bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the groups of care transition strategies used by U.S. hospitals: an application of factor analytic and latent class methods
Authors: Mays Glen , Li Jing , Clouser Jessica Miller , Du Gaixin , Stromberg Arnold , Jack Brian , Nguyen Huong Q. , Williams Mark V.
Published: October 2021

Background

After activation of the Hospital Readmission Reduction Program (HRRP) in 2012, hospitals nationwide experimented broadly with the implementation of Transitional Care (TC) strategies to reduce hospital readmissions. Although numerous evidence-based TC models exist, they are often adapted to local contexts, rendering large-scale evaluation difficult. Little systematic evidence exists about prevailing implementation patterns of TC strategies among hospitals, nor which strategies in which combinations are most effective at improving patient outcomes. We aimed to identify and define combinations of TC strategies, or groups of transitional care activities, implemented among a large and diverse cohort of U.S. hospitals, with the ultimate goal of evaluating their comparative effectiveness.

Methods

We collected implementation data for 13 TC strategies through a nationwide, web-based survey of representatives from short-term acute-care and critical access hospitals (N = 370) and obtained Medicare claims data for patients discharged from participating hospitals. TC strategies were grouped separately through factor analysis and latent class analysis.

Results

We observed 348 variations in how hospitals implemented 13 TC strategies, highlighting the diversity of hospitals’ TC strategy implementation. Factor analysis resulted in five overlapping groups of TC strategies, including those characterized by 1) medication reconciliation, 2) shared decision making, 3) identifying high risk patients, 4) care plan, and 5) cross-setting information exchange. We determined that the groups suggested by factor analysis results provided a more logical grouping. Further, groups of TC strategies based on factor analysis performed better than the ones based on latent class analysis in detecting differences in 30-day readmission trends.

Conclusions

U.S. hospitals uniquely combine TC strategies in ways that require further evaluation. Factor analysis provides a logical method for grouping such strategies for comparative effectiveness analysis when the groups are dependent. Our findings provide hospitals and health systems 1) information about what groups of TC strategies are commonly being implemented by hospitals, 2) strengths associated with the factor analysis approach for classifying these groups, and ultimately, 3) information upon which comparative effectiveness trials can be designed. Our results further reveal promising targets for comparative effectiveness analyses, including groups incorporating cross-setting information exchange.
Methodological quality for systematic reviews of adverse events with surgical interventions: a cross-sectional survey
Authors: Zhou Xiaoqin , Li Linji , Lin Lifeng , Ju Ke , Kwong Joey S. W. , Xu Chang
Published: October 2021

Background

An increasing number of systematic reviews assessed the safety of surgical interventions over time. How well these systematic reviews were designed and conducted determines the reliability of evidence. In this study, we aimed to assess the methodological quality of systematic reviews on the safety of surgical interventions.

Methods

We searched PubMed for systematic reviews of surgical interventions with safety as the exclusive outcome from 1st-Jan, 2015 to 1st-Jan, 2020. The methodological quality of eligible systematic reviews was evaluated according to the AMSTAR 2.0 instrument. The primary outcomes were the number of methodological weaknesses and the global methodological quality. The proportion of each methodological weakness among eligible systematic reviews was compared by three pre-defined stratification variables. The absolute difference of the proportion (PD) was used as the effect estimator, with the two-tailed z-test for the significance.

Results

We identified 127 systematic reviews from 18,636 records. None (n = 0, 0.00%) of them could be rated as “high” in terms of the global methodological quality; in contrast, they were either rated as “low” (n = 18, 14.17%) or as “critically low” (n = 109, 85.83%). The median number of methodological weaknesses of these systematic reviews was 8 (interquartile range, IQR: 6 to 9), in which 4 (IQR: 2 to 4) were critical weaknesses. Systematic reviews that used any reporting guideline (e.g., domain 13, PD = -0.22, 95% CI: − 0.39, − 0.06; p = 0.01) and developed a protocol in advance (e.g., domain 6, PD = -0.20, 95% CI: − 0.39, − 0.01; p = 0.04) were less likely to have methodological weakness in some domains but not for the rest (e.g., domain 8, PD = 0.04, 95% CI: − 0.14, 0.21; p = 0.68; with protocol vs. without).

Conclusions

The methodological quality of current systematic reviews of adverse events with surgical interventions was poor. Further efforts, for example, encouraging researchers to develop a protocol in advance, are needed to enhance the methodological quality of these systematic reviews.
The analysis of multilevel factors affecting adenoma detection rates for colonoscopies: a large-scale retrospective study
Authors: Huang Liang , Hu Yue , Liu Shan , Jin Bo , Lu Bin
Published: October 2021

Background

Adenoma detection rate (ADR) is a validated primary quality indicator for colonoscopy procedures. However, there is growing concern over the variability associated with ADR indicators. Currently, the factors that influence ADRs are not well understood.

Aims

In this large-scale retrospective study, the impact of multilevel factors on the quality of ADR-based colonoscopy was assessed.

Methods

A total of 10,788 patients, who underwent colonoscopies performed by 21 endoscopists between January 2019 and December 2019, were retrospectively enrolled in this study. Multilevel factors, including patient-, procedure-, and endoscopist-level characteristics were analyzed to determine their relationship with ADR.

Results

The overall ADR was 20.21% and ranged from 11.4 to 32.8%. Multivariate regression analysis revealed that higher ADRs were strongly correlated with the following multilevel factors: patient age per stage (OR 1.645; 95% CI 1.577–1.717), male gender (OR 1.959; 95% CI 1.772–2.166), sedation (OR 1.402; 95% CI 1.246–1.578), single examiner colonoscopy (OR 1.330; 95% CI 1.194–1.482) and senior level endoscopists (OR 1.609; 95% CI 1.449–1.787).

Conclusion

The ADR is positively correlated with senior level endoscopists and single examiner colonoscopies in patients under sedation. As such, these procedure- and endoscopist-level characteristics are important considerations to improve the colonoscopy quality.
A cluster of children with facial nerve palsy in a high prevalence area for COVID-19
Authors: Barron David , Richards Owen , Archer Fleur , Abdelrazek Mohamed , Ranjan Rajesh , Omolokun Omotakin
Published: October 2021

Background

COVID-19 is a disease of varying presentation and neurological sequelae of the disease are being studied. Following a cluster of paediatric facial nerve palsy (FNP) cases in an area of South Wales with a high prevalence of COVID-19, we conducted an opportunistic study to determine whether there has been an increase of incidence of FNP and if there is an association between the FNP and COVID-19 in children.

Methods

We performed a retrospective review of the incidence of FNP between 2015 and 2020 across two hospitals within the health board. The incidence was compared with that in 2020 including a cluster of six children in 14 weeks, presenting to Royal Glamorgan Hospital between June and October.

Results

There were 48 cases of children with FNP across both hospital within the study years. Seven (7) cases in 2020. The incidence was not statistically different in comparison to other years.

Five out of six of these children in 2020 had antibody testing for COVID-19. All serology testing (100%) returned negative for SARS-CoV- 2 antibodies.

Conclusions

In high prevalence area for COVID-19, cases of children with FNP have not shown a commensurate increase. we have found no causal link between COVID-19 and FNP in children. While this is a small study, larger cohort studies are needed to support this finding.

As new strains of COVID-19 are being reported in UK, South Africa and Brazil, physicians need to continue to be vigilant for consistent pattern of signs and symptoms, especially in children.
Twenty-four-hour mechanical power variation rate is associated with mortality among critically ill patients with acute respiratory failure: a retrospective cohort study
Authors: Chi Yi , Zhang Qing , Yuan Siyi , Zhao Zhanqi , Long Yun , He Huaiwu
Published: October 2021

Objectives

Defined as the energy applied to the respiratory system by ventilator, mechanical power (MP) of ventilation reflects the risk of ventilation-induced lung injury. This study aims to explore the relationship between dynamic changes in MP and prognosis in critically ill patients.

Methods

This was a single-centre retrospective cohort study. Patients receiving mechanical ventilation with acute respiratory failure (ARF) and MP > 10 J/min on admission in the ICU were included. MP (J/min) was calculated as 0.098 × minute ventilation (L/min) × [(peak inspiratory pressure + positive end-expiratory pressure)/2] and the MP variation rate (%) as ([baseline MP − 24-h MP]/baseline MP) × 100. Patients were divided into two groups according to whether MP decreased 24 h after admission (MP-improved group defined as 24-h MP variation rate > 0% vs. MP-worsened group defined as 24-h MP variation rate ≤ 0%).

Results

In total, 14,463 patients were screened between January 2015 and June 2020, and finally, a study cohort of 602 patients was obtained. The MP-improved group had a lower ICU mortality rate than the MP-worsened group (24% vs. 36%; p = 0.005). The 24-h MP variation rate was associated with ICU mortality after adjusting for confounders (odds ratio, 0.906 [95% CI 0.833–0.985]; p = 0.021), while baseline MP (p = 0.909) and 24-h MP (p = 0.059) were not. All MP components improved in the MP-improved group, while minute ventilation and positive end-expiratory pressure contributed to the increase in MP in the MP-worsened group.

Conclusions

The 24-h MP variation rate was an independent risk factor for ICU mortality among ARF patients with elevated MP. Early decreases in MP may provide prognostic benefits in this population.
Empowerment of nurses for integrating clients’ religion/spirituality into clinical practice: outcomes of an online training program
Authors: Amiri Hasan , Farokhzadian Jamileh , Tirgari Batool
Published: October 2021

Background

Integration of clients’ religion/spirituality (R/S) into nursing practice can have effective outcomes in clients’ health. In this regard, nurses’ lack of competency can disrupt this process and interfere with the treatment process. Limited studies examined the impact of training programs on nurses’ competency in spiritual care and integration of clients’ R/S into clinical practice. This study aimed to investigate the impact of an online training program on nurses’ empowerment for integrating clients’ R/S into clinical practice.

Methods

In the present interventional study, 80 nurses were selected by stratified sampling from two hospitals in the southeastern Iran. Nurses were randomly divided into the intervention (n = 40) and control (n = 40) groups. An online training program was performed for the intervention group in four 2-hour sessions during three weeks. Data were collected from all participants using the R/S Integrated Practice Assessment Scale (RSIPAS) before and one month after the intervention.

Results

Prior to the intervention, scores of integrating clients’ R/S into clinical practice were not significantly different between the intervention and control groups (t = 0.23, p = 0.81). However, after the training program, these scores increased significantly with a very large effect size compared to the control group (t = 4.31, p = 0.001). Although the control group scores improved significantly after the intervention compared to the pre-intervention stage, the effect size was very small (t = -2.55, p = 0.01).

Conclusions

The online training program had a positive effect on nurses’ competency for integrating clients’ R/S into clinical practice in the intervention group. Due to the importance of integrating clients’ R/S into clinical practice, nurses’ competency should be strengthened in this area. Managers are suggested to consider appropriate strategies in order to empower nurses in integrating clients’ R/S into clinical practice. Nurse educators can benefit from our experiences in application of online training programs in nursing schools.
Estimating population-based coverage of reproductive, maternal, newborn, and child health (RMNCH) interventions from health management information systems: a comprehensive review
Authors: Mwinnyaa George , Hazel Elizabeth , Maïga Abdoulaye , Amouzou Agbessi
Published: October 2021

Background

Routinely collected health facility data usually captured and stored in Health Management Information Systems (HMIS) are potential sources of data for frequent and local disaggregated estimation of the coverage of reproductive, maternal, newborn, and child health interventions (RMNCH), but have been under-utilized due to concerns over data quality. We reviewed methods for estimation of national or subnational coverage of RMNCH interventions using HMIS data exclusively or in conjunction with survey data from low- and middle-income countries (LMICs).

Methods

We conducted a comprehensive review of studies indexed in PubMed and Scopus to identify potential papers based on predefined search terms. Two reviewers screened the papers using defined inclusion and exclusion criteria. Following sequences of title, abstract and full paper reviews, we retained 18 relevant papers.

Results

12 papers used only HMIS data and 6 used both HMIS and survey data. There is enormous lack of standards in the existing methods for estimating RMNCH intervention coverage; all appearing to be highly author dependent. The denominators for coverage measures were estimated using census, non-census and combined projection-based methods. No satisfactory methods were found for treatment-based coverage indicators for which the estimation of target population requires the population prevalence of underlying conditions. The estimates of numerators for the coverage measures were obtained from the count of users or visits and in some cases correction for completeness of reporting in the HMIS following an assessment of data quality.

Conclusions

Standard methods for correcting numerators from HMIS data for accurate estimation of coverage of RMNCH interventions are needed to expand the use of these data. More research and investments are required to improve denominators for health facility-derived statistics. Improvement in routine data quality and analytical methods would allow for timely estimation of RMNCH intervention coverage at the national and subnational levels.
Comparing health care use and costs among new Medicaid enrollees before and during the COVID-19 pandemic
Authors: Wright Brad , Anderson David , Whitaker Rebecca , Shrader Peter , Bettger Janet Prvu , Wong Charlene , Shafer Paul
Published: October 2021

Background and Objective

To characterize health care use and costs among new Medicaid enrollees before and during the COVID pandemic. Results can help Medicaid non-expansion states understand health care use and costs of new enrollees in a period of enrollment growth.

Research Design

Retrospective cross-sectional analysis of North Carolina Medicaid claims data (January 1, 2018 - August 31, 2020). We used modified Poisson and ordinary least squares regression analysis to estimate health care use and costs as a function of personal characteristics and enrollment during COVID. Using data on existing enrollees before and during COVID, we projected the extent to which changes in outcomes among new enrollees during COVID were pandemic-related.

Subjects

340,782 new enrollees pre-COVID (January 2018 – December 2019) and 56,428 new enrollees during COVID (March 2020 – June 2020).

Measures

We observed new enrollees for 60-days after enrollment to identify emergency department (ED) visits, nonemergent ED visits, primary care visits, potentially-avoidable hospitalizations, dental visits, and health care costs.

Results

New Medicaid enrollees during COVID were less likely to have an ED visit (-46 % [95 % CI: -48 %, -43 %]), nonemergent ED visit (-52 % [95 % CI: -56 %, -48 %]), potentially-avoidable hospitalization (-52 % [95 % CI: -60 %, -43 %]), primary care visit (-34 % [95 % CI: -36 %, -33 %]), or dental visit (-36 % [95 % CI: -41 %, -30 %]). They were also less likely to incur any health care costs (-29 % [95 % CI: -30 %, -28 %]), and their total costs were 8 % lower [95 % CI: -12 %, -4 %]. Depending on the outcome, COVID explained between 34 % and 100 % of these reductions.

Conclusions

New Medicaid enrollees during COVID used significantly less care than new enrollees pre-COVID. Most of the reduction stems from pandemic-related changes in supply and demand, but the profile of new enrollees before versus during COVID also differed.
Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease
Authors: Li Naijian , Dai Zhouli , Wang Zhang , Deng Zhishan , Zhang Jiahuan , Pu Jinding , Cao Weitao , Pan Tianhui , Zhou Yumin , Yang Zhaowei , Li Jing , Li Bing , Ran Pixin
Published: October 2021

Background

Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood.

Methods

We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes.

Results

We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed.

Conclusion

These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.
Study on the methodology of striae gravidarum severity evaluation
Authors: Dai Hongyan , Liu Yangyang , Zhu Yan , Yu Yun , Meng Lin
Published: October 2021

Background

Striae gravidarum is a common occurrence in pregnancy and many women expect to prevent its development. At present, laser treatment has been used to improve the appearance of striae gravidarum, but the choice of laser type, treatment time, and frequency depend on the therapeutic effect. How to obtain an effective evaluation of striae gravidarum during and after treatment is very important. However, there is no unified evaluation parameter about striae gravidarum. In this paper, we studied the methodology evaluation of striae gravidarum severity. First, the laser therapeutic apparatus was selected as the experimental equipment and different striae gravidarum photos during treatment were obtained. Second, the subject evaluation parameters were chosen based on the literature research and the dermatologists’ guidance. Then, the striae gravidarum photos were divided into different groups by dermatologists based on these parameters. Finally, the objective detection parameters were designed based on the photos feature and subject evaluation parameters. Then, the objective detection parameters were used as the input of the support vector machine and the evaluation results were compared.

Results

Based on the subject evaluation parameters, the experimental data could be divided into mild, moderate and severe groups. The experiment results showed that the striae gravidarum severity of two randomly patients were improved before and after treatment, which verified the validity of the parameters. In addition, the chosen objective detection parameters were different among different groups. With all the objective parameters as the support vector machine input, we could achieve the best recognition rate (82.71%) in the striae gravidarum severity classification. The four parameters (color difference, average density, average width, distribution area) calculated from the photos as the input could achieve acceptable accuracy (81.69%).

Conclusions

The subject evaluation parameters and objective detection parameters proposed in this paper can be used to evaluate the striae gravidarum severity, which is of great significance for the construction of auxiliary diagnostic instrument for striae gravidarum treatment.
Modified minimally invasive technique for decompression and reduction of thoracolumbar burst fracture with neurological symptoms: Technical Note
Authors: Li Xu , Guan Zhiyuan , Chen Xiao , Chen Buzhou , Kong Lei , Han Jintao , Zhang Wenzhi
Published: October 2021

Purpose

There are few reports about minimally invasive decompression and fixation for patients with thoracolumbar fracture and neurological symptoms. The previously reported method requires complete laminectomy, and removal of the medial part of the pedicle to expose the spinal canal for reduction. Thus, some approach-related damage to the bony structure and soft tissue still occurs. This study was performed to describe a modified minimally invasive tube technique for decompression and reduction of thoracolumbar fracture with neurological symptoms. This modified technique preserves most of the posterior structures of the spine as well as the muscle.

Methods

Percutaneous pedicle screws were placed on the vertebrae superior and inferior to the fracture and at the fracture segment on the side with less severe symptoms. After retraction, the tube for decompression was placed on the facet joint where the decompression was needed. Under microscopic vision, part of the lamina and ligamentum flavum were removed to expose the spinal canal, and an L-shaped probe was used to reduce the bone fragment.

Results

The modified method was successfully used in eight patients. Complete decompression was achieved and the bone fragment was safely reduced through the tube under microscopy in all cases. Fluoroscopy confirmed that the positioning of the percutaneous pedicle screw was good and the bone fragment was reduced. The neurological status was improved in all patients at last follow up.

Conclusion

The modified method of minimally invasive decompression and fusion is effective in treating thoracolumbar fractures with neurological symptoms and preserves most of the ligaments and bone structure.
Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients
Authors: Gunst Jan , De Bruyn Astrid , Casaer Michael P. , Vander Perre Sarah , Langouche Lies , Van den Berghe Greet
Published: October 2021

Background

Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis.

Methods

This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test.

Results

In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1–3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1–3 and significantly lower than the ICU admission values for both groups (P < 0.0001).

Conclusion

Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.
Long-term improvement of psoriasis patients’ adherence to topical drugs: testing a patient-supporting intervention delivered by healthcare professionals
Authors: Svendsen Mathias Tiedemann , Feldman Steven R. , Möller Sören , Kongstad Line Planck , Andersen Klaus Ejner
Published: October 2021

Background

Psoriasis affects 2–4% of the Western adult population and is a socio-economic burden for patients and society. Topical drugs are recommended as first-line treatment for mild-to-moderate psoriasis, but low adherence is a barrier to treatment success. Psoriasis patients require support, in order to improve their long-term use of topical drugs. The project aims to test whether a patient-supporting intervention delivered by dermatology nurses can reduce the severity of psoriasis, improve the use of topical drugs, and is cost-effective compared to standard procedure.

Methods

The intervention consists of improved support delivered to patients by three experienced dermatology nurses, who will support patients on a regular basis by consultations with a focus on providing reminder systems, accountability, reinforcement, and building trust in the treatment. Each patient will be supported by the same dermatology nurse throughout the entire study period. The effect will be compared with standard procedure.

The intervention will be tested in a randomized controlled trial during a 48-week period. A group of patients with moderate-to-severe psoriasis (psoriasis affecting ≥ 4% of the total body surface area) and 18–85 years of age who are prescribed topical treatment will be randomized to a non-intervention (n ≈ 57) or intervention group (n ≈ 57). Participants in both arms will be prescribed topical preparations containing corticosteroid and/or calcipotriol.

The primary outcome will be a change in the severity of psoriasis, measured as reduction in the Lattice-System Physician’s Global Assessment. Secondary outcomes will include changes in health-related quality of life (measured by disease specific and generic questionnaires), primary adherence (i.e., proportion of filled prescriptions), and secondary adherence by objective measure (rate of topical drug consumption (obtained by weighing medication packages) compared to estimated recommended consumption). A health economic evaluation is planned to run alongside the trial. Participants’ total health costs will be estimated on the basis of health costs reported to the national health registries and costs spent on the intervention, after which a cost-utility and cost-effectiveness analysis will be carried out.

Discussion

If the intervention can reduce the severity of psoriasis in a significant manner and is economically favorable compared to standard treatment, there is potential for implementing the intervention in dermatology clinics.

Trial registration

Clinicaltrials.govNCT04220554. Registered on January 7, 2020. Study results, either positive, negative, or inconclusive, will be published on www.clinicaltrials.gov.

Trial registration no. with the Danish Regional Committee on Health Research Ethics, registration no. 72613.
Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes
Authors: Tsen Shaw-Wei D. , Springer Luke E. , Sharmah Gautam Krishna , Tang Rui , Liang Kexian , Sudlow Gail , Kucharski Amir , Pham Christine T. N. , Achilefu Samuel
Published: October 2021

Background

The development and optimization of therapies for rheumatoid arthritis (RA) is currently hindered by a lack of methods for early non-invasive monitoring of treatment response. Annexin A2, an inflammation-associated protein whose presence and phosphorylation levels are upregulated in RA, represents a potential molecular target for tracking RA treatment response.

Methods

LS301, a near-infrared dye-peptide conjugate that selectively targets tyrosine 23-phosphorylated annexin A2 (pANXA2), was evaluated for its utility in monitoring disease progression, remission, and early response to drug treatment in mouse models of RA by fluorescence imaging. The intraarticular distribution and localization of LS301 relative to pANXA2 was determined by histological and immunohistochemical methods.

Results

In mouse models of spontaneous and serum transfer-induced inflammatory arthritis, intravenously administered LS301 showed selective accumulation in regions of joint pathology including paws, ankles, and knees with positive correlation between fluorescent signal and disease severity by clinical scoring. Whole-body near-infrared imaging with LS301 allowed tracking of spontaneous disease remission and the therapeutic response after dexamethasone treatment. Histological analysis showed preferential accumulation of LS301 within the chondrocytes and articular cartilage in arthritic mice, and colocalization was observed between LS301 and pANXA2 in the joint tissue.

Conclusions

We demonstrate that fluorescence imaging with LS301 can be used to monitor the progression, remission, and early response to drug treatment in mouse models of RA. Given the ease of detecting LS301 with portable optical imaging devices, the agent may become a useful early treatment response reporter for arthritis diagnosis and drug evaluation.
High dose and hepatobiliary dysfunction are associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin: a retrospective study
Authors: Zhao Yanfang , Su Wenjia , Liang Guohua , Shan Xiaoyu , Ma Weiwei , Tang Dabei , Li Liru , Niu Xingjian , Zhao Shu , Zhang Qingyuan , Zhao Wenhui
Published: October 2021

Purpose

In clinical practice, the risk factors for pegylated liposomal doxorubicin-related hand-foot syndrome remain unclear. The purpose of this study was to determine the risk factors associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin.

Methods

This retrospective descriptive analysis included patients with lymphoma who received PLD treatment (≥ 2 cycles of chemotherapy) at our cancer centre and had complete follow-up data from January 2016 to February 2020. Clinical, laboratory data, as well as the occurrence of hand-foot syndrome (incidence, location, severity, impact on follow-up chemotherapy) were obtained. The primary end point was the incidence of hand-foot syndrome, which was classified according to the “Common Terminology Criteria for Adverse Events” (Version 4.0). A multivariate logistic regression analysis was used to identify risk factors for hand-foot syndrome in patients with lymphoma using doxorubicin liposomes.

Findings

A total of 167 patients met the inclusion criteria. 58 developed HFS, of which 45 occurred after the second course of chemotherapy. The multivariate logistic regression analysis revealed that a dose increase of pegylated liposomal doxorubicin and hepatobiliary dysfunction were significantly associated with an increased risk for hand-foot syndrome(dose intensity, OR = 6.479; 95% CI, 1.431–29.331 [P = 0.015]; history of gallstones, OR = 14.144, 95% CI, 1.512–132.346 [P = 0.020]; alanine aminotransferase, OR = 1.194, 95% CI, 1.056–1.350 [P = 0.005]; aspartate aminotransferase, OR = 1.162, 95% CI, 1.010–1.336 [P = 0.035]; and glutamine transpeptidase, OR = 1.092, 95% CI, 1.016–1.174 [P = 0.018]).

Implications

These findings contribute to the risk assessment of patients with lymphoma before using pegylated liposomal doxorubicin. For patients with the above risk factors, preventive measures should be taken in advance to reduce the incidence of HFS.
Validation of an 18-item version of the Swedish Knee Self-Efficacy Scale for patients after ACL injury and ACL reconstruction
Authors: Beischer S. , Hamrin Senorski E. , Thomeé P. , Thomeé R.
Published: October 2021

Purpose

To evaluate the measurement properties of a new version of the Swedish Knee Self-Efficacy Scale (K-SES) in samples of individuals with an anterior cruciate ligament (ACL) injury and after ACL reconstruction. A secondary aim was to translate the new version of K-SES into English in order to prepare for future complete cross-cultural adaptation.

Methods

The reliability, structural validity, internal consistency and construct validity of the new, 18-item version of the K-SES (K-SES18) were assessed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for evaluating methodological quality. The Swedish version of the K-SES18was translated to English using recommended guidelines.

Results

The test-retest reliability for the K-SES18subscalepresentand the K-SES18subscalefutureshowed an Interclass Correlation Coefficient (ICC) = 0.92. In addition, the K-SES18had a Cronbach’s α ranging from 0.93 to 0.96 for the K-SES18subscalepresentand from 0.81 to 0.91 for the K-SES18subscalefuture. No floor and ceiling effects were identified for the subscalepresentor the subscalefutureof the K-SES18. A factor analysis produced 2 factors of importance; K-SES18presentand K-SES18future. Seven predefined hypotheses were confirmed.

Conclusion

The K-SES18has acceptable reliability and validity to assess knee self-efficacy in patients up to 18 months after ACL injury and reconstruction.

Level of evidence

IV.
The burden of pharmacological treatment on health-related quality of life in people with a urea cycle disorder: a qualitative study
Authors: Yeowell Gillian , Burns Danielle Stephanie , Fatoye Francis
Published: October 2021

Background

Urea cycle disorders (UCD) are inborn errors of metabolism, typically presenting neonatally. Excess ammonia builds rapidly within the body risking hyperammonemic episodes and potentially death. Long-term management of the condition includes restrictive protein consumption, pharmacological interventions and, in extreme cases, liver transplantation. Pharmacological treatments such as sodium benzoate and sodium phenylbutyrate have proven effective but not without a multitude of negative attributes including poor taste, higher dosage and associated gastrointestinal discomfort that impacts health-related quality of life. Glycerol phenylbutyrate (GPB) has recently become a widely available pharmacological treatment with early reports of improved qualities, including taste and administration method. The following study aims to explore the burden of pharmacological treatment and the effects of the transition to GPB on health-related quality of life in people with a UCD.

Results

Nine carers of children living with a UCD (mean age = 12.44, SD = 10.26) were interviewed regarding their experiences of pharmacological treatment in relation to their, and their child’s, health-related quality of life after transitioning to GPB. Three main themes were identified: psychological health, physical health and social participation. Carers struggled with anxiety surrounding their child’s condition and the battle of administering medication. Medication administration was perceived to have improved since the transition to GPB, alleviating distress for both carer and child. Issues involving school were described, ranging from difficulties integrating their child into mainstream schooling and the impact of treatment on participation in school and extracurricular activities. Carers encountered issues sourcing syringes to administer GPB, which induced stress. It could be suggested that some burden had been relieved by the transition to GPB. However, it appeared that difficulties associated with the illness would persist despite treatment, owing to the continuing nature of the condition.

Conclusions

Adhering to a strict pharmacological regime caused immense stress for both carers and children, severely impacting on typical social activities such as eating at a restaurant or going on holiday. GPB was perceived to have alleviated some burden in terms of administration given improved characteristics concerning taste and dosage, important characteristics for both carers and children living with UCD. Practitioners should consider these findings when making clinical decisions for children with UCD and the effect of pharmacological treatment on carer’s health-related quality of life. Outreach work to facilitate greater understanding of the condition should be conducted with key locations, such as children’s schools. This would also help to alleviate carer burden.
An accurate and efficient multiscale finite-difference frequency-domain method for the scalar Helmholtz equation
Authors: Jiang Wei , Chen Xuehua , Lv Bingnan , Jiang Shuaishuai
Published: October 2021

Frequency-domain numerical modeling of the seismic wave equation can readily describe frequency-dependent seismic wave behaviors, yet it is computationally challenging to perform in finely discretized or large-scale geologic models. Conventional finite-difference frequency-domain (FDFD) methods for solving the Helmholtz equation usually lead to large linear systems that are difficult to solve with a direct or iterative solver. Parallel strategies and hybrid solvers can partially alleviate the computational burden by improving the performance of the linear system solver. We have developed a novel multiscale FDFD method to eventually construct a dimension-reduced linear system from the scalar Helmholtz equation based on the general framework of heterogeneous multiscale method. The methodology associated with multiscale basis functions in the multiscale finite-element method is applied to the local microscale problems of this multiscale FDFD method. Solved from frequency- and medium-dependent local Helmholtz problems, these multiscale basis functions capture fine-scale medium heterogeneities and are finally incorporated into the dimension-reduced linear system by a coupling of scalar Helmholtz problem solutions at two scales. We use several highly heterogeneous models to verify the performance in terms of the accuracy, efficiency, and memory cost of our multiscale method. The results indicate that our new method can solve the scalar Helmholtz equation in complicated models with high accuracy and quite low time and memory costs compared to the conventional FDFD methods.
Consequences of the MSW mechanism with Super-Kamiokande oscillation parameters and of the volume distribution of neutrino sources in the Sun
Authors: Slad L. M.
Published: October 2021

The knowledge of the parameters of the solar neutrino oscillation model, provided by the SNO and Super-Kamiokande Collaborations, enables us to obtain, with the Wolfenstein equation, a simple and clear analytical and numerical picture of the transformation of the neutrino state during its travel inside the Sun. We show that the resulting picture is not implicated in the characteristics of the neutrino state at the surface of the Sun and at the surface of the Earth. This circumstance with taking into account the volume distribution of solar neutrino sources indicates an obvious contradiction between the consequences of the MSW mechanism with parameters from SNO and Super-Kamiokande and the results of three of the five observed processes with solar neutrinos. The assertions at the base of the MSW mechanism are discussed.
Approach to the Patient With New-Onset Secondary Amenorrhea: Is This Primary Ovarian Insufficiency?
Authors: Stuenkel Cynthia A , Gompel Anne , Davis Susan R , Pinkerton JoAnn V , Lumsden Mary Ann , Santen Richard J
Published: October 2021

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy—an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New-onset amenorrhea with duration of 3 to 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary, and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population.
Hyperinsulinemic-Euglycemic Clamp Strengthens the Insulin Resistance in Nonclassical Congenital Adrenal Hyperplasia
Authors: Delai Ariane , Gomes Patricia M , Foss-Freitas Maria Cristina , Elias Jorge , Antonini Sonir R , Castro Margaret , Moreira Ayrton C , Mermejo Livia M
Published: October 2021

Objective

Insulin sensitivity evaluation by hyperinsulinemic-euglycemic clamp in nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency.

Design and Setting

Cross-sectional study at university hospital outpatient clinics.

Patients and Methods

NC-CAH patients (25 females, 6 males; 24 ± 10 years) subdivided into C/NC (compound heterozygous for 1 classical and 1 nonclassical allele) and NC/NC (2 nonclassical alleles) genotypes were compared to controls.

Results

At diagnosis, C/NC patients presented higher basal and adrenocorticotropin-stimulated 17-hydroxyprogesterone and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, body mass index, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and lower high-density lipoprotein cholesterol levels with no changes in fasting plasma glucose, glycated hemoglobin, homeostatic model assessment for insulin resistance, leptin, interleukin 6, tumor necrosis factor alpha, C-reactive protein, and carotid-intima-media thickness. All patients had used glucocorticoid (mean time of 73 months). Among the 22 patients with successful clamp, 13 were still receiving glucocorticoid—3 patients using cortisone acetate, 9 dexamethasone, and 1 prednisone (hydrocortisone equivalent dose of 5.5mg/m²/day), while 9 patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9mg/m2/day). The NC-CAH patients presented lower Mffm than controls (31 ± 20 vs 55 ± 23µmol/min-1/kg-1, P = 0.002). The Mffm values were inversely correlated with the duration of glucocorticoid treatment (r = −0.44, P = 0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels.

Conclusion

Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH.
Optimization of extraction conditions for polyphenols from the stem bark of Funtumia elastica (Funtum) utilizing response surface methodology
Authors: Fadjare Frempong Theophilus , Owusu Boadi Nathaniel , Badu Mercy
Published: October 2021

Background: The recovery of phenolic compounds is seen as an arduous task because phenolic compounds are available as free aglycones, as sugar or ester conjugates, or as polymers with several monomeric components. This study looks at the optimization of factors that affect the efficiency for the extraction of phenolic compounds from the stem-bark of Funtumia elastica.

Methods: Five independent variables (solvent concentration, time, the temperature, solid-liquid ratio, and pH) of the extraction process were selected. Single factor analysis as well as the response surface method was used to evaluate the impact of the selected factors on the total phenolic content. The effect of the extraction factors on the phenolic content was tested for its statistical significant (p <0.05). For the response surface method, a five/factor, five/level central composite design was used, and a fitted second-order polynomial regression model equation was used to show how the extraction parameters affected the total phenolic recovery.

Results: The predicted value (R² of 0.5917) agreed with the adjusted value (R² of 0.7707). The residuals for response predictions were less than 5%. The optimal factors for the extraction were ethanol concentration of 75.99% v/v, extraction time of 193.86 minutes, temperature of 63.66°C, pH of 5.62, and solid-liquid ratio of 1:21.12 g/mL. Actual overall content of the phenolic compounds was validated at 82.83 ± 3.335 mg gallic acid equivalent (GAE) /g weight of extract, which agreed with the predicted response of 89.467 mg GAE/g of the dried extract under the optimal factors.

Conclusions: The rich phenolic content of stem-bark of Funtumia elastica points to its potential as a functional medicinal product to alleviate diseases caused by oxidative stress such as asthma, breathing disorders, inflammation, and cardiovascular diseases. The results obtained indicate that, the studied optimal conditions support effective phenolics extraction of Funtumia elastica.