Surgical Treatment of Pressure Ulcers with a Fibrin Sealant in Patients with Spinal Cord Injury: A Cost-Consequence Analysis.

BACKGROUND: A comparative study was performed to evaluate the effectiveness and costs of a fibrin sealant (Tissucol Duo [known as Tisseel in the United States], Baxter International, Deerfield, Illinois) to improve postoperative outcomes in patients with spinal cord injury undergoing surgical treatment for pressure ulcers (PrUs). METHODS: Between January and June 2011, 27 patients underwent surgical treatment for PrUs with the direct application of Tissucol Duo sprayed before closure. The costs and outcomes obtained in this cohort were compared with those obtained in a previous retrospective study where 71 patients underwent conventional surgery. RESULTS: Lower rates of hematoma-seroma were observed in the study group (3.7% vs 33.8%; P < .05). Drain removal occurred earlier (10 vs 15 days; P < .05), and the average drain volume was also lower (155 vs 360 mL; P < .05) for this group. The mean length of hospital stay was significantly lower in the study group and was the main contributing factor to the overall costs. CONCLUSIONS: The application of Tissucol Duo during surgical treatment of PrUs in patients with spinal cord injury has been shown to be effective in reducing postoperative complications and in shortening the duration of the hospital stay with a consequent savings in costs.

Actionable mutational profiling in solid tumors using hybrid-capture-based next-generation sequencing in a real-world setting in Spain.

OBJECTIVE: This study aimed to describe the performance of a next-generation sequencing (NGS) panel for the detection of precise genomic alterations in cancer in Spanish clinical practice. The impact of tumor characteristics was evaluated on informative NGS and actionable mutation rates. MATERIALS AND METHODS: A cross-sectional study was conducted at the Fundación Jiménez Díaz University Hospital (May 2021-March 2022) where molecular diagnostic of 537 Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples of diverse solid tumors (lung, colorectal, melanoma, gastrointestinal stromal, among others) was performed using AVENIO Tumor Tissue Targeted Kit. A descriptive analysis of the features of all samples was carried out. Multivariable logistic analysis was conducted to assess the impact of sample characteristics on NGS performance defined by informative results rate (for all tumors and for lung tumors), and on actionable mutations rate (for lung tumors only). RESULTS: AVENIO performance rate was 75.2% in all tumor samples and 75.3% in lung cancer samples, and the multivariable analysis showed that surgical specimens are most likely to provide informative results than diagnostic biopsies. Regarding the mutational findings, 727 pathogenic, likely pathogenic, or variant of unknown significance mutations were found in all tumor samples. Single nucleotide variant was the most common genomic alteration, both for all tumor samples (85.3% and 81.9% for all solid tumors and lung samples, respectively). In lung tumors, multivariable analysis showed that it is more likely to find actionable mutations from non-smokers and patients with adenocarcinoma, large cell, or undifferentiated histologies. CONCLUSION: This is the largest cohort-level study in Spain to profile the analyses of biopsy samples of different tumors using NGS in routine clinical practice. Our findings showed that the use of NGS routinely provides good rates of informative results and can improve tumor characterization and identify a greater number of actionable mutations.

Cost-effectiveness Analysis of Maternal Immunization with RSVpreF Vaccine for the Prevention of Respiratory Syncytial Virus Among Infants in Spain.

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children under one year of age. In high-income countries, RSV infections cause a significant overload of care every winter, imposing a significant burden to the healthcare system, which has made the development of prevention strategies a major global health priority. In this context, a new bivalent RSV prefusion F protein-based vaccine (RSVpreF) has recently been approved. The objective of this study was to evaluate the cost-effectiveness of vaccinating pregnant women with the RSVpreF vaccine to prevent RSV in infants from the Spanish National Healthcare System (NHS) perspective. METHODS: A hypothetical cohort framework and a Markov-type process were used to estimate clinical outcomes, costs, quality-adjusted life years (QALY) and cost-per-QALY gained (willingness-to-pay threshold: €25,000/QALY) for newborn infants born to RSV-vaccinated versus unvaccinated mothers over an RSV season. The base case analysis was performed from the NHS perspective including direct costs (€2023) and applying a discount of 3% to future costs and outcomes. To evaluate the robustness of the model, several scenarios, and deterministic and probabilistic analyses were carried out. All the parameters and assumptions were validated by a panel of experts. RESULTS: The results of the study showed that year-round maternal vaccination program with 70% coverage is a dominant option compared to no intervention, resulting in direct cost savings of €1.8 million each year, with an increase of 551 QALYs. Maternal vaccination could prevent 38% of hospital admissions, 23% of emergency room visits, 19% of primary care visits, and 34% of deaths due to RSV. All scenario analyses showed consistent results, and according to the probabilistic sensitivity analysis (PSA), the probability of maternal vaccination being cost-effective versus no intervention was 99%. CONCLUSIONS: From the Spanish NHS perspective, maternal vaccination with bivalent RSVpreF is a dominant alternative compared with a non-prevention strategy.

The phthalocyanine prototype derivative Alcian Blue is the first synthetic agent with selective anti-human immunodeficiency virus activity due to its gp120 glycan-binding potential.

Alcian Blue (AB), a phthalocyanine derivative, is able to prevent infection by a wide spectrum of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strains in various cell types [T cells, (co)receptor-transfected cells, and peripheral blood mononuclear cells]. With the exception of herpes simplex virus, AB is inactive against a broad variety of other (DNA and RNA) viruses. Time-of-addition studies show that AB prevents HIV-1 infection at the virus entry stage, exactly at the same time as carbohydrate-binding agents do. AB also efficiently prevents fusion between persistently HIV-1-infected HUT-78 cells and uninfected (CD4(+)) lymphocytes, DC-SIGN-directed HIV-1 capture, and subsequent transmission to uninfected (CD4(+)) T lymphocytes. Prolonged passaging of HIV-1 at dose-escalating concentrations of AB resulted in the selection of mutant virus strains in which several N-glycans of the HIV-1 gp120 envelope were deleted and in which positively charged amino acid mutations in both gp120 and gp41 appeared. A mutant virus strain in which four N-glycans were deleted showed a 10-fold decrease in sensitivity to the inhibitory effect of AB. These data suggest that AB is likely endowed with carbohydrate-binding properties and can be considered an important lead compound in the development of novel synthetic nonpeptidic antiviral drugs targeting the glycans of the envelope of HIV.

A novel organogelator incorporating tert-butyl esters of asparagines.

A novel organogelator based on tert-butyl esters of asparagines has been synthesized and its organogelation abilities have been investigated. The rheological characterization has confirmed the gelation behavior, and its thixotropic properties. Furthermore, the morphological studies performed reveal a spherical structure. Thus, this organogelator can be considered as a new example of the emerging, but still reduced, list of gels with a non-fibrillar assembly.

Influence of Different Wood Chip Extracts Species on Color Changes and Anthocyanin Content in Synthetic Wine Solutions.

There is restricted knowledge about the potential impact of the use of different wood species on color and anthocyanin changes during the red wine aging process. This lack of knowledge is even greater when no oak wood species are used. Thus, the aim of this study was to carry out a comparative analysis of the impact of wood chip extracts from oak, acacia, and cherry species on the color characteristics and anthocyanins changes using synthetic wine solutions. In this context, several methodologies were used to quantify, color, and anthocyanins changes during the aging time studied. The results indicated that the contact between wood chip extracts and grape skin isolated anthocyanin extracts induced a decrease of color intensity (particularly red color), and the anthocyanin content in the different experimental synthetic wine solutions studied. All chromatic modifications are potentially detected by human eyes because ΔE values were much higher than 3 CIELab units. These tendencies seem to be independent of the wood species used, but are more pronounced for higher contact time between wood chip extracts and anthocyanins. The obtained results may contribute to a better understanding of the chromatic changes of red wines when aged in contact with different wood chip species.

Short-term cost and efficiency analysis of raltegravir versus atazanavir/ritonavir or darunavir/ritonavir for treatment-naive adults with HIV-1 infection in Spain.

INTRODUCTION: The AIDS Clinical Trial Group (ACTG) 5257 clinical trial showed that raltegravir (RAL) was superior to atazanavir/ritonavir (ATV/r) and darunavir/ritonavir (DRV/r), when used in combination with emtricitabine/tenofovir DF (FTC/TDF), in a 96-week composite endpoint combining virologic efficacy and tolerability for treatment-naive adults with HIV-1 infection. This study aimed to estimate the efficiency associated with these three regimens in Spain. METHODS: An economic model was developed to estimate costs for antiretroviral drugs, adverse event management, and HIV care for individuals initiating first-line therapy. Antiretroviral drug costs were based on hospital costs with mandatory discounts applied. Adverse event management costs and HIV care costs were obtained from published sources and inflated to 2015 euros. Head-to-head efficacy and safety data (discontinuation rates, mean CD4 cell-count changes, adverse event incidence) up to 96 weeks for each regimen were obtained from the clinical trial. The efficiency of each regimen, as measured by the cost per successfully treated patient (i.e. on first-line therapy for 96 weeks), was estimated and examined in sensitivity analyses. All cost outcomes were discounted at 3.0% annually. RESULTS: Total costs per successfully treated patient were €22,377 for RAL, €26,629 for ATV/r, and €23,928 for DRV/r. These results were found to be robust in sensitivity analyses. DISCUSSION: RAL has the lowest cost per successfully treated patient when compared with DRV/r and ATV/r, each used in combination with FTC/TDF, for treatment-naive adults with HIV-1 infection in Spain. This economic evidence complements the clinical benefits of RAL reported in the ACTG 5257 clinical trial.

Retinal findings in membranoproliferative glomerulonephritis.

PURPOSE: To assess the evolution of retinal findings in patients with membranoproliferative glomerulonephritis (MPGN) by funduscopy, intravenous fluorescein angiography and optical coherence tomography. OBSERVATIONS: Three women and one man were followed for a period of 1.5-37 years. Four patients (8 eyes) had drusen detected at first fundus exam at age 24, 29, 50 and 55. Three patients (6 eyes) had diffuse thickening of Bruch's membrane, and two patients (3 eyes) had detachment of the retinal pigment epithelium with serous retinal detachment. Drusen tended to widen over a period of 10-year follow-up in one case. CONCLUSIONS AND IMPORTANCE: Drusen remain the ocular stigmata for MPGN occuring at an early age. The retinal disease is progressive with gradual thickening of Bruch's membrane and occurrence of retinal pigment epithelium detachment.

Impact of a Dynamic Microbiological Environment on the Clinical Efficacy of Ertapenem and Piperacillin/Tazobactam in the Treatment of Complicated Community-Acquired Intra-Abdominal Infection in Spain: A Cost-Consequence Analysis.

BACKGROUND AND OBJECTIVE: The microbial susceptibility of many antibiotics has been affected by prescribing patterns and their extensive use. The purpose of this evaluation was to assess how these changes could affect the initial efficacy of ertapenem and piperacillin/tazobactam in the treatment of complicated intra-abdominal infections (IAIs) acquired in the community and the potential consequences this may have in healthcare costs in Spain. METHODS: The Initial efficacy of ertapenem and piperacillin/tazobactam for patients with APACHE (Acute Physiology and Chronic Health Evaluation) II scores <10 was extracted from a multicenter randomized study and were combined with the current microbial susceptibilities obtained from the SMART study, a multinational surveillance program. Country-specific pathogens distribution was extracted from a national study in patients with community-acquired IAI. The estimated effectiveness was used in a decision-analytic model to compare total costs between ertapenem and piperacillin/tazobactam in the treatment of complicated IAI. The model performs extensive one-way and probabilistic sensitivity analyses. RESULTS: The model suggested a savings of €209 (year 2012 values) per patient when complicated IAIs acquired in the community (APACHE II <10) were treated with ertapenem instead of piperacillin/tazobactam. One-way sensitivity analyses showed length of stay as the key driver parameter. Further analysis of this parameter and probabilistic sensitivity analysis confirmed the robustness of our evaluation, with a 58% likelihood of ertapenem being dominant. CONCLUSIONS: Ertapenem appears to be a cost-saving strategy over piperacillin/tazobactam for the treatment of patients with complicated IAIs acquired in the community in Spain.

Antibiotic expected effectiveness and cost under real life microbiology: evaluation of ertapenem and ceftriaxone in the treatment of community-acquired pneumonia for elderly patients in Spain.

BACKGROUND: Clinical efficacy of antibiotics may be affected by changes in the susceptibility of microorganisms to antimicrobial agents. The purpose of this study is to assess how these changes could affect the initial efficacy of ertapenem and ceftriaxone in the treatment of community-acquired pneumonia (CAP) in elderly patients and the potential consequences this may have in health care costs. METHODS: Initial efficacy in elderly was obtained from a combined analysis of two multicenter, randomized studies. An alternative scenario was carried out using initial efficacy data according to the pneumonia severity index (PSI). Country-specific pathogens distribution was obtained from a national epidemiological study, and microbiological susceptibilities to first- and second-line therapies were obtained from Spanish or European surveillance studies. A decision analytic model was used to compare ertapenem versus ceftriaxone for CAP inpatient treatment. Inputs of the model were the expected effectiveness previously estimated and resource use considering a Spanish national health system perspective. Outcomes include difference in proportion of successfully treated patients and difference in total costs between ertapenem and ceftriaxone. The model performed one-way and probabilistic sensitivity analyses. RESULTS: First-line treatment of CAP with ertapenem led to a higher proportion of successfully treated patients compared with ceftriaxone in Spain. One-way sensitivity analysis showed that length of stay was the key parameter of the model. Probabilistic sensitivity analysis showed that ertapenem can be a cost-saving strategy compared with ceftriaxone, with a 59% probability of being dominant (lower costs with additional health benefits) for both, elderly patients (>65 years) and patients with PSI >3. CONCLUSION: The incorporation of the current antimicrobial susceptibility into the initial clinical efficacy has a significant impact in outcomes and costs in CAP treatment. The treatment with ertapenem compared with ceftriaxone resulted in better clinical outcomes and lower treatment costs for two segments of the Spanish population: elderly patients and patients with severe pneumonia (PSI >3).

Cost effectiveness of first-line oral antiviral therapies for chronic hepatitis B : a systematic review.

BACKGROUND: Chronic hepatitis B is a common, progressive disease, particularly when viral replication is detected. Oral antivirals can suppress viral replication and prevent or delay the development of cirrhosis and liver-related complications. OBJECTIVE: The aim of this study was to systematically review the quality of cost-effectiveness evidence on first-line treatment with entecavir (ETV) or tenofovir difumarate (TDF) for patients with chronic hepatitis B. METHODS: We searched electronic databases and retrieved articles published up to October 2011, in which the cost effectiveness of ETV or TDF was compared with that of other oral antivirals. The quality of the studies identified was assessed with a standard checklist for critical appraisal. RESULTS: We selected 16 original papers, all published in the last 5 years. There was a conflict of interest in 12 of the 16 studies due to sponsorship by the corresponding pharmaceutical companies. According to the validity assessment, ten studies were classified as high quality. Five studies performed a cost-effectiveness analysis comparing ETV with TDF; they concluded that TDF dominates ETV. The other 11 studies compared ETV or TDF with other strategies; all concluded that ETV and TDF are both cost-effective interventions. CONCLUSIONS: This systematic review shows that there is valid evidence suggesting that ETV and TDF are cost-effective interventions for the treatment of patients with chronic hepatitis B in many health systems. In countries where both alternatives are available, it appears that TDF dominates ETV. These results could help decision makers and clinicians to understand economic issues regarding the available drugs for first-line treatment of hepatitis B.

Cost analysis of HIV treatment and drug-related adverse events when fixed-dose combinations of antiretrovirals (FDCs) were stopped, versus continuation with FDCs.

BACKGROUND: The lower sales price of generic lamivudine has caused healthcare administrators to consider abolishing fixed-dose antiretroviral combinations (FDCs) that contain lamivudine and emtricitabine. The alternative is to administer the individual components of the FDCs separately, thus incorporating the new generic lamivudine medication. METHODS: The Balearic Islands Health Service ordered the discontinuation of the treatment with FDCs in July 2010, but FDCs were reintroduced in August 2010. At that point, an independent, retrospective cost analysis was performed by Son Llàtzer Hospital. A total of 75 patients who were treated from July to August 2010 underwent replacement of their FDC treatment with the individual components. Additionally, 150 patients who continued using FDCs were randomly selected. For both patient groups, the antiretroviral therapy that was administered and the costs associated with management of adverse events were recorded. The study period used for the cost calculations was the average number of days that patients used separate components of FDCs (120 days). An alternative analysis was performed to consider the costs of the extra follow-up visit (consultation and clinical tests) that was required for patients who changed their antiretroviral therapy. RESULTS: Considering antiretroviral therapies and adverse events, the administration of the separate components increased the total daily cost by 0.72 € per patient compared to treatment with FDCs. When the cost of an extra follow-up visit was considered, the daily cost increased by 3.61 € per patient. CONCLUSIONS: Our study suggests that the discontinuation of FDC treatment and the replacement with the administration of separate antiretroviral agents could lead to an increase in healthcare costs due to the higher rate of adverse events that was observed with the discontinuation of FDCs.

Targeting HIV entry through interaction with envelope glycoprotein 120 (gp120): synthesis and antiviral evaluation of 1,3,5-triazines with aromatic amino acids.

On the basis of the interesting inhibitory properties that lectins show against HIV-replication through their interaction with glycoprotein 120 (gp120), we here describe the design, synthesis, and anti-HIV evaluation of three series of 1,3,5-triazine derivatives (monomers, dimers, and trimers) functionalized with aromatic amino acids meant to mimic interactions that lectins establish with gp120. While monomers were inactive against HIV replication, dimers showed limited anti-HIV activity that is, however, considerably more significant in the trimers series, with EC(50) values in the lower µM range. These findings most likely reflect the requirement of multivalency of the 1,3,5-triazine derivatives to display anti-HIV activity, as lectins do. The pronounced anti-HIV activity (EC(50) ∼ 20 µM) is accompanied by the absence of toxicity in CEM T-cell line (CC(50) > 250 µM). Moreover, SPR experiments revealed that the prototype trimers with a central core of 2,4,6-triethylbenzene and six l-Trp or six l-Tyr residues at the periphery were efficient binders of CXCR4- and CCR5-tropic HIV-1 gp120 (estimated K(D): lower micromolar range). The collected data support the interest of this novel family of anti-HIV agents and qualify them as potential novel microbicide lead compounds.

Secondary interactions in 3-bromopyridinium tribromoacetate.

The title compound, C(5)H(5)BrN(+).C(2)Br(3)O(2)(-), crystallizes with Z' = 2. The residues pack in two distinct (but interconnected) types of layer, namely, layers parallel to (102), in which the residues are connected by classical N-H...O hydrogen bonds, C-H...O interactions and Br...Br contacts, and anion layers parallel to the ab plane, connected by Br...O interactions. The two formula units are topologically equivalent with respect to all these contacts.

Secondary interactions in the isomorphous compounds 2,6-bis(chloromethyl)pyridinium chloride and 2,6-bis(bromomethyl)pyridinium bromide.

The title compounds, C7H8Cl2N+.Cl- and C7H8Br2N+.Br-, are isomorphous. In the crystal packing, layers parallel to the ac plane are formed by a classical N(+)-H...X- hydrogen bond (X = halogen) and two X...X contacts. A third X...X contact links the layers, and a fourth, which is however very long, completes a ladder-like motif of halogen atoms. Hydrogen bonds of the form C-H...X play at best a subordinate role in the packing.