristics in citations of articles published in Revista Española de Anestesiología y Reanimación (REDAR). METHOD: References cited in REDAR articles published from 1999 through 2003 were analyzed in terms of type of document, number of pages, language, country of publication, and visibility. Obsolescence was studied based on document age, Burton and Kebler's half-life index, and Price's index. Citation errors were also counted. RESULTS: A total of 14271 citations in 692 articles published in the aforementioned years were studied. Journal articles were the type of document cited most often (n=13113; 91.9%). The average length of documents cited in REDAR articles was 7.29 pages. The language of the cited articles was English in 80.7% of the cases and the majority (51.8%) were published in the United States of America. Journals with impact factors were the sources cited 76% (n=10 833) of the time. The average age of cited works was 9.81 years, the half-life was 6 years, and Price's index was 38.8%. A total of 1610 errors were detected; 609 of them interfered with access to the document. CONCLUSION: The bibliographic references in REDAR are similar to those of other Spanish medical journals and other anesthesiology journals.

The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript.

In a BRCA1 screening in familial breast cancer carried out in different centres in Spain, France, and United Kingdom, a missense mutation 330A>G which results in a Arg to Gly change at codon 71 (R71G) was independently identified in 6 families, all of them with Spanish ancestors. This residue coincides with the -2 position of the exon 5 donor splice site. We further investigated the effect of this base substitution on the splicing of BRCA1 mRNA. The sequence analysis of the cDNA indicated that 22 bp of exon 5 were deleted, creating with the first bases of exon 6 a termination codon at position 64, which results in a truncated protein. The BRCA1 haplotype of the R71G carrier patients and Spanish controls was analysed by use of six microsatellites located within or near BRCA1. Our results are consistent with the possibility that these families shared a common ancestry with BRCA1 R71G being a founder mutation of Spanish origin.

Morbidity and mortality associated with pharmacotherapy. Evolution and current concept of drug-related problems.

Medicines are a great contribution to the rising life expectancy in XX century. But a lot of drug safety problems were reported since 1960's. More recently, ineffectiveness is also being considered as a problem. Since 1975, the term 'drug-related problem' (DRP) is being used for several definition and purposes. This has led to a number of different DRP classifications. The aim of the present review is to gather different positions, definitions and classifications of DRP. And to present a more modern concept, which is also named as pharmacotherapy failure, corresponding to negative clinical outcomes resulting from the use or the lack of use of medicines. Those pharmacotherapy failures include necessity, effectiveness and safety problems.

Sister chromatid exchange induced by DNA topoisomerases poisons in late replicating heterochromatin: influence of inhibition of replication and transcription.

Previous studies have shown the importance of DNA replication fork progression for the cytotoxicity of topoisomerase inhibitors as well as for their ability to induce chromosomal aberrations and sister chromatid exchange (SCE). In the present report, we have carried out experiments in CHO cells in order to study the induction of SCE by topo I and topo II inhibitors in both euchromatin and late-replicating heterochromatin, as well as the possible influence of inhibition of DNA replication or transcription on the occurrence of SCE. Treatment with the DNA synthesis inhibitor aphidicolin reduced the frequency of SCE induced by topoisomerase inhibitors in constitutive heterochromatin of the X chromosome, while the RNA synthesis inhibitor actinomycin D also had an effect on SCE induced by high doses of the topoisomerase poisons, in spite of the lack of active transcription which characterizes this heterochromatic region.

Enhanced sensitivity to topoisomerase inhibitors in synchronous CHO cells pre-treated with 5-azacytidine.

Multidrug combination has been shown to be very useful to improve antitumor activity as well as to reduce the toxicity of different anti-cancer drugs. We have evaluated the interaction between the hypomethylating agent 5-azacytidine and the topoisomerase I and topoisomerase II inhibitors Camptothecin (CPT) and 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) respectively, based on the hypothesis that through the alteration of chromosome replication timing following DNA hypomethylation, the number of replication forks in early S phase might increase, so enhancing the probability of a collision between a blocked cleavable complex (DNA-topo I-CPT or DNA-topo II-m-AMSA) and a replication fork. We have tested the capacity of CPT and m-AMSA to induce chromosomal aberrations as well as reproductive cell death in synchronous cultured Chinese hamster ovary cells after a pretreatment with 5-azacytidine with positive results.

[Clinical and pathological characteristics and clinical course of patients with breast cancer and BRCA1/BRCA2 mutations]. / Características clinicopatológicas y evolución clínica de pacientes con cáncer de mama y mutaciones en los genes BRCA1 o BRCA2.

BACKGROUND: Clinico-pathological differences between BRCA1 or BRCA2 mutation-associated breast cancer (BC) and sporadic BC are little known. PATIENT AND METHODS: We analysed the clinico-pathological characteristics and clinical follow-up of 30 patients with BC. BRCA1 and BRCA2 mutations were detected by SSCP and PTT. RESULTS: There were no differences in age, size or nodal status at the time of diagnosis. Mammography features were more heterogeneous in BRCA2 than in BRCA1 BC. All BRCA1 mutation-associated BC corresponded to infiltrating ductal carcinomas (20% medullary carcinomas) with a more aggressive pathological behavior. The frequency of local recurrences was 14% in BRCA1 and 20% in BRCA2. Contralateral BC and ovarian cancer (OC) were observed in 27% and 20% of BRCA1 cases, respectively, and 6% and 6% of BRCA2 cases. The median follow-up in BRCA1 and BRCA2 BC was 131 and 54 months, respectively. CONCLUSIONS: There were no differences in age at diagnosis and stage between BRCA1 and BRCA2 breast cancer. The mammographic pattern in BRCA2 was more heterogeneous. BRCA1 mutations were associated with more aggressive histopathologic findings and a higher risk of a second BC and OC.