Early Withdrawal Research Articles

Early withdrawal of life-sustaining treatments after out-of-hospital cardiac arrest: a sub-analysis of a randomized trial of prehospital hypothermia (S17.005)

Early withdrawal of life-sustaining treatments after out-of-hospital cardiac arrest: a sub-analysis of a randomized trial of prehospital hypothermia (S17.005)

Cervical Ripening Efficacy of Synthetic Osmotic Cervical Dilator Compared With Oral Misoprostol at Term: A Randomized Controlled Trial.

To evaluate whether a synthetic osmotic cervical dilator is noninferior to oral misoprostol for cervical ripening. In an open-label, noninferiority randomized trial, pregnant women undergoing induction of labor at 37 weeks of gestation or more with Bishop scores less than 6 were randomized to either mechanical cervical dilation or oral misoprostol. Participants in the mechanical dilation group underwent insertion of synthetic osmotic cervical dilator rods, and those in the misoprostol group received up to six doses of 25 micrograms orally every 2 hours. After 12 hours of ripening, oxytocin was initiated, with artificial rupture of membranes. Management of labor was at the physician's discretion. The primary outcome was the proportion of women achieving vaginal delivery within 36 hours of initiation of study intervention. Secondary outcomes included increase in Bishop score, mode of delivery, induction-to-delivery interval, total length of hospital stay, and patient satisfaction. On the basis of a noninferiority margin of 10%, an expected primary outcome frequency of 65% for misoprostol and 71% for mechanical methods, and 85% power, a sample size of 306 participants was needed. From November 2018 through January 2021, 307 women were randomized, with 151 evaluable participants in the synthetic osmotic cervical dilator group and 152 in the misoprostol group (there were four early withdrawals). The proportion of women achieving vaginal delivery within 36 hours was higher with mechanical cervical dilation compared with misoprostol (61.6% vs 59.2%), with an absolute difference of 2.4% (95% CI -9% to 13%), indicating noninferiority for the prespecified margin. No differences were noted in the mode of delivery. Tachysystole was more frequent in the misoprostol group (70 [46.4%] vs 35 [23.3%]; P=.01). Participants in the synthetic osmotic cervical dilator group reported better sleep, less unpleasant abdominal sensations, and lower pain scores (P<.05). Synthetic osmotic cervical dilator is noninferior to oral misoprostol for cervical ripening. Advantages of synthetic osmotic cervical dilator include a better safety profile and patient satisfaction, less tachysystole, lower pain scores, and U.S. Food and Drug Administration approval. ClinicalTrials.gov, NCT03670836. Medicem Technology s.r.o., Czech Republic.

Early Withdrawal of Pandemic Unemployment Insurance: Effects on Employment and Earnings

We examine the effects of the sudden withdrawal of expanded pandemic unemployment benefits in June 2021 using anonymized bank transaction data for 16,253 individuals receiving unemployment insurance (UI) in April 2021. Comparing the difference-in-differences between states withdrawing and retaining expanded UI, we find that UI receipt falls 36.3 p.p., while employment rises by only 6.8 p.p. by early September. Average cumulative UI benefits fall by $2,529, while average cumulative earnings increase by only $292. Heterogeneity by unemployment duration implies that these effects are primarily driven by extensive margin expiration of benefits rather than by intensive margin reductions in the benefit level.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications

Rationale & ObjectiveDisorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures.Study DesignRetrospective database study.Setting & ParticipantsKidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims.ExposuresVarious immunosuppression regimens in the first 3 months after kidney transplantation.OutcomesThe development of fractures, as ascertained using diagnostic codes on Medicare billing claims.Analytical ApproachWe used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting.ResultsOverall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women.LimitationsThis was a retrospective study which lacked data on immunosuppression levels.ConclusionsFractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Early corticosteroid withdrawal is associated with improved adult height in pediatric kidney transplant recipients.

Catch-up growth after pediatric kidney transplantation (kTx) is usually insufficient to reach normal adult height. We aimed to analyze the effect of pre-transplant recombinant human growth hormone (rhGH) and corticosteroid withdrawal on linear growth in the first year after kidney transplantation and identify factors associated with final height (FH). Patients who underwent kTx between 1996 and 2018 at below 18years old in five Belgian and Dutch centers were included. We analyzed the differences between height Z-scores at kTx and 1year post-transplant (Δ height Z-score) in children with and without corticosteroids at 1year (CS + /CS -) and with and without rhGH treatment before kTx (rhGH + /rhGH -). Univariable and multivariable linear regression analysis was applied to identify factors associated with height Z-score at 1year post-kTx, Δ height Z-score, and FH Z-score. A total of 177 patients were included, with median age 9.3years at kTx. Median height Z-scores pre-kTx and 1year later in the CS - /rhGH - , CS + /rhGH - , CS - /rhGH + , and CS + /rhGH + groups were - 1.42/ - 0.80, - 0.90/ - 0.62, - 1.35/ - 1.20, and - 1.30/ - 1.60 (p = 0.001). CS use 1year post-kTx was the only factor associated with Δ height (p = 0.003) on multivariable analysis. CS use at 1year was the only variable associated with FH (p = 0.014) in children with pre-transplant height Z-score below - 1 (n = 52). Increase in height Z-score in the first year post-kTx was highest in the CS - /rhGH - group and lowest in the CS + /rhGH + group. The use of corticosteroids at 1year post-kTx is associated with catch-up growth and in children with pre-transplant height Z-score below - 1 also with final height. A higher resolution version of the Graphical abstract is available as Supplementary information.

Race and ethnicity disparities in post-arrest care in Texas

IntroductionPost-arrest care is essential to the chain of survival after out-of-hospital cardiac arrest (OHCA). Sparse literature evaluates disparities in post-arrest care. We sought to measure post-arrest care disparities using a statewide OHCA registry. MethodsWe evaluated 2014–2020 data in the Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES) and included adult OHCAs surviving to hospital admission. We stratified subjects by race/ethnicity. Outcomes were targeted temperature management (TTM), percutaneous intervention (PCI), early withdrawal of life-sustaining therapies (WLST), survival to discharge, and survival with cerebral performance category (CPC) of 1–2 (considered favorable). We used both multivariable and mixed-effects, logistic regression models to evaluate the association between race/ethnicity and outcomes, adjusting for confounders. We modeled receiving hospital as a random intercept for the mixed-models analysis. ResultsWe included 8,363 OHCAs; 3,916 White, 2,251 Black, 2,196 Hispanic/Latino. On multivariable analysis, Black patients had a lower PCI (aOR 0.4, 95% CI 0.3–0.5) and survival with good CPC (aOR 0.6, 95% CI 0.6–0.7). Hispanic/Latino patients had lower TTM (aOR 0.8, 95% CI 0.7–0.9), PCI (aOR 0.6, 95% CI 0.5–0.8), survival (aOR 0.8, 95% CI 0.7–0.9), and survival with good CPC (aOR 0.7, 95% CI 0.6–0.7). However, after adjusting for clustering by receiving hospital, most of the post-arrest care relationships were negated, and Black patients actually had a higher rate of TTM (aOR 1.2, 95% CI 1.1–1.3). ConclusionsMinority OHCA victims experienced disparities in post-arrest care and outcomes. However, adjusting for receiving hospital random-effect largely diminished these findings. Inter-hospital, post-arrest care disparities may exist.

Antibiotics versus placebo in adults with CT-confirmed uncomplicated acute appendicitis (APPAC III): randomized double-blind superiority trial.

Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested. A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work. From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. -0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar. The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov).

Edwin Bissell Holt (1873–1946): A Missing Portrait of a Forgotten Pioneer

This paper explores the biography of Edwin Bissell Holt (1873—1946), an American psychologist and philosopher. Although today Holt is almost completely forgotten, he was one of the leading figures in early twentieth century American science. In my work I am going to show that Holt's impact was remarkable and long-lasting both in psychology and in philosophy. In psychology, Holt was a pioneer of behaviorism (plausibly preceding John Watson), academic psychoanalysis and so-called ecological psychology. In philosophy, he arguably influenced the late philosophy of his teacher and cordial friend, William James. Holt was also one of the founders of the New Realism, a tradition that—although short-lived—transferred to American soil many ideas of British analytic movement and paved the way for American analytic philosophy. Unfortunately, due to Holt's early withdrawal from academic life, some of his achievements were adopted by his students (e.g., by Edward Chase Tolman and James Gibson), while other fell into oblivion. By following Holt's biography, I try to give him a proper place in the history of American science and—at the same time—to offer a kind of a prolegomena to more detailed studies on his thought that are certainly needed.

Trading behavior of Swedish retirement investors during the COVID-19 pandemic

PurposeHow did investors in the Swedish Premium Pension System (PPS) react to the stock market shock ignited by the COVID-19 pandemic?Design/methodology/approachThe authors use fund-level data from the Swedish Pensions Agency on investment choices in the PPS. For each fund, the authors use monthly information on the number of investors and holdings' market value up to November 2020. The authors also use information on the total number of portfolio changes per day. For analyzing whether PPS investors reacted to the pandemic with claiming their pension, the authors use monthly data on the number of investors of a certain age group who initiate their public pension payment.FindingsTrades more than doubled, and shifted capital from equity funds to low risk interest funds. In economic terms, however, trading stayed at low levels–less than two percent of investors traded in March 2020 and there was no effect on pension withdrawals. The increased trading during the market tumult was disproportionately concentrated among investors in the top of the pension capital distribution.Research limitations/implicationsWith fund-level data, the authors cannot investigate what in particular made retirement investors stay calm in the midst of a severe market decline. Either, those investors have a long-term investment horizon as they save for their pension or particular features of the system's choice architecture induce inertia and discourage from trading. The sub-group analyses are more consistent with the explanation that PPS-induced inertia is responsible for the relatively small increase in trading activity, but future research could exploit individual level data to explore this in more detail.Practical implicationsThe often-criticized PPS choice architecture provided positive side effects in times of a severe market shock by shielding retail investors from committing trading mistakes when trying to outsmart the market.Originality/valueThe study complements previous evidence on the effects of COVID-19 on investor activity. The small response of PPS investors to COVID-19 is in line with earlier US findings on 401(k) accounts during the 2007 financial crisis (Tang et al., 2012) and industry reports about the COVID-19 period (see, e.g. Mitchell, 2020). The authors find no effects at all on public pension withdrawals in Sweden, while evidence from US 401(k) plans indicates a small share of workers taking COVID-related early withdrawals.

Association of Leukocyte Adhesion and Rolling in Skin With Patient Outcomes After Hematopoietic Cell Transplantation Using Noninvasive Reflectance Confocal Videomicroscopy

Hematopoietic cell transplantation (HCT) is a potential cure for hematologic cancer but is associated with a risk of relapse and death. Dynamic biomarkers to predict relapse and inform treatment decisions after HCT are a major unmet clinical need. To identify a quantitative characteristic of leukocyte-endothelial interactions after HCT and test its associations with patient outcomes. In this prospective single-center cohort study from June 2017 to January 2020, patients of any age, sex, race, and ethnicity who had HCT for hematologic cancer were referred by health care professionals as either suspected of having symptoms or not having symptoms of acute graft-vs-host disease between 25 and 161 days after HCT. Patients underwent noninvasive skin videomicroscopy. Videos of dermal microvascular flow were recorded with a reflectance confocal microscope. Two blinded observers (J.R.P. and Z.Z.) counted leukocytes adherent to and rolling along the vessel wall per hour (A&R). Of 57 enrolled patients, 1 relapsed before imaging and was excluded, resulting in 56 patients included in analyses. Relapse of cancer, relapse-free survival, and overall survival. Among the 56 patients (median age, 59 years; 38 [68%] male) who underwent imaging a median of 40 days after HCT, 21 had high A&R and 35 had low A&R. After correcting for the revised Disease Risk Index, patients with high A&R had higher rates of relapse (hazard ratio [HR], 4.24; 95% CI, 1.32-13.58; P = .02), reduced relapse-free survival (HR, 3.29; 95% CI, 1.26-8.55; P = .02), and reduced overall survival (HR, 3.06, 95% CI, 1.02-9.19; P = .05). These associations were preserved after correcting for possible confounders, steroid treatment, and acute graft-vs-host disease status. In the prognostic adequacy calculation by using Cox models, the new imaging biomarker (A&R) accounted for 82% to 95% of the prognostic information to predict each outcome. By contrast, the best existing clinical predictor routinely available, the revised Disease Risk Index, accounted for 10% to 28% of the prognostic information in the same model. In this cohort study, leukocyte-endothelial interactions, visualized directly in skin after HCT, were associated with the patient outcomes of relapse, relapse-free survival, and overall survival. Assessing this dynamic marker could help patients at high risk for relapse who may benefit from interventions, such as early withdrawal of immunosuppression.

Cancer's Lasting Financial Burden: Evidence From a Longitudinal Assessment.

The purpose of this study was to conduct a longitudinal analysis of out-of-pocket expenditure (OOPE) trajectories for the assessment of cancer's lasting financial impact. We identified newly diagnosed cancer patients and constructed matched control group of noncancer participants from the 2002-2018 Health and Retirement Study. Outcomes included monthly OOPE for prescription drugs (RX-OOPE_MONTHLY) and OOPE for medical services other than drugs in the past 2 years (non-RX-OOPE_2YR), consumer debt, and new individual retirement account (IRA) withdrawals. Generalized linear models were used to compare OOPEs between cancer and matched control groups. Logistic regressions were used to compare household-level consumer debt or early IRA withdrawal. Subgroup analysis stratified patients by age, health status, and household income, with the low-income group stratified by Medicaid coverage. All statistical tests were 2-sided. The study cohort included 2022 cancer patients and 10 110 participants in the matched noncancer control group. Mean non-RX-OOPE_2YR of cancer patients was similar to that of participants in the matched control group before diagnosis but statistically significantly higher at diagnosis ($1157, P < .001), 2 ($511, P < .001) years, 4 ($360, P = .006) years, and 6 ($430, P = .01) years after diagnosis. A similar pattern was observed in RX-OOPE_MONTHLY. A statistically significantly higher proportion of cancer patients incurred consumer debt at diagnosis (34.5% vs 29.9%; P < .001) and 2 years after (32.5% vs 28.2%; P = .002). There was no statistically significant difference in new IRA withdrawals. Patients experienced lasting financial consequences following cancer diagnosis that were most pronounced among patients aged 65 years and older, in good-to-excellent health at baseline, and with low income, but without Medicaid coverage. Policies to reduce costs and expand insurance coverage options while reducing cost-sharing are needed.

Sex- and Dose-Dependent Differences in the Development of an Addiction-Like Phenotype Following Extended-Access Fentanyl Self-Administration.

Opioid use disorder (OUD) is a major epidemic in the United States, and fentanyl is a major culprit. The National Institute on Drug Abuse has highlighted an urgent need for research on the risks and outcomes of OUD with fentanyl; a better understanding of sex/gender differences is also critically needed given that the opioid epidemic has been particularly impactful on women. In response to this need, we developed a rat model of OUD with fentanyl and showed that sex impacts relapse vulnerability following extended-access self-administration under a low fentanyl dose. Here, our goal was to determine sex differences across a broad dose range, including high doses expected to maximize the expression of addiction-like features (e.g., vulnerability to relapse and physical dependence). Male and female rats were assigned to self-administer one of four fentanyl doses (0.25, 0.75, 1.5, and 3.0 µg/kg/infusion), and once they acquired, they were given extended (24-h/day), intermittent access (2, 5 min trials/h, fixed-ratio 1) to fentanyl for 10 days. Physical dependence (spontaneous weight loss) was assessed during early withdrawal, and relapse vulnerability was assessed on withdrawal day 15 using an extinction/cue-induced reinstatement procedure. Despite markedly higher intake in the high- versus low-dose groups, each group responded similarly during relapse testing (extinction and cue-induced reinstatement). However, number of infusions, or frequency of use, during extended access was predictive of later vulnerability to relapse, whereas total intake impacted physical dependence given that weight loss only occurred following the discontinuation of fentanyl self-administration at the three highest doses. Females self-administered more fentanyl each day and within each binge (active trial), and had longer lasting weight loss during withdrawal than males. Relapse vulnerability was also higher in females than males and highest in females tested during estrus. These findings indicate that sex is an important risk factor for patterns and levels of fentanyl intake, relapse, and physical dependence, and while fentanyl intake predicts physical dependence, frequency of use predicts relapse.

Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes.

Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.

Moderating effects of environmental stressors on the development of attention to threat in infancy.

An attention bias to threat has been linked to psychosocial outcomes across development, including anxiety (Pérez-Edgar, K., Bar-Haim, Y., McDermott, J. M., Chronis-Tuscano, A., Pine, D. S., & Fox, N. A. (2010). Attention biases to threat and behavioral inhibition in early childhood shape adolescent social withdrawal. Emotion (Washington, D.C.), 10(3), 349). Although some attention biases to threat are normative, it remains unclear how these biases diverge into maladaptive patterns of emotion processing for some infants. Here, we examined the relation between household stress, maternal anxiety, and attention bias to threat in a longitudinal sample of infants tested at 4, 8, and 12months. Infants were presented with a passive viewing eye-tracking task in which angry, happy, or neutral facial configurations appeared in one of the four corners of a screen. We measured infants' latency to fixate each target image and collected measures of parental anxiety and daily hassles at each timepoint. Intensity of daily parenting hassles moderated patterns of attention bias to threat in infants over time. Infants exposed to heightened levels of parental hassles became slower to detect angry (but not happy) facial configurations compared with neutral faces between 4 and 12months of age, regardless of parental anxiety. Our findings highlight the potential impact of the environment on the development of infants' early threat processing and the need to further investigate how early environmental factors shape the development of infant emotion processing.

Neurokinin-1 receptor antagonist rolapitant suppresses anxiety and alcohol intake produced by repeated withdrawal episodes.

Neurokinin-1 receptor (NK1r) antagonists have been shown to suppress operant self-administration of alcohol, voluntary alcohol consumption and stress-induced reinstatement of alcohol-seeking behaviour. Considering the long half-life and anxiolytic-like properties of NK1r antagonist rolapitant, we expected that it may be an effective option for reducing anxiety and alcohol motivation during early withdrawal. Voluntary alcohol intake (two-bottles paradigm) was recorded in male Wistar rats during the three periods: 24 days (basal level), 6-day period when rats received 5 mg·kg-1 rolapitant or vehicle and 12-h period after repeated withdrawal episodes (alcohol cessation for 36 h). We found that upon intraperitoneal (i.p.) administration, rolapitant rapidly penetrated into specific rat brain regions - amygdala, hypothalamus and neocortex - implicated in the control of anxiety and reward. Rolapitant did not affect basal voluntary alcohol intake, but significantly suppressed anxiety-like behaviour and alcohol consumption following withdrawal episodes. Our findings suggest that rolapitant should be further investigated as a novel treatment option for relapse prevention in alcohol-dependent patients.

Acute Symptomatic Seizures and Risk of Epilepsy in Autoimmune Encephalitis: A Retrospective Cohort Study.

PurposeTo investigate the clinical characteristics of acute symptomatic seizures and the predictors of the development of epilepsy in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis.MethodsWe retrospectively screened the medical records of 86 hospitalized patients with confirmed autoimmune encephalitis (AE). The clinical characteristics of acute symptomatic seizures were analyzed. The predictors of the development of epilepsy were investigated using logistic regression analysis.ResultsA total of 86 patients with AE were finally included. Eighty-six percent of patients (n = 74) experienced acute symptomatic seizures, and 28.4% of patients developed epilepsy during follow-up. Abnormal EEG findings were more frequent in AE patients with acute symptomatic seizures. A greater number of anti-seizure medications (ASMs), abnormal EEG findings, and delayed immunotherapy were found to be independently associated with the development of epilepsy.ConclusionAcute symptomatic seizures are a common manifestation in AE patients. During follow-up, 28.4% of AE patients developed epilepsy. The independent factors that predicted the development of epilepsy after the acute phase included a larger number of ASMs, EEG abnormalities, and delayed immunotherapy. In clinical practice, we should prioritize immunotherapy to control acute seizures as soon as possible. For AE patients with an increased risk of developing epilepsy, early withdrawal of ASM is not recommended.

Association of Acute Alteration of Consciousness in Patients With Acute Ischemic Stroke With Outcomes and Early Withdrawal of Care.

Early consciousness disorder (ECD) after acute ischemic stroke (AIS) is understudied. ECD may influence outcomes and the decision to withhold or withdraw life-sustaining treatment. We studied patients with AIS from 2010 to 2019 across 122 hospitals participating in the Florida Stroke Registry. We studied the effect of ECD on in-hospital mortality, withholding or withdrawal of life-sustaining treatment (WLST), ambulation status on discharge, hospital length of stay, and discharge disposition. Of 238,989 patients with AIS, 32,861 (14%) had ECD at stroke presentation. Overall, average age was 72 years (Q1 61, Q3 82), 49% were women, 63% were White, 18% were Black, and 14% were Hispanic. Compared to patients without ECD, patients with ECD were older (77 vs 72 years), were more often female (54% vs 48%), had more comorbidities, had greater stroke severity as assessed by the National Institutes of Health Stroke Scale (score ≥5 49% vs 27%), had higher WLST rates (21% vs 6%), and had greater in-hospital mortality (9% vs 3%). Using adjusted models accounting for basic characteristics, patients with ECD had greater in-hospital mortality (odds ratio [OR] 2.23, 95% CI 1.98-2.51), had longer hospitalization (OR 1.37, 95% CI 1.33-1.44), were less likely to be discharged home or to rehabilitation (OR 0.54, 95% CI 0.52-0.57), and were less likely to ambulate independently (OR 0.61, 95% CI 0.57-0.64). WLST significantly mediated the effect of ECD on mortality (mediation effect 265; 95% CI 217-314). In temporal trend analysis, we found a significant decrease in early WLST (<2 days) (R2 0.7, p = 0.002) and an increase in late WLST (≥2 days) (R2 0.7, p = 0.004). In this large prospective multicenter stroke registry, patients with AIS presenting with ECD had greater mortality and worse discharge outcomes. Mortality was largely influenced by the WLST decision.

Çocuklarda Santral Venöz Kateterle İlişkili Enfeksiyon ve Trombozu Önlemeye Yönelik Hemşirelik Girişimleri

Central venous catheter is usually placed in children in cases where peripheral venous access cannot be achieved or is inadequate in treatment by using a peripheral catheter. Central venous catheter is preferred in patients requiring long-term chemotherapy, parenteral nutrition, blood transfusion as well as intensive and recurrent intravenous intervention. Central venous catheter use is common in pediatric intensive care and hematology/oncology clinics. Central venous catheter allows to shorten the hospitalization process of the child, reduce costs and reduce the frequency of painful invasive procedures. Evidence-based interventions in clinics may lead to life-threatening complications if central venous catheter is not maintained in appropriate conditions. The most common complications are infection and thrombosis. Complications may lead to delay in the treatment process in children and early withdrawal of central venous catheter. In order to prevent central venous catheter complications, the dressing of the catheter region and the washing of the lumen are routinely performed by nurses in the clinic. However, central venous catheter complication rates are still high today. Nurses should be aware of the current evidence-based guidelines about the interventions they implement, and updating their knowledge for reducing the complications. More randomized controlled experimental studies are needed in this population.

A Radiologist's Perspective on Treatment-Related Pseudoprogression: Clues and Hues

AbstractPseudoprogression refers to the initial apparent increase in tumor burden observed on imaging after cancer therapy, with subsequent delayed response to the same treatment, thus giving a false initial appearance of disease progression. It is essential to differentiate pseudoprogression from true progression to prevent the patients from getting deprived of the benefits of their ongoing cancer therapy owing to their early withdrawal. It also affects their recruitment for clinical trials. Pseudoprogression, albeit uncommon, has been observed after various types of cancer therapy; however, this phenomenon has gained momentum of late due to the emergence of immunotherapy for the treatment of various malignancies. Besides immunotherapy, pseudoprogression has predominantly been of concern in a few patients after radiation therapy for brain tumors and metastasis, after molecular targeted therapy for a variety of tumors, and after chemotherapy in metastatic bone lesions. This article reviews the available data on imaging of pseudoprogression from various types of cancer therapies, highlighting ways to suspect or identify it on imaging.

Can exercise alleviate sleep disturbances during acute nicotine withdrawal in cigarette smokers?

Sleep disturbances, including insomnia (difficulty falling or staying asleep), are common nicotine withdrawal symptoms particularly during the initial stage of nicotine abstinence, and increase the likelihood of relapse within the first 4 weeks of quitting. Although clinically recognized as a key symptom of nicotine withdrawal, sleep disturbances are not addressed in the clinical guidelines for nicotine dependence treatment. Unfortunately, Nicotine Replacement Therapy (NRT) and other pharmacologic interventions do not attenuate withdrawal-provoked sleep disturbances, with several even exacerbating sleep disruption. The present study tested the impact of 30-min of daily moderate exercise, morning versus evening, on key polysomnographic indicators of sleep disturbances during initial 3 days (72 hr) of nicotine withdrawal. Forty-nine daily smokers (53% male) completed 3 separate abstinence periods, during which they completed either morning exercise, evening exercise, or a nonexercising magazine reading control condition. Order of condition was counterbalanced across subjects with a 1-week wash out in between each 3-day abstinence period. Exercise engagement mitigated several changes in sleep architecture associated with acute nicotine deprivation and other time-related effects on sleep, specifically frequency of arousals (B = -2.8, SE = .95; t(1271) = -3.0, p = .003) and reductions in sleep maintenance (B = .58, SE = .21; t(1270) = 2.8, p = .005). Additionally, smokers who reported greater perceived withdrawal severity had the longest latency to fall asleep but experienced the greatest attenuation of this effect following PM exercise. Overall, results suggest a role for exercise as an adjunct smoking cessation treatment to specifically target sleep disturbances during early acute nicotine withdrawal. (PsycInfo Database Record (c) 2022 APA, all rights reserved).