COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021.

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

The Cost-Effectiveness of Oral Semaglutide in Spain: A Long-Term Health Economic Analysis Based on the PIONEER Clinical Trials.

INTRODUCTION: Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. RESULTS: Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained. CONCLUSION: Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.

PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders.

Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis.

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021.

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45-74) for one dose only and 89% (95% CI: 79-94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.

Incidence and costs of cardiovascular events in Spanish patients with type 2 diabetes mellitus: a comparison with general population, 2015.

INTRODUCTION: Cardiovascular (CV) disease affects a high percentage of patients with type 2 diabetes mellitus (T2DM), especially in the hospital setting, impacting on mortality, complications, quality of life and use of health resources. The aim of this study was to estimate the incidence, mean length of hospital stay (LOHS) and costs attributable to hospital admissions due to CV events in patients with T2DM versus patients without diabetes mellitus (non-DM) in Spain. RESEARCH DESIGN AND METHODS: Retrospective observational study based on the Spanish National Hospital Discharge Database for 2015. Hospital admissions for patients aged ≥35 years with a diagnosis of CV death, non-fatal acute myocardial infarction (AMI), non-fatal stroke, unstable angina, heart failure and revascularization were evaluated. The International Classification of Diseases, Ninth Revision (250.x0 or 250.x2) coding was used to classify records of patients with T2DM. For each CV complication, the hospital discharges of the two groups, T2DM and non-DM, were precisely matched and the number of hospital discharges, patients, LOHS and mean cost were quantified. Additional analyses assessed the robustness of the results. RESULTS: Of the 276 925 hospital discharges analyzed, 34.71% corresponded to patients with T2DM. A higher incidence was observed in all the CV complications studied in the T2DM population, with a relative risk exceeding 2 in all cases. The mean LOHS (days) was longer in the T2DM versus the non-DM group for: non-fatal AMI (7.63 vs 7.02, p<0.001), unstable angina (5.11 vs 4.78, p=0.009) and revascularization (7.96 vs 7.57, p<0.001). The mean cost per hospital discharge was higher in the T2DM versus the non-DM group for non-fatal AMI (€6891 vs €6876, p=0.029) and unstable angina (€3386 vs €3304, p<0.001). CONCLUSIONS: Patients with T2DM had a higher incidence and number of hospital admissions per patient due to CV events versus the non-DM population. This generates a significant clinical and economic burden given the longer admission stay and higher costs associated with some of these complications.

Evaluation of the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Dulaglutide and Sitagliptin in the Spanish Setting.

INTRODUCTION: Healthcare systems aim to maximize the health of the population, but must work within constrained budgets. Therefore, choosing therapies that are both effective and cost-effective is paramount. The present analysis assessed the cost-effectiveness of once-weekly semaglutide 0.5 mg and 1 mg versus once-weekly dulaglutide 1.5 mg and versus once daily sitagliptin 100 mg for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications over patient lifetimes from a healthcare payer perspective in the Spanish setting. METHODS: Cost and clinical outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects on initiation of semaglutide 0.5 mg and 1 mg, dulaglutide 1.5 mg and sitagliptin 100 mg were based on the once-weekly semaglutide clinical trial program (SUSTAIN 7 and 2). Captured costs included treatment costs and costs of diabetes-related complications. Projected outcomes were discounted at 3.0% annually. RESULTS: Projections of long-term clinical outcomes indicated that once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted life expectancy of 0.02 and 0.11 years, respectively, and discounted quality-adjusted life expectancy of 0.03 and 0.11 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg. Compared with sitagliptin, once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted life expectancy of 0.17 and 0.24 years, respectively and discounted quality-adjusted life expectancy of 0.16 and 0.23 QALYs. The increased duration and quality of life with once-weekly semaglutide 0.5 mg and 1 mg resulted from a reduced cumulative incidence and delayed time to onset of diabetes-related complications. Avoided complications resulted in once-weekly semaglutide 0.5 mg and 1 mg being cost-saving versus dulaglutide 1.5 mg and versus sitagliptin 100 mg from a healthcare payer perspective. CONCLUSIONS: Once-weekly semaglutide 0.5 mg and 1 mg were considered dominant (more effective and less costly) versus sitagliptin 100 mg and dulaglutide 1.5 mg for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications and are likely to be a good use of healthcare resources in the Spanish setting.

Since healthcare systems aim to maximize the health of the population but must work within constrained budgets, choosing therapies that are both effective and cost-effective is paramount. We assessed the cost-effectiveness, from a Spanish healthcare payer perspective, of the newly marketed once-weekly semaglutide 0.5 mg and 1 mg versus two established therapies (dulaglutide 1.5 mg and sitagliptin 100 mg) for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications over patient lifetimes.Outcomes were projected using a computer simulation model, based on two trials conducted as part of the once-weekly semaglutide clinical trial program (SUSTAIN 2 and SUSTAIN 7). Captured costs included treatment costs and costs of diabetes-related complications.Projections of long-term clinical outcomes indicated that once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.03 and 0.11 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg, and 0.16 and 0.23 QALYs, respectively, versus sitagliptin 100 mg. The increased duration and quality of life with once-weekly semaglutide 0.5 mg and 1 mg resulted from a reduced cumulative incidence and delayed time to onset of diabetes-related complications. Avoided complications resulted in once-weekly semaglutide 0.5 mg and 1 mg being cost-saving versus dulaglutide 1.5 mg and versus sitagliptin 100 mg.Once-weekly semaglutide 0.5 mg and 1 mg were more effective and less costly and therefore were considered dominant in both comparisons, and are likely to be a good use of healthcare resources in the Spanish setting.

The Short-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Sitagliptin and Once-Weekly Dulaglutide for the Treatment of Patients with Type 2 Diabetes: A Cost of Control Analysis in Spain.

INTRODUCTION: Once-weekly semaglutide has been associated with greater reductions in glycated hemoglobin (HbA1c) and body weight than sitagliptin and dulaglutide in the SUSTAIN 2 and 7 clinical trials, respectively. These trials also assessed the proportions of patients achieving treatment targets capturing glycemic control and avoidance of hypoglycemia and weight gain. This study assessed the cost of bringing patients with type 2 diabetes to three clinically relevant endpoints with semaglutide versus sitagliptin and dulaglutide in Spain. METHODS: The proportions of patients achieving endpoints of HbA1c < 7.0%, HbA1c < 7.0% without hypoglycemia and without weight gain, and a ≥ 1.0% HbA1c reduction with ≥ 5.0% weight loss were taken from SUSTAIN 2 and 7. Cost of control was calculated as the annual per patient cost of each medication, expressed in 2019 euros (EUR), divided by the proportion of patients achieving each endpoint. RESULTS: Based on SUSTAIN 2, cost of control was lower for sitagliptin for the HbA1c < 7.0% endpoint, results were comparable for the HbA1c < 7.0% without hypoglycemia and without weight gain endpoint, and both doses of semaglutide were associated with lower costs of control for the ≥ 1.0% HbA1c reduction with ≥ 5.0% weight loss endpoint. Based on SUSTAIN 7, both doses of semaglutide were associated with lower costs of control for all three endpoints. CONCLUSION: Both doses of semaglutide were associated with comparable or lower costs of control versus sitagliptin when considering endpoints incorporating hypoglycemia and weight loss alongside glycemic control, and lower costs of control versus dulaglutide 1.5 mg for all endpoints in Spain. Plain language summary available for this article.

Assessing the cost-effectiveness of a once-weekly GLP-1 analogue versus an SGLT-2 inhibitor in the Spanish setting: Once-weekly semaglutide versus empagliflozin.

Aims: Controlling costs while maximizing healthcare gains is the predominant challenge for healthcare providers, and therefore cost-effectiveness analysis is playing an ever-increasing role in healthcare decision making. The aim of the present analysis was to assess the long-term cost-effectiveness of subcutaneous once-weekly semaglutide (0.5 mg and 1 mg) versus empagliflozin (10 mg and 25 mg) in the Spanish setting for the treatment of patients with type 2 diabetes (T2D) with inadequate glycemic control on oral anti-hyperglycemic medications.Material and methods: The IQVIA CORE Diabetes Model was used to project outcomes over patient lifetimes with once-weekly semaglutide versus empagliflozin, with treatment effects based on a network meta-analysis. The analysis captured treatment costs, costs of diabetes-related complications, and the impact of complications on quality of life, based on published sources. Outcomes were discounted at 3.0% per annum.Results: Once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted quality-adjusted life expectancy of 0.12 and 0.15 quality-adjusted life years (QALYs), respectively, versus empagliflozin 10 mg and improvements of 0.11 and 0.14 QALYs, respectively, versus empagliflozin 25 mg. Treatment costs were higher with once-weekly semaglutide compared with empagliflozin, but this was partially offset by cost savings due to avoidance of diabetes-related complications. Once-weekly semaglutide 0.5 mg and 1 mg were associated with incremental cost-effectiveness ratios of EUR 2,285 and EUR 161 per QALY gained, respectively, versus empagliflozin 10 mg, and EUR 3,090 and EUR 625 per QALY gained, respectively, versus empagliflozin 25 mg.Conclusions: Based on a willingness-to-pay threshold of EUR 30,000 per QALY gained, once-weekly semaglutide 0.5 mg and 1 mg were projected to be cost-effective versus empagliflozin 10 mg and 25 mg for the treatment of patients with T2D with inadequate glycemic control on oral anti-hyperglycemic medications in the Spanish setting, irrespective of patients' BMI at baseline.

Implementation of a 'Joint Clinic' to resolve unmet need for orthopaedic services in patients with hip and knee osteoarthritis: a program evaluation.

BACKGROUND: Osteoarthritis is the most common form of arthritis, principally affecting the older population. Highly prevalent, disabling diseases such as osteoarthritis strain the capacity of health systems, and can result in unmet need for services. The Joint Clinic was initiated to provide secondary care consultations and access to outpatient services for people with advanced hip or knee osteoarthritis, who were referred by their general practitioner for orthopaedic consultation but not offered an orthopaedic specialist appointment. METHODS: This longitudinal programme evaluation comprised four components: a proof-of-concept evaluation; an implementation evaluation; a process evaluation; and an outcomes evaluation. Interviews and surveys of general practitioners, staff, and patients were conducted pre- and post-implementation. Interviews were transcribed, and thematic analysis was completed. In addition, Joint Clinic patient visits and outcomes were reviewed. RESULTS: One hundred and eleven primary care physicians (GPs) and 66 patients were surveyed, and 28 semi-structured interviews of hospital staff and GPs were conducted. Proof of concept was satisfied. Interim and final implementation evaluations indicated adherence to the concept model, high levels of acceptance of and confidence in the programme and its staff, and timely completion within budget. Process evaluation revealed positive impacts of the programme and positive stakeholder perceptions, with some weaknesses in communication to the outer context of primary care. The Joint Clinic saw a total of 637 patient visits during 2 years of operation. Unmet need was reduced by 90%. Patient and referring physician satisfaction was high. Hospital management confirmed that the programme will continue. CONCLUSIONS: This evaluation indicates that the Joint Clinic concept model is fit for purpose, functioned well within the organisation, and achieved its primary objective of reducing unmet need of secondary care consultation for those suffering advanced hip or knee osteoarthritis.

Rectal and Vaginal Eradication of Streptococcus agalactiae (GBS) in Pregnant Women by Using Lactobacillus salivarius CECT 9145, A Target-specific Probiotic Strain.

Streptococcus agalactiae (Group B Streptococci, GBS) can cause severe neonatal sepsis. The recto-vaginal GBS screening of pregnant women and intrapartum antibiotic prophylaxis (IAP) to positive ones is one of the main preventive options. However, such a strategy has some limitations and there is a need for alternative approaches. Initially, the vaginal microbiota of 30 non-pregnant and 24 pregnant women, including the assessment of GBS colonization, was studied. Among the Lactobacillus isolates, 10 Lactobacillus salivarius strains were selected for further characterization. In vitro characterization revealed that L. salivarius CECT 9145 was the best candidate for GBS eradication. Its efficacy to eradicate GBS from the intestinal and vaginal tracts of pregnant women was evaluated in a pilot trial involving 57 healthy pregnant women. All the volunteers in the probiotic group (n = 25) were GBS-positive and consumed ~9 log10 cfu of L. salivarius CECT 9145 daily from week 26 to week 38. At the end of the trial (week 38), 72% and 68% of the women in this group were GBS-negative in the rectal and vaginal samples, respectively. L. salivarius CECT 9145 seems to be an efficient method to reduce the number of GBS-positive women during pregnancy, decreasing the number of women receiving IAP during delivery.

Prevention of Recurrent Acute Otitis Media in Children Through the Use of Lactobacillus salivarius PS7, a Target-Specific Probiotic Strain.

Acute otitis media (AOM) is one of the most common bacterial infections in children. Empiric antibiotherapy leads to increasing antimicrobial resistance rates among otopathogens and may impair the correct development of the microbiota in early life. In this context, probiotics seem to be an attractive approach for preventing recurrent AOM (rAOM) through the restoration of the middle ear and nasopharyngeal microbiota. The aim of this study was the selection of a probiotic strain (Lactobacillus salivarius PS7), specifically tailored for its antagonism against otopathogens. Since L. salivarius PS7 was safe and displayed a strong antimicrobial activity against otopathogens, its efficacy in preventing rAOM was assessed in a trial involving 61 children suffering from rAOM. Children consumed daily ~1 × 108 CFU of L. salivarius PS7, and the number of AOM episodes were registered and compared with that observed in the previous 6 and 12 months. The microbiota of samples collected from the external auditory canal samples was quantitatively and qualitatively assessed. The number of AOM episodes during the intervention period decreased significantly (84%) when compared to that reported during the 6 months period before the probiotic intervention. In conclusion, L. salivarius PS7 is a promising strain for the prevention of rAOM in infants and children.

Evaluating the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) for type 2 diabetes in Spain based on real-world clinical evidence.

AIM: To evaluate the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus comparator regimens for type 2 diabetes in Spain, based on real-world evidence. MATERIALS AND METHODS: Clinical data were taken from the European Xultophy Treatment Retrospective Audit (EXTRA) real-world evidence study in which patients failing to meet glycaemic targets were switched to IDegLira. Baseline regimens (prior to IDegLira treatment) were categorized as: multiple daily insulin injections (MDI; 28%); glucagon-like peptide-1 (GLP-1) receptor agonists in combination with insulin (24%); basal insulin (19%); GLP-1 receptor agonists (10%); and non-injectable medications (19%). The IQVIA CORE Diabetes Model was used to project long-term outcomes for patients switching to IDegLira or continuing their baseline regimens (excluding non-injectable regimens). Costs were accounted from a Spanish National Health System perspective. Future costs and clinical benefits were discounted at 3% annually and sensitivity analyses were performed. RESULTS: IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy versus all four comparators. IDegLira reduced direct medical costs versus GLP-1 receptor agonists in combination with insulin, and versus GLP-1 receptor agonist therapy, and was therefore considered dominant (cost saving while improving outcomes). IDegLira was found to be cost-effective versus MDI and basal insulin with incremental cost-effectiveness ratios of EUR 3013 per quality-adjusted life-year (QALY) gained and EUR 6890 per QALY gained, respectively. CONCLUSIONS: Long-term projections based on real-world evidence indicated that IDegLira is likely to improve clinical outcomes and reduce costs or be cost-effective compared with other injectable regimens in people with type 2 diabetes in Spain.

Software for Dosage Individualization of Voriconazole: a Prospective Clinical Study.

Voriconazole is a first-line antifungal agent. Therapeutic drug monitoring is a standard of care. The best way to adjust dosages to achieve desired drug exposure endpoints is unclear due to nonlinear and variable pharmacokinetics. Previously described software was used to prospectively adjust voriconazole dosages. The CYP2C19, CYP3A4, and CYP3A5 genotypes were determined. The primary endpoint was the proportion of patients with a Cmin at 120 h in the range 1 to 3 mg/liter using software to adjust voriconazole dosages. A total of 19 patients were enrolled, and 14 were evaluable. Of these, 12/14 (85.7%; 95% confidence interval = 57.2 to 98.2%) had a Cmin at 120 h posttreatment initiation of 1 to 3 mg/liter, which was higher than the a priori expected proportion of 33%. There was no association of CYP genotype-derived metabolizer phenotype with voriconazole AUC. Software can be used to adjust the dosages of voriconazole to achieve drug exposures that are safe and effective. (The clinical trial discussed in this paper has been registered in the European Clinical Trials Database under EudraCT no. 2013-0025878-34 and in the ISRCTN registry under no. ISRCTN83902726.).

Uso de bevacizumab para el tratamiento de la epistaxis en telangiectasia hemorrágica hereditaria: a propósito de un caso / No disponible

No disponible

Population pharmacokinetics and dosing considerations for the use of daptomycin in adult patients with haematological malignancies.

Objectives: To assess the population pharmacokinetics (popPK) of daptomycin at the conventional dose of 6 mg/kg/day in a cohort of oncohaematological patients. Methods: Patients underwent serial blood sampling on day 3 of therapy (before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9 and 12 h after dosing) to assess the pharmacokinetic profile of daptomycin. PopPK and Monte Carlo simulation were performed to define the probability of target attainment (PTA) with 6, 8, 10 and 12 mg/kg/day of the pharmacokinetic/pharmacodynamic target of AUC 24 /MIC >1081. Results: Thirty patients were recruited. A two-compartment open model with first-order intravenous input and first-order elimination was developed. Estimated creatinine clearance (CL CR ), serum albumin concentration (Alb) and presence of AML were covariates included in the final model. Monte Carlo simulation showed that the conventional 6 mg/kg/day dose resulted in optimal PTAs (≥80%) in the presence of pathogens with an MIC up to 0.5 mg/L only in patients with CL CR 50-100 mL/min/1.73 m 2 , Alb 26-45 g/L and a haematological diagnosis other than AML. Conversely, higher dosages, up to 12 mg/kg/day, were needed to achieve this goal in the presence of pathogens with an MIC of 0.25-0.5 mg/L in all of the other tested scenarios. In patients with CL CR 101-150 mL/min/1.73 m 2 and Alb 15-25 g/L, suboptimal PTAs (<60%) were predicted even with 12 mg/kg/day dosing . Conclusions: Our study provides a strong rationale for considering daptomycin dosages of ≥ 8 mg/kg/day in several clinical scenarios for oncohaematological patients. In some of these scenarios therapeutic drug monitoring could be a useful adjunct for optimized care.

Attention to emotion through a go/no-go task in children with oppositionality and callous-unemotional traits.

BACKGROUND: There is debate about whether the difficulties that children with different degrees of oppositionality (ODD) and callous-unemotional traits (CU) have in processing emotions are global or specific. The aim of this study is to identify difficulties in recognizing emotion (happiness, anger, sadness and fear) through a go/no-go task in children with different levels of ODD and CU traits. METHOD: A total of 320 8-year-old children were assessed through questionnaires filled out by teachers about oppositional defiant symptoms and CU traits and were then distributed into four groups: LowCU-HighODD, HighCU-LowODD, HighCU-HighODD and a comparison group (LowCU-LowODD). RESULTS: The analyses of variance comparing the 4 groups showed that the two groups with high ODD were less accurate than the control group in recognizing the emotion when the stimuli expressed happiness, fear or neutral emotion. The HighCU-HighODD group differed in the quality of the response (correct/wrong responses) but not in the reaction time in relation to the comparison group. The LowCU-HighODD group was faster to respond to emotions than the comparison group. IMPLICATIONS: The results show that the deficit in emotion processing is not restricted to specific distressing emotions such as fear or sadness, but they point to a global impairment in emotion processing in children scoring high in the constructs studied. The results also suggest that the difficulties that children with combined CU traits and oppositional conduct problems have in processing emotions are more of an emotional rather than an attentional nature.