bluuebunny/crossref_metadata_2025 huggingface dataset:
From behaviour-based to ecological: Multi-agency partnership responses to extra-familial harm
Authors: Owens Rachael , Lloyd Jenny
Published: March 2023

In the United Kingdom (UK), inquiries into the abuse of adolescents harmed in contexts beyond their families frequently document failures in multi-agency arrangements. Forms of extra-familial harm, such as criminal and sexual exploitation, often feature near-fatal violence and serious abuse. UK welfare policy has shifted towards place-based approaches to harm, leading to safeguarding partnerships forming between welfare agencies and neighbourhood crime reduction agencies. However, forming partnerships between those who have differing epistemological underpinnings raises challenges. This article explores these by drawing on a research project implementing contextual safeguarding theory and practice within five child welfare social care departments in England and Wales. Data is presented from 10 pilots (33 focus groups, 24 interviews, 59 meeting observations, 36 reviews of cases, review of 100 documents).

Findings

Multi-agency partnerships prioritise safeguarding practice that targets behaviour, over addressing the social conditions of abuse. Assumptions that partnerships will automatically align means that there is little space for negotiating a shared conceptual/ideological approach. Particularly in high-risk situations, welfare agencies defer to policing methods that target individuals rather than environments. Where ecological approaches are utilised, this is experienced as ‘against the grain’ and requiring support.

Applications

To advance contextual approaches to safeguarding young people, multi-agency partnerships must go beyond altering the behaviour of those who are harmed. Partnerships that engage in reflective discussion about their conceptual approach are more likely to build the awareness and trust required for ecological methods to succeed. Enhancing ecological social work leadership within partnerships responding to extra-familial harm is a key factor.
Validity of Novel Outcome Measures for Hand Function Performance After Stroke Using Egocentric Video
Authors: Tsai Meng-Fen , Wang Rosalie H. , Zariffa José
Published: March 2023

Background

Evaluating upper limb (UL) interventions after stroke calls for outcome measures that describe impact on daily life in the community. UL use ratio has been used to quantify the performance domain of UL function, but generally focuses on arm use only. A hand use ratio could provide additional information about UL function after stroke. Additionally, a ratio based on the role of the more-affected hand in bilateral activities (stabilizer or manipulator) may also reflect hand function recovery. Egocentric video is a novel modality that can record both dynamic and static hand use and hand roles at home after stroke.

Objective

To validate hand use and hand role ratios from egocentric video against standardized clinical UL assessments.

Methods

Twenty-four stroke survivors recorded daily tasks in a home simulation laboratory and their daily routines at home using egocentric cameras. Spearman’s correlation was used to compare the ratios with the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and Motor Activity Log-30 (MAL, Amount of Use (AoU), and Quality of Movement (QoM)).

Results

Hand use ratio significantly correlated with the FMA-UE (0.60, 95% CI: 0.26, 0.81), ARAT (0.44, CI: 0.04, 0.72), MAL-AoU (0.80, CI: 0.59, 0.91), and MAL-QoM (0.79, CI: 0.57, 0.91). Hand role ratio had no significant correlations with the assessments.

Conclusion

Hand use ratio automatically extracted from egocentric video, but not hand role ratio, was found to be a valid measure of hand function performance in our sample. Further investigation is necessary to interpret hand role information.
Primary aldosteronism during pregnancy and eplerenone use – a case report
Authors: Balachandran Divya Mecheril , Subbaiah Murali , Dorairajan Gowri
Published: March 2023

Primary aldosteronism is one of the important causes of secondary hypertension. However, pregnancy with primary aldosteronism is rare. Eplerenone is an aldosterone antagonist which is used in the treatment of primary aldosteronism. This is a case of successful pregnancy outcome in a young woman who was known to have primary aldosteronism and was on oral eplerenone from preconception. There are only five case reports on eplerenone use during pregnancy in the literature.
Head Impact Exposure in Youth Soccer: Comparing across Activity Types
Authors: Pritchard Nicholas Stewart , Filben Tanner M , Haja Sebastian J , Miller Logan E , Espeland Mark A , Stitzel Joel D , Urban Jillian E
Published: March 2023

Soccer is a popular youth sport in the United States, but the effect of repetitive head impacts experienced during training on neurocognitive outcomes is not well understood. Modifying practice structure may be an avenue for reducing head impact exposure and concussion risk in soccer, but research has yet to characterize head impact exposure across common soccer activities. The objective of this study was to compare head impact exposure across common training activities in soccer. Eight female soccer players practicing on an age 15 and under (U15) club team participated in this study for two soccer seasons. Players wore an instrumented mouthpiece sensor during all practice and game sessions. Research personnel recorded duration of all activities performed by each player to characterize player-specific exposure time. Film review was performed to identify head contact events during each session and classify events according to the activity and drill the player was performing. Head impact exposure for each athlete was quantified in terms of peak kinematics and impact rate. Mixed effects models were used to compare peak kinematics and generalized linear models were used to compare impact rates across drills and activity type. Drill and activity type were associated with peak kinematics and impact rate. Technical training activities accounted for the second-highest exposure time and were associated with higher impact rates and lower mean kinematics than other activity types. Team interaction activities and game play were associated with the highest rotational kinematics but the lowest impact rates. Head impact exposure in female youth soccer is influenced by the type of activity in which the athlete is engaged. Interventions designed to reduce head impact frequency in female youth soccer can benefit from targeting technical training activities; whereas, interventions designed to reduce head impact magnitude should target team interaction and game activities.
Diagnostic value of whole-mount crypt analysis of ileal biopsy specimens for the patients with familial small intestinal neuroendocrine tumors
Authors: Sei Yoshitatsu , Forbes Joanne , Da Ben , Chitsaz Ehsan , Feng Jianying , Zhao Xilin , Hughes Marybeth S. , Wank Stephen A.
Published: March 2023

Background and Aims:

Early-stage small intestinal neuroendocrine tumors (SI-NETs) are generally asymptomatic and difficult to diagnose. As a result, patients often present with late-stage incurable disease. SI-NETs originate from enterochromaffin (EC) cells, which develop enteroendocrine cell (EEC) clusters consisting of a subset of EC cells at the crypt bottom at an early stage of tumor progression. In a familial form of SI-NET, EEC clusters arise in a multifocal and polyclonal fashion. We sought to determine whether early detection and analysis of cryptal EEC clusters could provide insight into the development of SI-NETs and allow successful pre-symptomatic screening for at risk family members of patients with SI-NETs.

Methods:

Isolated crypts from endoscopic ileal biopsies or surgically removed specimens from 43 patients with familial SI-NET and 20 controls were formalin-fixed, immunostained for chromogranin A, and examined by confocal three-dimensional analysis for the presence of EEC cluster formations.

Results:

Examination of multiple areas of macroscopic tumor-free mucosa in surgically resected specimens from patients with familial SI-NET revealed widely distributed, independent, multifocal EEC micro-tumor formations of varying sizes. Consistent with this finding, randomly sampled ileal biopsy specimens identified aberrant crypt containing endocrine cell clusters (ACECs) in patients. ACECs were found exclusively in patients (23/43, 53%) and not in controls (0/20). Furthermore, analysis of positions and numbers of EECs in crypts and ACECs indicated significant increases in EECs at the crypt bottom, predominantly at positions 0 and 1′ ( p < 0.0001 compared to controls), suggesting the progression of EEC accumulation below +4 position as the early process of ACEC formation. These findings also suggested that ACECs were precursors in the development of micro-tumors and subsequent macro-tumors.

Conclusion:

This study indicates that SI-NETs develop from deep crypt EC cells to become ACECs, micro-tumors, and ultimately gross tumors. This process occurs widely throughout the distal small intestine in patients with familial SI-NETs consistent with but not exclusively explained by germline disease. Finally, analysis of crypts from ileal biopsies could contribute in part to earlier diagnostic screening processes avoiding late-stage presentation of incurable disease.
Regulatory Verification by Health Canada of Content in Recombinant Human Insulin, Human Insulin Analog, and Porcine Insulin Drug Products in the Canadian Market Using Validated Pharmacopoeial Methods Over Nonvalidated Approaches
Authors: Lorbetskie Barry , Bigelow Stewart , Walrond Lisa , Klein Agnes V. , Loo Shih-Miin , Green Nancy , Rosu-Myles Michael , Zhang Xu , Lu Huixin , Girard Michel , Sauvé Simon
Published: March 2023

Background:

For diabetes mellitus treatment plans, the consistency and quality of insulin drug products are crucial for patient well-being. Because biologic drugs, such as insulin, are complex heterogeneous products, the methods for drug product evaluation should be carefully validated for use. As such, these criteria are rigorously evaluated and monitored by national authorities. Consequently, reports that describe significantly lower insulin content than their label claims are a concern. This issue was raised by a past publication analyzing insulin drug products available in Canada, and, as a result, consumers and major patient organizations have requested clarification.

Methods:

To address these concerns, this study independently analyzed insulin drug products purchased from local Canadian pharmacies—including human insulin, insulin analogs, and porcine insulin—by compendial and noncompendial reversed-phase high-performance liquid chromatography (RP-HPLC) methods.

Results:

We demonstrated the importance of using methods fit for purpose when assessing insulin quality. In a preliminary screen, the expected insulin peak was seen in all products except two insulin analogs—insulin detemir and insulin degludec. Further investigation showed that this was not caused by low insulin content but insufficient solvent conditions, which demonstrated the necessity for methods to be adequately validated for product-specific use. When drug products were appropriately assessed for content using the validated type-specific compendial RP-HPLC methods for insulin quantitation, values agreed with the label claim content.

Conclusions:

Because insulin drug products are used daily by over a million Canadians, it is important that researchers and journals present data using methods fit for purpose and that readers evaluate such reports critically.
Applying frontier approach to measure the financial efficiency of hospitals
Authors: Wu Jih-Shong
Published: March 2023

Objectives

The growth in global healthcare capacity has led to increased healthcare costs and a deterioration in the finances of universal health insurance. Hospitals must consider how to improve financial efficiency and service quality in order to survive and operate sustainably.

Methods

This study applies data envelopment analysis (DEA) and stochastic frontier analysis (SFA) to measure the financial efficiency of hospitals and to identify the factors and business strategies to improve profitability.

Results

The findings and recommendations show that (1) the DEA and SFA methods are similar and have reference values; (2) financial efficiency should be improved by reducing medical costs; (3) the quality of medical staff should be improved and manpower reduced; and (4) information, computerisation, and human intelligence in healthcare and management should be enhanced.

Conclusions

In terms of practical applications, this study recommends the promotion of smart healthcare to improve the efficiency and quality of healthcare services, as well as the introduction of artificial intelligence and big data analysis to optimise the use of healthcare manpower. Electronic medical records can be used to reduce the wastage of resources and labour costs, a medication management system can be established, and changes to the procurement system can be made to reduce inventory and improve the efficiency of medical equipment use. It is hoped that this study will provide reference materials and applications for healthcare organisations to improve their operational efficiency and strategies.
Smartphone app-based intervention for reducing stress, depression, and anxiety in caregivers of people with dementia in Vietnam: Study protocol for a pilot randomized controlled trial
Authors: Than The NH , Nguyen Tran TT , Nguyen Tuan C , Vu Lan TD , Vo Phong T , TTruong Khoa , Schofield Penelope , Nguyen Tuan A
Published: March 2023

Objectives

This study aims to: (1) identify the information required by family caregivers of people with dementia to be targeted within our dementia family caregiver intervention and (2) test the feasibility of the intervention and methodology to underpin a fully powered randomized controlled trial.

Methods

The study setting will be the Department of Geriatrics at Gia Dinh People's Hospital in Ho Chi Minh City. Inclusion criteria will be the family caregivers of people with dementia living in the community, who attend the Department and use smartphones. In phase 1, we will identify the intervention content with family caregivers of people with dementia through 20 in-depth interviews to determine what information and skills they need. In phase 2, a pilot randomized control trial design will be conducted, with 60 family caregivers of people with dementia being assigned to the intervention or control group by the block randomization method with a ratio of 1:1. The intervention will include weekly, online, psycho-educational, group sessions hosted on the Zalo app. The participants will complete questionnaires at baseline, immediately postintervention, and 3-month postintervention. The feasibility of the intervention and methodology will be assessed, including the rates of recruitment, retention, completion of assessments, and acceptability of the intervention.

Results

The required information and skills in phase 1 may include dealing with worrying behavior changes in people with dementia, emotional support, and seeking support sources. The rates of recruitment, retention, completion of assessments, and acceptability of the intervention will be obtained in phase 2. The scores of symptoms of stress, depression, and anxiety in the intervention group may be lower than those in the control group at postintervention and 3-month postintervention.

Conclusion

The study will provide a foundation for a fully powered clinical trial for the smartphone app-based intervention to reduce stress, depression, and anxiety among family caregivers of people with dementia in Vietnam.
A retrospective cohort study of the effect of intravenous tranexamic acid infusion on geriatric hip fractures patients undergoing proximal femoral nail antirotation
Authors: Lam Ka Mun , Hsu Yung Chak
Published: March 2023

Background: Tranexamic acid (TXA) has been used in the management of bleeding. We are conducting a retrospective cohort study to analyse the effect of intravenous TXA infusion on the surgical outcomes of geriatric hip fracture cases which undergoes proximal femoral nail antirotation.  Methods: In this study, 364 patients who had undergone proximal femoral nail antirotation between January 2018 and December 2019 in United Christian Hospital have been recruited. Two-hundred thirteen patients were recruited in controlled group and 151 patients were recruited in TXA group. One gram of TXA acid was injected intravenously on induction of anaesthesia and before surgical incision. Outcomes including length of stay, operation time, intraoperative blood loss, haemoglobin and haematocrit drop and post-operative blood transfusion have been measured. Results: There was a reduction in operative time, intraoperative blood loss, post-operative haemoglobin and haematocrit drop and post-operative blood transfusion in TXA group, with a reduction in the intraoperative blood loss (Controlled group: 97.8 ±  67.7 ml, TXA group: 76.0 ± 71.4, Difference −22.3%, p-value: 0.0036) and post-operative haematocrit drop (Controlled group: 0.04 ± 0.03, TXA group: 0.03 ± 0.03, Difference −25%, p-value: 0.05) being statistically significant. The length of stay is not statistically significant between the two groups. TXA is an antifibrinolytic agent which acts by binding to plasminogen which inhibits plasma formation. It has a potential reduction in blood loss in major operations.  Conclusion: Intravenous TXA infusion helps to reduce blood loss in a patient undergoing proximal femoral nail antirotation. It is safe to use in the geriatric group of patients. We would recommend the usage of TXA infusion to improve the surgical outcome.
The Determinants of Inbound Tourism Demand in India: New Evidence from ARDL Co-Integration Approach
Authors: Sharma Manu , Mohapatra Geetilaxmi , Giri Arun Kumar
Published: March 2023

The research used the Autoregressive Distributive Lag (ARDL) model to examine the long- and short-term impact of changes in currency rates and global income on tourist demand in India employing monthly data from 2003 (1) to 2020 (12). We find that exchange rate volatility, global income, and tourism demand are all significantly interrelated. A 15% convergence to the long-run equilibrium path of tourism demand occurs in line with the pace of adjustment through the channel of global income and currency rate. Positive and substantial effects of rising global income are shown over the short and long terms. There is, nevertheless, a positive short-term relationship between currency depreciation and visitor numbers. Additionally, the Toda–Yamamoto method is used for Granger non-causality. The results point to a one-way causal relationship between the currency exchange rate and the number of visitors. It has also been shown that there is a causal relationship in both directions between the demand for tourism and global GDP. The nation is in a special position due to its location, physical characteristics, cultural heritage, and other comparative advantages. According to the findings, a stable currency rate and global income are the two most important factors in increasing tourist interest in India.
Food Demand and Its Differential Effects on Household Food Access in Nigeria
Authors: Adebola Ikudayisi Adesola
Published: March 2023

This paper aims to examine how urban households’ food demand pattern differs with the extent of urbanization using a cross-sectional survey in southwest Nigeria. Using principal component analysis, sampled households were categorized by urbanicity index. A quadratic almost ideal demand system (QUAIDS) was employed to estimate expenditure and price elasticities. From the result, all seven food groups were normal goods across the urban categories, with the meat group being more expenditure-elastic than the others (1.16–2.42). The own-price elasticities differ among food commodities, with the meat and roots/tubers groups being most elastic at the low (−1.35) and middle (−1.05) urban categories, respectively. Findings suggest that changes in urbanicity levels have a substantial impact on the composition of household food demand and, by extension, the extent of food access in Nigeria. Therefore, the use of aggregate demand estimates for the entire urban population might underestimate the effect of expected changes in the urbanization level on food demand.

JEL Classifications: C31, D12, Q18
Orphanage Trafficking and the Sustainable Development Goals
Authors: van Doore Kathryn E. , Nhep Rebecca
Published: March 2023

This article examines the intersections of orphanage trafficking, a form of child trafficking and modern slavery, and the sale and sexual exploitation of children with reference to the Sustainable Development Goals. It outlines the contextual challenges of these intersections highlighting the special protection needs of children residing in institutions and outlines how orphanage tourism and funding undermine care reform efforts of national authorities. To address these issues, we make recommendations to address both the in-country and external causal factors that drive and enable orphanage trafficking suggesting that governments of host and sending countries should work in tandem, under the framework of international cooperation, to implement practical measures to combat orphanage trafficking.
Surface Pressures in Lower Extremity Splints: A Biomechanical Study
Authors: Walley Kempland C. , Farrar Nicholas , Shams Kameron , Anastasio Albert T. , Gong Davin , Mell Kristopher , Holmes James R. , Walton David M. , Talusan Paul G.
Published: March 2023

Background:

Though ubiquitously used in orthopaedic trauma, lower extremity splints may have associated iatrogenic risk of morbidity. Although clinicians pad bony prominences to minimize skin pressure, the effect of joint position on skin pressure and, more specifically, changing joint position, is understudied. The purpose of this biomechanical study is to determine the effect of various short-leg splint application techniques on anterior ankle surface pressure in the development of iatrogenic skin pressure ulcers.

Methods:

Various constructs of lower extremity, short-leg splints were applied to 3 healthy subjects (6 limbs total) with an underlying pressure transducer (Tekscan I-Scan system) on the skin surface centered on the tibialis anterior tendon at the level of the ankle. All subjects underwent anterior ankle surface pressure assessment when padding was applied in maximum plantar flexion and neutral position for conventional short-leg splints application in clinically relevant patient scenarios. Percentage change from initial contact pressure centered on the tibialis anterior with cast padding were calculated.

Results:

The percentage change in anterior ankle contact pressure when padding was applied in maximum plantar flexion (PF) and then definitively placed in neutral was increased at least 2-fold without the addition of plaster in lower extremity short-leg splints. Removing anterior ankle padding following final splint application in neutral reduced contact forces at the anterior ankle 46% and 59% in splints applied in maximum PF and neutral ankle position, respectively.

Conclusion:

The present study is the first of its kind to underscore and quantify clinically relevant technical pearls that can be useful in reducing risk of iatrogenic risk of skin breakdown at the anterior ankle when placing short-leg splints, mainly, that it is imperative to apply padding in the intended final splint position and to remove anterior ankle padding following splint application when able.

Level of Evidence:

Level IV, biomechanical study with clear hypothesis.
The Chemokine, CCL20, and Its Receptor, CCR6, in the Pathogenesis and Treatment of Psoriasis and Psoriatic Arthritis
Authors: Shi Zhen-Rui , Mabuchi Tomotaka , Riutta Sarah J. , Wu Xuesong , Peterson Francis C. , Volkman Brian F. , Hwang Sam T.
Published: March 2023

Background

Chemokines represent a superfamily of immune-modulatory small protein molecules that regulate leukocyte migration to inflammatory sites through their chemoattractant and cell signaling properties. This review focuses on the immunological functions of the CCR6 chemokine receptor and is chemokine ligand, CCL20, that contribute to it role in inflammation in human psoriasis.

Methods

Peer-reviewed relevant articles are searched and selected from 2000 to 2022 using the search engines including PubMed and Google Scholar.

Results

After selectively reviewing and evaluating over seventy articles, a comprehensive overview on the immunology of CCL20-CCR6 axis in psoriasis and psoriatic arthritis, the X-ray crystal structures of CCL20 monomers, and the potential of developing clinical therapies targeting this axis is summarized.

Conclusions

Over the past decade, preclinical studies carried out in animal models of psoriasis involving agents targeting CCL20-CCR6 axis have yielded promising results. Other studies that this axis may play a role in a number of other autoimmune diseases, including rheumatoid arthritis, suggesting a rationale for further investigation into this key signaling/migratory pathway.
Actually existing intersectionality: The place-based and embodied politics of animal and human rights activism
Authors: Alloun Esther , Cook Nicole
Published: March 2023

Critiques of intersectionality as an additive and simplistic model of understanding identity politics has led to calls for renewed concepts that better grasp the complexity and potential of shared struggle. In this article, we contend that the experiences of activists attempting to practice an intersectional human and animal rights politics are a crucial yet overlooked resource in the development of such conceptual imaginaries and ethical practice. Drawing on an historical case study conducted with activists involved in the 1990s anarchist collective ‘One Struggle’ in Israel/Palestine, we argue that an ethic of shared human and animal rights struggle cannot be separated from place-based and embodied politics. We show that activists cultivating intersectional politics in practice must negotiate affective forces of discomfort, alienation and exhaustion that wear down and constrain the potential for intersectional coalitions and joint struggles. These affects are generated through state disincentives, violence the cultural politics of nationalism and incommensurable differences. In this context, intersectional politics are a precarious achievement, dependent on the capacities of activists to continue to compromise and negotiate affectively charged encounters in everyday settings. To better capture the precarious, contingent and provisional nature of animal and human rights activism, we therefore propose the concept of ‘actually existing intersectionality’, illustrating how intersectionality is retheorised via emplaced, embodied activist practices. In so doing we make visible the work through which intersectional politics coheres through negotiation by actors in particular places and times.
Enhancing quality of scoping reviews in paramedicine research – guidance for authors
Authors: Simpson Paul , Pap Robin
Published: March 2023

Scoping reviews are an increasingly common method for conducting evidence synthesis in paramedicine. Over the past decade clear methodological guidance has emerged, adding rigour and credibility to this review approach. Paramedicine receives many scoping review submissions, and views these as valid evidence synthesis capable of helping the journal achieve its strategic vision and mission. However the Editorial Board has noted that submissions frequently fail to adhere to essential elements of scoping methodology and reporting standards. This editorial aims to provide guidance to authors regarding Paramedicine's expectations and requirements for scoping review submissions, with the hope of contributing to a greater understanding of scoping review science and enhancement of quality.
Possibilities of urban research: Temporal difference and the politics of the future
Authors: MacLeavy Julie
Published: March 2023

Reflecting on Ihnji Jon's contention that urban conflicts emerge from the ‘different conceptualisations of temporality’ that groups of residents hold, this paper considers how urban practitioners might productively engage with time as a situated experience. Specifically, it considers the methodological techniques, forms of collaboration and modes of engagement that enable a focus on the entanglements of past, present and future times which underpin different ways of thinking about urban issues and generate new possibilities for building solidarity in the process. Orientating research enquiries towards non-linear and relational conceptions of time unsettles traditional forms of problem-solving in which historically set goals are prioritised over the exploration of different ideas and trajectories as a means of enacting new urban realities. This requires a commitment to a distinctive way of working in which new ideas, meanings and effects are seen to emerge slowly from a creative and collaborative process of academic engagement, which runs counter to expectations of quick and time-limited interventions in both academia and urban policy and politics.
Concurrent pembrolizumab with AVD for untreated classical Hodgkin lymphoma
Authors: Lynch Ryan C , Ujjani Chaitra S , Poh Christina , Warren Edus H , Smith Stephen D , Shadman Mazyar , Till Brian G. , Raghunathan Vikram , Alig Stefan , Alizadeh Ash A , Gulhane Avanti , Chen Delphine , Tseng Yolanda , Coye Hilary , Shelby Megan , Ottemiller Susan , Keo Sarith , Verni Kaitlin , Du Hongyan , Vandermeer Jacquelin , Gaston Ashley , Rasmussen Heather , Martin Paul , Marzbani Edmond , Voutsinas Jenna M , Gopal Ajay K
Published: March 2023

Concurrent administration pembrolizumab with chemotherapy in untreated classical Hodgkin lymphoma (CHL) has not previously been studied. To investigate this combination, we conducted a single arm study of concurrent pembrolizumab with AVD (APVD) for untreated CHL. We enrolled 30 patients (6 early favorable, 6 early unfavorable, and 18 advanced stage, median age 33 years (range 18-69 years)) and met the primary safety endpoint with no observed significant treatment delays in the first two cycles. Twelve patients experienced grade 3-4 non-hematologic adverse events (AEs) most commonly febrile neutropenia (5, 17%) and infection/sepsis (3, 10%). Grade 3-4 immune-related AEs were seen in 3 patients, including ALT elevation (3, 10%) and AST elevation (1, 3%). One patient experienced an episode of grade 2 colitis and arthritis. Six (20%) patients missed at least one dose of pembrolizumab due to adverse events, primarily grade 2 or higher transaminitis (5, 17%). Among 29 response-evaluable patients, the best overall response rate was 100% and CR rate of 90%. With median follow up of 2.1 years, 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, no patient who withheld or discontinued pembrolizumab due to toxicity has progressed. Clearance of ctDNA was associated with superior PFS when measured after cycle 2 (p=0.025) and at end of treatment (EOT, p=0.0016). None of the 4 patients with persistent disease by FDG-PET at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy, but may yield spurious PET findings in some patients. Trial Registration Number: NCT03331341
The effect of dichotomization of skewed adjustment covariates in the analysis of clinical trials
Authors: Herschtal Alan
Published: March 2023

Baseline imbalance in covariates associated with the primary outcome in clinical trials leads to bias in the reporting of results. Standard practice is to mitigate that bias by stratifying by those covariates in the randomization. Additionally, for continuously valued outcome variables, precision of estimates can be (and should be) improved by controlling for those covariates in analysis. Continuously valued covariates are commonly thresholded for the purpose of performing stratified randomization, with participants being allocated to arms such that balance between arms is achieved within each stratum. Often the thresholding consists of a simple dichotomization. For simplicity, it is also common practice to dichotomize the covariate when controlling for it at the analysis stage. This latter dichotomization is unnecessary, and has been shown in the literature to result in a loss of precision when compared with controlling for the covariate in its raw, continuous form. Analytic approaches to quantifying the magnitude of the loss of precision are generally confined to the most convenient case of a normally distributed covariate. This work generalises earlier findings, examining the effect on treatment effect estimation of dichotomizing skew-normal covariates, which are characteristic of a far wider range of real-world scenarios than their normal equivalents.
Screening behaviors for diabetic foot risk and their influencing factors among general practitioners: a cross-sectional study in Changsha, China
Authors: Zhao Nan , Xu Jingcan , Zhou Qiuhong , Hu Juanyi , Luo Wenjing , Li Xinyi , Ye Ying , Han Huiwu , Dai Weiwei , Chen Qirong
Published: March 2023

Background

Diabetic foot is a serious complication of diabetes with a high disability and mortality rate, which can be prevented by early screening. General practitioners play an essential role in diabetic foot risk screening, yet the screening behaviors of general practitioners have rarely been studied in primary care settings. This study aimed to investigate foot risk screening behaviors and analyze their influencing factors among general practitioners.

Methods

A cross-sectional study was conducted among 844 general practitioners from 78 community health centers in Changsha, China. A self-designed and validated questionnaire was used to assess the general practitioner’s cognition, attitude, and behaviors on performing diabetic foot risk screening. Multivariate linear regression was conducted to investigate the influencing factors of risk screening behaviors.

Results

The average score of diabetic foot risk screening behaviors among the general practitioners was 61.53 ± 14.69, and 271 (32.1%) always or frequently performed foot risk screening for diabetic patients. Higher training frequency (β = 3.197,p < 0.001), higher screening cognition (β = 2.947,p < 0.001), and more positive screening attitude (β = 4.564,p < 0.001) were associated with more diabetic foot risk screening behaviors, while limited time and energy (β=-5.184,p < 0.001) and lack of screening tools (β=-6.226,p < 0.001) were associated with fewer diabetic foot screening behaviors.

Conclusion

The score of risk screening behaviors for the diabetic foot of general practitioners in Changsha was at a medium level. General practitioners’ diabetic foot risk screening behaviors may be improved through strengthening training on relevant guidelines and evidence-based screening techniques, improving cognition and attitude towards foot risk screening among general practitioners, provision of more general practitioners or nurse practitioners, and user-friendly screening tools.
The assessment in patients with acute fatty liver of pregnancy (AFLP) treated with plasma exchange: a cohort study of 298 patients
Authors: Li Lingxia , Huang Dengchao , Xu Jing , Li Miaojing , Zhao Juan , Shi Qindong , Guo Qinyue
Published: March 2023

Background

To assess the prevalence, risk factors, clinical characteristics of Acute fatty liver of pregnancy (AFLP) patients, and outcomes of AFLP patients treated with plasma exchange (PE).

Methods

We retrospectively reviewed the AFLP patients admitted to the First Affiliated Hospital of Xi’an Jiaotong University and Xijing Hospital of Air Force Medical University from January 2012 to May 2022. Final prediction model for death among AFLP by means of stepwise backward elimination withpvalue < 0.05. Patients treated with and without PE were compared by propensity-matched cohort study.

Results

Two hundred ninety eight patients with the diagnosis of AFLP, and finally 290 patients were enrolled in the cohort study, 50 of whom (17.2%) were dead. Compared with AFLP patients alive, the dead of patients were more likely to be combined encephalopathy (p < 0.01), postpartum hemorrhage (p < 0.01), and found significantly higher frequency of fetal distress (p = 0.04), fetal death (p < 0.01). we developed a predicted probability value and with an area under the receiver operating characteristics (ROC) curve of 0.94 (95%CI 0.87 to 1.00), indicating AFLP patients’ death. The patients treated with PE had a significantly lower 60-day mortality rate (OR 0.42, 95% CI 0.29 to 2.64,p = 0.04), and significantly shorter duration of hospital-free days at day 28 (p = 0.01).

Conclusions

In conclusion, our study indicated that liver function were risk factors for maternal mortality, and PE was a protective factor for maternal 60-day mortality and hospital-free days at day 28 in AFLP patients.
Monitoring of T790M in plasma ctDNA of advanced EGFR-mutant NSCLC patients on first- or second-generation tyrosine kinase inhibitors
Authors: Huang Chun-Ta , Lin Chih-An , Su Te-Jen , Yang Ching-Yao , Tsai Tzu-Hsiu , Hsu Chia-Lin , Liao Wei-Yu , Chen Kuan-Yu , Ho Chao-Chi , Yu Chong-Jen
Published: March 2023

Background

The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis.

Methods

This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019. Plasma samples were collected before TKI therapy and at tri-monthly intervals thereafter. Genotyping of ctDNA for T790M was performed using a ddPCR EGFR Mutation Assay. Patients were followed up until the date of death or to the end of 2021.

Results

Seventy-five of 80 patients experienced progressive disease. Fifty-three (71%) of 75 patients underwent rebiopsy, and T790M mutation was identified in 53% (28/53) of samples. Meanwhile, plasma ddPCR detected T790M mutation in 23 (43%) of 53 patients. The concordance rate of T790M between ddPCR and rebiopsy was 76%, and ddPCR identified 4 additional T790M-positive patients. Ten (45%) of 22 patients who did not receive rebiopsy tested positive for T790M by ddPCR. Serial ddPCR analysis showed the time interval from detection of plasma T790M to objective progression was 1.1 (0–4.1) months. Compared to 28 patients with rebiopsy showing T790M, the overall survival of 14 patients with T790M detected solely by ddPCR was shorter(41.3 [95% CI, 36.6–46.0] vs. 26.6 months [95% CI, 9.9–43.3], respectively).

Conclusion

Plasma ddPCR-based genotyping is a useful technology for detection and monitoring of the key actionable genomic alteration, namely, T790M, in patients treated with gefitinib, erlotinib, or afatinib for activating mutations, to achieve better patient care and outcome.
Comorbidity-stratified estimates of 30-day mortality risk by age for unvaccinated men and women with COVID-19: a population-based cohort study
Authors: Abdel-Qadir Husam , Austin Peter C. , Sivaswamy Atul , Chu Anna , Wijeysundera Harindra C. , Lee Douglas S.
Published: March 2023

Background

The mortality risk following COVID-19 diagnosis in men and women with common comorbidities at different ages has been difficult to communicate to the general public. The purpose of this study was to determine the age at which unvaccinated men and women with common comorbidities have a mortality risk which exceeds that of 75- and 65-year-old individuals in the general population (Phases 1b/1c thresholds of the Centre for Disease Control Vaccine Rollout Recommendations) following COVID-19 infection during the first wave.

Methods

We conducted a population-based retrospective cohort study using linked administrative datasets in Ontario, Canada. We identified all community-dwelling adults diagnosed with COVID-19 between January 1 and October 31st, 2020. Exposures of interest were age (modelled using restricted cubic splines) and the following conditions: major cardiovascular disease (recent myocardial infarction or lifetime history of heart failure); 2) diabetes; 3) hypertension; 4) recent cancer; 5) chronic obstructive pulmonary disease; 6) Stages 4/5 chronic kidney disease (CKD); 7) frailty. Logistic regression in the full cohort was used to estimate the risk of 30-day mortality for 75- and 65-year-old individuals. Analyses were repeated after stratifying by sex and medical condition to determine the age at which 30-day morality risk in strata exceed that of the general population at ages 65 and 75 years.

Results

We studied 52,429 individuals (median age 42 years; 52.5% women) of whom 417 (0.8%) died within 30 days. The 30-day mortality risk increased with age, male sex, and comorbidities. The 65- and 75-year-old mortality risks in the general population were exceeded at the youngest age by people with CKD, cancer, and frailty. Conversely, women aged < 65 years who had diabetes or hypertension did not have higher mortality than 65-year-olds in the general population. Most people with medical conditions (except for Stage 4–5 CKD) aged < 45 years had lower predicted mortality than the general population at age 65 years.

Conclusion

The mortality risk in COVID-19 increases with age and comorbidity but the prognostic implications varied by sex and condition. These observations can support communication efforts and inform vaccine rollout in jurisdictions with limited vaccine supplies.
Comparison of antegrade robotic assisted VS laparoscopic inguinal lymphadenectomy for penile cancer
Authors: Yang Mengjun , Liu Zhicheng , Tan Qi , Hu Xiaofei , Liu Yang , Wei Ling , Deng Chunyan , Zhou Shikai , Yang Nengrui , Duan Guangjie , Zheng Yiming , Li Xuemei , Chen Zhiwen , Zhou Zhansong , Zheng Ji
Published: March 2023

Background

Minimally invasive modifications of inguinal lymphadenectomy (IL), including laparoscopic IL (LIL) and robotic-assisted IL (RAIL), have been utilized for penile cancer. Comparative study is necessary to guide the decision about which minimally invasive technique to select for IL. Therefore we compared RAIL with LIL performed via an antegrade approach in terms of perioperative outcomes.

Methods

We conducted a retrospective study of 43 patients who underwent RAIL (n = 20) or LIL (n = 23) for penile cancer from 2016 to 2020. The key surgical procedures and techniques are described. Complications were graded by the Clavien-Dindo classification, and operative time, estimated blood loss (EBL), lymph nodal yield, nodal positivity, postoperative drain duration, and disease recurrence during follow-up were assessed. Categorical variables were compared using chi-squared whereas continuous variables were compared by t-tests.

Results

The operative time for RAIL was significantly shorter than that of LIL (median 83 vs 95 min). Significantly less blood loss was reported with RAIL than with LIL (median 10 vs 35 ml). Lymph node yield, pathological positive nodes, the hospital stay, postoperative drain duration, postoperative complications and recurrence were similar for RAIL and LIL.

Conclusions

For patients with penile cancer, perioperative outcomes of RAIL and LIL were similar, but there was less blood loss, a shorter operative time for robotic cases.
A study of primary health care service efficiency and its spatial correlation in China
Authors: Mei Kangni , Kou Ruxin , Bi Yuqing , Liu Yuzhuo , Huang Jingwen , Li Wei
Published: March 2023

Background

China’s primary health care system has undergone major changes since the new round of medical reform in 2009, but the current status of primary health care institution service efficiency is still unsatisfactory. The purpose of this study is to compare and evaluate the China’s primary health care institution service efficiency and provide a reference for improving the efficiency and promoting the development of primary health care institution.

Methods

Based on panel data of 31 provinces (municipalities directly under the central government and autonomous regions) in mainland China from 2011 to 2020, using the super efficiency slack-based measure-data envelopment analysis model, to analyze the data from a static perspective, and the changes in the efficiency of primary health care services were analyzed from a dynamic perspective by using the Malmquist index method. Spatial autocorrelation analysis method was used to verify the spatial correlation of primary health care service efficiency among various regions.

Results

The number of Primary health care institutions increased from 918,000 in 2011 to 970,000 in 2020. The average primary health care institution service efficiency in the northeastern region including Jilin (0.324), Heilongjiang (0.460), Liaoning (0.453) and northern regions such as Shaanxi (0.344) and Neimenggu (0.403) was at a low level, while the eastern coastal regions such as Guangdong (1.116), Zhejiang (1.211), Shanghai (1.402) have higher average service efficiency levels. The global Moran’s I showed the existence of spatial autocorrelation, and the local Moran’s I index suggested that the problem of uneven regional development was prominent, showing a contiguous regional distribution pattern. Among them, H–H (high-efficiency regions) were mainly concentrated in Jiangsu, Anhui and Shanghai, and L-L regions (low-efficiency regions) were mostly in northern and northeastern China.

Conclusion

The service efficiency of primary health care institution in China showed a rising trend in general, but the overall average efficiency was still at a low level, and there were significant geographical differences, which showed a spatial distribution of “high in the east and low in the west, high in the south and low in the north”. The northwestern region, after receiving relevant support, has seen a rapid development of primary health care, and its efficiency was steadily improving and gradually reaching a high level. The average primary health care institution service efficiency in the northeastern region including the northern region of China was at a low level, while the average efficiency in the eastern coastal region and some economically developed regions was high, which also verifies the dependence and high symbiosis of primary health care institution service efficiency on regional economy.