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Initial empirical antibiotics of non-carbapenems for ESBL-producing E. coli and K. pneumoniae bacteremia in children: a retrospective medical record review

BMC Infect Dis. 2022 Nov 21;22(1):866. doi: 10.1186/s12879-022-07881-7.

ABSTRACT

BACKGROUND: The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum β-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia.

METHODS: Data from pediatric patients aged ≤ 18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia at Asan Medical Center Children’s Hospital, Seoul, Korea between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by the sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables.

RESULTS: A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n = 29) and K. pneumoniae (n = 24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure on day 2 and 30-day all-cause mortality [adjusted odds ratio (OR) 1.0; 95% confidence interval (CI) 0.22-4.88, and adjusted OR 0.1; 95% CI 0.01-1.56].

CONCLUSIONS: The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible.

PMID:36404302 | DOI:10.1186/s12879-022-07881-7

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A phase 3, randomised, placebo-controlled study of erenumab for the prevention of chronic migraine in patients from Asia: the DRAGON study

J Headache Pain. 2022 Nov 21;23(1):146. doi: 10.1186/s10194-022-01514-9.

ABSTRACT

ABSTACT: BACKGROUND: DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study.

METHODS: DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18-65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD.

RESULTS: At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was – 8.2 days for erenumab and – 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: – 1.57 [95%CI: – 2.83, – 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (- 5.34 vs – 4.66) and mMIDAS scores (- 14.67 vs – 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo).

CONCLUSION: DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials.

TRIAL REGISTRATION: NCT03867201.

PMID:36404301 | DOI:10.1186/s10194-022-01514-9

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Genome-wide analyses identify novel risk loci for cluster headache in Han Chinese residing in Taiwan

J Headache Pain. 2022 Nov 21;23(1):147. doi: 10.1186/s10194-022-01517-6.

ABSTRACT

BACKGROUND: Cluster headache is a highly debilitating neurological disorder with considerable inter-ethnic differences. Genome-wide association studies (GWAS) recently identified replicable genomic loci for cluster headache in Europeans, but the genetic underpinnings for cluster headache in Asians remain unclear. The objective of this study is to investigate the genetic architecture and susceptibility loci of cluster headache in Han Chinese resided in Taiwan.

METHODS: We conducted a two-stage genome-wide association study in a Taiwanese cohort enrolled from 2007 through 2022 to identify the genetic variants associated with cluster headache. Diagnosis of cluster headache was retrospectively ascertained with the criteria of International Classification of Headache Disorders, third edition. Control subjects were enrolled from the Taiwan Biobank. Genotyping was conducted with the Axiom Genome-Wide Array TWB chip, followed by whole genome imputation. A polygenic risk score was developed to differentiate patients from controls. Downstream analyses including gene-set and tissue enrichment, linkage disequilibrium score regression, and pathway analyses were performed.

RESULTS: We enrolled 734 patients with cluster headache and 9,846 population-based controls. We identified three replicable loci, with the lead SNPs being rs1556780 in CAPN2 (odds ratio = 1.59, 95% CI 1.42‒1.78, p = 7.61 × 10-16), rs10188640 in MERTK (odds ratio = 1.52, 95% CI 1.33‒1.73, p = 8.58 × 10-13), and rs13028839 in STAB2 (odds ratio = 0.63, 95% CI 0.52‒0.78, p = 2.81 × 10-8), with the latter two replicating the findings in European populations. Several previously reported genes also showed significant associations with cluster headache in our samples. Polygenic risk score differentiated patients from controls with an area under the receiver operating characteristic curve of 0.77. Downstream analyses implicated circadian regulation and immunological processes in the pathogenesis of cluster headache.

CONCLUSIONS: This study revealed the genetic architecture and novel susceptible loci of cluster headache in Han Chinese residing in Taiwan. Our findings support the common genetic contributions of cluster headache across ethnicities and provide novel mechanistic insights into the pathogenesis of cluster headache.

PMID:36404298 | DOI:10.1186/s10194-022-01517-6

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Preoperative chemotherapy combined with para-aortic lymph node dissection has clinical value in the treatment of gastric cancer with para-aortic lymph node metastases

BMC Surg. 2022 Nov 20;22(1):401. doi: 10.1186/s12893-022-01844-0.

ABSTRACT

BACKGROUND: Lymph node metastases often occur in advanced gastric cancer, with some patients presenting with metastases in the para-aortic lymph nodes. There are persistent Controversies about the benefit of para-aortic lymph node dissection (PAND). Our purpose is to probe whether PAND following preoperative chemotherapy had any clinical significance in individuals with PALNs in gastric cancer.

MATERIAL AND METHODS: To retrospectively analyze the clinical data of 86 gastric cancer patients (40 in the D2 + PAND group and 46 in the D2 group) who attended the abdominal surgery department of Zhejiang Cancer Hospital between September 1, 2008, and July 30, 2018.

RESULTS: In the D2 + PAND group (40 cases), the average number of lymph nodes cleared per case was 4.3 in group 16 (16a2, 16b1), and the postoperative pathology confirmed lymph node positivity in 16 cases, with a metastasis rate of 40%. The median overall survival times were 63 and 34 months for the patients in the D2 + PAND group and D2 group, respectively. The 3-year overall survival (OS) compared to the D2 group (D2 + PAND 69.1% vs. D2 50%, P = 0.012) and a statistically significant difference in 3-year disease-free survival (DFS) (D2 + PAND 69.6% vs. D2 38.3%, P = 0.007). Lymph node dissection extent and recurrence of para-aortic lymph nodes were independent prognostic variables for the patients. The recurrence rate was reduced in the D2 + PAND group compared to the D2 group (D2 + PAND 7.5% vs. D2 26.1%, p = 0.023).

CONCLUSIONS: For patients with gastric cancer whose imaging suggests metastasis in the para-aortic lymph nodes, preoperative chemotherapy combined with PAND is an effective and safe treatment that may benefit patient survival.

PMID:36404297 | DOI:10.1186/s12893-022-01844-0

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Psychometric testing of the facilitative student-patient relationship scale within six EUROPEAN countries

Nurs Open. 2022 Nov 20. doi: 10.1002/nop2.1485. Online ahead of print.

ABSTRACT

AIM: The aim of the study was to test the psychometric properties of the Facilitative Student-Patient Relationship (FSPR) Scale in clinical practicum in hospital settings within six European countries.

DESIGN: A multi-country, cross-sectional survey design was applied.

METHODS: A convenience sample of graduating nursing students (N = 1,796) completed the FSPR Scale. Psychometric testing was carried out through explorative factor analysis and confirmatory factor analysis. Internal consistency was assessed using Cronbach’s alpha.

RESULTS: Both validity and reliability of the scale were confirmed. The explorative factor analysis yielded a two-factor construct explaining 47.7% of the total variance, identifying two sub-scales: caring relationship and learning relationship. Confirmatory factor analysis confirmed the two-factor structure. The Cronbach alpha coefficients (0.8-0.9) indicated acceptable reliability of the scale.

PMID:36404294 | DOI:10.1002/nop2.1485

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Nursing experiences in antimicrobial optimisation in the intensive care unit: A convergent analysis of a national survey

Aust Crit Care. 2022 Nov 17:S1036-7314(22)00196-5. doi: 10.1016/j.aucc.2022.09.005. Online ahead of print.

ABSTRACT

BACKGROUND: Recent evidence highlights the need for an interdisciplinary approach to antimicrobial stewardship (AMS). Nursing involvement in optimising antimicrobials in the intensive care unit (ICU) remains understudied.

OBJECTIVE: The objective of this study was to explore nurses’ perceptions and experiences of antimicrobial optimisation or stewardship in ICUs in Australia.

METHODS: An anonymous web-based survey was deployed nationally in early 2021 through two ICU nursing networks. Associations between survey responses were analysed descriptively and by using nonparametric tests (with statistical significance established at p ≤ 0.05). Free-text survey responses underwent qualitative thematic analysis. Interpretation and reporting of quantitative and qualitative data were integrated.

RESULTS: A total of 226 ICU nurses completed the survey. The majority (197/226; 87%) responded that lack of education limits engagement in AMS. Only 13% (30/226) reported the presence of AMS education and training for nurses in their ICUs. Only about half (108/226; 48%) of the nurses were confident to question prescribers when they considered that the antimicrobial prescribed was unnecessary, with nurses in senior roles more likely to do so than nurses providing bedside care (p < 0.05). Gaps in education (including unfamiliarity with AMS roles), noninclusive antimicrobial discussions, moral distress, and potential workload burden were seen as potential barriers/challenges to engagement.

CONCLUSION: The multifactorial barriers identified that inhibit nurses from performing AMS tasks could be addressed by strengthening interprofessional education at all levels and by applying practical AMS interventions that are inclusive for nursing participation. A purposeful culture change that fosters psychological safety and collaborative practice is paramount to supporting nurses in these roles.

PMID:36404269 | DOI:10.1016/j.aucc.2022.09.005

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Interrater reliability in assigning a lung ultrasound score

Aust Crit Care. 2022 Nov 17:S1036-7314(22)00221-1. doi: 10.1016/j.aucc.2022.10.008. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Lung ultrasound (LUS) for physiotherapists is an emerging bedside tool. The LUS score of aeration presents as a possible means of assessing and monitoring lung aeration associated with respiratory physiotherapy treatments. There are no studies to date that have assessed the interrater reliability (IRR) of physiotherapists assigning the LUS score of aeration. This study assessed the IRR of assigning the LUS score among adult, mechanically ventilated patients in an intensive care unit with a clinical suspicion of acute lobar atelectasis.

METHODS: A convenience sample of patients had an LUS performed by a physiotherapist, and images were independently reviewed by two physiotherapists. Each lung zone was assigned an LUS score between 0 and 3 (with 0 being normal aeration and 3 being complete consolidation, presence of effusion, or pneumothorax). IRR was assessed using the kappa statistic.

RESULTS: A total of 1032 LUS images were obtained. Assigning of the LUS across all lung zones demonstrated substantial agreement with kappa 0.685 (95% confidence interval: 0.650, 0.720). Right (0.702 [0.653, 0.751]) and left (0.670 [0.619, 0.721]) lung zones also demonstrated substantial agreement.

CONCLUSION: We found substantial IRR between physiotherapists in assigning the LUS score in a mechanically ventilated adult population in the intensive care unit.

AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRATION NUMBER: ACTRN12619000783123.

PMID:36404268 | DOI:10.1016/j.aucc.2022.10.008

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Geriatric assessment in hematology scale predicts treatment tolerability in older patients diagnosed with hematological malignancies: The RETROGAH study

J Geriatr Oncol. 2022 Nov 17:S1879-4068(22)00520-3. doi: 10.1016/j.jgo.2022.10.016. Online ahead of print.

ABSTRACT

INTRODUCTION: The GAH (Geriatric Assessment in Hematology) scale is a psychometrically valid tool aimed at identifying older patients with hematological malignancies at higher risk of treatment-related toxicity. Our objective in this study was to determine the weights for each dimension of the GAH scale and the cut-off point to reliably predict treatment tolerability in this population, estimated by a weighted receiver operating characteristic (ROC) analysis and quantified by the area under the curve (AUC).

MATERIAL AND METHODS: The RETROGAH was a retrospective cohort study including 126 patients who had previously participated in the GAH study. Patients were ≥ 65 years old with newly diagnosed myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), multiple myeloma (MM), or chronic lymphoid leukemia (CLL) and treated with standard front-line therapy within three months after having completed the GAH scale.

RESULTS: The optimal cut-off value of the GAH total score to discriminate patients at higher risk of treatment toxicity was 42, with 68.5% sensitivity and 55.8% specificity. Using this value, 66.1% of patients evaluated were found to develop some type of toxicity. The AUC was 0.6259 (95% CI: 0.512-0.739; p = 0.035).

DISCUSSION: The GAH scale not only would enable clinicians to individualize therapy based on individual risk of toxicity but also discriminate patients that will benefit most from intensive treatments from those requiring an adapted approach. While futures studies in clinical practice may improve the model and overcome its limitations, the GAH scale should not be used alone when making treatment decisions.

PMID:36404260 | DOI:10.1016/j.jgo.2022.10.016

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Prognostic value of lymphadenectomy in node-negative intrahepatic cholangiocarcinoma: A multicenter, retrospectively study

Eur J Surg Oncol. 2022 Nov 8:S0748-7983(22)00736-3. doi: 10.1016/j.ejso.2022.11.008. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the prognostic value of lymph node dissection (LND) in node-negative intrahepatic cholangiocarcinoma (ICC) and identify the appropriately total number of lymph nodes examined (TNLE).

METHODS: Data from node-negative ICC patients who underwent curative intent resection in ten Chinese hepatobiliary centers from January 2010 to December 2018 were collected. Overall survival (OS), relapse-free survival (RFS) and postoperative complications were analyzed. Propensity score matching (PSM) was performed to reduce the bias due to confounding variables in LND group and non-lymph node dissection (NLND) group. The optimal TNLE was determined by survival analysis performed by the X-tile program using the enumeration method.

RESULTS: A total of 637 clinically node-negative ICC patients were included in this study, 74 cases were found lymph node (LN) positive after operation. Among the remaining 563 node-negative ICC patients, LND was associated with longer OS but not RFS before PSM (OS: 35.4 vs 26.0 months, p = 0.047; RFS: 15.0 vs 15.4 months, p = 0.992). After PSM, patients in LND group had better prognosis on both OS and RFS (OS: 38.0 vs 23.0 months, p < 0.001; RFS: 15.0 vs 13.0 months, p = 0.029). There were no statistically differences in postoperative complications. When TNLE was greater than 8, OS (48.5 vs 31.1 months, p = 0.025) and RFS (21.0 vs 13.0 months, p = 0.043) were longer in the group with more dissected LNs.

CONCLUSION: Routinely LND for node-negative ICC patients is recommended for it helps accurate tumor staging and associates with better prognosis. The optimal TNLE is more than 8.

PMID:36404249 | DOI:10.1016/j.ejso.2022.11.008

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Concentration of Fibroblasts in the Vocal Fold of Elderly

J Voice. 2022 Nov 17:S0892-1997(22)00345-9. doi: 10.1016/j.jvoice.2022.10.017. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the concentration of fibroblasts in the vocal folds of elderly people.

MATERIAL AND METHODS: The vocal folds of 13 cadavers were removed and divided into two age groups: Control group: n-5, 18-40 years; Elderly group: n-8, ≥75 years). The vocal folds were dissected and prepared for immunohistochemical analysis using the SA100 antibody to fibroblasts. The sites analyzed were maculae flavae and medial (or vibrating) portion of the vocal folds. The AVsoft program was used to count the cells.

RESULTS: A higher concentration of fibroblasts was identified in the maculae flavae of the larynx of young adults and in the medial portion of the vocal folds of the elderly. However, these results did not determine statistically significant differences, allowing us to conclude that there was no effect of age on the concentration of fibroblasts in the vocal folds.

CONCLUSION: In the larynx of the elderly, the fibroblast population remains similar to the young adults, both in the maculae flavae and in the body of the vocal folds, possibly being responsible for the constant production of fibrous matrix in the lamina propria. Functional changes in these cells are probably more marked than quantitative ones.

PMID:36404202 | DOI:10.1016/j.jvoice.2022.10.017