Search

BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, repre-sentativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline $10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 + 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.CHEST 2023; 163(3):586-598

Many solid tumors present with perineural invasion (PNI), and innervation correlates with worsened prognosis. The effects that commonly administered therapies such as radiation therapy (RT) have on PNI status remain unknown. We investigated the contribution of RT on the nervous system and elucidated the implications that increased nerve signaling can have on tumor burden using our previously developed orthotopic murine model of rectal cancer (RC) and our targeted and clinically relevant short-course RT (SCRT) regimen.Medical charts for patients with RC treated at the Wilmot Cancer Institute were obtained and PNI status was analyzed. Human data were accompanied by an orthotopic murine model of RC. Briefly, luciferase-expressing murine colon-38 (MC38-luc) tumor cells were injected orthotopically into the rectal wall of C57BL6 mice. Targeted SCRT (5 gray (Gy) per fraction for 5 consecutive fractions) was administered to the tumor. Intratumoral innervation was determined by immunohistochemistry (IHC), local norepinephrine (NE) concentration was quantified by enzyme-linked immunosorbent assay (ELISA), and β2-adrenergic receptor (B2AR) expression was assessed by flow cytometry. Chronic NE signaling was mirrored by daily isoproterenol treatment, and the effect on tumor burden was determined by overall survival, presence of metastatic lesions, and tumor size. Isoproterenol signaling was inhibited by administration of propranolol.Human RC patients with PNI have decreased overall survival compared with patients without PNI. In our mouse model, SCRT induced the expression of genes involved in neurogenesis, increased local NE secretion, and upregulated B2AR expression. Treating mice with isoproterenol resulted in decreased overall survival, increased rate of metastasis, and reduced SCRT efficacy. Interestingly, the isoproterenol-induced decrease in SCRT efficacy could be abrogated by blocking the BAR through the use of propranolol, suggesting a direct role of BAR stimulation on impairing SCRT responses.Our results indicate that while SCRT is a valuable treatment, it is accompanied by adverse effects on the nervous system that may impede the efficacy of therapy and promote tumor burden. Therefore, we could speculate that therapies aimed at targeting this signaling cascade or impairing nerve growth in combination with SCRT may prove beneficial in future cancer treatment.

Peripheral intravenous catheters (PIVCs) are ubiquitous in acute care settings however failure rates are unacceptably high, with around half failing before prescribed treatment is complete. The most effective dressing and securement option to prolong PIVC longevity is unclear.To determine feasibility of conducting a definitive randomized controlled trial (RCT) investigating evidence-based securement bundles (medical adhesive tapes and supplementary securement products) to reduce PIVC failure.In this pilot non-masked 3-group RCT, adults requiring a PIVC for24 hrs were randomized to Standard care (bordered polyurethane dressing plus non-sterile tape over extension tubing), Securement Bundle 1 (two sterile tape strips over PIVC hub plus Standard care) or Securement Bundle 2 (Bundle 1 plus tubular bandage) with allocation concealed until study entry.laboratory-confirmed positive blood culture, current/high-risk of skin tear, or study product allergy.feasibility (eligibility, recruitment, retention, protocol fidelity, participant/staff satisfaction).PIVC failure, PIVC dwell time, adverse skin events, PIVC colonization and cost.Of 109 randomized participants, 104 were included in final analyses. Feasibility outcomes were met, except eligibility criterion (79%). Absolute PIVC failure was 38.2% (13/34) for Bundle 2, 25% (9/36) for Bundle 1 and 23.5% (8/34) for Standard care. Incidence rate ratio for PIVC failure/1000 catheter days, compared to Standard care, was 1.1 (95% confidence interval [CI] 0.4-2.7) and 2.1 (95% CI 0.9-5.1) for Bundles 1 and 2, respectively.A large RCT testing securement bundles is feasible, with adjustment to screening processes. Innovative dressing and securement solutions are needed to reduce unacceptable PIVC failure rates. Trial registration ACTRN12619000026123.

Needleless connectors (NCs) are essential devices designed to provide safe, needle-free connection between venous access devices, syringes and infusions. There is a variety of designs, and associated decontamination products and practices; the resulting confusion can cause detrimental patient outcomes. This study aimed to explore nurses' attitudes, techniques, and practices around the use and decontamination of NCs in clinical practice.Qualitative inquiry was conducted with seven focus groups of 4-6 participants each in the cancer and surgical units of a large tertiary hospital in Australia between January and March 2019. Participants comprised nurses who had taken part in a recent clinical trial of NC decontamination. Focus group sessions were recorded, transcribed and synthesised using content analysis.Seven focus groups were conducted (total, N = 30 participants), lasting 16-20 min. Six major themes were identified surrounding needleless connector use and decontamination: 'safety and utility'; 'terminology and technological understanding'; 'clinical practice determinants'; 'decontamination procedures and influencers'; 'education and culture'; and 'research and innovation'.The participants articulated positive attitudes towards needleless connector use for needle-stick and infection prevention, however rationales for care and maintenance practices demonstrated limited understanding of guidelines (e.g., disinfection time) and specific NC function (e.g., positive, negative pressure). The findings indicated the need for targeted, standardised needleless connector education, to enhance staff confidence, improve consistency of care and ensure patient safety.

The New York Neurotrauma Consortium (NYNC) is a nascent multidisciplinary research and advocacy organization based in the New York Metropolitan Area (NYMA). It aims to advance health equity and optimize outcomes for traumatic brain and spine injury patients. Given the extensive racial, ethnic, and socioeconomic diversity of the NYMA, global health frameworks aimed at eliminating disparities in neurotrauma may provide a relevant and useful model for the informing research agendas of consortia like the NYNC. In this review, we present a comparative analysis of key health disparities in traumatic brain injury (TBI) that persists in the NYMA as well as in low- and middle-income countries (LMICs). Examples include (a) inequitable access to quality care due to fragmentation of healthcare systems, (b) barriers to effective prehospital care for TBI, and (c) socioeconomic challenges faced by patients and their families during the subacute and chronic postinjury phases of TBI care. This review presents strategies to address each area of health disparity based on previous studies conducted in both LMIC and high-income country settings. Increased awareness of healthcare disparities, education of healthcare professionals, effective policy advocacy for systemic changes, and fostering racial diversity of the trauma care workforce can guide the development of trauma care systems in the NYMA that are free of racial and related healthcare disparities.

Routine quarrying activity at the Nesher-Ramla Quarry, in the Judean Lowlands, Israel, has recently exposed a new Early Holocene archaeological site located in a small natural sinkhole, one of many dolines scattered in the area, dated to the Early Pre-Pottery Neolithic B (EPPNB). It is the first site of this period to be uncovered in the narrow strip of land between the Judean Mts. and the coastal plain. This site, dubbed NRQN, contains lithic artifacts, groundstone tools, shells and beads as well as botanical and faunal remains. Here we combine data from a series of studies on the site's stratigraphy and radiometric dating, paleoenvironment, sediments and material culture, with the aim of understanding the role of the site in the EPPNB sphere. Various human activities took place in or immediately adjacent to the sinkhole, predominantly domestic in nature, including stone-tool making and food consumption. However, some of the sediments deep within the sinkhole underwent intense in situ combustion, possibly associated with episodes of lime-plaster production. The filling of the sinkhole appears to have occurred rapidly, not exceeding a few hundred years (ca. 10,500–10,300 cal. BP) and was driven by both geogenic and anthropogenic sedimentation processes. Good preservation of microvertebrate, macrovertebrae, short-lived plants and wood remains at the site, provides a unique opportunity to study the environmental characteristics of this geographical area during the Early Holocene, which appears to have been of an open grassy landscape with patchy Mediterranean forest, resembling the current environmental conditions. Studying the characteristics of Early Holocene human activity at the site, its paleoenvironment, and the site formation mechanisms, also provides useful comparisons with the nearby NRQ Middle Paleolithic site (this issue).

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Purpose: Our aim was to determine whether breast cancer survivors are at increased risk of obstetric and maternal complications at time of delivery. Methods: The USA 'National Inpatient Sample' database was queried for hospitalizations associated with deliveries, between 2015 and 2018. The incidence of maternal and fetal complications was compared between women with, and without, a personal history of breast cancer. Results: Of the 2,103,216 birth related admissions, 617 (0.03%) of the women were breast cancer survivors, with the proportion increasing over time (from 0.02% in 2015 to 0.04% in 2018). Breast cancer survivors had a higher socioeconomic status (p < 0.001) and were significantly older compared to other mothers (34 vs. 28 years, p < 0.001). Additionally, they were more likely to suffer from preexisting chronic diseases including cardiopulmonary disease and diabetes mellitus, and had a higher incidence of multiple gestation (4.4% vs. 1.6%) [OR 2.7, 95% CI 1.9-4.0, p < 0.001]. The incidence of acute adverse events at time of delivery including fetal distress, preterm labor, cesarean section and maternal infection was higher amongst the breast cancer survivors. On multivariate analysis age, ethnic group, comorbidities, multiple gestations, and a previous breast cancer diagnosis, but not cancer treatment, were associated with an increased risk of an obstetric adverse event. Conclusion: Breast cancer survivors have more comorbidities and are at increased risk of acute obstetrical complications at time of delivery. Further studies are required to validate these findings, and evaluate the ability of interventions to improve obstetrical outcomes amongst breast cancer survivors.

Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls.A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020 at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups.Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N = 43, 20-27.6 weeks); 2) 3rd trimester (N = 47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P = 0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P 0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons.Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons.

The use of the RAND/UCLA appropriateness method is an innovative way to provide practical, evidence based clinical guidance to infection preventionist (IP) in the absence of clinical trial data. This brief primer aims to introduce the IP to the methodology, including a short case study demonstrating the utilization of the method in the arena of infection prevention and management.