The role of process variables in the design of multiproduct batch protein production plants

This work reports findings about the role of process variables in the design of multiproduct batch plants. Unlike continuous processes, batch processes are subject to size and time constraints which depend on the structure of the plant: the number of units at each stage and the provision of intermediate storage. We used simple process performance models (yet involving all the process variables with significant economic impact) to get explicit expressions for these size and time factors. The traditional approach uses fixed size and time factors. So the addition of those expressions to the original fixed factors model, permitted to simultaneously optimize the plant structure and process variables, and study the role of the latter in the design. We found that if the plant structure constraints are disregarded (with a Free Unlimited Storage operating policy), process variables behave just alike in continuous processes. They trade off cost components with the Total Annual Cost being quite insensitive to them in the neighborhood of the optimal solution. As setting the process variables sets the size and time factors, this means that near the optimal set of process variables, cycle times and size factors can be accommodated to the plant structure, with little effect on the cost of equipment.Fil: Montagna, Jorge Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Vecchietti, Aldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Iribarren, Oscar Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Pinto, José M.. Universidade de Sao Paulo; BrasilFil: Asenjo, Juan A.. Universidad de Chile; Chil

Análisis de Costes y de Coste/Eficacia de las Pautas Recomendadas por GESIDA/Plan Nacional sobre el Sida en 2018 Para el Tratamiento Antirretroviral Inicial en Adultos Infectados Por el VIH

[Background]: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. [Methods]: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. [Results]: In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC + RAL (PR). The effectiveness varies from 0.82 for TAF/FTC + DRV/r (AR) to 0.91 for TAF/FTC + DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC + RAL (PR), respectively. [Conclusion]: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR).[Introducción]: El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP), pautas alternativas (PA) y otras pautas (OP) para el tratamiento antirretroviral (TAR) como terapia de inicio en pacientes infectados por VIH para 2018. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con PP y PA. [Métodos]: Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral <50 copias/ml en la semana 48 en análisis por intención de tratar. Se definió coste de iniciar tratamiento con una pauta como los costes del TAR y de todas sus consecuencias (efectos adversos, cambios de pauta y estudio de resistencias) que se producen en las siguientes 48 semanas. Se utilizó la perspectiva del Sistema Nacional de Salud, considerando solo costes directos diferenciales: TAR (a precio oficial), manejo de efectos adversos, estudios de resistencias y determinación de HLA-B*5701. El ámbito es España, con costes de 2018. Se realizó un análisis de sensibilidad determinista construyendo 3 escenarios para cada pauta: basal, más favorable y más desfavorable. [Resultados]: En el escenario basal, los costes de iniciar tratamiento oscilaron entre 6.788 para TAF/FTC/RPV (PA) y 10.649 para TAF/FTC + RAL (PP). La eficacia osciló entre 0,82 para TAF/FTC + DRV/r (PA) y 0,91 para TAF/FTC + DTG (PP). La eficiencia, en términos de coste/eficacia, osciló entre 7.814 y 12.412 por respondedor a las 48 semanas, para ABC/3TC/DTG (PP) y TAF/FTC + RAL (PP), respectivamente. [Conclusión]: Considerando el precio oficial del TAR, la pauta más eficiente fue ABC/3TC/DTG (PP), seguida de TAF/FTC/RPV (PA) y TAF/FTC/EVG/COBI (PA)

Economic burden of recurrent Clostridioides difficile infection in adults admitted to Spanish hospitals. A multicentre retrospective observational study

Objective: Clostridioides difficile infection (CDI) is associated with increased hospital stays and mortality and a high likelihood of rehospitalization, leading to increased health resource use and costs. The objective was to estimate the economic burden of recurrent CDI (rCDI). Methods: observational, retrospective study carried out in six hospitals. Adults aged ≥18 years with ≥1 confirmed diagnosis (primary or secondary) of rCDI between January 2010 and May 2018 were included. rCDI-related resource use included days of hospital stay (emergency room, ward, isolation and ICU), tests and treatments. For patients with primary diagnosis of rCDI, the complete hospital stay was attributed to rCDI. When diagnosis of rCDI was secondary, hospital stay attributed to rCDI was estimated using 1:1 propensity score matching as the difference in hospital stay compared to controls. Controls were hospitalizations without CDI recorded in the Spanish National Hospital Discharge Database. The cost was calculated by multiplying the natural resource units by the unit cost. Costs (euros) were updated to 2019. Results: we included 282 rCDI episodes (188 as primary diagnosis): 66.31% of patients were aged ≥65 years and 57.80% were female. The mean hospital stay (SD) was 17.18 (23.27) days: 86.17% of rCDI episodes were isolated for a mean (SD) of 10.30 (9.97) days. The total mean cost (95%-CI) per episode was 10,877 (9,499-12,777), of which the hospital stay accounted for 92.56. Conclusions: there is high cost and resource use associated with rCDI, highlighting the importance of preventing rCDI to the Spanish National Health System

Trasplante cardíaco

A heart transplant is at present considered the treatment of choice in cases of terminal cardiac insufficiency refractory to medical or surgical treatment. Due to factors such as the greater life expectancy of the population and the more efficient management of acute coronary syndromes, there is an increasing number of people who suffer from heart failure. It is estimated that the prevalence of the disease in developed countries is around 1%; of this figure, some 10% are in an advanced stage and are thus potential receptors of a heart transplant. The problem is that it is still not possible to offer this therapeutic form to all of the patients that require it. Consequently, it is necessary to optimise the results of the heart transplant through the selection of patients, selection and management of donors, perioperative management and control of the disease due to graft rejection. Since the first transplant carried out in 1967, numerous advances and changes have taken place, which has made it possible to increase survival and quality of life of those who have received a new heart. In this article we review the most relevant aspects of the heart transplant and the challenges that are currently faced

Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH

El objetivo de este documento es actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el VIH del año 2010. La función renal debe monitorizarse en todos los pacientes e incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación CKD-EPI), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. También se revisan las indicaciones de la biopsia renal, cuándo enviar el paciente al nefrólogo y las indicaciones, evaluación y manejo del paciente en diálisis o del trasplante renal

Immunomodulatory properties of carvone inhalation and Its effects on contextual fear memory in mice

A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and cognitive activity. We performed an exploratory study of the immunomodulatory ability of a series of compounds representing each of the 10 odor categories or clusters described previously. We evaluated the impact of each particular odor on the immune response after immunization with the model antigen ovalbumin in combination with the TLR3 agonist poly I:C. We found that some odors behave as immunostimulatory agents, whereas others might be considered as potential immunosuppressant odors. Interestingly, the immunomodulatory capacity was, in some cases, strain-specific. In particular, one of the fragrances, carvone, was found to be immunostimulatory in BALB/c mice and immunosuppressive in C57BL/6J mice, facilitating or impairing viral clearance, respectively, in a model of a viral infection with a recombinant adenovirus. Importantly, inhalation of the odor improved the memory capacity in BALB/c mice in a fear-conditioning test, while it impaired this same capacity in C57BL/6J mice. The improvement in memory capacity in BALB/c was associated with higher CD3+ T cell infiltration into the hippocampus and increased local expression of mRNA coding for IL-1β, TNF-α, and IL-6 cytokines. In contrast, the memory impairment in C57BL/6 was associated with a reduction in CD3 numbers and an increase in IFN-γ. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals. These results highlight the potential of studying odors as therapeutic agents for CNS-related diseases

Human Immunodeficiency Virus/Hepatitis C Virus Coinfection in Spain: Prevalence and Patient Characteristics

Background: The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods: The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results: The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions: The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy.This study was supported by grant GLD14-00279 from the GILEAD Fellowship Programme (Spain). J. B. is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS) (Ref. no. INT15/00079).S

Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial

[Purpose] To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture.[Methods] Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. Primary outcome: early-PJI after HHA.[Results] Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33–3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15–7.10]). [Conclusions] Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.This work was supported by the Spanish Clinical Research Network (SCReN), co-finaced by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, through the project PI15/02161 and by the Plan Nacional de I+D+i 2013-016 and ISCIIII, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)-co-financed by European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014-2020.Peer reviewe

Prosthetic shoulder joint infection by Cutibacterium acnes: does rifampin improve prognosis? a retrospective, multicenter, observational study.

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3-75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included β-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80-58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08-105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with β-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI

Cutibacterium spp. Infections after Instrumented Spine Surgery Have a Good Prognosis Regardless of Rifampin Use: A Cross-Sectional Study

Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin