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Association of Early Norepinephrine Administration With 24-Hour Mortality Among Patients With Blunt Trauma and Hemorrhagic Shock

JAMA Netw Open. 2022 Oct 3;5(10):e2234258. doi: 10.1001/jamanetworkopen.2022.34258.

ABSTRACT

IMPORTANCE: Hemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged.

OBJECTIVE: To evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of >10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022.

EXPOSURE: Continuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines.

MAIN OUTCOMES AND MEASURES: The primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE.

RESULTS: A total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from -4.6 (95% CI, -11.9 to 2.7) to 2.1 (95% CI, -2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from -1.3 (95% CI, -9.5 to 6.9) to 5.3 (95% CI, -2.1 to 12.8).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock.

PMID:36205999 | DOI:10.1001/jamanetworkopen.2022.34258

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Association of Incident Delirium With Short-term Mortality in Adults With Critical Illness Receiving Mechanical Ventilation

JAMA Netw Open. 2022 Oct 3;5(10):e2235339. doi: 10.1001/jamanetworkopen.2022.35339.

ABSTRACT

IMPORTANCE: Intensive care unit (ICU)-acquired delirium and/or coma have consequences for patient outcomes. However, contradictory findings exist, especially when considering short-term (ie, in-hospital) mortality and length of stay (LOS).

OBJECTIVE: To assess whether incident delirium, days of delirium, days of coma, and delirium- and coma-free days (DCFDs) are associated with 14-day mortality, in-hospital mortality, and hospital LOS among patients with critical illness receiving mechanical ventilation.

DESIGN, SETTING, AND PARTICIPANTS: This single-center prospective cohort study was conducted in 6 ICUs of a university-affiliated tertiary hospital in Taiwan. A total of 267 delirium-free patients (aged ≥20 years) with critical illness receiving mechanical ventilation were consecutively enrolled from August 14, 2018, to October 1, 2020.

EXPOSURES: Participants were assessed daily for the development of delirium and coma status over 14 days (or until death or ICU discharge) using the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively.

MAIN OUTCOMES AND MEASURES: Mortality rates (14-day and in-hospital) and hospital LOS using electronic health records.

RESULTS: Of 267 participants (median [IQR] age, 65.9 [57.4-75.1] years; 171 men [64.0%]; all of Taiwanese ethnicity), 149 patients (55.8%) developed delirium for a median (IQR) of 3.0 (1.0-5.0) days at some point during their first 14 days of ICU stay, and 105 patients (39.3%) had coma episodes also lasting for a median (IQR) of 3.0 (1.0-5.0) days. The 14-day and in-hospital mortality rates were 18.0% (48 patients) and 42.1% (112 of 266 patients [1 patient withdrew from the study]), respectively. The incidence and days of delirium were not associated with either 14-day mortality (incident delirium: adjusted hazard ratio [aHR], 1.37; 95% CI, 0.69-2.72; delirium by day: aHR, 1.00; 95% CI, 0.91-1.10) or in-hospital mortality (incident delirium: aHR, 1.00; 95% CI, 0.64-1.55; delirium by day: aHR, 1.02; 95% CI, 0.97-1.07), whereas days spent in coma were associated with an increased hazard of dying during a given 14-day period (aHR, 1.16; 95% CI, 1.10-1.22) and during hospitalization (aHR, 1.10; 95% CI, 1.06-1.14). The number of DCFDs was a protective factor; for each additional DCFD, the risk of dying during the 14-day period was reduced by 11% (aHR, 0.89; 95% CI, 0.84-0.94), and the risk of dying during hospitalization was reduced by 7% (aHR, 0.93; 95% CI, 0.90-0.97). Incident delirium was associated with longer hospital stays (adjusted β = 10.80; 95% CI, 0.53-21.08) when compared with no incident delirium.

CONCLUSIONS AND RELEVANCE: In this study, despite prolonged LOS, ICU delirium was not associated with short-term mortality. However, DCFDs were associated with a lower risk of dying, suggesting that future research and intervention implementation should refocus on maximizing DCFDs to potentially improve the survival of patients receiving mechanical ventilation.

PMID:36205994 | DOI:10.1001/jamanetworkopen.2022.35339

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Survival Benefit of First Single-Organ Deceased Donor Kidney Transplantation Compared With Long-term Dialysis Across Ages in Transplant-Eligible Patients With Kidney Failure

JAMA Netw Open. 2022 Oct 3;5(10):e2234971. doi: 10.1001/jamanetworkopen.2022.34971.

ABSTRACT

IMPORTANCE: Kidney transplant is considered beneficial in terms of survival compared with continued dialysis for patients with kidney failure. However, randomized clinical trials are infeasible, and available evidence from cohort studies is at high risk of bias.

OBJECTIVE: To compare restricted mean survival times (RMSTs) between patients who underwent transplant and patients continuing dialysis across transplant candidate ages and depending on waiting time, applying target trial emulation methods.

DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, patients aged 18 years or older appearing on the wait list for their first single-organ deceased donor kidney transplant between January 1, 2000, and December 31, 2018, in Austria were evaluated. Available data were obtained from the Austrian Dialysis and Transplant Registry and Eurotransplant and included repeated updates on wait-listing status and relevant covariates. Data were analyzed between August 1, 2019, and December 23, 2021.

EXPOSURES: A target trial was emulated in which patients were randomized to either receive the transplant immediately (treatment group) or to continue dialysis and never receive a transplant (control group) at each time an organ became available.

MAIN OUTCOMES AND MEASURES: The primary outcome was time from transplant allocation to death. Effect sizes in terms of RMSTs were obtained using a sequential Cox approach.

RESULTS: Among the 4445 included patients (2974 men [66.9%]; mean [SD] age, 52.2 [13.2] years), transplant was associated with increased survival time across all considered ages compared with continuing dialysis and remaining on the wait list within a 10-year follow-up. The estimated RMST differences were 0.57 years (95% CI, -0.14 to 1.84 years) at age 20 years, 3.01 years (95% CI, 2.50 to 3.54 years) at age 60 years, and 2.48 years (95% CI, 1.88 to 3.04 years) at age 70 years. The survival benefit for patients who underwent transplant across ages was independent of waiting time.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that kidney transplant prolongs the survival time of persons with kidney failure across all candidate ages and waiting times.

PMID:36205998 | DOI:10.1001/jamanetworkopen.2022.34971

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Systematic Literature Review of the Use of Productivity Losses/Gains in Cost-Effectiveness Analyses of Immune-Mediated Disorders

Adv Ther. 2022 Oct 7. doi: 10.1007/s12325-022-02321-z. Online ahead of print.

ABSTRACT

INTRODUCTION: In light of the lack of an agreed international standard for how to conduct cost-effectiveness analyses (CEAs), including cost-utility analyses (CUAs) from a societal perspective, there is uncertainty regarding to what extent the inclusion of productivity losses/gains in economic evaluations can affect cost-effectiveness results and subsequently decisions on whether to recommend new health technologies. To investigate this, we conducted a systematic review of CEAs and CUAs of drug-based therapies for a set of chronic immune-mediated disorders to understand how cost elements and calculation methods related to productivity losses/gains are used, examine the impact on the incremental cost-effectiveness ratio (ICER) of including productivity costs, and explore factors that affect the inclusion of productivity loss.

METHODS: Databases (MEDLINE® In-process, MEDLINE, Embase and Cochrane Library) were searched from January 2010 to October 2020 by two independent reviewers for all CEAs and CUAs in adults with any of the following conditions: ankylosing spondylitis, chronic idiopathic urticaria, Crohn’s disease, fibromyalgia, juvenile idiopathic arthritis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis. Relevant study data were extracted and evidence was synthesized for both qualitative and quantitative analysis. Productivity cost elements including absenteeism, presenteeism, unemployment/early retirement, premature mortality and informal care were extracted, along with the method used to determine them. A multivariate analysis was performed to identify factors associated with the inclusion of productivity loss.

RESULTS: Our searches identified 5016 records, culminating in 198 unique studies from 234 publications following screening. Most of the studies investigated rheumatoid arthritis (37.0%) or psoriasis (32.0%). The majority were CUAs, with some including both a CEA and a CUA (73.0%). Most studies used a payer perspective only (28.5%) or a societal perspective only (21.0%). Of the 49 studies incorporating productivity losses/gains, 42 reported the type of cost element used; all of these used patient absenteeism, either alone or in addition with other elements. Only 16 studies reported the method used to value productivity changes, of which eight used a human capital approach, four used a friction cost approach and four used both approaches. Twenty-eight of the 49 studies (57.1%) reported inclusion of productivity losses/gains as contributing to more favourable cost-effectiveness outcomes and ICERs, while 12 (24.5%) reported no substantial impact. On the basis of a multivariate analysis, rheumatoid arthritis as the target disease had a statistically significant association with the inclusion of productivity loss compared with psoriasis and inflammatory bowel disease.

CONCLUSIONS: The results of our review suggest that incorporating productivity cost elements may positively affect cost-effectiveness outcomes in evaluations of therapeutics for immune-mediated disorders. Our work highlights the continued need for clarity when reporting how CEAs and CUAs in this disease area are conducted, in order to better inform healthcare decision-making.

PMID:36205907 | DOI:10.1007/s12325-022-02321-z

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A PLS-SEM approach to determine farmers’ awareness about climate change mitigation and adaptation strategies: pathway toward sustainable environment and agricultural productivity

Environ Sci Pollut Res Int. 2022 Oct 7. doi: 10.1007/s11356-022-23471-1. Online ahead of print.

ABSTRACT

This research was conducted in a significant agricultural region to gauge farmers’ knowledge of climate change adaption strategies. We employed a semi-structured questionnaire based on the literature; it was broken up into sections, and used certain statistical techniques (PLS-SEM) to examine the results. Farmers who had sufficient assets and resources thought they were safer and could withstand the adverse effects of climate change. A total of 900 completed questionnaires were gathered to investigate the link between the control, moderator, and DV variables in the future. As a consequence, the PLS-SEM path analysis findings showed that our model is fit. PLS-SEM direct path analysis revealed AM > FACC, UA- > FACC, SA- > FACC, FS- > FACC, PR- > FACC, and SI- > FACC are significant. The established hypotheses H1-H6 are strengthened by these findings. We also examined the respondents’ ages and genders to use as controls; whereas gender showed no correlation with FACC, there was a strong link between age and the dependent variable. There is no statistically significant correlation between gender and climate change awareness, but older people tend to have a broader understanding of the topic and its consequences. Education significantly moderates the relationship of farmer’s awareness (climate change) associated with AM, UA, SA, FS, PR, and SI. depicts the moderation role of education on the relationship between AM*Education- > FACC, UA*Education- > FACC, SA*Education- > FACC, FS*Education- > FACC, PR*Education- > FACC, and SI*Education- > FACC. H2a and H5a in this study showed significant correlations with education as a moderator; however, H1a, H3a, H4, and H6a did not demonstrate any moderator relationships. There is a medium to strong correlation between various factors, and the correlation values of a few chosen variables are significant when compared to all other variables in the current study. Highly significant correlations were found between PR, SA, SI, and UA with FACC. Governmental policies and effective monitoring systems will be developed as a result of the research to enable integrated and sustainable water development.

PMID:36205864 | DOI:10.1007/s11356-022-23471-1

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Oviposition Model for a Southern Population of Mountain Pine Beetle

Bull Math Biol. 2022 Oct 7;84(11):133. doi: 10.1007/s11538-022-01089-1.

ABSTRACT

We develop a predictive oviposition model for a southern population of mountain pine beetle (MPB) using a previously developed rate curve, incorporating variation in both oviposition rate and fecundity. We also introduce a method for determining the time delay before oviposition. The model describes the probability of oviposition for a season of MPB attacks using hourly phloem temperature and adult MPB attack data. We also develop an asymptotic approximation of MPB oviposition that is much less computationally taxing. The detailed oviposition model and its asymptotic approximation are compared with other ovipositional models for MPB; the predictive capacity of each model is evaluated using previously published observations.

PMID:36205824 | DOI:10.1007/s11538-022-01089-1

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Active vaccination campaign to increase seasonal influenza vaccination coverage: a monocenter experience in a cohort of Italian patients with systemic autoimmune diseases

Clin Rheumatol. 2022 Oct 7. doi: 10.1007/s10067-022-06380-z. Online ahead of print.

ABSTRACT

Seasonal influenza is a frequent cause of hospitalization and mortality among patients with systemic autoimmune diseases. Despite this evidence, vaccination coverage is generally much lower than the minimum 75% target proposed by the WHO. Therefore, an active campaign was implemented in the years 2019/2020 and 2020/2021 within the Rheumatology Department of the Niguarda Hospital (Milan, Italy) to improve the vaccination coverage in patients with inflammatory arthritis. This study aims to evaluate the vaccination coverage in the 2019/2020 and 2020/2021 (active campaigns) seasons and to compare these results with the 2018/2019 season. A monocenter observational study was conducted among adult patients with rheumatoid arthritis, spondylarthritis, or psoriatic arthropathy, who were referred to the Rheumatology Department of the Niguarda Hospital. Patients were given a questionnaire to investigate previous years’ vaccination coverage and to propose an influenza vaccine for the 2020/2021 season. Compared with 2018/2019, a trend for increase in vaccination coverage was reported in 2019/2020 season (+ 10.7%, p = 0.055; 45.5% of coverage) and a statistically significant increase was reported in 2020/2021 (+ 31.2%, p < 0.001; 65.9% of coverage). The increase was also significant when comparing the 2020/2021 and 2019/2020 seasons (+ 20.5%, p < 0.001). The greatest increase in vaccination coverage was observed among under-65-year-old patients. Obtained results support the implementation of active vaccination campaigns to increase vaccination coverage among patients with systemic autoimmune diseases and highlight the importance of external factors (such as the COVID-19 pandemic) in directing the patient to adopt preventive measures to avoid infections and related complications.

PMID:36205812 | DOI:10.1007/s10067-022-06380-z

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The effect of pelvic floor muscle-strengthening exercises on low back pain: a systematic review and meta-analysis on randomized clinical trials

Neurol Sci. 2022 Oct 7. doi: 10.1007/s10072-022-06430-z. Online ahead of print.

ABSTRACT

BACKGROUND: Low back pain is a musculoskeletal disorder (MSD), and Kegel exercise is considered as one of the non-surgical management methods. Therefore, the present systematic review and meta-analysis aimed to estimate the results of randomized clinical trials (RCT) about the effect of pelvic floor muscle-strengthening exercises on reducing low back pain‏.‏ METHODS: The present study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline (2020) to January 2022. The relevant studies were searched in the MagIran, SID, PubMed, Embase, Web of Science (WoS), Scopus, ClinicalTrials.gov databases and Google Scholar motor engine using related MeSH/Emtree terms, which were combined with free text word. The heterogeneity of the studies was checked using I2 statistic.

RESULTS: Finally, 19 RCTs with a sample size of 456 subjects in the intervention group and 470 in the control group were included in the meta-analysis. The low back pain intensity in the intervention group decreased up to 1.261 ± 0.213 (SMD ± 95% CI) with I2 = 87.60 more than that in the control group (P <0.001). The low back pain intensity in postpartum women decreased up to 1.614 ± 0.312 (95% CI) followed by pregnant women as 1.282 ± 0.479 (SMD ± 95% CI) more than that in other populations. But due to high the heterogeneity in all sub-groups (I2 > 80%) this result should be considered with caution. Meta-regression analysis showed the effect of pelvic floor muscle-strengthening exercises increased by increasing the year of publication, quality assessment score of the article, and the number of weeks of intervention (P<0.05).

CONCLUSION: Based on the results of the present meta-analysis, pelvic floor muscle-strengthening exercises significantly reduce the low back pain intensity. Therefore, these exercises can be regarded as a part of a low back pain management plan.

PMID:36205811 | DOI:10.1007/s10072-022-06430-z

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Thyroglobulin is a poor predictor of differentiated thyroid cancer in patients who undergo surgery for thyroid nodular diseases

Eur Arch Otorhinolaryngol. 2022 Oct 7. doi: 10.1007/s00405-022-07678-z. Online ahead of print.

ABSTRACT

OBJECTIVES: Thyroglobulin, produced exclusively by thyroid follicular cells, serves as a specific tumor marker for the follow-up of differentiated thyroid cancer (DTC) patients after thyroidectomy. However, its role as a predictor of malignancy in patients with thyroid nodules is controversial. We assessed the potential role of preoperative serum thyroglobulin concentration to predict DTC in patients without a preoperative diagnosis of malignancy who underwent partial or total thyroidectomy.

METHODS: This retrospective study included patients with a preoperative diagnosis of benign multinodular goiter (MNG) or a thyroid nodule with indeterminate cytology (INC) (Bethesda system categories III/IV) who underwent partial or total thyroidectomy between January 2014 and May 2019. We compared the patients’ demographic, clinical, imaging, and biochemical data according to their final diagnosis: DTC or benign thyroid nodular disease. Further statistical analysis included odds ratio calculation and receiver operating characteristic (ROC) curve analysis.

RESULTS: Of 131 patients who met inclusion and exclusion criteria, the indication for surgery was benign MNG in 69 patients and a thyroid nodule with INC in 62 patients. A final diagnosis of DTC was reported in 18 of the 69 benign MNG patients (26%) and in 30 of the 62 thyroid nodule with INC patients (48%). The preoperative measurements of nodule diameter and serum thyroid-stimulating hormone and thyroglobulin concentrations did not significantly differ between patients with a final diagnosis of DTC and those with benign histology.

CONCLUSIONS: Preoperative serum thyroglobulin alone is insufficient to differentiate between malignant and benign thyroid nodular disease.

PMID:36205785 | DOI:10.1007/s00405-022-07678-z

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Components of carotid atherosclerotic plaque in spectral photon-counting CT with histopathologic comparison

Eur Radiol. 2022 Oct 7. doi: 10.1007/s00330-022-09155-x. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core (LRNC) area, in excised carotid atherosclerotic plaques by comparing it with histopathological measurements.

METHODS: This is a single-center ex vivo cross-sectional observational study. Excised plaques of 20 patients (71 +/- 6 years; 13 men), obtained from carotid endarterectomy were scanned with SPCCT using standardized acquisition settings (120k Vp/19 μA; 7-18 keV, 18-30 keV, 30-45 keV, 45-75 keV, and 75-118 keV). FC thickness, FC area, and LRNC area were quantified and compared between high-resolution 3D multi-energy CT images and histopathology using the Wilcoxon signed-ranks test and Bland-Altman analysis. Images were interpreted twice by two radiologists separately, blinded to the histopathology; inter- and intra-rater reliability were assessed with the intra-class correlation coefficients (ICC).

RESULTS: FC thickness and FC area did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements (p value range 0.15-0.51 for FC thickness and 0.053-0.30 for FC area). For the LRNC area, the p value was statistically non-significant for reader 1 (range 0.36-0.81). The Bland-Altman analysis showed mean difference and 95% confidence interval for FC thickness, FC area, and LRNC area, 0.04 (-0.36 to 0.12) square root mm, -0.18 (-0.34 to -0.02) log10 mm2 and 0.10 (-0.088. to 0.009) log10 mm2 respectively.

CONCLUSION: The result demonstrated a viable technique for quantifying FC thickness, FC area, and LRNC area due to the combined effect of high spatial and energy resolution of SPCCT.

KEY POINTS: • SPCCT can identify and quantify different components of carotid atherosclerotic plaque in ex vivo study. • Components of atherosclerotic plaque did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements.

PMID:36205768 | DOI:10.1007/s00330-022-09155-x