Mid-term results of a modified arterial switch operation using the direct reconstruction technique of the pulmonary artery

Background: There is ongoing discussion as to whether it is beneficial to avoid pulmonary sinus augmentation in the arterial switch operation. We report a single-surgeon series of mid-term results for direct pulmonary artery anastomosis during switch operation for transposition of the great arteries (TGA). Methods: This retrospective study includes 17 patients with TGA, combined with an atrial septal defect, patent foramen ovale or ventricular septal defect. Patient data was analyzed from hospital charts, including operative reports, post-operative course, and regular follow-up investigations. The protocol included cardiological examination by a single pediatric cardiologist. Echocardiographic examinations were performed immediately after arrival on the intensive unit, before discharge, and then after three, six, and 12 months, followed by yearly intervals. Pulmonary artery stenosis (PAS) was categorized into three groups according to the Doppler-measured pulmonary gradient: grade I (trivial stenosis) = increased pulmonary flow with a gradient below 25 mm Hg; grade II (moderate stenosis) = a gradient ranging from 25 to 49 mm Hg; and grade III (severe stenosis) = a gradient above 50 mm Hg. Follow-up data was available for all patients. The length of follow-up ranged from 1.2 to 9.7 years, median: 7.5 years (mean 6.1 years ± 14 months). Results: During follow-up, 12 patients (70.6%) had no (or only trivial) PAS, five patients (29.4%) had moderate stenosis without progress, and no patient had severe PAS. Cardiac catheterization after arterial switch operation was performed in 11 patients (64.7%) and showed a good correlation with echocardiographic findings. During follow-up there was no reintervention for PAS. Conclusions: Direct reconstruction of the neo-pulmonary artery is a good option in TGA with antero-posterior position of the great vessels, with very satisfactory mid-term results. (Cardiol J 2010; 17, 6: 574-579

Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany

Damm O, Eichner M, Rose MA, et al. Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany. The European Journal of Health Economics. 2015;16(5):471-488.In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old children. Our objective was to estimate the potential epidemiological impact and cost-effectiveness of an LAIV-based extension of the influenza vaccination programme to healthy children in Germany. An age-structured dynamic model of influenza transmission was developed and combined with a decision-tree to evaluate different vaccination strategies in the German health care system. Model inputs were based on published literature or were derived by expert consulting using the Delphi technique. Unit costs were drawn from German sources. Under base-case assumptions, annual routine vaccination of children aged 2-17 years with LAIV assuming an uptake of 50 % would prevent, across all ages, 16 million cases of symptomatic influenza, over 600,000 cases of acute otitis media, nearly 130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions of antibiotics and over 165,000 hospitalisations over 10 years. The discounted incremental cost-effectiveness ratio was a,not sign1,228 per quality-adjusted life year gained from a broad third-party payer perspective (including reimbursed direct costs and specific transfer payments), when compared with the current strategy of vaccinating primarily risk groups with the conventional trivalent inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms of productivity losses resulted in discounted 10-year cost savings of a,not sign3.4 billion. In conclusion, adopting universal influenza immunisation of healthy children and adolescents would lead to a substantial reduction in influenza-associated disease at a reasonable cost to the German statutory health insurance system. On the basis of the epidemiological and health economic simulation results, a recommendation of introducing annual routine influenza vaccination of children 2-17 years of age might be taken into consideration

Lower Respiratory Tract Infections in Pediatric Patients with Severe Neurological Impairments: Clinical Observations and Perspectives in a Palliative Care Unit

Pediatric palliative care (PPC) patients with a severe neurologic impairment (SNI) suffer considerable morbidity and increased mortality from lower respiratory tract infections (LRTIs). The indication and choice of antibiotic therapy for bacterial LRTIs are often challenging given the lack of evidence-based treatment recommendations for this vulnerable patient population. We conducted an observational study before the SARS-CoV-2 pandemic in an eight-bed pediatric palliative care inpatient unit. During two years of surveillance, we diagnosed and treated 33 cases of a bacterial LRTI in patients with an SNI; 5 patients were hospitalized with an LRTI more than once. Two patients died from complications due to LRTIs during hospitalization. Three patients (15%) were colonized with multidrug-resistant organisms. An initial antibiotic treatment failed in one-third of the cases; a successful therapy of the LRTI was achieved with broad-spectrum and extended-spectrum penicillins (n = 13; in combination with β-lactamase inhibitors for n = 5 cases), cephalosporins (n = 13: n = 4 second-generation and n = 9 third-generation cephalosporins; in combination with other substances for n = 5 cases), ciprofloxacin (n = 3), and meropenem plus vancomycin (n = 2) or meropenem (n = 1). A respiratory specimen was obtained in 66.7% of cases with P. aeruginosa, E. coli, and K. pneumoniae accounting for the majority of the detected species. In most cases, there was no definite confirmation that the LRTI was caused by the species detected. The diagnostics and treatment of bacterial LRTIs in PPC patients with an SNI are challenging. The lack of controlled studies and the heterogeneity of this population often necessitate an individual approach. This lack of controlled studies may partly be compensated by a set of diagnostic and antibiotic stewardship criteria

Immunogenicity and tolerability of an MF59-adjuvanted, egg-derived, A/H1N1 pandemic influenza vaccine in children 6-35 months of age

Background: Vaccines against pandemic A/H1N1 influenza should provide protective immunity in children, because they are at greater risk of disease than adults. This study was conducted to identify the optimal dose of an MF59 (R)-adjuvanted, egg-derived, A/H1N1 influenza vaccine for young children. Methods: Children 6-11 months (N = 144) and 12-35 months (N = 186) of age received vaccine formulations containing either 3.75 mu g antigen with half the standard dose of MF59 or 7.5 mu g antigen with a standard dose of MF59, or a nonadjuvanted formulation containing 15 mu g antigen (children 12-35 months only). Participants were given 2 primary vaccine doses 3 weeks apart, followed by 1 booster dose of MF59-adjuvanted seasonal influenza vaccine 1 year later. Immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Results: All vaccine formulations were highly immunogenic and met all 3 European licensure criteria after 2 doses. MF59-adjuvanted vaccines met all licensure criteria after 1 dose in both age cohorts, while nonadjuvanted vaccine did not meet all criteria after 1 dose in children 12-35 months. A single booster dose was highly immunogenic, and stable antibody persistence was observed in response to all vaccines. All vaccines were well tolerated. Conclusions: In this study, a single dose of 3.75 mu g antigen with half the standard dose of MF59 was shown to be optimal, providing adequate levels of immediate and long-term antibodies in pediatric subjects 6-35 months of age. These data demonstrated that MF59 adjuvant allowed for reduced antigen content and promoted significant long-term antibody persistence in children, with a satisfactory safety profile

The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study

Rose MA, Damm O, Greiner W, et al. The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study. BMC Infectious Diseases. 2014;14(1): 40.Background Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions Our results demonstrate that vaccinating children 2–17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany

Significance of patient categorization for perioperative management of children with tetralogy of Fallot, with special regard to co-existing malformations

Background: The aim of our study was to facilitate perioperative calculation of potential risk factors on the outcome of corrective surgery for children with tetralogy of Fallot. Methods: The medical records of 81 (44 female and 37 male) out of a total of 87 patients undergoing complete surgical repair of tetralogy of Fallot between 1988 and 2004 at the Children’s Hospital of the Johannes Gutenberg University of Mainz were reviewed. Patients were divided into four categories, depending on the severity of pulmonary stenosis and cyanosis, as well as on the type of pulmonary circulation. Results: Additional malformations did not affect mortality rates, but did directly affect the number of pleural effusions, time of epinephrine administration, duration of surgery, bypass, and ischemia, as well as length of hospitalization and intensive care unit treatment. In contrast to longer periods of extracorporeal circulation and ischemia during surgery, which are directly related not only to more complex anatomical situations but also to higher mortality and complication rates, the much-debated question of age at surgery had no influence either on the surgical approach itself or on the post-operative outcome. Conclusions: Our patient categorization, and evaluation of potential pre-operative risk factors and intraoperative parameters, should prove useful for the future planning and execution of therapeutic procedures in institutions around the world. (Cardiol J 2010; 17, 1: 20-28

Comparing the meningococcal serogroup C immune response elicited by a tetanus toxoid conjugate quadrivalent meningococcal vaccine (MenACYW-TT) versus a quadrivalent or monovalent C tetanus toxoid conjugate meningococcal vaccine in healthy meningococcal vaccine-naïve toddlers : A randomised, controlled trial

MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for use in individuals ≥12 months. This study assessed whether serogroup C immune responses with MenACYW-TT were at least non-inferior, or superior, to those of quadrivalent meningococcal ACWY (MCV4-TT; Nimenrix®) and monovalent meningococcal C (MenC-TT; NeisVac-C®) vaccines in toddlers (12–23 months). In this modified, double-blind Phase III study (NCT03890367), 701 toddlers received one dose of MenACYW-TT (n = 230), MCV4-TT (n = 232) or MenC-TT (n = 239). Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure anti-meningococcal serogroup C antibodies at baseline and 30 days post-vaccination. A sequential statistical approach was used for primary and secondary objectives. For the primary objectives, superiority of serogroup C was assessed in terms of hSBA seroprotection rates (defined as titers ≥1:8) and GMTs for MenACYW-TT compared to MCV4-TT, and rSBA GMTs compared to MenC-TT. The safety of all vaccines within 30 days post-vaccination was described. When administered as a single dose to meningococcal vaccine-naïve healthy toddlers the superiority of the MenACYW-TT serogroup C immune response versus MCV4-TT was demonstrated for hSBA GMTs (ratio 16.3 [12.7–21.0]) and seroprotection (difference 10.43% [5.68–16.20]); and versus MenC-TT in terms of rSBA GMTs (ratio 1.32 [1.06–1.64]). The safety profiles of a single dose of MenACYW-TT, MCV4-TT and MenC-TT were similar. In meningococcal vaccine-naïve toddlers, MenACYW-TT induced superior immune responses to serogroup C versus MCV4-TT in terms of hSBA seroprotection and GMTs and versus MenC-TT in terms of rSBA GMTs.publishedVersionPeer reviewe

S2k guidelines for the diagnosis and treatment of herpes zoster and postherpetic neuralgia

The present guidelines are aimed at residents and board-certified specialists in the fields of dermatology, ophthalmology, ENT, pediatrics, neurology, virology, infectious diseases, anesthesiology, general medicine and any other medical specialties involved in the management of patients with herpes zoster. They are also intended as a guide for policymakers and health insurance funds. The guidelines were developed by dermatologists, virologists, ophthalmologists, ENT physicians, neurologists, pediatricians and anesthesiologists/pain specialists using a formal consensus process (S2k). Readers are provided with an overview of the clinical and molecular diagnostic workup, including antigen detection, antibody tests and viral culture. Special diagnostic situations and complicated disease courses are discussed. The authors address general and special aspects of antiviral therapy for herpes zoster and postherpetic neuralgia. Furthermore, the guidelines provide detailed information on pain management including a schematic overview, and they conclude with a discussion of topical treatment options

Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source : A prospective, multicentre cohort study

Background To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. Study Design In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. Results Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39–0.91) and young age (IRR 0.62, 95% CI 0.49–0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18–0.61), low TRAIL (IRR 0.25, 95% CI 0.08–0.76), and high VL (IRR 1.16, 95% CI 1.00–1.33) were predictive of longer oxygen therapy. Conclusion These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity