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We present a protocol to improve confidence in reported radon activity concentrations, facilitating direct site-to-site comparisons and integration with co-located greenhouse gas (GHG) measurements within a network of three independently managed observatories in the UK. Translating spot measurements of atmospheric GHG amount fractions into regional flux estimates (“top-down” analysis) is usually performed with atmospheric transport models (ATMs), which calculate the sensitivity of regional emissions to changes in observed GHGs at a finite number of locations. However, the uncertainty of regional emissions is closely linked to ATM uncertainties. Radon, emitted naturally from the land surface, can be used as a tracer of atmospheric transport and mixing to independently evaluate the performance of such models. To accomplish this, the radon measurements need to have a comparable precision to the GHGs at the modelled temporal resolution. Australian Nuclear Science and Technology Organisation (ANSTO) dual-flow-loop two-filter radon detectors provide output every 30 min. The measurement accuracy at this temporal resolution depends on the characterization and removal of instrumental background, the calibration procedure, and response time correction. Consequently, unless these steps are standardized, measurement precision may differ between sites. Here we describe standardized approaches regarding (1) instrument maintenance, (2) quality control of the raw data stream, (3) determination and removal of the instrumental background, (4) calibration methods, and (5) response time correction (by deconvolution). Furthermore, we assign uncertainties for each reported 30 min radon estimate (assuming these steps have been followed) and validate the final result through comparison of diurnal and sub-diurnal radon characteristics with co-located GHG measurements. While derived for a network of UK observatories, the proposed standardized protocol could be equally applied to two-filter dual-flow-loop radon observations across larger networks, such as the Integrated Carbon Observation System (ICOS) or the Global Atmosphere Watch (GAW) baseline network.

Objective. While administration of intravenous tissue plasminogen activator (IV-tPA) is the standard of care in acute ischemic stroke and has been shown to have statistically significant benefit, there can also be potentially life-threatening complications; however, there is no standard informed consent approach. The purpose of this study was to present a parental, technical, and general model of informed consent for IV-TPA and to determine which approach was preferred. Methods. Survey respondents were asked to hypothetically decide whether or not to provide consent for their family member to receive IV-tPA. Respondents were presented with 3 informed consent models: one emphasizing parental qualities, one emphasizing statistical data, and one representing a general consent statement. After being presented each model, the respondents had to select their preferred consent model, as well as rate their level of agreeability toward their family member receiving the medication following each approach. Results. The results of 184 surveys showed respondents were equally as likely to give consent for their family member to receive IV-TPA following all three approaches; however, respondents were significantly more likely to prefer the parental approach compared to a technical or general approach. Conclusion. Our results indicate that while paternalism is generally discouraged in the medical community, some degree of parental language may be preferred by patients in tough decision-making situations toward consent to receive medical interventions.

Opsoclonus myoclonus syndrome (OMS) is an extremely rare neurological syndrome typically affecting as few as 1 in 10,000,000 people annually. OMS is characterized by the presence of involuntary, saccadic eye movements, as well as ataxia, including gait incoordination, rigidity, and tremor. The origin of OMS is unclear, but a significant percentage of OMS cases are indicative of an underlying malignancy, most commonly neuroblastoma and small cell lung cancer. Here we describe an adult patient with OMS, who was ultimately diagnosed with a small ductal adenocarcinoma of the pancreas. To our knowledge, this is the third published report of an association between OMS and pancreatic malignancy, and the only case where the pancreatic malignancy was detected prior to metastasis or autopsy at death. This case report highlights the importance of careful, aggressive malignancy screening with OMS, as the pancreatic duct cut-off sign may be overlooked if pancreatic malignancy is not suspected.

Objective: Superior laryngeal nerve (SLN) function is critical to laryngeal sensation. Sensory dysfunction in the larynx, mediated through the internal branch of the superior laryngeal nerve (iSLN), is thought to occur with aging and neurodegenerative disease. However, objective analysis of iSLN neurophysiology is difficult due to its anatomic location and small diameter. This study measures sensory nerve action potentials (SNAP) from the iSLN in a rat model., Methods: SNAP data were obtained from two adult rat strains (Sprague-Dawley, SD and Fischer 344 × Brown Norway F1 Hybrid rats, FBN). Evoked responses were obtained by stimulating the main trunk of the SLN and recording the response using a 160-μm cuff electrode placed around the iSLN. SNAP were averaged from 10 stimulations. Laryngeal adductor reflex (LAR) threshold measurements were obtained with stimulation of the iSLN and direct laryngoscopy. The sections of the iSLN were obtained for histologic analysis., Results: SLN-evoked responses were successfully obtained in 18 hemi-laryngeal preparations (SD n = 13 and FBN n = 5) with corresponding LAR threshold measurements. Mean(±SD) SNAP latency, total duration, amplitude, negative durations, and intensity were 2.28 ms (±0.56), 2.13 ms (±0.70), 879 μV (±535), and 0.69 mA (±0.25), respectively. SLN stimulation threshold to elicit an LAR was of 0.84 mA (±0.31)., Conclusion: It is feasible to record evoked SLN responses in two adult rat strains. This work may lead to a tractable animal model for objective measurements of SLN neurophysiology with various disease states., Level of Evidence: NA Laryngoscope, 134:5028-5033, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: The bowing index (BI) and normalized glottal gap area (NGGA) are used to quantify vocal fold morphology in ARVA; however, the influence of the distance between the flexible laryngoscope lens and the target area is not known. The goal is to test whether the endoscopic distance impacts vocal fold morphology measurements in patients with ARVA during flexible video laryngostroboscopy (VLS)., Method: Patients with ARVA who underwent VLS were included. Images were classified into near (close to the petiole of the epiglottis) and far (below nasopharynx, with tongue base and entire epiglottis visible) conditions. BI was calculated using a mobile application, and NGGA was measured using ImageJ., Results: This study included 23 patients; the mean age was 77 ± 7 years. Mean BI measured at the near distance was higher than far distances with a mean difference of 1.94 (95% CI: 0.92-2.96, p = 0.001). NGGA showed difference with changed distance -0.24 (95% CI: -0.48 to 0.01, p < 0.05).When stratifying patients into two groups based on median BI measurement, there was a statistically significant difference between near and far conditions, with increased BI in the near condition for patients above the median (p < 0.05), but no difference between the near and far condition for patients with BI below the median., Conclusion: The BI and NGGA were impacted by the endoscopic distance during flexible VLS. BI was significantly higher in the near condition compared with the far condition. The difference in BI between the near and far conditions was more pronounced when the vocal fold bowing was greater. These findings call for heightened awareness of measurement discrepancies secondary to the endoscopic distance during flexible laryngostroboscopy., Level of Evidence: 2 Laryngoscope, 134:4649-4655, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Tinnitus subtypes are proposed to lie on a continuum of different symptom dimensions rather than be categorical. However, there is no comprehensive empirical data showing this complex relationship between different tinnitus symptoms. The objective of this study is to provide empirical evidence for the dimensional nature of tinnitus and how different auditory and non-auditory symptoms interact with each other through complex interactions. We do this using graph theory, a mathematical tool that empirically maps this complex interaction. This way, graph theory can be utilised to highlight a new and possibly important outlook on how we can understand the heterogeneous nature of tinnitus., Design: In the current study, we use the screening databases of the Treatment Evaluation of Neuromodulation for Tinnitus-Stage A1 (TENT-A1) and A2 (TENT-A2) randomised trials to delineate the dimensional relationship between different clinical measures of tinnitus as a secondary data analysis. We first calculate the empirical relationship by computing the partial correlation. Following this, we use different measures of centrality to describe the contribution of different clinical measures to the overall network. We also calculate the stability of the network and compare the similarity and differences between TENT-A1 and TENT-A2., Results: Components of the auditory subnetwork (loudness discomfort level, sound sensitivity, average hearing loss and high frequency hearing loss) are highly inter-connected in both networks with sound sensitivity and loudness discomfort level being highly influential with high measures of centrality. Furthermore, the relationship between the densely connected auditory subnetwork with tinnitus-related distress seems to vary at different levels of distress, hearing loss, duration and age of the participants., Conclusion: Our findings provide first-time evidence for tinnitus varying in a dimensional fashion illustrating the heterogeneity of this phantom percept and its ability to be perceptually integrated, yet behaviourally segregated on different symptomatic dimensions., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Recent technological improvements have positioned us at the threshold of innovative discoveries that will assist in new perspectives and avenues of research. Increased attention has been directed towards peripheral nerve stimulation, particularly of the vagus, trigeminal, or greater occipital nerve, due to their unique pathway that engages neural circuits within networks involved in higher cognitive processes. Here, we question whether the effects of transcutaneous electrical stimulation are mediated by synergistic interactions of multiple neuromodulatory networks, considering this pathway is shared by more than one neuromodulatory system. By spotlighting this attractive transcutaneous pathway, this opinion piece aims to acknowledge the contributions of four vital neuromodulators and prompt researchers to consider them in future investigations or explanations., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: One of the most important aspects of the transition to outpatient (OP) arthroplasty is patient selection, with guidance traditionally recommending that OP total knee arthroplasty (TKA) be reserved for patients <80 years old. However, there are limited data as to whether older age should really be considered a contraindication to OP-TKA. The purpose of this study is to assess the risk of complications and readmissions following OP-TKA in patients ≥80 years old., Methods: This is a retrospective, propensity-matched cohort study of the National Surgical Quality Improvement Program database from 2011 to 2019. Patients ≥80 years undergoing OP (same-day discharge) TKA were propensity matched to patients ≥80 years undergoing inpatient (IP) TKA based on age, gender, race, body mass index, American Society of Anesthesiologists classification, functional status, smoking status, anesthetic type, and medical comorbidities. There were 1,418 patients (709 IPs and 709 OPs) included. All baseline factors were successfully matched between IP-TKA versus OP-TKA (P ≥ .18 for all). Thirty-day complications, readmissions, reoperations, and mortality were subsequently analyzed., Results: Thirty-day readmission rates were identical between patients undergoing IP-TKA and OP-TKA (3.5% versus 3.5%, P = 1.0). Similarly, there was no significant difference in the incidence of major complications (2.7% versus 2.0%, P = .38), reoperations (1.3% versus 0.8%, P = .44), or mortalities (0.3% versus 0.3%, P = 1.0) within 30 days., Conclusion: Octogenarians undergoing OP-TKA had comparable complication rates to similar patients undergoing IP-TKA. OP-TKA can be performed safely in select octogenarians and age ≥80 years likely does not need to be a uniform contraindication to OP-TKA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lymphoproliferative disease virus (LPDV) is an exogenous alpharetrovirus that sporadically causes fatal lymphoid neoplasia in affected turkeys. Previous studies of wild turkeys ( Meleagridis gallopavo ) in the United States have demonstrated geographically widespread LPDV infection and frequent coinfection with avian poxvirus (APV) and reticuloendotheliosis virus (REV). This study was conducted to better understand health risks to Mississippi wild turkeys, including the relative importance of LPDV, APV, and REV in contributing to mortality. Thirteen wild turkeys, which died naturally or were euthanized due to illness, were submitted to Mississippi State University's Poultry Research and Diagnostic Laboratory for postmortem examinations. Birds originated from nine counties across the state over the past 5 yr. Carcasses were submitted as fresh (nonfrozen) or frozen. At autopsy, 9 of 13 turkeys had severe, proliferative cutaneous lesions on the head and neck, with diphtheritic or proliferative oral and esophageal lesions. Samples were collected for molecular diagnostic testing (LPDV and REV PCR), histopathology, and bacterial culture and isolation. External and internal parasites were preserved in formalin for identification. APV (cutaneous and/or diphtheritic forms) was diagnosed in 9 of 13 birds by identification of pathognomonic histologic lesions (including intracytoplasmic inclusion bodies). Interestingly, all birds with APV were also REV PCR positive. Furthermore, eight turkeys were positive for LPDV, and LPDV was commonly associated with coinfections with APV and REV.

Spinal Muscular Atrophy (SMA) is characterized by muscle atrophy and weakness and has an incidence of 1:11. 000 live births which projects an estimated population in the UK of 650-1,300 affected patients. Standards of Care (SoC) were updated in 2017 and they have been widely adopted as a reference for implementation of care in SMA across the globe. The effectiveness of implementation and adherence to these standards across different countries is unclear. The aim of this study is to describe the experience of individuals with SMA regarding their care in the UK. An online anonymised survey was sent out via patient organizations, the UK SMA Patient Registry, professional networks, and social media to reach across the UK. The survey captured demographic profile, professionals involved in a patient's care, Interventions and access to mobility aids and home adaptations. Participants responded about their access to services and to rate how important each professional and intervention was for their health and wellbeing. One hundred and twenty-eight responses were collected with a median age of 34 years (1-81). Seventy-three percent of participants were adults and 60% men. Overall good access to neurologist (>90%) but limited to nurse specialist (48%) and physiotherapist (57%). Good access to respiratory support was reported but limited for interventions for positioning and bracing and exercise. This survey highlights that access to certain professionals for people with SMA is limited in the UK. Striking differences were noted between pediatric and adult populations. Limited access to care were regularly reported, with half of the study population consistently not accessing full multidisciplinary care. Access to interventions for contracture management were recorded to have significant limitations. Mobility aids and home adaptations are widely available and were also reported as the most valued interventions. Access to nutritional support or speech and language therapy appears only to be available for a small proportion of the participants. Access to respiratory care was good especially in severe forms of SMA. We found pockets of good practice in the UK that align with the SoC. However, access is not equal for adults and children and access to certain professionals is significantly limited., Competing Interests: LR was employed by SMAUK. JI was employed by Treat SMA and KA was employed by MDUK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muni-Lofra, Murphy, Adcock, Farrugia, Irwin, Lilleker, McConville, Merrison, Parton, Ryburn, Scoto, Marini-Bettolo and Mayhew.)

Report of a human death and exposure of white-tailed deer to Heartland virus (HRTV) in Georgia, USA, prompted the sampling of questing ticks during 2018-2019 in 26 sites near where seropositive deer were captured and the residence of the human case-patient. We processed 9,294 Amblyomma americanum ticks in pools by virus isolation in Vero E6 cells and reverse transcription PCR. Positive pools underwent whole-genome sequencing. Three pools were positive for HRTV (minimum infection rate 0.46/1,000 ticks) and none for Bourbon virus. Cell cultures confirmed HRTV presence in 2 pools. Genome sequencing, achieved for the 3 HRTV isolates, showed high similarity among samples but marked differences with previously sequenced HRTV isolates. The isolation and genomic characterization of HRTV from A. americanum ticks in Georgia confirm virus presence in the state. Clinicians and public health professionals should be aware of this emerging tickborne pathogen.

Objective: Assess the role of online resources and apps for women's help seeking and staff's response to concerns in the perinatal period., Design: Online survey. Descriptive analysis of women's use and experiences of digital resources for self-diagnosis and help seeking, drawing on numerical and free-text responses., Setting: Two tertiary referral centres and one district general hospital in two UK geographic locations., Participants: 632 postnatal women, surveyed over a 4 month period., Measurements: Women's access to digital devices; frequency and type of health concerns experienced after 22 weeks' gestation; variability in use and experiences of websites/apps; perceptions of staff's response to concerns after help-seeking., Findings: 1254 women were approached over a 4-month period; 632 participated (response rate: 50%). Women reported a 'mix and match' blended use of digital resources to both learn about, and self-diagnose/self-triage for potential complications in pregnancy as an adjunct to care provided by maternity staff. Over half the participants experienced concerns about themselves or their baby after 22 weeks. The top concern was fetal movements, reported by 62%. Women used 91 different digital resources to help with understanding and decision-making, in addition to seeking support from family, friends and healthcare professionals. Enabling features of staff responses were identified from free-text responses (n = 292) by women who sought professional help regarding their health concerns, and influencing factors at clinical, organisational and digital level., Key Conclusions and Implications for Practice: Online information retrieval and digital self-monitoring is increasingly integral to women's self-care during pregnancy and offers opportunities to support escalation of care and shared decision-making. Further work should assess optimal inclusion of this 'digital work' into clinical consultations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Patient preference studies are increasingly used to inform decision-making during the medical product lifecycle but are rarely used to inform early stages of drug development.  The primary aim of this study is to quantify treatment preferences of patients with neuromuscular disorders, which represent serious and debilitating conditions with limited or no treatment options available. Methods: This quantitative patient preferences study was designed as an online survey, with a cross-over design.  This study will target two different diseases from the neuromuscular disorders disease group, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM). Despite having different physio-pathological pathways both DM1 and MM manifest in a clinically similar manner and may benefit from similar treatment options.  The sample will be stratified into three subgroups: two patient groups differentiated by age of symptom onset and one caregivers group.   Each subgroup will be randomly assigned to complete two of three different preference elicitation methods at two different time points: Q-methodology survey, discrete choice experiment, and best-worst scaling type 2, allowing cross-comparisons of the results across each study time within participants and within elicitation methods. Additional variables such as sociodemographic, clinical and health literacy will be collected to enable analysis of potential heterogeneity. Ethics and Dissemination: This study protocol has undergone ethical review and approval by the Newcastle University R&D Ethics Committee (Ref: 15169/2018). All participants will be invited to give electronic informed consent to take part in the study prior accessing the online survey. All electronic data will be anonymised prior analysis. This study is part of the Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle (IMI-PREFER) project, a public-private collaborative research project aiming to develop expert and evidence-based recommendations on how and when patient preferences can be assessed and used to inform medical product decision making., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Jimenez-Moreno AC et al.)

Kentucky has the second highest adult smoking rate, has the highest incidence of lung cancer in the nation, and does not have a state law prohibiting smoking inside workplaces. These tobacco disparities and policy gap leave Kentucky behind tobacco control progress made in other areas of the United States. Williamstown is a rural community with a population of 3,900 and a strong history of tobacco use. In 2017, the Northern Kentucky Health Department, in partnership with Interact for Health, worked with two coalitions to collect data, educate the community, and advocate for a local smoke-free policy. Coalition members collected 227 public opinion surveys. Community leaders-including the mayor-and advocates participated in Citizen Science, a research collaboration between scientists and volunteers. Advocates were trained on AirBeam monitors, wearable devices that gather air quality data in real time, and then were deployed in six establishments. The indoor air quality in smoking establishments was two times worse than the outdoor air quality standard. Community leaders and advocates then mobilized to educate City Council members on the benefits of a smoke-free policy, focusing on business, health, and tourism. In 2018, the Williamstown City Council voted in favor of the smoke-free policy, becoming the first jurisdiction in the Northern Kentucky region with a comprehensive smoke-free policy. The Citizen Science process helped develop coalition capacity, build community support, and engage policymakers in a successful smoke-free policy effort. Through participatory and inclusive efforts, local residents were able to affect policy change in the direction of health for all people.

Aim: To evaluate how efficacy outcomes from real-world data (RWD) can support those from randomized controlled trials (RCTs), in the context of first-line tyrosine kinase inhibitor treatment of metastatic renal cell carcinoma. Patients & methods: PubMed, Ovid, MEDLINE and EMBASE were searched for RCTs and RWD studies with ≥50 adult patients per arm published in 2000-2017. Outcome measures were median progression-free survival, median overall survival and objective response rate. Results: A total of 13 RCTs and 22 RWD studies met eligibility criteria; 31, 28 and 25 studies, respectively, reported median progression-free survival, median overall survival and objective response rate. Summary outcome measures were similar in RWD and RCTs. Conclusion: RWD validates efficacy-based outcomes from RCTs and may provide supportive evidence to inform clinical decisions.

Background: Randomized controlled trials (RCTs) have stringent inclusion criteria and may not fully represent patients seen in everyday clinical practice. Real-world data (RWD) can provide supportive evidence for the effectiveness of medical interventions in more heterogeneous populations than RCTs. Sunitinib is a widely used first-line treatment for patients with metastatic renal cell carcinoma (mRCC)., Objective: This is the first comprehensive meta-analysis to evaluate the efficacy of sunitinib using the novel approach of combining RCTs and RWD., Methods: RCTs and RWD studies published between 2000 and 2017 were identified from PubMed, Ovid, MEDLINE, and EMBASE. Eligible studies contained a cohort of ≥ 50 adult patients with mRCC receiving first-line sunitinib treatment. The meta-analysis combined RWD and RCT treatment groups, adjusting for data type (RCT or RWD). Recorded outcomes were median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR). Publication bias was assessed via review of funnel plots for each outcome measure. A random effects model to account for study heterogeneity was applied to each endpoint. Sensitivity analyses evaluated the robustness of the overall estimates., Results: Of the 3611 studies identified through medical database searches, 22 (15 RWD studies, 7 RCTs) met eligibility criteria and were analyzed. mPFS (18 studies), mOS (19 studies), and ORR (15 studies) were reported for aggregate measures based on 4815, 5321, and 4183 patients, respectively. Reported mPFS (RWD, 7.5-11.0 months; RCTs, 5.6-15.1 months) and ORR data (RWD, 14.0-34.6%; RCTs, 18.8-46.9%) were consistent with the overall confidence estimates (95% confidence interval [CI]) of 9.3 (8.6-10.2) months and 27.9% (24.2-32.0), respectively. Reported mOS showed greater variation in RWD (6.8-33.2 months) compared with RCTs (21.8-31.5 months), with an overall confidence estimate (95% CI) of 23.0 (19.2-27.6) months. Inspection of funnel plots and sensitivity analyses indicated that there was no publication bias for any efficacy endpoint. Sensitivity analyses showed no evidence of lack of robustness for mPFS, mOS, or ORR. Interpretation of these results is limited by differences in trial design, cohort characteristics, and missing data., Conclusions: This novel, comprehensive meta-analysis validates sunitinib as an effective first-line treatment for patients with mRCC in both RCTs and everyday clinical practice. The methodology provides a framework for future analyses combining data from RCTs and RWD.

Traditional home healthcare reimbursement models emphasize intervention after a medical or functional issue occurs, and there is little evidence of preventative home-based physical therapy services for those at highest risk of becoming homebound due to illness, injury, or functional limitation. The purpose of this study was to describe the development and initial pilot results of the Home-based Older Person Upstreaming Prevention Physical Therapy (HOP-UP-PT) Program. The prospective observational pilot study included five participants referred from a community center. The HOP-UP-PT Program utilized fall risk, functional, environmental, cognitive, and health-related assessments. Two males and three females aged 73 to 92 years were enrolled. Outcomes suggest that health, functional, and environmental benefits may be achieved when an older person participates in the HOP-UP-PT Program. Safety and health benefits gained by two individuals referred to the program, but who did not meet inclusion criteria, are also reported. Evidence emerging from this pilot study suggests trends toward improved functional outcomes associated with reduced fall risk and customized home-based safety recommendations among older adults participating in the HOP-UP-PT Program.

Species translocations are remarkable experiments in evolutionary ecology, and increasingly critical to biodiversity conservation. Elaborate socio-ecological hypotheses for translocation success, based on theoretical fitness relationships, are untested and lead to complex uncertainty rather than parsimonious solutions. We used an extraordinary 89 reintroduction and 102 restocking events releasing 682 black rhinoceros (Diceros bicornis) to 81 reserves in southern Africa (1981-2005) to test the influence of interacting socio-ecological and individual characters on post-release survival. We predicted that the socio-ecological context should feature more prominently after restocking than reintroduction because released rhinoceros interact with resident conspecifics. Instead, an interaction between release cohort size and habitat quality explained reintroduction success but only individuals' ages explained restocking outcomes. Achieving translocation success for many species may not be as complicated as theory suggests. Black rhino, and similarly asocial generalist herbivores without substantial predators, are likely to be resilient to ecological challenges and robust candidates for crisis management in a changing world.

Objectives: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG., Methods: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion., Results: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm., Conclusions: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

Background: Sepsis commonly complicates the clinical course of critically ill very low birth weight infants, with as many as 30% developing hospital-acquired bacteremia. The tumor necrosis factor alpha (TNF-alpha) -- 308 G/A single nucleotide polymorphism (SNP) is associated with adverse outcome in septic adult patients., Methods: One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-alpha -- 308 G/A SNP., Results: One hundred twenty (69%) infants were homozygous GG, 45 (26%) were heterozygous AG and 8 (5%) were homozygous AA; 2 of 120 (2%) infants developed early bacteremia in the GG group, and 1 of 53 (2%) developed early bacteremia in the AA/AG group (P = 0.919). One or more episodes of late bacteremia/fungemia developed in 59 of 120 (49%) infants with the GG genotype and 23 of 53 (43%) infants with the AG/AA genotype (P = 0.484). Endotracheal tube colonization rates were 65 of 120 (54%) for infants with the GG genotypes and 28 of 53 (53%) for infants with the AG/AA genotypes (P = 0.871). Nosocomial pneumonia developed in a similar number of infants in both genotype groups (9 of 120 infants vs. 3 of 53 infants; P = 0.461). Mortality from sepsis was 3 times greater in infants with the AA/AG genotypes than in those with the GG genotype (10%vs. 3%; P = 0.038). This difference in sepsis mortality was even greater when only bacteremic/fungemic infants are considered (4 of 59 infants vs. 6 of 23 infants; P = 0.026)., Conclusions: These data suggest that the TNF-alpha -- 308 A allele does not affect the development of sepsis in ventilated premature infants but may increase mortality once sepsis develops.