bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of APACHE II score system for disease severity based on XGBoost algorithm
Authors: Luo Yan , Wang Zhiyu , Wang Cong
Published: August 2021

Background

Prognostication is an essential tool for risk adjustment and decision making in the intensive care units (ICUs). In order to improve patient outcomes, we have been trying to develop a more effective model than Acute Physiology and Chronic Health Evaluation (APACHE) II to measure the severity of the patients in ICUs. The aim of the present study was to provide a mortality prediction model for ICUs patients, and to assess its performance relative to prediction based on the APACHE II scoring system.

Methods

We used the Medical Information Mart for Intensive Care version III (MIMIC-III) database to build our model. After comparing the APACHE II with 6 typical machine learning (ML) methods, the best performing model was screened for external validation on anther independent dataset. Performance measures were calculated using cross-validation to avoid making biased assessments. The primary outcome was hospital mortality. Finally, we used TreeSHAP algorithm to explain the variable relationships in the extreme gradient boosting algorithm (XGBoost) model.

Results

We picked out 14 variables with 24,777 cases to form our basic data set. When the variables were the same as those contained in the APACHE II, the accuracy of XGBoost (accuracy: 0.858) was higher than that of APACHE II (accuracy: 0.742) and other algorithms. In addition, it exhibited better calibration properties than other methods, the result in the area under the ROC curve (AUC: 0.76). we then expand the variable set by adding five new variables to improve the performance of our model. The accuracy, precision, recall, F1, and AUC of the XGBoost model increased, and were still higher than other models (0.866, 0.853, 0.870, 0.845, and 0.81, respectively). On the external validation dataset, the AUC was 0.79 and calibration properties were good.

Conclusions

As compared to conventional severity scores APACHE II, our XGBoost proposal offers improved performance for predicting hospital mortality in ICUs patients. Furthermore, the TreeSHAP can help to enhance the understanding of our model by providing detailed insights into the impact of different features on the disease risk. In sum, our model could help clinicians determine prognosis and improve patient outcomes.
Quantifying Covid19-vaccine location strategies for Germany
Authors: Leithäuser Neele , Schneider Johanna , Johann Sebastian , Krumke Sven O. , Schmidt Eva , Streicher Manuel , Scholz Stefan
Published: August 2021

Background

Vaccines are an important tool to limit the health and economic damage of the Covid-19 pandemic. Several vaccine candidates already provided promising effectiveness data, but it is crucial for an effective vaccination campaign that people are willing and able to get vaccinated as soon as possible. Taking Germany as an example, we provide insights of using a mathematical approach for the planning and location of vaccination sites to optimally administer vaccines against Covid-19.

Methods

We used mathematical programming for computing an optimal selection of vaccination sites out of a given set (i.e., university hospitals, health department related locations and general practices). Different patient-to-facility assignments and doctor-to-facility assignments and different constraints on the number of vaccinees per site or maximum travel time are used.

Results

In order to minimize the barriers for people to get vaccinated, i.e., limit the one-way travel journey (airline distance) by around 35 km for 75% of the population (with a maximum of 70 km), around 80 well-positioned facilities can be enough. If only the 38 university hospitals are being used, the 75% distance increases to around 50 km (with a maximum of 145 km). Using all 400 health departments or all 56 000 general practices can decrease the journey length significantly, but comes at the price of more required staff and possibly wastage of only partially used vaccine containers.

Conclusions

In the case of free assignments, the number of required physicians can in most scenarios be limited to 2 000, which is also the minimum with our assumptions. However, when travel distances for the patients are to be minimized, capacities of the facilities must be respected, or administrative assignments are prespecified, an increased number of physicians is unavoidable.
Empirically identified networks of healthcare providers for adults with mental illness
Authors: Breslau Joshua , Dana Beth , Pincus Harold , Horvitz-Lennon Marcela , Matthews Luke
Published: August 2021

Background

Policies target networks of providers who treat people with mental illnesses, but little is known about the empirical structures of these networks and related variation in patient care. The goal of this paper is to describe networks of providers who treat adults with mental illness in a multi-payer database based medical claims data in a U.S. state.

Methods

Provider networks were identified and characterized using paid inpatient, outpatient and pharmacy claims related to care for people with a mental health diagnosis from an all-payer claims dataset that covers both public and private payers.

Results

Three nested levels of network structures were identified: an overall network, which included 21% of providers (N = 8256) and 97% of patients (N = 476,802), five communities and 24 sub-communities. Sub-communities were characterized by size, provider composition, continuity-of-care (CoC), and network structure measures including mean number of connections per provider (degree) and average number of connections who were connected to each other (transitivity). Sub-community size was positively associated with number of connections (r = .37) and the proportion of psychiatrists (r = .41) and uncorrelated with network transitivity (r = −.02) and continuity of care (r = .00). Network transitivity was not associated with CoC after adjustment for provider type, number of patients, and average connection CoC (p = .85).

Conclusions

These exploratory analyses suggest that network analysis can provide information about the networks of providers that treat people with mental illness that is not captured in traditional measures and may be useful in designing, implementing, and studying interventions to improve systems of care. Though initial results are promising, additional empirical work is needed to develop network-based measures and tools for policymakers.
Incremental burden of comorbid major depressive disorder in patients with type 2 diabetes or cardiovascular disease: a retrospective claims analysis
Authors: Kangethe Anne , Lawrence Debra F. , Touya Maëlys , Chrones Lambros , Polson Michael , Evangelatos Themmi
Published: August 2021

Background

The estimated prevalence of comorbid major depressive disorder (.

MDD) is 11% in patients with type 2 diabetes (T2D) and 15–20% in those with cardiovascular disease (CVD). Comorbid MDD continues to be a significant source of economic burden to the healthcare system.

Methods

We assessed the incremental healthcare burden of comorbid MDD in patients with T2D or CVD. This real-world, retrospective, administrative claims study analyzed commercially insured adults with T2D or CVD diagnosed on at least 2 separate claims within 12 months of each other (between January 1, 2011, and September 30, 2018). CVD included congestive heart failure, peripheral vascular disease, coronary heart disease, and cerebrovascular disease. The study compared patients with and without MDD with either T2D or CVD. Study assessments included all-cause healthcare resource utilization (proportion of patients with hospitalization, emergency department [ED] visits, and outpatient visits) and cost.

Results

Patients were matched by propensity score for demographics and baseline characteristics, resulting in similar baseline characteristics for the respective subcohorts. After matching, 22,892 patients with T2D (11,446 each with and without MDD) and 28,298 patients with CVD (14,149 each with and without MDD) were included.

At follow-up, patients with T2D and MDD had significantly higher rates of hospitalization (26.1% vs 17.4%, P < 0.0001) and ED visits (55.3% vs 43.0%, P < 0.0001) than those observed in patients without MDD. The total cost for patients with T2D and MDD at follow-up was significantly higher than for those without MDD ($16,511 vs $11,550, P < 0.0001). Similarly, at follow-up, patients with CVD and MDD had significantly higher rates of hospitalization (45.4% vs 34.1%, P < 0.0001) and ED visits (66.5% vs 55.4%, P < 0.0001) than those observed in patients without MDD. Total cost at follow-up for patients with CVD and MDD was significantly higher than for those without MDD ($25,546 vs $18,041, P < 0.0001).

Conclusions

Patients with either T2D or CVD and comorbid MDD have higher total all-cause healthcare utilization and cost than similar patients without MDD. Study findings reinforce the need for appropriate management of MDD in patients with these comorbid diseases, which in turn may result in cost reductions for payers.

Trial registration

Not applicable.
Adverse childhood experiences and child mental health: an electronic birth cohort study
Authors: Lowthian Emily , Anthony Rebecca , Evans Annette , Daniel Rhian , Long Sara , Bandyopadhyay Amrita , John Ann , Bellis Mark A. , Paranjothy Shantini
Published: August 2021

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34–2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52–1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.
Effect of local ozone treatment on rats with anterior rectal resection and the possible mechanisms
Authors: Zhang Wei , Wu Meng , Chen Peng , Zhang Jiamin , Ma Jiaze , Cheng Yile , Li Xiaoliu , Hu Junjie , Li Wanli , Du Yuxin , Ding Kang , Fan Zhimin
Published: August 2021

Background

Anterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR).

Material and methods

After establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin–eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting.

Results

Ozone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment.

Conclusions

Taken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.
Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
Authors: Su Junhao , Duan Xinhao , Qiu Yu , Zhou Lixiao , Zhang Hongyang , Gao Min , Liu Yijun , Zou Zhen , Qiu Jingfu , Chen Chengzhi
Published: August 2021

Background

Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO2NPs remains very limited.

Methods

In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring.

Results

The results clearly demonstrated that exposure to TiO2NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO2NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO2NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis.

Conclusions

This is the first report elucidated that pregnancy exposure to TiO2NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women.

Graphical abstract
pH-sensitive dual drug loaded janus nanoparticles by oral delivery for multimodal analgesia
Authors: Liu Lin , Yao Wendong , Xie Xiaowei , Gao Jianqing , Lu Xiaoyang
Published: August 2021

Background

Based on the concept of “multimodal analgesia”, a novel dual drug delivery system was designed to achieve synergistic analgesia between najanajaatra venom protein (αCT) and resveratrol (Res). In order to meet the joint loading of two drugs with different physicochemical properties without affecting each other, an oral Janus nanoparticle (JNP) with a unique cavity structure and synergistic drug delivery was constructed using an improved double emulsion solvent evaporation method, and combined with low-molecular-weight chitosan/sodium alginate and PLGA to achieve its pH-responsive.

Results

The synthesized αCT/Res-JNPs are homogeneous in shape, with a two-compartment structure, approximately 230 nm in size, and zeta potential of 23.6 mV. Drug release assayed in vitro show that JNP was stable in simulated gastric juice (pH = 1.2) but was released in phosphate buffer saline (pH = 7.4). After intragastric administration in rats, PK evaluation showed that αCT/Res-JNPs could significantly improve the oral bioavailability, and the simultaneous encapsulation of the two drugs had no significant interaction on PK parameters. An obvious synergistic analgesic effects of αCT/Res-JNPs was confirmed in a spinal cord injury and acute pain model. Confocal laser scanning microscopy and single-pass intestinal perfusion model provided strong evidence that αCT/Res-JNPs could pass through intestinal epithelial cells, and the endocytosis pathway was mainly involved in the mediation and pinocytosis of reticulin. The concentrations of αCT and Res from αCT/Res-JNP in lymphatic transport were only about 8.72% and 6.08% of their blood concentrations at 1 h, respectively, which indicated that lymphatic transport in the form of JNP has limited advantages in improving the oral bioavailability of Res and αCT. Cellular uptake efficiency at 4 h was about 10–15% in Caco-2 cell lines for αCT/Res-JNP, but was reduced to 7% in Caco-2/HT29-MTX co-culture models due to the hindrance by the mucus layers. Approximately 12–17% of αCT/Res-JNP were transported across Caco-2/HT29-MTX/Raji monolayers. The cumulative absorption of JNP in three cell models was higher than that of free drug.

Conclusions

This study investigated the contribution of Janus nanoparticles in oral absorption, and provide a new perspective for oral administration and analgesic treatment of dual drug delivery system containing peptide drugs.

Graphic Abstract
Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target
Authors: Kong Fanyun , Zhang Fulong , Liu Xiangye , Qin Suping , Yang Xiaoying , Kong Delong , Pan Xiucheng , You Hongjuan , Zheng Kuiyang , Tang Renxian
Published: August 2021

As a ubiquitous second messenger, calcium (Ca2+) can interact with numerous cellular proteins to regulate multiple physiological processes and participate in a variety of diseases, including hepatitis B virus (HBV) infection, which is a major cause of hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In recent years, several studies have demonstrated that depends on the distinct Ca2+ channels on the plasma membrane, endoplasmic reticulum, as well as mitochondria, HBV can elevate cytosolic Ca2+ levels. Moreover, within HBV-infected cells, the activation of intracellular Ca2+ signaling contributes to viral replication via multiple molecular mechanisms. Besides, the available evidence indicates that targeting Ca2+ signaling by suitable pharmaceuticals is a potent approach for the treatment of HBV infection. In the present review, we summarized the molecular mechanisms related to the elevation of Ca2+ signaling induced by HBV to modulate viral propagation and the recent advances in Ca2+ signaling as a potential therapeutic target for HBV infection.
Applications of various range shifters for proton pencil beam scanning radiotherapy
Authors: Lin Haibo , Shi Chengyu , Huang Sheng , Shen Jiajian , Kang Minglei , Chen Qing , Zhai Huifang , McDonough James , Tochner Zelig , Deville Curtiland , Simone Charles B. , Both Stefan
Published: August 2021

Background

A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors.

Methods

Three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system.

Results

A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body.

Conclusion

We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB.
Health care transition for patients with vascular malformations: a French multicenter cross-sectional study
Authors: Vermersch Camille , Boccara Olivia , Chiaverini Christine , Mazereeuw-Hautier Juliette , Sigg Nina , Mallet Stéphanie , Vabres Pierre , Herbreteau Denis , Le Touze Anne , Maruani Annabel , Leducq Sophie ,   Research Group of the Société Française de Dermatologie Pédiatrique (French Society of Pediatric Dermatology)
Published: August 2021

Background

Health care transition (i.e., transition from pediatric to adult care) is challenging in chronic conditions but has been poorly studied in rare chronic skin diseases. We investigated the proportion of lost to follow-up among patients with superficial vascular malformations after health care transition. We also collected patients’ opinions. This prospective, multicenter, cross-sectional study was performed at 7 French hospitals. We included patients aged 19–25 years, who were followed for a superficial vascular malformation before age 16, and who had completed the transition period in 2020. Data were collected from medical records and a questionnaire was sent to included patients asking about the health care transition.

Results

Among the 90 patients included, 41 (46%) were lost to follow-up after health care transition period. The age at diagnosis was significantly higher for lost to follow-up than non- lost to follow-up patients. The lost to follow-up proportion was similar between patients who changed and did not change hospitals during the transition. Responses to the questionnaire were obtained for 47 of 90 patients (52.2% response rate); most were satisfied with their care (n = 31/36, 86.1%); however, a lack of psychological support was reported.

Conclusions

Health care transition is associated to a high rate of lost to follow-up. Early management seems associated to less lost to follow-up. Further studies are needed to better understand risk factors for a failed health care transition and its consequences.
Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study
Authors: Stelten Bianca M. L. , Dotti Maria Teresa , Verrips Aad , Elibol Bülent , Falik-Zaccai Tzipora C. , Hanman Kate , Mignarri Andrea , Sithole Belina , Steiner Robert D. , Verma Surabhi , Yahalom Gilad , Zubarioglu Tanyel , Mochel Fanny , Federico Antonio
Published: August 2021

Background

Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established.

Aim

To assess expert opinion on best care practices for patients with CTX using a modified Delphi method.

Methods

A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1–2 (disagreement) or 5–6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions.

Results

Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients’ care.

Conclusions

The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.
Antibiotic-resistant profile and the factors affecting the intravenous antibiotic treatment course of generalized Staphylococcal Scalded Skin Syndrome: a retrospective study
Authors: Yang Tao , Wang Jiangyi , Cao Junya , Zhang Xinyue , Lai Yun , Li Longnian , Ye Xiaoying , You Cong
Published: August 2021

Background

Staphylococcal Scalded Skin Syndrome (SSSS) is caused by a special type of Staphylococcus aureus (S.aureus) which can produce exfoliative toxins. The generalized SSSS is recommended to be admitted and treated with intravenous antibiotics. However, there were limited reports on whether personal and clinical factors can have impacts on the duration of intravenous antibiotic application for pediatric patients with generalized SSSS.

We performed a study to assess the factors affecting intravenous antibiotic treatment course of SSSS patients. Additionally, the positive culture rates of S.aureus in different samples and the antibiotic-resistant profile were investigated.

Methods

Two hundred nineteen patients with generalized SSSS were included. Gender, age, area, season, maximum axillary temperature, white blood cell (WBC) count, C-reactive protein (CRP) level, types of intravenous antibiotics, and types of external antibiotics were recorded as the baseline. Simple linear regression was applied in the univariate analysis to determine the variables with statistical significance and then these variables were further examined in multivariate linear regression model. The positive culture rates of S.aureus in different sample sources were calculated and the drug sensitivity results were statistically compared by pairwise Chi square test.

Results

According to the multiple linear regression, older ages (β = − 0.01, p < 0.05) and external application of fusidic acid (β = − 1.57, p < 0.05) were associated with shorter treatment course, elevated leukocytes (β = 0.11, p < 0.001) and CRP level (β = 1.64, p < 0.01) were associated with longer treatment course. The positive culture rates of periorificial swabs, throat swabs, and blood samples were 54.55, 30.77, and 5.97% respectively. The resistant rates of levofloxacin (8.33%), gentamycin (8.33%), tetracycline (25%), oxacillin (8.33%), vancomycin (0%) were significantly lower than the ones of erythromycin (100%), trimethoprim-sulfamethoxazole (TMP/SMX) (83.33%), clindamycin (91.67%), penicillin G(100%) (p < 0.001).

Conclusion

Elevated leukocytes and CRP level indicated prolonged intravenous antibiotic treatment course. Older ages and external application of fusidic acid helped to reduce the treatment course. Compared with blood samples, the culture positive rates of S.aureus in periorificial and throat swabs were higher. Oxacillin and vancomycin resistance was rare and clindamycin resistance was common. Clindamycin monotherapy for SSSS should be avoided.
The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) program: study protocol for a randomized controlled trial
Authors: Yeung Kar-Fu , Gandhi Mihir , Lam Amanda Yun Rui , Julianty Selly , Chia Alvin Yeow Meng , Tan Gilbert Choon Seng , Goh Su-Yen , Ho Emily Tse Lin , Koh Angela Fang Yung , Tan Gavin Siew Wei , Shum Eugene Jin Wen , Finkelstein Eric A. , Jafar Tazeen H. , Teoh Yee Leong , van Dam Rob M. , Whitton Clare , Thumboo Julian , Bee Yong Mong
Published: August 2021

Background

Community-based diabetes prevention programs varied widely in effectiveness, and the intervention strategy consisting of lifestyle interventions, stepwise addition of metformin, and financial incentives has not been studied in real-world clinical practice settings. The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) trial is a pragmatic trial that aims to compare the effectiveness of a community-based stepwise diabetes prevention program with added financial incentives (intervention) versus the standard of care (control) in reducing the risk of type 2 diabetes over 3 years among overweight or obese individuals with pre-diabetes.

Methods

This is an open-label, 1:1 randomized controlled trial which aims to recruit 846 adult individuals with isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or both IFG and IGT from Singapore. Intervention arm participants attend 12 group-based sessions (2 nutrition workshops, 9 exercise sessions, and a goal-setting workshop) delivered at community sites (weeks 1 to 6), receive weekly physical activity and nutrition recommendations delivered by printed worksheets (weeks 7 to 12), and receive monthly health tips delivered by text messages (months 4 to 36). From month 6 onwards, intervention arm participants who remain at the highest risk of conversion to diabetes are prescribed metformin. Intervention arm participants are also eligible for a payment/rewards program with incentives tied to attendance at the group sessions and achievement of the weight loss target (5% of baseline weight). All participants are assessed at baseline, month 3, month 6, and every 6 months subsequently till month 36. The primary endpoint is the proportion of participants with diabetes at 3 years. Secondary endpoints include the mean change from baseline at 3 years in fasting plasma glucose, 2-hour plasma glucose, HbA1c, body weight, body mass index, physical activity, and dietary intake.

Discussion

The Pre-DICTED trial will provide evidence of the effectiveness and feasibility of a community-based stepwise diabetes prevention program with added financial incentives for individuals with pre-diabetes in Singapore. The study will provide data for a future cost-effectiveness analysis, which will be used to inform policymakers of the value of a nationwide implementation of the diabetes prevention program.

Trial registration

ClinicalTrials.govNCT03503942. Retrospectively registered on April 20, 2018.

Protocol version: 5.0 Date: 1 March 2019
An epidemiological survey of Dirofilaria spp. and Acanthocheilonema spp. in dogs from the Republic of Moldova
Authors: Dumitrache Mirabela Oana , D’Amico Gianluca , Voiniţchi Eugeniu , Maximenco Serghei , Mircean Viorica , Ionică Angela Monica
Published: August 2021

Background

During the last decades, filarial infections caused by Dirofilaria spp. have spread rapidly within dog populations of several European countries. Increasing scientific interest in filariasis, and the availability of new diagnostic tools, has led to improved knowledge of the biology, morphology, and epidemiology of different species of filarial worms. However, data are still scarce for a number of countries, including the Republic of Moldova. Thus, we assessed the epidemiological status of canine filariasis in the Republic of Moldova to address part of this knowledge gap.

Methods

A total of 120 blood samples were collected between June 2018 and July 2019 from dogs originating from the cities of Cahul and Chişinău. The samples were examined microscopically, and multiplex polymerase chain reaction was performed to evaluate filarioid species diversity.

Results

Microscopic examination revealed that 12 dogs (10.0%) were positive for circulating microfilariae. The molecular test showed that one dog was positive for Acanthocheilonema reconditum (0.8%), one for Dirofilariaimmitis (0.8%), six for Dirofilariarepens (5.0%), and four (3.3%) harboured a co-infection with D. immitis and D. repens. Prevalence was significantly higher in dogs aged ≥ 2 years.

Conclusions

The epidemiological survey presented here for the Republic of Moldova confirmed the presence D. immitis, D. repens and A. reconditum in dogs that had not received any heartworm preventive.

Graphical abstract
Trabecular bone texture analysis of conventional radiographs in the assessment of knee osteoarthritis: review and viewpoint
Authors: Almhdie-Imjabbar Ahmad , Podsiadlo Pawel , Ljuhar Richard , Jennane Rachid , Nguyen Khac-Lan , Toumi Hechmi , Saarakkala Simo , Lespessailles Eric
Published: August 2021

Background

Trabecular bone texture analysis (TBTA) has been identified as an imaging biomarker that provides information on trabecular bone changes due to knee osteoarthritis (KOA). Consequently, it is important to conduct a comprehensive review that would permit a better understanding of this unfamiliar image analysis technique in the area of KOA research.

We examined how TBTA, conducted on knee radiographs, is associated to (i) KOA incidence and progression, (ii) total knee arthroplasty, and (iii) KOA treatment responses. The primary aims of this study are twofold: to provide (i) a narrative review of the studies conducted on radiographic KOA using TBTA, and (ii) a viewpoint on future research priorities.

Method

Literature searches were performed in the PubMed electronic database. Studies published between June 1991 and March 2020 and related to traditional and fractal image analysis of trabecular bone texture (TBT) on knee radiographs were identified.

Results

The search resulted in 219 papers. After title and abstract scanning, 39 studies were found eligible and then classified in accordance to six criteria: cross-sectional evaluation of osteoarthritis and non-osteoarthritis knees, understanding of bone microarchitecture, prediction of KOA progression, KOA incidence, and total knee arthroplasty and association with treatment response. Numerous studies have reported the relevance of TBTA as a potential bioimaging marker in the prediction of KOA incidence and progression. However, only a few studies have focused on the association of TBTA with both OA treatment responses and the prediction of knee joint replacement.

Conclusion

Clear evidence of biological plausibility for TBTA in KOA is already established. The review confirms the consistent association between TBT and important KOA endpoints such as KOA radiographic incidence and progression. TBTA could provide markers for enrichment of clinical trials enhancing the screening of KOA progressors. Major advances were made towards a fully automated assessment of KOA.
Gut microbiota influence in type 2 diabetes mellitus (T2DM)
Authors: Cunningham A. L. , Stephens J. W. , Harris D. A.
Published: August 2021

A strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.
Implanted subcutaneous versus intraperitoneal bioscaffold seeded with hepatocyte-like cells: functional evaluation
Authors: Fares Amal Elham , Gabr Hala , ShamsEldeen Asmaa Mohammed , Farghali Haithem A. M. , Rizk Mazen Mohamed Salem Mohamed , Mahmoud Bassem Essam , Tammam Ahmed Bakr Ahmed , Mahmoud Ayman Magdy Ahmed , Suliman Alaa Abdulfattah Mahmoud , Ayyad Mohamed Abdelhamid Ali , Ahmed Sahar Hassan , Hassan Rokia Mohamad
Published: August 2021

Background and objectives

The X-linked bleeding disorder, hemophilia A, is caused by defective production of factor VIII (FVIII). Hemophilic patients require regular FVIII infusions. Recombinant factor replacement poses the safest line of therapy. However, its main drawbacks are high expenses and the higher liability for formation of inhibitors. Recent studies confirmed the ability of bone marrow-derived stem cells to secrete FVIII. This study aims to generate bioscaffold from decellularized liver and subsequently seed it with trans-differentiated human stem cells into hepatic-like cells. This scaffold can then be implanted intraperitoneally or subcutaneously to provide FVIII.

Methods

After generation of the bioscaffold, seeding of discoid scaffolds with trans-differentiated human hepatocyte-like cells was performed. Then, the generated organoid was implanted into peritoneal cavity or subcutaneous tissue of experimental rats.

Results

Serum human FVIII was significantly increased in rats subjected to subcutaneous implantation compared intraperitoneal implantation. Immunostaining for detecting Cytokeratin 19 and human anti-globulin confirmed the presence of mature human hepatocytes that were significantly increased in subcutaneous implanted scaffold compared to the intraperitoneal one.

Conclusion

Implantation of decellularized bioscaffold seeded with trans-differentiated stem cells in rats was successful to establish production of FVIII. Subcutaneous implantation showed higher FVIII levels than intraperitoneal implantation.
Applications of Orlicz–Pettis theorem in vector valued multiplier spaces of generalized weighted mean fractional difference operators
Authors: Raj Kuldip , Jasrotia Swati , Mursaleen M.
Published: August 2021

In this study, we deal with some new vector valued multiplier spaces$S_{G_{h}}(\sum_{k}z_{k})$SGh(∑kzk)and$S_{wG_{h}}(\sum_{k}z_{k})$SwGh(∑kzk)related with$\sum_{k}z_{k}$∑kzkin a normed spaceY. Further, we obtain the completeness of these spaces via weakly unconditionally Cauchy series inYand$Y^{*}$Y∗. Moreover, we show that if$\sum_{k}z_{k}$∑kzkis unconditionally Cauchy inY, then the multiplier spaces of$G_{h}$Gh-almost convergence and weakly$G_{h}-$Gh−almost convergence are identical. Finally, some applications of the Orlicz–Pettis theorem with the newly formed sequence spaces and unconditionally Cauchy series$\sum_{k}z_{k}$∑kzkinYare given.
“… I would have left that man long time ago but, …” exploring circumstances of and motivators for repeat adolescent birth in Eastern Uganda
Authors: Amongin Dinah , Kaharuza Frank , Hanson Claudia , Nakimuli Annettee , Mutesi Susan , Benova Lenka , Atuyambe Lynn
Published: August 2021

Background

First birth before 18 years has declined in Uganda unlike repeat adolescent birth (=second or more births before age 20 years). We explored the circumstances of and motivators for repeat adolescent birth in Eastern Uganda.

Methods

Between January and March 2020, we conducted a qualitative study involving 70 individual in-depth interviews with purposively selected respondents - 20-25-year-old women with and without repeat adolescent birth, their partners, and parents, in the communities of Teso sub-region. We conducted latent content analysis.

Results

Four major themes emerged: poverty, vulnerability, domestic violence, and demotivators. Sub-themes identified under poverty were: “limited provisions”, “peasantry”, “large families”, “dropping out of school”, “alcohol abuse”, and “broken family structure”. Vulnerability included “marital entrapment” and “partner coercion”. Demotivators included: “abandonment”, “stern warning”, “objection to marriage”, and “empowerment”. Extreme poverty resulted in inadequate provision of basic needs leading to unprotected sexual activity in a bid to secure financial support. Following the first birth, more than three quarters of the women with repeat adolescent birth reported increased economic distress that forced them to remain in unwanted marriage/union, often characterized by partner coercion, despite wanting to delay that repeat birth. Women without repeat adolescent birth avoided a second birth by empowerment through: an economic activity, contraception use, and resumption of schooling.

Conclusion

Repeat adolescent birth in Uganda is premised around attempts to address the economic distress precipitated by first birth. Many women want to delay that repeat birth but the challenges robbed them of their reproductive autonomy. Beyond efforts to prevent first birth, programs need to address economic empowerment, ensure contraceptive access, and school re-integration for adolescent mothers in order to prevent shortly-spaced repeat births.
Fluctuations in barriers to medication treatment for opioid use disorder prescribing over the course of a one-year external facilitation intervention
Authors: Gustavson Allison M. , Kenny Marie E. , Wisdom Jennifer P. , Salameh Hope A. , Ackland Princess E. , Gordon Adam J. , Hagedorn Hildi J.
Published: August 2021

Background

The Veterans Health Administration (VHA) is invested in expanding access to medication treatment for opioid use disorder (MOUD) to save lives. Access varies across VHA facilities and, thus, requires implementation strategies to promote system-wide adoption of MOUD. We conducted a 12-month study employing external facilitation that targeted MOUD treatment among low-adopting VHA facilities. In this study, we sought to evaluate the patterns of perceived barriers over 1 year of external implementation facilitation using the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework.

Methods

We randomly selected eight VHA facilities from the bottom quartile of the proportion of Veterans with an OUD diagnosis receiving MOUD (< 21%). The 1-year external implementation intervention included developmental evaluation to tailor the facilitation, an on-site visit, and monthly facilitation calls. Facilitators recorded detailed notes for each call on a structured template. Qualitative data was analyzed by coding and mapping barriers to the constructs in the i-PARIHS framework (Innovation, Recipients, Context). We identified emerging themes within each construct by month.

Results

Barriers related to the Innovation, such as provider perception of the need for MOUD in their setting, were minimal throughout the 12-month study. Barriers related to Recipients were predominant and fluctuated over time. Recipient barriers were common during the initial months when providers did not have the training and waivers necessary to prescribe MOUD. Once additional providers (Recipients) were trained and waivered to prescribe MOUD, Recipient barriers dropped and then resurfaced as the facilities worked to expand MOUD prescribing to other clinics. Context barriers, such as restrictions on which clinics could prescribe MOUD and fragmented communication across clinics regarding the management of patients receiving MOUD, emerged more prominently in the middle of the study.

Conclusions

VHA facilities participating in 12-month external facilitation interventions experienced fluctuations in barriers to MOUD prescribing with contextual barriers emerging after a facilitated reduction in recipient- level barriers. Adoption of MOUD prescribing in low-adopting VHA facilities requires continual reassessment, monitoring, and readjustment of implementation strategies over time to meet challenges. Although i-PARIHS was useful in categorizing most barriers, the lack of conceptual clarity was a concern for some constructs.