Cost-Effectiveness Analysis Comparing QuantiFERON-TB Gold Plus Test and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Immunocompetent Subjects in Colombia.

OBJECTIVES: To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. METHODS: A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). RESULTS: QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. CONCLUSIONS: The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context.

Immune-competent in vitro co-culture models as an approach for skin sensitisation assessment.

There is a complex interplay between numerous cell types that act at different steps of the mechanism leading to allergic contact dermatitis. The validated in vitro methods for skin sensitisation assessment provide good statistical correspondence to local lymph node assay (LLNA) or to human data but, for the most part, poorly represent the actual in vivo situation as they generally involve single cell type culture in 2D. Significant progress has been made over the past decades to develop new technologies of data generation concurrently with novel approaches to improve the models especially by the use of co-culture. The importance of heterotypic cell-cell interactions in the in vitro assessment of skin sensitisation should not be overlooked. This review addresses the technical aspects to take into consideration when co-culturing depending on the desired objective and describes the different keratinocytes and dendritic cells co-cultures developed in 2D and 3D. To date, from a regulatory point of view, no alternative method to animal testing for skin sensitisation potential assessment using a keratinocytes and dendritic cells co-culture model is yet proposed. This review also presents several directions of further development.

Systematic Review of Chronic Discrimination and Changes in Biology During Pregnancy Among African American Women.

Profound racial health disparities in maternal and infant health exist in the USA. Discrimination based on race may contribute to these disparities, but the biological pathways through which racial discrimination acts on health are not fully known. Even less is known about these pathways during development. Examining how racial discrimination becomes biology is paramount because it may shed light on how and when such social forces result in lasting biological consequences for health and wellbeing. To begin exploring this issue, we performed a systematic review of the relationships between experiences of chronic racial discrimination and relevant biomarkers measured during pregnancy among African American women. The literature search included studies published prior to August 2018 in the MEDLINE, Embase, and PsycINFO databases, and 11 studies met our inclusion criteria. We evaluated the articles based on the biological system that the authors investigated, which included the immune, neuroendocrine, and cardiovascular systems. We found that the current literature provides preliminary evidence that experiences of chronic racial discrimination are associated with changes in maternal biology during pregnancy. However, the literature was limited in both quantity and quality. We found only 11 studies that addressed this subject, four of which only provided indirect evidence, and many studies had small sample sizes. Future work in this area should develop more informative methods that consider the interaction between interpersonal and structural racial discrimination, individual variation, and sociocultural factors. We conclude researchers should continue to work in this area and focus on developing more effective study designs and larger sample sizes.

Herpes zoster related healthcare burden and costs in immunocompromised (IC) and IC-free populations in England: an observational retrospective database analysis.

OBJECTIVE: Individuals with immunocompromised (IC) conditions are at a higher risk of developing herpes zoster (HZ) than IC-free individuals. This study assessed the healthcare resource utilisation (HCRU) burden and costs, of HZ in IC and IC-free individuals ≥18 years of age (YOA). METHODS: We conducted an observational retrospective study in a cohort of IC (n=621 588) and IC-free (n=621 588) individuals, matched by age, gender and General Practitioner practice region, contributing to the Clinical Practice Research Datalink database from 2000 to 2012 and linked to the Hospital Episode Statistics inpatient data. HCRU (ie, primary and secondary care consultations, hospital inpatient stays and treatment prescriptions) was analysed from 7 days before to: (1) 30, (2) 365 days after the HZ diagnosis date for individuals with (1) HZ only (no postherpetic neuralgia (PHN)) and (2) individuals with HZ and PHN only. Healthcare costs were computed by multiplying the number of units of resources used by the unit costs, summed across all HCRU categories to obtain a total cost per subject. Values were expressed in 2014 UK pound sterling (£) and presented for HZ cases overall, stratified by age (ie, 18-49, 50-59, 60-69, 70-79 and ≥80 YOA) and IC status. RESULTS: The percentage of HZ cases requiring hospitalisation was higher in IC individuals (2.7% vs 0.4% in IC and IC-free individuals aged 18-49 YOA, respectively and 9.5% vs 7.5% in IC and IC-free individuals aged ≥80 YOA, respectively). Similarly, HZ-related mean treatment costs per subject were higher in IC individuals (£189 vs £104 in IC and IC-free individuals aged 18-49 YOA, respectively and £557 vs £401 in IC and IC-free individuals aged ≥80 YOA, respectively). Costs varied considerably by IC condition. CONCLUSIONS: Individuals with IC conditions, have a high burden of HZ, associated with an increased risk of HZ and high HZ-related healthcare costs.

Overexpression of PGE2 synthase by in vivo transient expression enhances immunocompetency along with fitness cost in a lepidopteran insect.

Prostaglandins (PGs) mediate various physiological functions in insects. Specifically, PGE2 is known to mediate immunity and egg-laying behavior in the beet armyworm, Spodoptera exigua A PGE2 synthase 2 (Se-PGES2) has been identified to catalyze the final step to produce PGE2 in S. exigua Its expression is inducible in response to immune challenge. Inhibition of the gene expression results in immunosuppression. In contrast, any physiological alteration induced by its uncontrolled overexpression was not recognized in insects. This study used the in vivo transient expression (IVTE) technique to induce overexpression and assessed subsequent physiological alteration in S. exiguaSe-PGES2 was cloned into a eukaryotic expression vector and transfected to Sf9 cells to monitor its heterologous expression. The Sf9 cells expressed the recombinant Se-PGES2 (rSe-PGES2) at an expected size (∼47 kDa), which was localized in the cytoplasm. The recombinant expression vector was then used to transfect larvae of S. exigua Hemocytes collected from the larvae treated with IVTE expressed the rSe-PGES2 gene for at least 48 h. The larvae treated with IVTE exhibited an enhanced competency in cellular immune response measured by hemocyte nodule formation. In addition, IVTE treatment of Se-PGES2 induced gene expression of antimicrobial peptides without any immune challenge. The larvae treated with IVTE became significantly resistant to infection of an entomopathogenic nematode, Steinernema monticolum, or to infection to its symbiotic bacterium, Xenorhabdus hominickii However, IVTE-treated S. exigua larvae suffered from reduced pupal size and fecundity.

Assessment of Diagnostic Yield of Nonculture Infection Testing on Cerebrospinal Fluid in Immune-Competent Children.

Importance: Nonculture infection tests of cerebrospinal fluid (CSF) samples using polymerase chain reaction and antigen or antibody assays are frequently ordered on lumbar puncture specimens concurrently with routine CSF cell counts, but the value of CSF infection testing in otherwise healthy children is unknown. Objective: To determine the value of nonculture CSF infection testing in immune-competent children with normal CSF cell counts. Design, Setting, and Participants: This cross-sectional study reviewed screening and diagnostic tests in the electronic medical record system of a large academic tertiary care children's hospital. Records of children aged 0.5 to 18.9 years (n = 4083) who underwent lumbar puncture (n = 4811 procedures) in an inpatient or outpatient facility of Children's Hospital of Philadelphia between July 1, 2007, and December 31, 2016, were reviewed. Those with indwelling CSF shunts or catheters; those with active or past oncologic, immunologic, or rheumatologic conditions; or those taking immune-suppressing medications were excluded from analysis. This study was conducted from July 20, 2017, to March 13, 2019. Main Outcomes and Measures: Outcome variables included frequency of nonculture CSF infection testing and frequency of positive results in the entire cohort, and among those with normal cell counts. Normal cell counts were defined as CSF white blood cell counts lower than 5 cells/µL and CSF red blood cell counts lower than 500 cells/µL. Results: In total, 4811 lumbar puncture procedures were performed on 4083 unique children, with a median (range) age of 7.4 (0.5-18.9) years, 2537 boys (52.7%), and 3331 (69.2%) with normal CSF cell counts. At least 1 nonculture CSF infection test was performed on 1270 lumbar puncture specimens with normal cell counts (38.1%; 95% CI, 36%-40%), and more tests were performed in the summer months. Only 18 (1.4%; 95% CI, 0.9%-2.2%) of 1270 lumbar puncture specimens with normal cell counts had at least 1 nonculture infection test with a positive result; 2 of these 18 children required clinical intervention for their positive results, but each also had other clear clinical signs of infection. Conclusions and Relevance: Nonculture CSF infection testing appeared to be common in immune-competent children with normal CSF cell counts, but positive results were uncommon and were not independently associated with clinical care; delaying the decision to send nonculture infection tests until CSF cell counts are available could reduce unnecessary diagnostic testing and medical costs, which may improve value-based care.

Costs of herpes zoster complications in older adults: A cohort study of US claims database.

BACKGROUND/OBJECTIVES: Herpes zoster (HZ) incidence increases with age, and the burden of HZ is expected to grow with aging of populations worldwide. We aim to determine the incremental healthcare resource utilization and associated costs of patients with common HZ-related complications other than postherpetic neuralgia (cutaneous, neurologic and ophthalmic) compared to uncomplicated HZ. METHODS: We conducted a retrospective cohort study of commercial health insurance claims covering about 40 million immunocompetent individuals aged ≥50 years at study entry from all over the US, from 2008 to 2013, with follow-up for one year after HZ onset. All-cause healthcare resource utilization and direct healthcare costs were recorded and calculated from six months before until 12 months after HZ onset. The mean costs for HZ patients with complications were compared to the mean costs for patients with uncomplicated HZ. Multivariable regression analyses estimated mean incremental costs adjusted for demographics, comorbidities, type of complication and time period. RESULTS: Over the five-year study period, 22,948 HZ patients (60% women, median age 62 years) who experienced at least one of the selected complications were compared to 213,232 patients (63% women, median age 61 years) with uncomplicated HZ. Overall, the mean annual incremental unadjusted costs for the patients with HZ-related complications were US$4716, ranging from US$2173 for ophthalmic to US$18,323 for neurologic complications. Most of the incremental costs associated with HZ complications were accrued during the first quarter after HZ onset. For each complication type the incremental costs increased with age up to, but not including the oldest group, aged ≥80 years. CONCLUSIONS: Approximately 10% of immunocompetent older patients with HZ develop complications which considerably increase the economic burden of HZ. Vaccination of older adults will offset some of the burden of HZ, including costs associated with HZ-related complications.

Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection.

Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is the most severe form of viral hepatitis, affecting at least 20 million hepatitis B virus (HBV)-infected patients worldwide. HDV/HBV co- or superinfections are major drivers for hepatocarcinogenesis. Antiviral treatments exist only for HBV and can only suppress but not cure infection. Development of more effective therapies has been impeded by the scarcity of suitable small-animal models. We created a transgenic (tg) mouse model for HDV expressing the functional receptor for HBV and HDV, the human sodium taurocholate cotransporting peptide NTCP. Both HBV and HDV entered hepatocytes in these mice in a glycoprotein-dependent manner, but one or more postentry blocks prevented HBV replication. In contrast, HDV persistently infected hNTCP tg mice coexpressing the HBV envelope, consistent with HDV dependency on the HBV surface antigen (HBsAg) for packaging and spread. In immunocompromised mice lacking functional B, T, and natural killer cells, viremia lasted at least 80 days but resolved within 14 days in immunocompetent animals, demonstrating that lymphocytes are critical for controlling HDV infection. Although acute HDV infection did not cause overt liver damage in this model, cell-intrinsic and cellular innate immune responses were induced. We further demonstrated that single and dual treatment with myrcludex B and lonafarnib efficiently suppressed viremia but failed to cure HDV infection at the doses tested. This small-animal model with inheritable susceptibility to HDV opens opportunities for studying viral pathogenesis and immune responses and for testing novel HDV therapeutics.

The Mechanisms for Within-Host Influenza Virus Control Affect Model-Based Assessment and Prediction of Antiviral Treatment.

Models of within-host influenza viral dynamics have contributed to an improved understanding of viral dynamics and antiviral effects over the past decade. Existing models can be classified into two broad types based on the mechanism of viral control: models utilising target cell depletion to limit the progress of infection and models which rely on timely activation of innate and adaptive immune responses to control the infection. In this paper, we compare how two exemplar models based on these different mechanisms behave and investigate how the mechanistic difference affects the assessment and prediction of antiviral treatment. We find that the assumed mechanism for viral control strongly influences the predicted outcomes of treatment. Furthermore, we observe that for the target cell-limited model the assumed drug efficacy strongly influences the predicted treatment outcomes. The area under the viral load curve is identified as the most reliable predictor of drug efficacy, and is robust to model selection. Moreover, with support from previous clinical studies, we suggest that the target cell-limited model is more suitable for modelling in vitro assays or infection in some immunocompromised/immunosuppressed patients while the immune response model is preferred for predicting the infection/antiviral effect in immunocompetent animals/patients.

Rapid Adenovirus typing method for species identification.

Adenoviruses are characterized by a large variability, reflected by their classification in species A to G. Certain species, eg A and C, could be associated with increased clinical severity, both in immunocompetent and immunocompromised hosts suggesting that in some instances species identification provides clinically relevant information. Here we designed a novel "pVI rapid typing method" to obtain quick, simple and cost effective species assignment for Adenoviruses, thanks to combined fusion temperature (Tm) and amplicon size analysis. Rapid typing results were compared to Sanger sequencing in the hexon gene for 140 Adenovirus-positive clinical samples included in the Typadeno study. Species A and C could be identified with a 100% positive predictive value, thus confirming the value of this simple typing method.

Analysis of real-world health care costs among immunocompetent patients aged 50 years or older with herpes zoster in the United States.

Few peer-reviewed publications present real-world United States (US) data describing resource utilization and costs associated with herpes zoster (HZ) and postherpetic neuralgia (PHN). The primary objective of this analysis (GSK study identifier: HO-14-14270) was to assess direct costs associated with HZ and PHN in the US using a retrospective managed care insurance claims database. Patients ≥ 50 y at HZ diagnosis were selected. Patients were excluded if they were immunocompromised before diagnosis or received an HZ vaccine at any time. A subsample of patients with PHN was identified. Each patient with HZ was matched to ≤ 4 controls without HZ based on age, sex, and health plan enrollment. Incremental differences in mean HZ-related costs ("incremental costs") were assessed overall and stratified by age. Multivariable regression models controlled for the effect of demographic characteristics, prediagnosis costs, and comorbidity burden on costs using a recycled predictions approach. Overall, 142,519 patients with HZ (9,470 patients [6.6%] had PHN) and 357,907 matched controls without HZ were identified. Resource utilization was greater among patients with HZ than controls. After adjusting for demographic and clinical characteristics, annual incremental health care costs for HZ patients vs. controls were $1,210 for patients aged 50-59 years, $1,629 for those 60-64 years, $1,876 for those 65-69 years, $2,643 for those 70-79 years, and $3,804 for those 80+ years; adjusted annual incremental costs among PHN patients vs. controls were $4,670 for patients 50-59 years, $6,133 for those 60-64 years, $6,451 for those 65-69 years, $8,548 for those 70-79 years, and $11,147 for those 80+ years. HZ is associated with a significant cost burden, which increases with advancing patient age. Vaccination may reduce costs associated with HZ through case avoidance.

Medicolegal Implications of Nosocomial Infections: A Case Report of Aspergillus Contamination during Cardiac Surgery.

Nosocomial infections have become a major issue of public health and lead to an increasing number of suits for damages. We present a rare case of Aspergillus contamination during cardiac surgery, describe the medicolegal investigation, and present the new system for compensation of bodily injury after nosocomial infection in France, based on the law of March 4, 2002 on patient rights and quality in the health system. This case demonstrates the limits of compensation for nosocomial infections on the grounds of national solidarity. The expert report requested by the regional commission for conciliation and compensation is of fundamental importance in enabling the commission to decide between fault and inherent risk of treatment.

Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England.

BACKGROUND: Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years. METHOD: A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. RESULTS: The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust. CONCLUSIONS: Vaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective.

[A Dynamic Model to Estimate the Budget Impact of a Pneumococcal Vaccination Program in a 65 Year-old immunocompetent Spanish Cohort with 13-Valent Pneumococcal Conjugate Vaccine]. / La vacunación anti-neumocócica con la vacuna conjugada 13-valente en población inmunocompetente de 65 años: análisis del impacto presupuestario en España aplicando un modelo de transmisión dinámica.

OBJECTIVE: To estimate the 5-year clinical and economic impact of a pneumococcal vaccination program on immunocompetent population aged 65-year-old in Spain. METHODS: A 5 year dynamic model based on differential equations was built for the conceptualization of the burden of pneumococcal disease (PD) on a 65 year-old cohort. A 36.5% of the cohort was vaccinated with an expected efficacy rate of 52.5% as observed in the CAPITA study. The serotype vaccination coverage used was 63.4% (CAPA study), the incidence of pneumococcal disease was 162.2 per 100,000 cases per year (CMBD 2010-2013) and a rate of vaccinated subjects previously from the start of the model of 0.99%. The study used the perspective of The National Health System, and included the costs associated to PD and the conjugate vaccine laboratory selling price. RESULTS: In a 5 years-period, the vaccination with 13-valent pneumococcal conjugate vaccine is expected to avoid 10,360 cases of pneumococcal disease (7,411 in-patient pneumonias) and 699 deaths (14,736 Life Years Gained) in the 65 year old cohort. Vaccination costs of 36.5 million euros would be completely offset by medical cost reduction of 41.5 million euros, yielding to a net saving of 3.8 million constant euros (4.9 million undiscounted). CONCLUSIONS: PCV13 vaccination targeting the cohort of 65 year-old immunocompetent Spanish adults is expected to result in net savings for the National Health System, while decreasing disease burden and averting a substantial number of related deaths.

OBJETIVO: Analizar el impacto económico y sanitario en 5 años de la vacunación de la cohorte española de 65 años inmunocompetente con la vacuna antineumocócica conjugada 13-valente. METODOS: Mediante un modelo de transmisión dinámica basado en ecuaciones diferenciales se analizó la carga de la enfermedad neumocócica (EN) en sujetos de 65 años en 5 años, siendo vacunada anualmente el 36,5% de la cohorte. Se aplicó la eficacia de la vacuna del 52,5% observada en el estudio CAPITA en pacientes de 65 años inmunocompetentes, cobertura de serotipos vacunales del 63,4% (estudio CAPA), incidencia de infección neumocócica de 162,2/100.000 casos año (CMBD 2010-2013) y proporción de vacunados previamente al arranque del modelo del 0,99%. La perspectiva fue la del Sistema Nacional de Salud (SNS). Costes de casos de EN según CMBD y precio de venta de laboratorio de la vacuna conjugada. RESULTADOS: En 5 años la vacunación con vacuna conjugada 13-valente espera evitar 10.360 casos de EN (7.411 hospitalizaciones por neumonías) y 699 muertes (14.736 años de vida ganados -AVG-), en una cohorte de 65 a 69 años de edad. El coste de vacunación esperado de 36,5 millones de euros se compensaría completamente por la reducción de 41,5 millones de costes médicos evitados, con un ahorro neto acumulado de 3,8 millones de euros a precios constantes (4,9 a precios corrientes). CONCLUSIONES: La vacunación con vacuna conjugada 13-valente en adultos de 65 años inmunocompetentes resulta eficiente para el Sistema Nacional de Salud, reduciendo la carga de enfermedad y evitando un número importante de muertes.

[An assessment of the immune status of the children population as a marker of technogenic pollution of the environment].

This article describes results of the immunological study of school-aged children residing in cities with different levels of the technogenic air pollution. Children from cities with the highest level of the technogenic pollution had a high number of immature neutrophils (band cells) and eosinophils. The children living in these ecologically unfavorable areas have presented a reduction of T-cell antigen receptor CD3, CD4, CD8, CD20, CD16, CD95. This indicates to that both T-cell and B-cell immunity is suppressed. The decline of the phagocytic function in neutrophils indicates to the suppression of the nonspecific host defense mechanisms also.

Quantitative assessment of the effects of sulfamethoxazole on Toxoplasma gondii loads in susceptible WT C57BL/6 mice as an immunocompetent host model.

The abundance of Toxoplasma gondii with or without sulfamethoxazole (SMX) treatment was evaluated with quantitative competitive polymerase chain reaction in various organs of wild-type C57BL/6 mice, a susceptible immunocompetent host, after peroral infection with a cyst-forming Fukaya strain of T. gondii. SMX affected different organs in three ways: T. gondii was reduced independently of SMX (skin and kidney); T. gondii was not eradicated with continuous treatment (brain, heart, and lung); and T. gondii was eradicated with continuous treatment (tongue, skeletal muscle, and small intestine). The SMX concentrations in the brains, hearts, and lungs were higher in infected mice than in uninfected mice. These results indicate that even in an immunocompetent host, chemotherapy is necessary to reduce the parasite load and thus reduce the risk of recurrent disease.

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA): what is the future of pneumococcal conjugate vaccination in elderly?

Pneumococcal community-acquired pneumonia (PCAP) and invasive pneumococcal disease (IPD) are important causes of morbidity and mortality in elderly. In the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a randomized double-blind placebo-controlled trial of 84,496 community-dwelling immunocompetent adults over 65 years of age, the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of first episode of vaccine-type (VT) PCAP with 38 and of VT-IPD with 76% in the modified intention-to-treat population. In The Netherlands, where PCV7 immunization of newborns was introduced in 2007 and replaced by PCV10 in 2011, introduction of PCV13 immunization of elderly--based on 2012 data--would be highly cost effective. However, this is probably different in countries where the VT disease burden has declined more, for instance due to herd effects following child immunization with PCV13. Apart from cost-effectiveness analyses, ethical aspects of PCAP prevention should be taken into account in policy making for pneumococcal vaccination in elderly.

Interest of preoperative immunonutrition in liver resection for cancer: study protocol of the PROPILS trial, a multicenter randomized controlled phase IV trial.

BACKGROUND: Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT®) can reduce postoperative morbidity in liver resection for cancer. METHODS/DESIGN: Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT®) or control supplement (isocaloric isonitrogenous supplement--IMPACT CONTROL®) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis. DISCUSSION: The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02041871.

Cost-effectiveness of pneumococcal vaccines for adults in the United States.

INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices (ACIP) revised recommendations for adult pneumococcal vaccination to include a sequential regimen of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) for certain high-risk adults with immunocompromising conditions. This study, from a payer perspective, examined: (1) the cost-effectiveness of the new 2012 ACIP vaccine policy recommendation relative to the 1997 ACIP recommendation; (2) the cost-effectiveness of potential future pneumococcal vaccination policies; and (3) key assumptions that influence study results. METHODS: A static cohort model that incorporated costs, health outcomes, and quality-adjusted life-year (QALY) losses associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia (NBPP) was developed to evaluate seven pneumococcal vaccination strategies for a 50-year-old adult cohort over a 50-year period using incremental cost-effectiveness ratios (ICERs). RESULTS: For objective 1, the 2012 ACIP recommendation is the more economically efficient strategy (ICER was $25,841 per QALY gained vs. no vaccination). For objective 2, the most efficient vaccination policy would be to maintain the 2012 recommendation for PPSV23 for healthy and immunocompetent adults with comorbidities, and to modify the recommendation for adults with immunocompromising conditions by replacing PPSV23 with a sequential regimen of PCV13 and PPSV23 at age 65 (ICER was $23,416 per QALY gained vs. no vaccination). For objective 3, cost-effectiveness ratios for alternative pneumococcal vaccine policies were highly influenced by assumptions used for vaccine effectiveness against NBPP and accounting for the herd protection effects of pediatric PCV13 vaccination on adult pneumococcal disease. CONCLUSION: Modifying the 2012 recommendation to include an additional dose of PCV13 at age 65, followed by PPSV23, for adults with immunocompromising conditions appears to be a cost-effective vaccine policy. Given the uncertainty in the available data and the absence of key influential data, comprehensive sensitivity analyses should be conducted by policy-makers when evaluating new adult pneumococcal vaccine strategies.