Impact of adherence to individual quality-of-care indicators on the prognosis of bloodstream infection due to Staphylococcus aureus: a prospective observational multicentre cohort.

OBJECTIVES: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. METHODS: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. RESULTS: A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59-0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61-0.91; p 0.004) were associated with low 90-day mortality. DISCUSSION: Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality.

Therapeutic and Preventive Efficacy of an Intervention on Workers in a Back School.

Back pain and its ailments are the main cause of absenteeism and sick leave. Furthermore, the cause of pain and disability in a large number of workers is unknown, and treatments are not effective in controlling it. For this reason, the Back Schools (BSs) provide theoretical and practical training to workers so that they can acquire knowledge and skills that will allow them to adequately manage their back problems, enabling them to recover their autonomy and prevent relapses. The aim of the study is to analyse the efficacy of a BS by means of the evaluation of pain and disability scales in workers in different sectors and in construction. The most important clinical benefits obtained after the intervention of a BS are the reduction of pain and disability. Statistically significant and clinically relevant results have been observed between the initial assessment and the 6-month review. BS has been shown to be effective in reducing low back and neck pain and disability during the first 6 months of follow-up. Construction workers have pain and disability rates at the overall mean and with improvements between the initial assessment and the 6-month review. Their rates of improvement are clinically more relevant than for the overall population analysed.

Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies.

Autistic spectrum disorder (ASD) is a complex neurodevelopmental disability with a genetic basis, and several studies have suggested a potential role of the reelin gene (RELN) in ASD susceptibility. Accordingly, genetic association studies have explored this potential association, but the results have been controversial thus far. For this reason, we assessed the association of four genetic variants of RELN (the 5'UTR CGG triplet repeat and polymorphisms rs736707, rs362691, and rs2229864) with ASD by means of a systematic review and meta-analysis. We retrieved studies comparing the distribution of the above-mentioned genetic variants between ASD patients and healthy controls. A meta-analysis was conducted using a random effects model, and calculations of the odds ratios (ORs) and confidence intervals (CIs) were performed. A sensitivity analysis and tests to determine the heterogeneity of the results were also performed. Eleven previous studies fulfilled the inclusion criteria and analyzed the association of the above-mentioned genetic variants and ASD. We did not find any significant association between the allele or genotype frequencies of the analyzed polymorphisms and ASD, and large heterogeneity was found for the rs736707 polymorphism. Moreover, no significant differences were found between the 5'UTR triplet repeat and this disorder. In light of current evidence, no single genetic variant within this gene is clearly associated with the development of ASD, and ethnic differences may explain part of the observed heterogeneity. Larger studies among different ethnic groups are needed to establish the role of specific genetic variants within RELN in the etiology of this disorder.

Implicaciones en el movimiento humano de las adaptaciones del esquema e imagen corporal secundarias a una amputación / Implications in human movement of the adjustments about the scheme and body image as an outcome of an amputation

Introducción: el movimiento corporal humano es el resultado de la interacción entre elementos psicológicos, biológicos y sociales. Las amputaciones generan alteraciones en la estructura mental del individuo ocasionando restricciones en la participación social; por ello, es necesario comprender la influencia de la imagen y el esquema corporal de los sujetos con amputación según la teoría del movimiento continuo. Métodos: se realizó una revisión de la literatura en las bases de datos PubMed, Science Direct, Clinical Key, PEDro, SciELO en el mes de abril de 2020; la selección de artículos se dividió en 3 fases, utilizando los términos"body schema", "body image", "amputee" y "movement".Resultados: se encontró un total de 142 artículos, de los cuales se incluyeron 13 que cumplían con los criterios de selección. Discusión: posterior a una amputación se producen alteraciones de la imagen y el esquema corporal, además de cambios plásticos en el sistema nervioso central; derivado de esto existirán modificaciones en el movimiento corporal de la persona.Se requiere favorecer el manejo integral del sujeto con amputación basado en la teoría del movimiento continuo abarcando esferas psicológicas, biológicas y sociales. Conclusión: la aceptación e integración de la imagen y esquema corporal son fundamentales para restablecer la capacidad máxima de movimiento de la persona con amputación.

Introduction: Human body movement is the result of the interaction among psychological, biological and social elements; ampu-tations generate alterations in the individual's mental structure causing restrictions on social participation; therefore, it is necessary to understand the influence of the image and body schema of amputee subjects according to the theory of continuous movement. Methods:A review of the literature was carried out in the databases PubMed, Science Direct, Clinical Key, PEDro, SciELO in April 2020; the selection of articles was divided into 3 phases, using the terms "body schema", "body image", "amputee" and "movement". Results: A total of 142 articles were found, of which 13 that met the selection criteria were included. Discussion: After an amputation, alterations of the image and body schema will occur. In addition to plastic changes in the central nervous system, therefore will be modifications in the person's body movement. It is necessary to favor the comprehensive management of the subject with amputation based on the theory of continuous movement, covering psychological, biological and social spheres. Conclusion: The acceptance and integration of the image and body schema are fundamental to reestablish the maximum capacity of movement of the person with amputation

Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study.

BACKGROUND: Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. METHODS: We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. FINDINGS: Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001). INTERPRETATION: We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. FUNDING: None.

The Pitt Bacteremia Score, Charlson Comorbidity Index and Chronic Disease Score are useful tools for the prediction of mortality in patients with Candida bloodstream infection.

Candida bloodstream infection (CBI) is associated with high mortality. The aim of this study was to compare the utility of the combined use of the Pitt Bacteremia Score (PBS) and Charlson Comorbidity Index (CCI) or Chronic Disease Score (CDS) to predict mortality among patients with CBI. Thereby, all consecutive patients with CBI at our institution between 2010 and 2014 were included. The PBS was used to evaluate CBI severity and the CCI and CDS were used to assess comorbidities of patients with CBI. Logistic regression analysis was used to estimate odds ratios for 30-day mortality in models including the PBS and CCI or CDS. A total of 189 CBI episodes were identified. Logistic regression models including the PBS and either CCI or CDS showed that the combined use of a comorbidity score and a severity score significantly predicted 30-day mortality. The performance of the different models was similar. Aggregated scores of comorbidity (CCI and CDS) and disease severity (PBS) are useful for the prediction of 30-day mortality risk in patients with CBI. Their use may facilitate the analysis of risk factors for poorer outcome and the development of an index for CBI mortality.

ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13.

ATP6V1H is a component of a large protein complex with vacuolar ATPase (V-ATPase) activity. We identified two generations of individuals in which short stature and osteoporosis co-segregated with a mutation in ATP6V1H. Since V-ATPases are highly conserved between human and zebrafish, we generated loss-of-function mutants in atp6v1h in zebrafish through CRISPR/Cas9-mediated gene knockout. Homozygous mutant atp6v1h zebrafish exhibited a severe reduction in the number of mature calcified bone cells and a dramatic increase in the expression of mmp9 and mmp13. Heterozygous adults showed curved vertebra that lack calcified centrum structure and reduced bone mass and density. Treatment of mutant embryos with small molecule inhibitors of MMP9 and MMP13 significantly restored bone mass in the atp6v1h mutants. These studies have uncovered a new, ATP6V1H-mediated pathway that regulates bone formation, and defines a new mechanism of disease that leads to bone loss. We propose that MMP9/MMP13 could be therapeutic targets for patients with this rare genetic disease.

Correction: ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13.

[This corrects the article DOI: 10.1371/journal.pgen.1006481.].

[Intravenous ferric carboxymaltose-associated hypophosphatemia in patients with iron deficiency anemia. A common side effect]. / Hipofosfatemia asociada a la administración intravenosa de hierro carboximaltosa en pacientes con anemia ferropénica. Un efecto secundario frecuente.

OBJECTIVES: To determine the frequency, severity, time of onset and factors associated with the development of hypophosphatemia (HF) in patients with iron deficiency anemia treated with intravenous ferric carboxymatose (ivFCM). MATERIAL AND METHODS: Retrospective cohort study in patients iron deficiency anemia who received ivFCM and had an a prior and subsequent determination of serum phosphate. We carried out a comparative analysis between baseline and post-ivFCM levels of serum phosphate. In order to identify variables independently associated with HF a logistic regression analysis was also performed. RESULTS: One hundred twenty-five patients were included. HF frequency was 58%. The median time to onset of HF was 18 days. Age, baseline ferritin levels and baseline phosphate levels were independently associated with the development of HF. The risk of HF in patients with baseline phosphate levels ≤ 3.1mg/dl was 67% higher than patients with ≥ 3.7 mg/dl. CONCLUSIONS: ivFCM-associated HF is a frequent, early and, sometimes, prolonged effect in patients with iron deficiency anemia. Serum phosphate levels should be monitored after ivFCM administration, especially in older patients and in those with lower baseline phosphate or ferritin levels.

Genetic variation and RNA binding proteins: tools and techniques to detect functional polymorphisms.

At its most fundamental level the goal of genetics is to connect genotype to phenotype. This question is asked at a basic level evaluating the role of genes and pathways in genetic model organism. Increasingly, this question is being asked in the clinic. Genomes of individuals and populations are being sequenced and compared. The challenge often comes at the stage of analysis. The variant positions are analyzed with the hope of understanding human disease. However after a genome or exome has been sequenced, the researcher is often deluged with hundreds of potentially relevant variations. Traditionally, amino-acid changing mutations were considered the tractable class of disease-causing mutations; however, mutations that disrupt noncoding elements are the subject of growing interest. These noncoding changes are a major avenue of disease (e.g., one in three hereditary disease alleles are predicted to affect splicing). Here, we review some current practices of medical genetics, the basic theory behind biochemical binding and functional assays, and then explore technical advances in how variations that alter RNA protein recognition events are detected and studied. These advances are advances in scale-high-throughput implementations of traditional biochemical assays that are feasible to perform in any molecular biology laboratory. This chapter utilizes a case study approach to illustrate some methods for analyzing polymorphisms. The first characterizes a functional intronic SNP that deletes a high affinity PTB site using traditional low-throughput biochemical and functional assays. From here we demonstrate the utility of high-throughput splicing and spliceosome assembly assays for screening large sets of SNPs and disease alleles for allelic differences in gene expression. Finally we perform three pilot drug screens with small molecules (G418, tetracycline, and valproic acid) that illustrate how compounds that rescue specific instances of differential pre-mRNA processing can be discovered.

A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity.

The National Institutes of Health Undiagnosed Diseases Program evaluates patients for whom no diagnosis has been discovered despite a comprehensive diagnostic workup. Failure to diagnose a condition may arise from the mutation of genes previously unassociated with disease. However, we hypothesized that this could also co-occur with multiple genetic disorders. Demonstrating a complex syndrome caused by multiple disorders, we report two siblings manifesting both similar and disparate signs and symptoms. They shared a history of episodes of hypoglycemia and lactic acidosis, but had differing exam findings and developmental courses. Clinical acumen and exome sequencing combined with biochemical and functional studies identified three genetic conditions. One sibling had Smith-Magenis Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de novo mutation in GRIN2B, which resulted in markedly reduced glutamate potency of the encoded receptor. Both siblings had a protein-destabilizing homozygous mutation in PCK1, which encodes the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). In summary, we present the first clinically-characterized mutation of PCK1 and demonstrate that complex medical disorders can represent the co-occurrence of multiple diseases.

Glycosylation, hypogammaglobulinemia, and resistance to viral infections.

Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections.

Cornelia de Lange syndrome: further delineation of phenotype, cohesin biology and educational focus, 5th Biennial Scientific and Educational Symposium abstracts.

Cornelia de Lange syndrome (CdLS) is the prototype for the cohesinopathy disorders that have mutations in genes associated with the cohesin subunit in all cells. Roberts syndrome is the next most common cohesinopathy. In addition to the developmental implications of cohesin biology, there is much translational and basic research, with progress towards potential treatment for these conditions. Clinically, there are many issues in CdLS faced by the individual, parents and caretakers, professionals, and schools. The following abstracts are presentations from the 5th Cornelia de Lange Syndrome Scientific and Educational Symposium on June 20-21, 2012, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting, Lincolnshire, IL. The research committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts and subsequently disseminates the information to the families. In addition to the basic science and clinical discussions, there were educationally-focused talks related to practical aspects of management at home and in school. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD.

Persistence of immunological alterations after thymectomy in Good's syndrome: a clue to its pathogenesis.

Analyzing the phenotypic characterization of the immune system cells involved in the pathogenesis of immunodeficiency with thymoma (Good's syndrome) is difficult due to the low number of studies on that subject. We describe the immunological alterations observed in a case of Good's syndrome, and we summarize the pathogenic explanations found in the literature.

Compartmental syndrome of the upper limb due to Moraxella lacunata infection: a link to patera foot syndrome?

We report a case of compartmental syndrome of the left upper limb secondary to a severe Moraxella lacunata infection, an unusual pathogen, occurring in a young black male immigrant to the island of Gran Canaria, Spain. We propose a pathophysiological relationship with patera foot syndrome.

Mumps orchitis in the post-vaccine era (1967-2009): a single-center series of 67 patients and review of clinical outcome and trends.

Since the introduction of the mumps vaccine, the age of appearance of mumps infection has shifted from children to adolescents and young adults, groups with a higher incidence of disease complications and sequelae. During the years 2000-2001, the Gran Canaria Island was part of an epidemic of mumps. In that period, our institution attended 67 cases of serologically confirmed acute mumps orchitis, the most serious complication of mumps infection in young postpubertal males. We conducted a descriptive and prospective study of this cohort and extensively reviewed the literature from 1967 (the year the first mumps vaccine was introduced) to 2009. Fifty-six patients were admitted because of general impairment and were treated with alpha-interferon. Sixty-six patients presented parotitis previous to orchitis (interval from parotitis to orchitis, 4.9 d). Orchitis was unilateral in 89.5% and bilateral in 10.4% of cases. More than 98% of patients had orchitis-associated fever. Nine patients had clinical and biochemical data showing acute mumps meningitis, and 11 had subclinical pancreatitis. The mean duration of symptoms was 4.6 days (range, 1-9). During the acute phase, more than 41% of the evaluated testes had a volume >25 mL. Acute hormonal disturbances were highly prevalent. These included decreased levels of testosterone and inhibin B with low or normal levels of gonadotropins in 35% of subjects, and, to our knowledge not previously reported, an atypical hormonal pattern consisting of low levels of free testosterone and inhibin B, along with increased measures of luteinizing hormone but low or normal follicle-stimulating hormone levels (11% of cases). During the follow-up period (mean, 331 d) a high incidence of sperm disturbance was found.

Genome-wide DNA methylation analysis in cohesin mutant human cell lines.

The cohesin complex has recently been shown to be a key regulator of eukaryotic gene expression, although the mechanisms by which it exerts its effects are poorly understood. We have undertaken a genome-wide analysis of DNA methylation in cohesin-deficient cell lines from probands with Cornelia de Lange syndrome (CdLS). Heterozygous mutations in NIPBL, SMC1A and SMC3 genes account for ∼65% of individuals with CdLS. SMC1A and SMC3 are subunits of the cohesin complex that controls sister chromatid cohesion, whereas NIPBL facilitates cohesin loading and unloading. We have examined the methylation status of 27 578 CpG dinucleotides in 72 CdLS and control samples. We have documented the DNA methylation pattern in human lymphoblastoid cell lines (LCLs) as well as identified specific differential DNA methylation in CdLS. Subgroups of CdLS probands and controls can be classified using selected CpG loci. The X chromosome was also found to have a unique DNA methylation pattern in CdLS. Cohesin preferentially binds to hypo-methylated DNA in control LCLs, whereas the differential DNA methylation alters cohesin binding in CdLS. Our results suggest that in addition to DNA methylation multiple mechanisms may be involved in transcriptional regulation in human cells and in the resultant gene misexpression in CdLS.