Tag: pubmed

J Natl Compr Canc Netw. 2023 Aug;21(8):821-830.e3. doi: 10.6004/jnccn.2023.7036.

ABSTRACT

BACKGROUND: Radiotherapy (RT) causes adverse events for which there are no effective treatments. This study investigated the clinical benefits of compound Kushen injection (CKI) in managing radiation injury in patients with lung cancer.

METHODS: A multicenter, open-label, randomized clinical trial randomly assigned patients with lung cancer to receive either CKI (20 mL/d for at least 4 weeks) integrated with curative RT (RT + CKI group; n=130) or RT alone (control group; n=130). The primary outcome was the incidence of grade ≥2 radiation-induced lung injury (RILI) in the lungs, esophagus, or heart. Secondary outcomes included patient-reported symptoms, quality of life, objective response rate (ORR), and toxic effects.

RESULTS: During the 16-week trial, the RT + CKI group had a significantly lower incidence of grade ≥2 RT-related injury than the control group (12.3% [n=16] vs 23.1% [n=30]; P=.02). Compared with the control group, the RT + CKI group experienced a significant decrease in moderate-to-severe symptoms of fatigue, cough, and pain (P<.001 for the treatment and time interaction term); significantly less physical symptom interference (P=.01); and significantly better quality of life by the end of the trial (P<.05). No statistically significant difference in ORR was found. Adverse reactions associated with CKI were rare.

CONCLUSIONS: This study demonstrated low toxicity of CKI and its effectiveness in patients with lung cancer in reducing the incidence of grade ≥2 RILI and symptom burden, improving patients’ quality of life.

PMID:37549911 | DOI:10.6004/jnccn.2023.7036

J Natl Compr Canc Netw. 2023 Aug;21(8):813-820.e1. doi: 10.6004/jnccn.2023.7033.

ABSTRACT

BACKGROUND: Early palliative care is increasingly used in solid organ malignancy but is less established in patients with hematologic malignancy. Disease-related factors increase the demand for hospitalization, treatment, and supportive care in patients with hematologic malignancy. The terminal phase of illness in patients with hematologic malignancy can be difficult to predict, resulting in complexities in establishing a standard for quality end-of-life care.

METHODS: This is a retrospective single-center cohort study of adult patients with hematologic malignancy who died between October 2019 and July 2022. Patients were identified, and disease characteristics, therapy, and outcomes were extracted from medical records. Descriptive statistics are reported and univariate analyses were performed across a range of factors to assess for associations.

RESULTS: A total of 229 patients were identified, with a median age of 77 years and 35% female. In the final 30 days of life, 65% presented to the emergency department, 22% had an ICU admission, 22% had an invasive procedure, 48% received cytotoxic therapy, 61% received a RBC transfusion, and 46% received a platelet transfusion. Use of intensive chemotherapy was particularly associated with hospitalization and ICU admission. A total of 74% referred to palliative care, with a median time from referral to death of 13 days. Of these patients, one-third were referred within the last 5 days of life. In terms of place of death, 54% died in the acute hospital setting and 30% in hospice, with a median hospice length of stay of 4 days.

CONCLUSIONS: These findings highlight the need for further research into quality indicators for end of life in hematologic malignancy and earlier integration of specialist supportive and palliative care in both inpatient and outpatient settings.

PMID:37549908 | DOI:10.6004/jnccn.2023.7033

J Am Med Dir Assoc. 2023 Aug 4:S1525-8610(23)00610-2. doi: 10.1016/j.jamda.2023.06.020. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the effect of a tailored, multifaceted improvement strategy on hand hygiene compliance in long-term care facilities (LTCFs). We also performed a process evaluation to explore the mechanisms through which our strategy brought about change.

DESIGN: We conducted a stepped-wedge cluster-randomized controlled trial with a sequential rollout of the improvement strategy to all participating LTCFs. The strategy consisted of education, training, reminders, observation sessions (including feedback), and team meetings (including feedback).

SETTING AND PARTICIPANTS: The study included nursing professionals from 14 LTCFs (23 wards) in the Netherlands.

METHODS: Hand hygiene compliance was observed during 5 measurement periods using WHO’s “Five Moments for Hand Hygiene.” Multilevel analyses and corresponding tests were completed on an intention-to-treat basis.

RESULTS: The absolute intervention effect of overall hand hygiene compliance (primary outcome measure) was 13% (95% CI 9.3-16.7, P < .001), adjusted for time and clustering. The adjusted absolute effect was 23% (95% CI 7-39, P < .002) before a clean and aseptic procedure, 18% (95% CI 10-26, P < .001) after touching a resident, 14% (95% CI 7-22, P < .003) before touching a resident, 10% (95% CI 5-15, P < .001) after contact with body fluid, and 1% (95% CI -11 to 13, P = .8) after touching a resident’s surroundings. With the exception of leadership, participants at LTCFs with more exposure to the intervention components showed statistically significantly more improvement than those at facilities with lower exposure scores.

CONCLUSIONS AND IMPLICATIONS: Our strategy was successful in improving hand hygiene compliance. LTCFs with more team members exposed to the different intervention components, demonstrated a greater effect from the intervention. To strengthen the impact of our intervention, we recommend that future improvement strategies provide more support to managers to ensure they are better equipped to take on their leadership roles and enable their teams to improve and maintain hand hygiene compliance.

PMID:37549888 | DOI:10.1016/j.jamda.2023.06.020

Ageing Res Rev. 2023 Aug 5:102028. doi: 10.1016/j.arr.2023.102028. Online ahead of print.

ABSTRACT

The present paper identifies a critical factor that leads to false negative results (i.e., failing to indicate efficacy when beneficial results did occur) in randomized human drug trials. The paper demonstrates that human performance can only be enhanced by a maximum of 30-60% as described by the hormetic dose response which defines the limits of biological plasticity. However, human epidemiological/clinical trials typically contain such extensive variability that often requires responses greater than 2-3 times control group responses to show statistical significance. Thus, many potentially beneficial agents may be missed because the clinical trial fails to recognize and take into consideration the limits of biological plasticity. The paper proposes that this hormesis-biological plasticity-clinical trial conundrum can be addressed successfully via the use of a weight-of-evidence methodology similar to that used by regulatory agencies such as EPA in environmental assessment of chemical toxicity.

PMID:37549872 | DOI:10.1016/j.arr.2023.102028

Placenta. 2023 Jul 31;140:90-99. doi: 10.1016/j.placenta.2023.07.297. Online ahead of print.

ABSTRACT

INTRODUCTION: To characterize early-gestation changes in placental structure, perfusion, and oxygenation in the context of ischemic placental disease (IPD) as a composite outcome and in individual sub-groups.

METHODS: In a single-center prospective cohort study, 199 women were recruited from antenatal clinics between February 2017 and February 2019. Maternal magnetic resonance imaging (MRI) studies of the placenta were temporally conducted at two timepoints: 14-16 weeks gestational age (GA) and 19-24 weeks GA. The pregnancy was monitored via four additional study visits, including at delivery. Placental volume, perfusion, and oxygenation were assessed at both MRI timepoints. The primary outcome was defined as pregnancy complicated by IPD, with group assignment confirmed after delivery.

RESULTS: In early gestation, mothers with IPD who subsequently developed fetal growth restriction (FGR) and/or delivered small-for gestational age (SGA) infants showed significantly decreased MRI indices of placental volume, perfusion, and oxygenation compared to controls. The prediction of FGR or SGA by multiple logistic regression using placental volume, perfusion, and oxygenation revealed receiver operator characteristic curves with areas under the curve of 0.81 (Positive predictive value (PPV) = 0.84, negative predictive value (NPV) = 0.75) at 14-16 weeks GA and 0.66 (PPV = 0.78, NPV = 0.60) at 19-24 weeks GA.

DISCUSSION: MRI indices showing decreased placental volume, perfusion and oxygenation in early pregnancy were associated with subsequent onset of IPD, with the greatest deviation evident in subjects with FGR and/or SGA. These early-gestation MRI changes may be predictive of the subsequent development of FGR and/or SGA.

PMID:37549442 | DOI:10.1016/j.placenta.2023.07.297

J Chem Inf Model. 2023 Aug 7. doi: 10.1021/acs.jcim.3c00165. Online ahead of print.

ABSTRACT

The medically relevant field of protein-based therapeutics has triggered a demand for protein engineering in different pH environments of biological relevance. In silico engineering workflows typically employ high-throughput screening campaigns that require evaluating large sets of protein residues and point mutations by fast yet accurate computational algorithms. While several high-throughput pK_a prediction methods exist, their accuracies are unclear due to the lack of a current comprehensive benchmarking. Here, seven fast, efficient, and accessible approaches including PROPKA3, DeepKa, PKAI, PKAI+, DelPhiPKa, MCCE2, and H++ were systematically tested on a nonredundant subset of 408 measured protein residue pK_a shifts from the pK_a database (PKAD). While no method outperformed the null hypotheses with confidence, as illustrated by statistical bootstrapping, DeepKa, PKAI+, PROPKA3, and H++ had utility. More specifically, DeepKa consistently performed well in tests across multiple and individual amino acid residue types, as reflected by lower errors, higher correlations, and improved classifications. Arithmetic averaging of the best empirical predictors into simple consensuses improved overall transferability and accuracy up to a root-mean-square error of 0.76 pK_a units and a correlation coefficient (R²) of 0.45 to experimental pK_a shifts. This analysis should provide a basis for further methodological developments and guide future applications, which require embedding of computationally inexpensive pK_a prediction methods, such as the optimization of antibodies for pH-dependent antigen binding.

PMID:37549424 | DOI:10.1021/acs.jcim.3c00165

J Fam Pract. 2023 Jul;72(6 Suppl):S55-S60. doi: 10.12788/jfp.0624.

ABSTRACT

Stroke is a significant cause of mortality worldwide, and diabetes is an independent risk factor for ischemic stroke occurrence and recurrence. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lower the risk of ischemic stroke through beneficial effects on traditional stroke risk factors such as hyperglycemia, hypertension, and dyslipidemia. Primary care practitioners (PCPs) can play a substantial role in reducing ischemic stroke; studies have indicated that patients who have a PCP at the time of first stroke have a lower risk of stroke recurrence. Clinical practice guidelines recommend treating type 2 diabetes in patients with or at risk for cardiovascular (CV) disease with glucose-lowering agents with proven CV benefit, such as GLP-1 RAs and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Based on meta-analyses of CV outcomes trials, GLP-1 RAs have a substantial and statistically significant benefit on ischemic stroke risk reduction, whereas SGLT2 inhibitors have a nonsignificant effect. The use of GLP-1 RAs, in addition to non-pharmacologic and pharmacologic management of traditional stroke risk factors, is a key component of complex therapy for ischemic stroke risk reduction.

PMID:37549420 | DOI:10.12788/jfp.0624

Int J Radiat Biol. 2023 Aug 7:1-12. doi: 10.1080/09553002.2023.2241897. Online ahead of print.

ABSTRACT

PURPOSE: Development of an integrated time and dose model to explore the dynamics of gene expression alterations and identify biomarkers for biodosimetry following low- and high-dose irradiations at high dose rate.

MATERIAL AND METHODS: We utilized multiple transcriptome datasets (GSE8917, GSE43151, and GSE23515) from Gene Expression Omnibus (GEO) for identifying candidate biological dosimeters. A linear mixed-effects model with random intercept was used to explore the dose-time dynamics of transcriptional responses and to functionally characterize the time- and dose-dependent changes in gene expression.

RESULTS: We identified genes that are correlated with dose and time and discovered two clusters of genes that are either positively or negatively correlated with both dose and time based on the parameters of the model. Genes in these two clusters may have persistent transcriptional alterations. Twelve potential transcriptional markers for dosimetry-ARHGEF3, BAX, BBC3, CCDC109B, DCP1B, DDB2, F11R, GADD45A, GSS, PLK3, TNFRSF10B, and XPC were identified. Of these genes, BAX, GSS, and TNFRSF10B are positively associated with both dose and time course, have a persistent transcriptional response, and might be better biological dosimeters.

CONCLUSIONS: With the proposed approach, we may identify candidate biomarkers that change monotonically in relation to dose, have a persistent transcriptional response, and are reliable over a wide dose range.

PMID:37549410 | DOI:10.1080/09553002.2023.2241897

Ann Intern Med. 2023 Aug 8. doi: 10.7326/M23-0133. Online ahead of print.

ABSTRACT

BACKGROUND: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women.

OBJECTIVE: To estimate overdiagnosis associated with breast cancer screening among older women by age.

DESIGN: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age.

SETTING: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program.

PATIENTS: Women 70 years and older who had been recently screened.

MEASUREMENTS: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up.

RESULTS: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening.

LIMITATIONS: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram.

CONCLUSION: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question.

PRIMARY FUNDING SOURCE: National Cancer Institute.

PMID:37549389 | DOI:10.7326/M23-0133

J Speech Lang Hear Res. 2023 Aug 7:1-16. doi: 10.1044/2023_JSLHR-23-00059. Online ahead of print.

ABSTRACT

PURPOSE: Despite co-occurrence of swallowing and speech disorders in childhood, there is limited research on shared and separate neuromuscular underpinnings of these functions. The purpose of this study was to (a) compare neuromuscular control of swallowing and speech between younger and older children and (b) determine similarities and differences in neuromuscular control of swallowing and speech.

METHOD: Twenty-six typically developing children (thirteen 7- to 8-year-olds and thirteen 11- to 12-year-olds) completed this cross-sectional study. Neuromuscular control was evaluated using surface electromyography of submental muscles and superior and inferior orbicularis oris muscles during parallel tasks of swallowing and speech. Outcome measures included normalized mean amplitude, burst duration, time to peak amplitude, and bilateral synchrony, which were examined using mixed-effects models.

RESULTS: For normalized mean amplitude, burst duration, and time to peak amplitude, there were significant two- and three-way interactions between muscle group, task, and age group, indicating that older and younger children demonstrated different muscle activation patterns, and these patterns varied by muscle and task. No differences were noted between groups for bilateral synchrony. For parallel tasks, children demonstrated different magnitudes of normalized mean amplitude and time to peak amplitude of speech and swallowing. However, they demonstrated a similar pattern: increases in magnitude as task complexity increased.

CONCLUSIONS: Children continue to demonstrate refinement of their neuromuscular control of swallowing and speech between 7-8 and 11-12 years of age, and there are both shared and separate elements of neuromuscular control between these two vital functions. To improve generalizability of findings, future research should include longitudinal analysis of swallowing and speech development, as well as measures of central neurophysiology.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23796258.

PMID:37549377 | DOI:10.1044/2023_JSLHR-23-00059