Nevin Manimala

Bone Jt Open. 2023 Aug 8;4(8):573-579. doi: 10.1302/2633-1462.48.BJO-2023-0049.

ABSTRACT

AIMS: Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted.

METHODS: As part of the SpInOuT-F study, a pilot randomized trial was carried out across five NHS hospitals. Patients were randomized to either spinal decompression alone or spinal decompression plus instrumented fusion. Patient-reported outcome measures were collected at baseline and three months. The intended sample size was 60 patients.

RESULTS: Of the 90 patients screened, 77 passed the initial screening criteria. A total of 27 patients had a PI-LL mismatch and 23 had a dynamic spondylolisthesis. Following secondary inclusion and exclusion criteria, 31 patients were eligible for the study. Six patients were randomized and one underwent surgery during the study period. Given the low number of patients recruited and randomized, it was not possible to assess completion rates, quality of life, imaging, or health economic outcomes as intended.

CONCLUSION: This study provides a unique insight into the prevalence of dynamic spondylolisthesis and PI-LL mismatch in patients with symptomatic spinal stenosis, and demonstrates that there is a need for a definitive RCT which stratifies for these groups in order to inform surgical decision-making. Nonetheless a definitive study would need further refinement in design and implementation in order to be feasible.

PMID:37549931 | DOI:10.1302/2633-1462.48.BJO-2023-0049

Diabetes Metab J. 2023 Aug 7. doi: 10.4093/dmj.2023.0041. Online ahead of print.

ABSTRACT

BACKGROUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES).

METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured.

RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. Conclusion: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

PMID:37549924 | DOI:10.4093/dmj.2023.0041

Eur J Haematol. 2023 Aug 7. doi: 10.1111/ejh.14066. Online ahead of print.

ABSTRACT

PURPOSE: Hodgkin’s disease is a common malignant disorder in adolescent patients. Although most patients are cured, approximately 10%-15% of patients experience a relapse or have resistant disease. Furthermore, there are no definitive molecular predictors for early identification of patients at high risk of treatment failure to first line therapy. The aim of this study was to evaluate the deep learning-based classifier model of medical image classification to predict clinical outcome that may help in appropriate therapeutic decisions.

METHODS: Eighty-three FFPE biopsy specimens from patients with Hodgkin’s disease were stratified according to the patient’s qPET scores, stained with picrosirius red dye and digitalized by whole slide image scanning. The resulting whole slide images were cut into tiles and annotated by two classes based on the collagen fibers’ degree of coloring with picrosirius red. The neural network (YOLOv4) was then trained with the annotated data. Training was performed with 30 cases. Prognostic power of the weakly stained picrosirius red fibers was evaluated with 53 cases. The same neural network was trained with MMP9 stained tissue slides from the same cases and the quantification results were compared with the variant from the picrosirius red cases.

RESULTS: There was a weak monotonically increasing relationship by parametric ANOVA between the qPET groups and the percentages of weakly stained fibers (p = .0185). The qPET-positive cases showed an average of 18% of weakly stained fibers, and the qPET-negative cases 10%-14%. Detection performance showed an AUC of 0.79.

CONCLUSIONS: Picrosirius red shows distinct associations as a prognostic metric candidate of disease progression in Hodgkin’s disease cases using whole slide images but not sufficiently as a prognostic device.

PMID:37549921 | DOI:10.1111/ejh.14066

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