Economic burden of skin and skin structure infections due to Gram-positive bacteria in patients on hospital at home-based outpatient parenteral antibiotic therapy (OPAT).

OBJECTIVE: To describe and quantify resource use and direct health costs associated with skin and skin structure infections (SSSIs) caused by Gram-positive bacteria in adults receiving outpatient parenteral antimicrobial therapy (OPAT), administered by Hospital at Home units (HaH) in Spain. METHODS: Observational, multicenter, retrospective study. We included patients of both sexes included in the HaH-based OPAT Registry during 2011 to 2017 who were hospitalized due to SSSIs caused by Gram-positive bacteria. Resource use included home visits (nurses and physician), emergency room visits, conventional hospitalization stay, HaH stay and antibiotic treatment. Costs were quantified by multiplying the natural units of the resources by the corresponding unit cost. All costs were updated to 2019 euros. RESULTS: We included 194 episodes in 189 patients from 24 Spanish hospitals. The most frequent main diagnoses were cellulitis (26.8%) and surgical wound infection (24.2%), and 94% of episodes resulted in clinical improvement or cure after treatment. The median HaH stay was 13 days (interquartile range [IR]:8-22.7), and the conventional hospitalization stay was 5 days (IR: 1-10.7). The mean total cost attributable to the complete infectious process was €7,326 (95% confidence interval: €6,316-€8,416). CONCLUSIONS: Our results suggest that OPAT administered by HaH is a safe and efficient alternative for the management of these infections and could lead to lower costs compared with hospital admission.

Using a pharmacogenomic algorithm to guide the treatment of depression.

The objective of this study was to evaluate the potential benefit of utilizing a pharmacogenomic testing report to guide the selection and dosing of psychotropic medications in an outpatient psychiatric practice. The non-randomized, open label, prospective cohort study was conducted from September 2009 to July 2010. In the first cohort, depressed patients were treated without the benefit of pharmacogenomic testing (the unguided group). A DNA sample was obtained from patients in the unguided group, but the results were not shared with either the physicians or patients until the end of the 8-week study period. In the second cohort (the guided group), testing results were provided at the beginning of the 8-week treatment period. Depression ratings were collected at baseline and after 2 weeks, 4 weeks and 8 weeks of treatment using the Quick Inventory of Depressive Symptomatology, Clinician Rated (QIDS-C16) and the 17-item Hamilton Rating Scale for Depression (HAM-D17). Clinician and patient satisfaction was also assessed. The reduction in depressive symptoms achieved within the guided treatment group was greater than the reduction of depressive symptoms in the unguided treatment group using either the QIDS-C16 (P=0.002) or HAM-D17 (P=0.04). We concluded that a rapidly available pharmacogenomic interpretive report provided clinical guidance that was associated with improved clinical outcomes for depressed patients treated in an outpatient psychiatric clinic setting.

Control metabólico en un paciente con diabetes tipo 2 mal controlada que presenta complicaciones crónicas establecidas / Metabolic control in a patient with poor-controlled type 2 diabetes, which presents established chronic complications

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Changing the p53 master regulatory network: ELEMENTary, my dear Mr Watson.

The p53 master regulatory network provides for the stress-responsive direct control of a vast number of genes in humans that can be grouped into several biological categories including cell-cycle control, apoptosis and DNA repair. Similar to other sequence-specific master regulators, there is a matrix of key components, which provide for variation within the p53 master regulatory network that include p53 itself, target response element sequences (REs) that provide for p53 regulation of target genes, chromatin, accessory proteins and transcription machinery. Changes in any of these can impact the expression of individual genes, groups of genes and the eventual biological responses. The many REs represent the core of the master regulatory network. Since defects or altered expression of p53 are associated with over 50% of all cancers and greater than 90% of p53 mutations are in the sequence-specific DNA-binding domain, it is important to understand the relationship between wild-type or mutant p53 proteins and the target response elements. In the words of the legendary detective Sherlock Holmes, it is 'Elementary, my dear Mr. Watson'.

Loss of the short arm of the Y chromosome in human prostate carcinoma.

A change in Y chromosome number is one of the many cytogenetic abnormalities reported in human prostate tumors. However, reports in the literature have varied regarding the frequency of Y loss or gain and the significance of Y aneusomy with respect to the biology of the disease. We have conducted an analysis of the Y chromosome in malignant and benign hyperplastic human prostate epithelium in order to determine whether regional Y loss occurs in prostate cancer. To accomplish this we performed dual-color fluorescence in situ hybridization (FISH) on serial sections of paraffin-embedded prostate tumor tissues using either a Yp (SRY), Ycen (alpha-satellite) or Yq (satellite 3) probe, and an Xcen (alpha-satellite) probe that served as a control for hybridization and nuclear truncation. The results of our FISH analysis demonstrated loss of Yp in the malignant epithelium of 14/40 (35%) prostate tumor sections examined. We also found loss of Yq in 4/40 (10%) of the samples, with one of these exhibiting accompanying Yp loss. The remaining samples, 23/40 (58%), retained both Yp and Yq markers, with no evidence of either Ycen loss or Y gain in any of the tumor samples examined. In addition, Y loss was detected in the benign hyperplastic regions in nearly one-half of the tissue sections that exhibited Y loss in the malignant epithelium. These results demonstrate that regional chromosome Y loss occurs in prostate cancer, that loss of Yp is the most frequent event, and suggest that this loss may in some cases be a precursor to prostate malignancy.

Patient-centred consultations: a comparison of student experience and understanding in two clinical environments.

OBJECTIVES: To explore students' perspectives on doctor-patient communication. DESIGN: We interviewed students in focus groups before and after their placements. In semistructured interviews they were asked about their experiences of learning through clinical contact, with particular emphasis on patient-centred consultations, on the wards and during their community attachment. Students whose clinical skills training remained hospital-based were also interviewed to compare the range of experiences. SETTING: Leeds University. SUBJECTS: Third-year medical students. RESULTS: During hospital training students are rarely introduced, either through teaching or observation, to the idea of patient-centred consultations. In contrast both the principles underpinning and/or the practice of such consultations were routinely encountered during the general practice placement. Students considered the community attachment to have helped them appreciate the value of exploring patients' concerns both in terms of enhancing the patients' overall healthcare experience and promoting effective clinical management. While they considered the nature and purpose of hospital care to be qualitatively different from that conducted in the community, the relevance of adopting a patient-centred approach on the wards was confirmed. CONCLUSIONS: Recommendations for clinical training are made. The relevance and best use of community and hospital-based attachments need to be evaluated further.

Minimal forces to move patients.

OBJECTIVES: Health care workers who have patient transfer duties are at risk for back injury. Transferring patients between beds and gurneys is a rigorous pulling task that requires back, leg, and arm strength. This study analyzed the efficiency of commercially available transfer devices, namely a patient roller, patient shifter, and draw sheet. METHOD: With the use of one or two force scales attached to each transfer device, the amount of force needed to transfer 15 participants, weighing from 101 lb to 240 lb, back and forth between a bed and a gurney was measured. Ten transfers per device per participant were performed. RESULTS: The patient roller was superior to the patient shifter and draw sheet in reducing transfer forces. Additionally, gurney-to-bed transfers tended to be more demanding for all transfer devices and for heavier participants. CONCLUSIONS: The patient roller was the most efficient transfer device in moving participants compared with the draw sheet and patient shifter. Transfer forces can be estimated with the use of linear equations, with patient weight, direction of transfer, and transfer device as the independent variables. These estimated forces can assist occupational therapists in the returning their injured health care coworkers to patient transfer duties. The results further indicated that high forces are required to transfer patients; therefore, patient-transfer personnel should obtain assistance when moving patients.

Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors.

A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity relationships were developed for a set of these compounds, and a representative analog 1-(3,4-dichlorobenzoyl)-3-phenyl-1,4,5,6-tetrahydropyridazine++ + (1i, RWJ 25333) was chosen for further evaluation. RWJ 25333 stimulated the in vitro proliferation of human osteoblast-like cells but not human breast cells.

Lamellar keratoplasty performed with a corneal scleral button.

Tissue for lamellar corneal surgical procedures is usually harvested from whole eyes. We describe a surgical technique for the rehabilitation of corneoscleral defects with lamellar keratoplasty in which the donor tissue is obtained from a preserved corneoscleral button instead of a whole globe. This technique is illustrated with a case involving the treatment of a limbal dermoid in a 26-month-old boy.

A surgical technique for the treatment of central corneal perforations.

BACKGROUND: Generally, corneal perforations of 2 mm in diameter or greater are treated using graft material for tectonic support. A surgical technique for the primary repair of such perforations without the use of any additional tissue is presented. METHODS: This procedure is demonstrated by a case report. The technique involves creation of an elliptical defect out of a circular one, thus allowing for primary closure, with the addition of glue. A definitive penetrating keratoplasty was subsequently performed with several important modifications described herein. RESULTS: A water-tight closure was obtained with this technique for 1 month while the inflammation subsided. Preoperative visual acuity was light perception. One year postoperatively, it was count fingers at 8 feet with mild irregular astigmatism. CONCLUSION: This technique is useful for perforations which are central, larger than 2 mm in diameter, and when corneal or scleral material is not readily available for patch grafting.

Mouse ovarian tumor cells: an experimental model for progestin-mediated radiotherapy.

Mouse ovarian tumor (MOT) cells have been grown in C3HeB/FeJ mice as an ascites and as a subcutaneous tumor and in cell culture as a suspension. These cells contain saturable, high-affinity, specific progesterone receptors. Estrogen receptors were not detectable in these cells. MOT cells can be used as both an in vivo and an in vitro model for progestin-mediated radiotherapy.

The abnormal exercise electrocardiogram in apparently healthy men: a predictor of angina pectoris as an initial coronary event during long-term follow-up.

A group of 916 apparently healthy men between the ages of 27 and 55 years (mean 37) were followed up with serial medical and exercise test evaluations for a period of 8 to 15 years (mean 12.7) to determine (1) the prevalence and specific types of new coronary events observed in subjects with and without abnormal ST segment responses to exercise and (2) the predictive value of a serial conversion to an abnormal ST segment response to exercise for new coronary events. During the initial evaluation there were 23 subjects (2.5%) with an abnormal ST segment response to exercise. During follow-up there were nine (39%) coronary events in this group: eight cases of angina and one of sudden death. With serial testing, an additional 38 subjects (5.1%) experienced conversion to an abnormal ST segment response to exercise. During follow-up there were 12 (32%) coronary events in this group: 10 cases of angina, one of myocardial infarction, and one other. There were 833 subjects with normal ST segment responses to exercise with all tests. In this group there were 44 (5.3%) coronary events: 25 cases of myocardial infarction, seven of sudden death, and 12 of angina. We conclude that in apparently healthy middle-aged men an abnormal ST segment response to exercise is predictive of angina pectoris but not of myocardial infarction or sudden cardiac death as an initial coronary event.

Antigenically active nonhistone chromatin proteins in cancer cells.

Two-dimensional polyacrylamide gel electrophoresis shows that in nuclei of Novikoff hepatoma ascites cells there are approximately 75 proteins in the chromatin fraction soluble in 3 M NaCl:7 M urea. Dialysis of this fraction to an ionic strength of 0.15 produces a soluble fraction and a precipitate. The proteins in the soluble fraction have been reported to be active in gene control. Antibodies to the soluble fraction distribute diffusely throughout the nucleus, and antibodies to the precipitate localized primarily in the nucleolus and the nuclear ribonucleoprotein network. The nucleolar proteins differ from the extranucleolar proteins in antigenicity and labeling patterns. The development of methods for isolation, purification, and identification of nuclear proteins provided the opportunity for analysis of chromatin antigens in tumor cells. Utilizing two-dimensional preparative polyacrylamide gel techniques as well as conventional procedures, several nuclear proteins have been isolated in electrophoretically homogeneous states including protein A-24, a histone-like nonhistone protein; C-14, a protein that stimulates nucleolar RNA polymerase; and a chromatin antigen soluble in 3 M NaCl:7 M urea that remains soluble after dialysis to 0.15 M NaCl to precipitate the histones and the DNA. This antigen has been found in the chromatin of both the Novikoff hepatoma and the Walker 256 carcinosarcoma but not in the chromatin of either normal or regenerating liver. It is a nonhistone nuclear protein as indicated by its amino acid analysis in which the ratio of the number of acidic to basic amino acids is approximately 1.4. Further studies are in progress on the function and structure of this chromatin protein. As an approach to analysis of relative rates of synthesis of this antigen and otherproteins, the products of translation of messenger RNA of Novikoff hepatoma and normal liver are being analyzed by autoradiography of two-dimensional electrophoretic gels.

A fetal protein in chromatin of Novikoff hepatoma and Walker 256 carcinosarcoma tumors that is absent from normal and regenerating rat liver.

Antibodies to chromatin proteins of Novikoff hepatoma cells formed precipitin bands in the double-diffusion immunoprecipitation assay with chromatin proteins of Novikoff hepatoma, Walker 256 carcinosarcoma, and 18-day fetal rat liver. The antigen used for preparation of antiserum was the chromatin proteins initially extracted with 3 M NaCl-7 M urea and soluble after dialysis to 0.14 M NaCl-0.35 M urea. The chromatin proteins used for analytical studies were extracted with 0.6 M NaCl containing 0.01 M Tris-HCl (pH 8) and 100 muM phenylmethylsulfonyl fluoride. Corresponding chromatin proteins of normal and 18-hr regenerating rat liver, heart, and kidney did not form precipitin bands. The antigen was purified from the chrmatin of Novikoff hepatoma cells by exclusion chromatography on Sephadex G-150 and preparative nondenaturing polyacrylamide gel electrophoresis. Its migration on denaturing sodium dodecyl sulfate-polyacrylamide gels corresponded to a molecular weight of 26,000. Amino acid analysis showed that the ratio of acidic to basic amino acids was 1.4 to 1.0. Evidence for its homogeneity included its migration as a single protein spot on two-dimensional polyacrylamide gel electrophoresis and its single lysine amino-terminal amino acid. This protein is a glycoprotein, as shown by the presence of 15 moles of galactosamine per mole of antigen. These studies demonstrate the presence of a fetal glycoprotein in the chromatin of two tumors that may have an important role in determining their gene products.

Quantitative analysis of the distribution of 3H-leucine in acid soluble chromatin proteins of Noviknoff hepatoma cells separated by two-dimensional polyacrylamide gel electrophoresis.

The acid soluble proteins of Novikoff hepatoma chromatin were labeled linearly with 3H-leucine for 16 minutes. Analysis on two-dimensional polyacrylamide gels showed that 13 of the 18 stained proteins were detected by autoradiography after a 16-minute in vitro incubation. The labeled molecules include the histones H2A, H2B, H3, and H4; and proteins A3, Aj, A8, A8', A15, A16, A24, B7, and B13. Relatively large amounts of isotope were incorporated into two other proteins, A3 and Aj, in addition to the histones. Some proteins, notably Aj, A8, A8' and A16 were labeled to a greater extent than would be expected on the basis of uptake of Coomassie Brilliant Blue R. None of the labeling patterns were characteristic of a precursor-product relationship either the histones or the nonhistone proteins.

Early and late changes in nonhistone chromatin proteins accompanying rat liver regeneration.

Chromatin was isolated from 0.025 M citric acid nuclei of regenerating rat liver at 1,5,18,24, and 48 hr posthepatectomy. The total protein to DNA ratios did not change significantly during this time period. However, 2-dimensional polyacrylamide gel electrophoresis of nonhistone proteins of "Chromatin Fraction II" revealed changes in the amounts of some protein spots. As early as 1 hr after hepatectomy, decreases in size and intensity were detected for protein spots Bp, B24, C18, and CQ, and increases were detected for protein spots CBL and C13. Late changes in size and intensity were found for protein spots BA and CN, which decreased in size and intensity 5 hr after hepatectomy. The spot densities and sizes for most of the nonhistone proteins underwent no significant changes in the course of liver regeneration. The increases and decreases observed in specific protein spots represent an ordered series of changes in a limited number of nonhistone proteins.