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Patients on dialysis are at high risk for severe COVID-19 and associated morbidity and mortality. We examined the humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in a maintenance dialysis population.
Single-center cohort study.
Setting and participants:
Adult maintenance dialysis patients at 3 outpatient dialysis units of a large academic center.
Participants were vaccinated with 2 doses of BNT162b2, 3 weeks apart. We assessed anti–SARS-CoV-2 spike antibodies (anti-S) ∼4–7 weeks after the second dose and evaluated risk factors associated with insufficient response. Definitions of antibody response are as follows: nonresponse (anti-S level, <50 AU/mL), low response (anti-S level, 50–839 AU/mL), and sufficient response (anti-S level, ≥840 AU/mL).
Among the 173 participants who received 2 vaccine doses, the median age was 60 years (range, 28–88), 53.2% were men, 85% were of Black race, 86% were on in-center hemodialysis and 14% were on peritoneal dialysis. Also, 7 participants (4%) had no response, 27 (15.6%) had a low response, and 139 (80.3%) had a sufficient antibody response. In multivariable analysis, factors significantly associated with insufficient antibody response included end-stage renal disease comorbidity index score ≥5 and absence of prior hepatitis B vaccination response.
Although most of our study participants seroconverted after 2 doses of BNT162b2, 20% of our cohort did not achieve sufficient humoral response. Our findings demonstrate the urgent need for a more effective vaccine strategy in this high-risk patient population and highlight the importance of ongoing preventative measures until protective immunity is achieved.
To investigate associations between multimodal analgesia and post-operative pain among patients undergoing transoral robotic surgery for oropharyngeal squamous cell carcinoma.
Records of patients who underwent surgery from 5 September 2012 to 30 November 2016 were abstracted. Associations were assessed using multivariable analysis.
A total of 216 patients (mean age of 59.1 years, 89.4 per cent male) underwent transoral robotic surgery (92.6 per cent were human papilloma virus positive, 87.5 per cent had stage T1–T2 tumours, and 82.9 per cent had stage N0–N1 nodes). Gabapentin (n = 86) was not associated with a reduction in severe pain. Ibuprofen (n = 72) was administered less often in patients with severe pain. Gabapentin was not associated with increased post-operative sedation (p = 0.624) and ibuprofen was not associated with increased bleeding (p = 0.221). Post-operative opioid usage was not associated with surgical duration, pharyngotomy, bilateral neck dissections, tumour stage, tumour size, subsite or gabapentin.
Scheduled low-dose gabapentin was not associated with improved pain control or increased respiratory depression. Ibuprofen was not associated with an increased risk of bleeding and may be under-utilised.
The 90-km long Stuoragurra Fault Complex, part of the approximately 4–5-km wide Precambrian Mierojávri–Sværholt Shear Zone, constitutes the Norwegian part of the larger Lapland province of postglacial faults. It consists of three separate fault systems being 6–12 km apart. The faults dip 30–75° to the SE and can be traced to about 500 m depth. Deep seismic profiling shows that the shear zone dips at an angle of about 43° to the southeast and can be traced to about 3 km depth. A total of approximately 80 earthquakes were registered here between 1991 and 2019. Most of them occurred to the southeast of the fault scarps. The maximum moment magnitude was 4.0. The formation of postglacial faults in northern Fennoscandia has previously been associated with the deglaciation of the last inland ice. Dating of fault reactivation reveals, however, a late Holocene age (between around 700 and 4000 a BP). The reverse displacement of around 9 m and fault system lengths of 14 and 21 km of the two southernmost fault systems indicate a moment magnitude of about 7. The results from this study indicate that the expected maximum magnitude of future earthquakes in Fennoscandia is about 7.
Atrial septal defects are a common form of CHD and dependent on the size and nature of atrial septal defects, closure may be warranted. The paper aims to compare outcomes of transcatheter versus surgical repair of atrial septal defects.
A comprehensive electronic literature search was conducted. Primary studies were included if they compared both closure techniques. Primary outcomes included procedural success, mortality, and reintervention rate. Secondary outcomes included residual defect and mean hospital stay.
A total of 33 studies were included in meta-analysis. Mean total hospital stay was significantly shorter in the transcatheter cohort across both the adult (95% confidence interval, mean difference −4.05 (−4.78, −3.32) p < 0.00001) and paediatric populations (95% confidence interval, mean difference −4.78 (−5.97, −3.60) p < 0.00001). There were significantly fewer complications in the transcatheter group across both the adult (odds ratio 0.45, 95% confidence interval, [0.28, 0.72], p < 0.00001) and paediatric cohorts (odds ratio 0.26, 95% confidence interval, [0.14, 0.49], p < 0.00001). No significant difference in overall mortality was found between transcatheter versus surgical closure across the two groups, adult (odds ratio 0.76, 95% confidence interval, [0.40, 1.45], p = 0.41), paediatrics (odds ratio 0.62, 95% confidence interval, [0.21, 1.83], p = 0.39).
Both transcatheter and surgical approaches are safe and effective techniques for atrial septal defect closure. Our study has demonstrated the benefits of transcatheter closure in terms of lower complication rates and mean hospital stay. However, surgery still has a place for more complex closure and, as we have demonstrated, shows no difference in mortality.
Prophylactic antibiotics are commonly prescribed at discharge for mastectomy, despite guidelines recommending against this practice. We investigated factors associated with postdischarge prophylactic antibiotic use after mastectomy with and without immediate reconstruction and the impact on surgical-site infection (SSI).
We studied a cohort of women aged 18–64 years undergoing mastectomy between January 1, 2010, and June 30, 2015, using the MarketScan commercial database. Patients with nonsurgical perioperative infections were excluded. Postdischarge oral antibiotics were identified from outpatient drug claims. SSI was defined using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Generalized linear models were used to determine factors associated with postdischarge prophylactic antibiotic use and SSI.
The cohort included 38,793 procedures; 24,818 (64%) with immediate reconstruction. Prophylactic antibiotics were prescribed after discharge after 2,688 mastectomy-only procedures (19.2%) and 17,807 mastectomies with immediate reconstruction (71.8%). The 90-day incidence of SSI was 3.5% after mastectomy only and 8.8% after mastectomy with immediate reconstruction. Antibiotics with anti–methicillin-sensitive Staphylococcus aureus (MSSA) activity were associated with decreased SSI risk after mastectomy only (adjusted relative risk [aRR], 0.74; 95% confidence interval [CI], 0.55–0.99) and mastectomy with immediate reconstruction (aRR, 0.80; 95% CI, 0.73–0.88), respectively. The numbers needed to treat to prevent 1 additional SSI were 107 and 48, respectively.
Postdischarge prophylactic antibiotics were common after mastectomy. Anti-MSSA antibiotics were associated with decreased risk of SSI for patients who had mastectomy only and those who had mastectomy with immediate reconstruction. The high numbers needed to treat suggest that potential benefits of postdischarge antibiotics should be weighed against potential harms associated with antibiotic overuse.
A laboratory intercomparison project was carried out on 20 annually resolved late-wood samples from the Danish oak record. The project included the following three laboratories: (1) the University of Arizona AMS Laboratory, University of Arizona, USA (AA); (2) HEKAL AMS Laboratory, MTA Atomki, Hungary (DeA); and (3) Aarhus AMS Centre (AARAMS), Aarhus University, Denmark (AAR). The large majority of individual data points (96%) lie within ±2σ of the weighted mean. Further assessment of the accuracy associated with the individual laboratories showed good agreement, indicating that consistent and reliable 14C measurements well in agreement with each other are produced at the three laboratories. However, the quoted analytical uncertainties appear to be underestimated when compared to the observed variance of differences from the geometric mean of the samples. This study provides a general quality check of the single-year tree-ring 14C measurements that are included in the new calibration curve.
In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.
Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.
Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.
These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.
To examine rural–urban differences in temporal trends and risk of inappropriate antibiotic use by agent and duration among women with uncomplicated urinary tract infection (UTI).
Observational cohort study.
Using the IBM MarketScan Commercial Database (2010–2015), we identified US commercially insured women aged 18–44 years coded for uncomplicated UTI and prescribed an oral antibiotic agent. We classified antibiotic agents and durations as appropriate versus inappropriate based on clinical guidelines. Rural–urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural–urban status and inappropriate antibiotic receipt, accounting for patient- and provider-level characteristics. We used multivariable logistic regression to estimate trends in antibiotic use by rural–urban status.
Of 670,450 women with uncomplicated UTI, a large proportion received antibiotic prescriptions for inappropriate agents (46.7%) or durations (76.1%). Compared to urban women, rural women were more likely to receive prescriptions with inappropriately long durations (adjusted risk ratio 1.10, 95% CI, 1.10–1.10), which was consistent across subgroups. From 2011 to 2015, there was slight decline in the quarterly proportion of patients who received inappropriate agents (48.5% to 43.7%) and durations (78.3% to 73.4%). Rural–urban differences varied over time by agent (duration outcome only), geographic region, and provider specialty.
Inappropriate antibiotic prescribing is quite common for the treatment of uncomplicated UTI. Rural women are more likely to receive inappropriately long antibiotic durations. Antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing and to reduce unnecessary exposure to antibiotics, particularly in rural settings.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
We here present a comparison of methods for the pretreatment of a batch of tree rings for high-precision measurement of radiocarbon at the Aarhus AMS Centre (AARAMS), Aarhus University, Denmark. The aim was to develop an efficient and high-throughput method able to pretreat ca. 50 samples at a time. We tested two methods for extracting α-cellulose from wood to find the most optimal for our use. One method used acetic acid, the other used HCl acid for the delignification. The testing was conducted on background 14C samples, in order to assess the effect of the different pretreatment methods on low-activity samples. Furthermore, the extracted wood and cellulose fractions were analyzed using Fourier transform infrared (FTIR) spectroscopy, which showed a successful extraction of α-cellulose from the samples. Cellulose samples were pretreated at AARAMS, and the graphitization and radiocarbon analysis of these samples were done at both AARAMS and the radiocarbon dating laboratory at Lund University to compare the graphitization and AMS machine performance. No significant offset was found between the two sets of measurements. Based on these tests, the pretreatment of tree rings for high-precision radiocarbon analysis at AARAMS will henceforth use HCI for the delignification.
More than 50% of women with clinically apparent infection after mastectomy did not meet the 2020 National Healthcare Safety Network (NHSN) definition for surgical site infection (SSI). Implant loss was similar whether the 2020 NHSN SSI definition was met or not, suggesting equivalent adverse outcomes regardless of restriction to the surveillance definition.
Multiple guidelines recommend discontinuation of prophylactic antibiotics <24 hours after surgery. In a multicenter, retrospective cohort of 2,954 mastectomy patients ± immediate breast reconstruction, we found that utilization of prophylactic postdischarge antibiotics varied dramatically at the surgeon level among general surgeons and was virtually universal among plastic surgeons.
An examination of invasive procedure cancellations found that the lack of pre-procedural oral screening was a preventable cause, for children with congenital heart disease. The purpose of this study was to implement an oral screening tool within the paediatric cardiology clinic, with referral to paediatric dental providers for positive screens. The target population were children aged ≥6 months to <18 years old, being referred for cardiac procedures.
The quality implementation framework method was used for this study design. The multi-modal intervention included education, audit and feedback, screening guidelines, environmental support, and interdisciplinary collaboration. Baseline rates for oral screenings were determined by retrospective chart audit from January 2018 to January 2019 (n = 211). Provider adherence to the oral screening tool was the outcome measure. Positive oral screens, resulting in referral to the paediatric dental clinic, were measured as a secondary outcome. Provider adherence rates were used as a process measure.
Data collected over 14 weeks showed a 29% increase in documentation of oral screenings prior to referral, as compared to the retrospective chart audit. During the study period, 13% of completed screenings were positive (n = 5). Provider compliance for the period was averaged at 70% adherence.
A substantial increase in pre-procedural oral screenings by paediatric cardiologists was achieved using the quality implementation framework and targeted interventions.
San José 520 is a Classic period hamlet of single-family residences in the urban periphery of Teotihuacan, just beyond the southeast edge of the city. Three burial features were associated with one of the residences, AF2. One of the features contained the burial of a single adult, another the successive burials of eight adults and one neonate, and the third held a neonate. We analyzed 29 bone and enamel samples from the adults for bioapatite phosphate oxygen-isotope composition; we also considered isotopic data for another five bone samples analyzed in a separate project. The isotopic results suggest a pattern of birth in the Teotihuacan region and then movement in early childhood to a “relocation” region, the geographic location of which is unknown. Later, probably in adolescence, the individuals returned to live, and eventually die, in San José 520. Without knowing more about the occupation of the relocation region, it is difficult to say what concerns or beliefs underlay this unusual but long-established settlement system.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data base http://calib.org/marine/.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Despite recommendations to discontinue prophylactic antibiotics after incision closure or <24 hours after surgery, prophylactic antibiotics are continued after discharge by some clinicians. The objective of this study was to determine the prevalence and factors associated with postdischarge prophylactic antibiotic use after spinal fusion.
Multicenter retrospective cohort study.
This study included patients aged ≥18 years undergoing spinal fusion or refusion between July 2011 and June 2015 at 3 sites. Patients with an infection during the surgical admission were excluded.
Prophylactic antibiotics were identified at discharge. Factors associated with postdischarge prophylactic antibiotic use were identified using hierarchical generalized linear models.
In total, 8,652 spinal fusion admissions were included. Antibiotics were prescribed at discharge in 289 admissions (3.3%). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole (22.1%), cephalexin (18.8%), and ciprofloxacin (17.1%). Adjusted for study site, significant factors associated with prophylactic discharge antibiotics included American Society of Anesthesiologists (ASA) class ≥3 (odds ratio [OR], 1.31; 95% CI, 1.00–1.70), lymphoma (OR, 2.57; 95% CI, 1.11–5.98), solid tumor (OR, 3.63; 95% CI, 1.62–8.14), morbid obesity (OR, 1.64; 95% CI, 1.09–2.47), paralysis (OR, 2.38; 95% CI, 1.30–4.37), hematoma/seroma (OR, 2.93; 95% CI, 1.17–7.33), thoracic surgery (OR, 1.39; 95% CI, 1.01–1.93), longer length of stay, and intraoperative antibiotics.
Postdischarge prophylactic antibiotics were uncommon after spinal fusion. Patient and perioperative factors were associated with continuation of prophylactic antibiotics after hospital discharge.
Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD).
A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function.
Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline.
These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.