bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare service use in paediatric inflammatory bowel disease: a questionnaire on patient and parent care experiences in Germany
Authors: Boerkoel Aletta , Tischler Luisa , Kaul Kalina , Krause Heiko , Stentzel Ulrike , Schumann Stefan , van den Berg Neeltje , de Laffolie Jan ,   CEDNA study group
Published: November 2023

Background

Paediatric inflammatory bowel disease (PIBD) patients require chronic care over the lifespan. Care for these patients is complex, as it is adapted for childrens’ life stages and changing disease activity. Guideline based care for this patient group recommends a multidisciplinary approach, which includes in addition to paediatric gastroenterologists, nutritional and psychological care services. For PIBD patients, a discrepancy between available guideline-based multidisciplinary care and actual care has been found from the provider side, but to what extent patients experience this is unclear.

Objectives

To identify which healthcare services were used and whether socio-demographic, geographic or disease related factors have an influence on health service utilisation.

Methods

A standardised questionnaire (CEDNA) was distributed amongst parents of children aged 0–17 diagnosed with PIBD and adolescents (aged 12–17) with a PIBD. Items related to health service use were analysed, these included specialist care, additional care services, reachability of services and satisfaction with care. Logistic regression models on additional service use were calculated. Service availability and reachability maps were made.

Results

Data was analysed for 583 parent and 359 adolescent questionnaires. Over half of the respondents had Crohn’s Disease (CD, patients n = 186 parents n = 297). Most patients and parents reported their paediatric gastroenterologist as their main care contact (patients 90.5%; parents 93%). Frequently reported additional services were nutritional counselling (patients 48.6%; parents 42.2%) and psychological support (patients 28.1%; parents 25.1%). Nutritional counselling was more frequently reported by CD patients in both the patient (OR 2.86; 95%CI 1.73–4.70) and parent (OR 3.1; 95%CI 1.42–6.71) sample. Of the patients, 32% reported not using any additional services, which was more likely for patients with an illness duration of less than one year (OR 3.42; 95%CI 1.26–9.24). This was also observed for the parent population (OR 2.23; 95%CI 1.13–4.4). The population-based density of specialised paediatric gastroenterologists was not proportionate to the spatial distribution of patients in Germany, which may have an influence on access.

Conclusions

Parents and children reported highly specialised medical care. Multidisciplinary care offers do not reach the entire patient population. Access to multidisciplinary services needs to be ensured for all affected children.
Epidemiologic changes of infectious diseases in the post-SARS era in China, 2004–2018
Authors: Luo Yizhe , Wu Binxiong , Xu Yameng , Ai Lele , Lv Heng , Wu Jiahong , Tan Weilong
Published: November 2023

Objectives

To outline 44 major infectious diseases in the post-SARS (severe acute respiratory syndrome) in China and describe their long-term trends and changes by age, sex, epidemic season, and province.

Background

After the outbreak of severe acute respiratory syndrome (SARS) in 2003, with the change of infectious disease prevention and control system and the improvement of residents’ quality of life, the incidence and mortality of infectious diseases have undergone major changes.

Methods

The data of 44 major infectious diseases in China from 2004 to 2018 were obtained from the monthly analysis report of the China Information System for Disease Control and Prevention (CISDCP) and the Public Health Science Data Center. Joinpoint r regression models were used to examine trends in incidence and mortality for 44 major and important infectious diseases from 2004 to 2018.

Results

From 2004 to 2018, 20,105, 500, 772 patients (10, 306, 546, 523 males and 9, 798, 954, 249 females) were diagnosed with 44 major infectious diseases. The overall incidence of 44 infectious diseases increased significantly from 294.6 per 100,000 people in 2004 to 479.1 per 100,000 people in 2010, with 7.9% APC (95% CI 5.2% -10.7%, P < 0.001), then slowed, and then increased to 561.2 per 100,000 people in 2018, with 1.5% APC (-0.1%—3.2%, P = 0.070). The overall mortality rose significantly, from 0.49 to 1.13 per 100,000 people between 2004 and 2011, with an APC increase of 11.6% (7.7% -15.6%, P < 0.001), and then remained stable until 2018. Among these, the prevalence of vaccine-preventable diseases and gastrointestinal & enteroviral diseases remained high and increased year by year. Patients with zoonotic diseases have the greatest risk of death, while patients with sexually transmitted and blood-borne diseases have the greatest number of deaths. Incidence rates vary considerably across geographic regions. Western China has a disproportionate burden of infectious diseases compared with eastern regions.

Conclusions

After the event of SARS in 2003, infectious disease preventing and controlling model has undergone major changes in China, and certain achievements have been made in this field. Although overall morbidity and case fatality rates are still rising, they have leveled off. In reducing the disproportionate disease burden in the western region, expanding vaccination programs, preventing further increases in rates of sexually transmitted diseases, renewing efforts for emerging and persistent infectious diseases, and addressing seasonal and unpredictable outbreaks (such as the COVID-19 pandemic), there are still remain many challenges.
Discovering patterns in outpatient neurology appointments using state sequence analysis
Authors: Biggin Fran , Ashcroft Quinta , Howcroft Timothy , Knight Jo , Emsley Hedley
Published: November 2023

Background

Outpatient services in the UK, and in particular outpatient neurology services, are under considerable pressure with an ever-increasing gap between capacity and demand. To improve services, we first need to understand the current situation. This study aims to explore the patterns of appointment type seen in outpatient neurology, in order to identify potential opportunities for change.

Methods

We use State Sequence Analysis (SSA) on routinely collected data from a single neurology outpatient clinic. SSA is an exploratory methodology which allows patterns within sequences of appointments to be discovered. We analyse sequences of appointments for the 18 months following a new appointment. Using SSA we create groups of similar appointment sequence patterns, and then analyse these clusters to determine if there are particular sequences common to different diagnostic categories.

Results

Of 1315 patients 887 patients had only one appointment. Among the 428 patients who had more than one appointment a 6 monthly cycle of appointments was apparent. SSA revealed that there were 11 distinct clusters of appointment sequence patterns. Further analysis showed that there are 3 diagnosis categories which have significant influence over which cluster a patient falls into: seizure/epilepsy, movement disorders, and headache.

Conclusions

Neurology outpatient appointment sequences show great diversity, but there are some patterns which are common to specific diagnostic categories. Information about these common patterns could be used to inform the structure of future outpatient appointments.
Axonal polyneuropathy and ataxia in children: consider Perrault Syndrome, a case report
Authors: Munson Hannah E. , De Simone Lenika , Schwaede Abigail , Bhatia Avanti , Mithal Divakar S. , Young Nancy , Kuntz Nancy , Rao Vamshi K.
Published: November 2023

Background

Perrault Syndrome (PRLTS) is a rare, autosomal recessive disorder that presents with bilateral sensorineural hearing loss in all patients and gonadal dysfunction in females. It has been linked to variants in CLPP, ERAL1, HARS2, HSD17B4, LARS2, and TWNK genes. All reported cases due to TWNK variants have included neurologic features, such as ataxia and axonal sensorimotor neuropathy.

Case presentation

A 4.5-year-old female presented to neuromuscular clinic due to ataxia. Neurological examination revealed truncal ataxia and steppage gait, reduced deep tendon reflexes, and axonal sensorimotor polyneuropathy. Auditory brainstem response testing revealed an uncommon type of sensorineural hearing loss known as auditory neuropathy/auditory synaptopathy (AN/AS) affecting both ears. Magnetic Resonance Imaging (MRI) revealed subtle cauda equina enhancement. Nerve conduction studies led to a provisional diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), and intravenous immune globulin (IVIG) was initiated. The patient was unresponsive to treatment, thus whole exome testing (WES) was conducted in tandem with IVIG weaning. WES revealed a compound heterozygous state with two variants in the TWNK gene and a diagnosis of Perrault Syndrome was made.

Conclusions

Perrault Syndrome should be considered in the differential for children who present with bilateral sensorineural hearing loss, axonal polyneuropathy, and ataxia. Further examination includes testing for ovarian dysgenesis and known PRLTS genetic variants.
RB1 screening of retinoblastoma patients in Sri Lanka using targeted next generation sequencing (NGS) and gene ratio analysis copy enumeration PCR (GRACE-PCR)
Authors: Kugalingam Nirosha , De Silva Deepthi , Abeysekera Hiranya , Nanayakkara Sriyani , Tirimanne Shamala , Ranaweera Dinali , Suravajhala Prashanth , Chandrasekharan Vishvanath
Published: November 2023

Background

Retinoblastoma (RB) a tumour affecting those under 5 years, has a prevalence of 1 in 20,000, with around twenty new diagnoses per year in Sri Lanka. Unilateral and bilateral RB presents around 24 and 15 months respectively. Approximately 10% are familial. Systematic genetic testing for germline pathogenic variants of RB1, the only gene associated with an inherited risk of RB, is unavailable in Sri Lanka. Genetic testing optimizes management of affected children and at-risk siblings. This study aimed to develop accessible genetic testing to identify children with a germline pathogenic variant of RB1 in Sri Lanka.

Methods

Targeted next generation sequencing (NGS) for detecting pathogenic sequence variants and Gene Ratio Analysis Copy Enumeration PCR (GRACE-PCR) for detecting RB1 copy number variations (CNVs) were performed for 49 consecutive RB patients treated between 2016 and 2020 at the designated RB care unit, Lady Ridgway hospital, Colombo. Patients (bilateral RB (n = 18; 37%), unilateral n = 31) were recruited following ethical clearance and informed consent.

Results

There were 26 (53%) females. Mean age at diagnosis was 18 months. Thirty-five patients (71%) had undergone enucleation. Germline pathogenic variants of RB1 identified in 22/49 (45%) patients including 18 (37%; 12 bilateral and 6 unilateral) detected by targeted NGS (2 missense, 7 stop gained, 1 splice donor, 8 frameshift variants). Six were previously undescribed, likely pathogenic frameshift variants. Four bilateral RB patients had GRACE-PCR detected CNVs including one whole RB1, two intragenic deletions (exon 12/13; exon 11 and 23) and a partial duplication of exon 27. The only familial case (affected mother and child) shared the duplication. Only 2 of 4 CNVs and 10 of 18 pathogenic variants were confirmed by whole exome sequencing and Sanger sequencing respectively, due to funding limitations.

Conclusions

The study identified pathogenic or likely pathogenic germline RB1 sequence variants and copy number variants in 16/18 (89%) bilateral and 6/31(19%) unilateral cases, which is comparable to worldwide data (10–15% unilateral, 80–85% bilateral). Targeted NGS combined with GRACE-PCR significantly reduce the cost of RB1 testing in Sri Lanka, and may widen access for genetic diagnosis of RB patients in other low and middle income countries.
Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia
Authors: Shin Ji Eun , Kim Soo-Hyun , Kong Mingyu , Kim Hwa-Ryeon , Yoon Sungmin , Kee Kyung-Mi , Kim Jung Ah , Kim Dong Hyeon , Park So Yeon , Park Jae Hyung , Kim Hongtae , No Kyoung Tai , Lee Han-Woong , Gee Heon Yung , Hong Seunghee , Guan Kun-Liang , Roe Jae-Seok , Lee Hyunbeom , Kim Dong-Wook , Park Hyun Woo
Published: November 2023

Background

Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML.

Methods

We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients.

Results

We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3− patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models.

Conclusion

Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.

Graphical Abstract
The association between triglyceride-glucose index and cognitive function in nondiabetic elderly: NHANES 2011–2014
Authors: Wei Baojian , Dong Qianni , Ma Jinlong , Zhang Aihua
Published: November 2023

Background

The relationship between Insulin resistance (IR) evaluated through homeostasis model assessment insulin resistance (HOMA-IR) and cognitive function is controversial among nondiabetic individuals. No study so far has reported the association between the IR evaluated through triglyceride glucose (TyG) index and cognitive function among nondiabetics. This study aims to assess this association among US nondiabetic older elderly.

Methods

Data were obtained from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Low cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease Battery for immediate word list learning (CERAD-WL) and delayed recall (CERAD-DR) test, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Logistic regression analyses were conducted to compute the odds ratio (OR) and 95% confidential interval (CI) to examine the association between the TyG index (continuous and quartiles) and low cognitive function.

Results

A total of 661 nondiabetic older adults were included with a mean age of 68.62 ± 6.49 years. Compared to the 1st quartile of the TyG index, participants in the TyG index 4th quartile were associated with low cognitive function evaluated through the CERAD test (CERAD-WL and CERAD-DR) [OR: 2.62; 95% CI (1.31, 5.23); P < 0.05]. Subgroup analyses showed that females (ORQ4 VS Q1: 3.07; 95% CI (1.04, 9.05); P < 0.05) and smokers (OR Q4 VS Q1: 2.70; 95% CI (1.01, 7.26); P < 0.05) categories were related with a higher risk of low cognitive function.

Conclusions

A high TyG index was strongly correlated with low cognitive function evaluated through the CERAD test (CERAD-WL and CERAD-DR) among US nondiabetic older women. The management of IR in women might be beneficial to primarily prevent low cognitive function among nondiabetic older elderly.
Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect
Authors: Siak Pui Yan , Heng Win Sen , Teoh Sharon Siew Hoon , Lwin Yu Yu , Cheah Shiau-Chuen
Published: November 2023

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high propensity for lymphatic spread and distant metastasis. It is prominent as an endemic malignancy in Southern China and Southeast Asia regions. Studies on NPC pathogenesis mechanism in the past decades such as through Epstein Barr Virus (EBV) infection and oncogenic molecular aberrations have explored several potential targets for therapy and diagnosis. The EBV infection introduces oncoviral proteins that consequently hyperactivate many promitotic pathways and block cell-death inducers. EBV infection is so prevalent in NPC patients such that EBV serological tests were used to diagnose and screen NPC patients. On the other hand, as the downstream effectors of oncogenic mechanisms, the promitotic pathways can potentially be exploited therapeutically. With the apparent heterogeneity and distinct molecular aberrations of NPC tumor, the focus has turned into a more personalized treatment in NPC. Herein in this comprehensive review, we depict the current status of screening, diagnosis, treatment, and prevention in NPC. Subsequently, based on the limitations on those aspects, we look at their potential improvements in moving towards the path of precision medicine. The importance of recent advances on the key molecular aberration involved in pathogenesis of NPC for precision medicine progression has also been reported in the present review. Besides, the challenge and future outlook of NPC management will also be highlighted.
Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of juvenile idiopathic arthritis in Canada: a scoping review
Authors: Gheshlaghi Niloofar , Thomas Megan , Trehan Natasha , Harrison Mark , De Vera Mary A.
Published: November 2023

Background

Juvenile Idiopathic Arthritis (JIA) is the most common form of childhood inflammatory arthritis. The disease burden of JIA is substantial as patients require specialized medical practitioners for diagnosis and chronic treatments that are both costly and time intensive. Discrepancies in access to care due to health inequities such as socioeconomic status or geographic location may lead to vastly different health outcomes. As research informs advances in care, is important to consider inclusion and diversity in JIA research.

Methods

We reviewed and synthesized randomized controlled trials for juvenile idiopathic arthritis, the most common type of arthritis among children and adolescents, in Canada with the aim of characterizing participants and identifying how determinants of health inequities are reported. To do so, we searched Medline (1990 to July 2022), Embase (1990 to July 2022), and CENTRAL (inception to July 2022) for articles meeting all of the following criteria: Canadian randomized controlled trials evaluating pharmacological or non-pharmacological interventions on juvenile idiopathic arthritis populations. Data extraction was guided by the Campbell and Cochrane Equity Methods Group’s PROGRESS-Plus framework on determinants that lead to health inequities (e.g., Place of residence; Race; Occupation; Gender/Sex; Religion; Education; Socioeconomic status; and Social capital).

Results

Of 4,074 unique records, 5 were deemed eligible for inclusion. From these determinants of health inequities, Gender/Sex and Age were the only that were reported in all studies with most participants being female and 12.6 years old on average. In addition, Race, Socioeconomic status, Education and Features of relationships were each reported once in three different studies. Lastly, Place of residence, Occupation, Religion, Social Capital and Time-dependent relationships were not reported at all.

Conclusions

This scoping review suggests limited reporting on determinants of health inequities in randomized controlled trials for JIA in Canada and a need for a reporting framework that reflects typical characteristics of juvenile patient populations.
Heterogeneous deposition of regular and mentholated little cigar smoke in the lungs of Sprague-Dawley rats
Authors: Lin Kaisen , Wallis Christopher , Wong Emily M. , Edwards Patricia , Cole Austin , Van Winkle Laura , Wexler Anthony S.
Published: November 2023

Background

Quantifying the dose and distribution of tobacco smoke in the respiratory system is critical for understanding its toxicity, addiction potential, and health impacts. Epidemiologic studies indicate that the incidence of lung tumors varies across different lung regions, suggesting there may be a heterogeneous deposition of smoke particles leading to greater health risks in specific regions. Despite this, few studies have examined the lobar spatial distribution of inhaled particles from tobacco smoke. This gap in knowledge, coupled with the growing popularity of little cigars among youth, underscores the need for additional research with little cigars.

Results

In our study, we analyzed the lobar deposition in rat lungs of smoke particles from combusted regular and mentholated Swisher Sweets little cigars. Twelve-week-old male and female Sprague-Dawley rats were exposed to smoke particles at a concentration of 84 ± 5 mg/m3 for 2 h, after which individual lung lobes were examined. We utilized Inductively Coupled Plasma Mass Spectrometry to quantify lobar chromium concentrations, serving as a smoke particle tracer. Our findings demonstrated an overall higher particle deposition from regular little cigars than from the mentholated ones. Higher particle deposition fraction was observed in the left and caudal lobes than other lobes. We also observed sex-based differences in the normalized deposition fractions among lobes. Animal study results were compared with the multi-path particle dosimetry (MPPD) model predictions, which showed that the model overestimated particle deposition in certain lung regions.

Conclusions

Our findings revealed that the particle deposition varied between different little cigar products. The results demonstrated a heterogenous deposition pattern, with higher particle deposition observed in the left and caudal lobes, especially with the mentholated little cigars. Additionally, we identified disparities between our measurements and the MPPD model. This discrepancy highlights the need to enhance the accuracy of models before extrapolating animal study results to human lung deposition. Overall, our study provides valuable insights for estimating the dose of little cigars during smoking for toxicity research.
Prediction nomogram for coronary artery aneurysms at one month in Kawasaki disease
Authors: Tang Yunjia , Ding Chuxin , Xu Qiuqin , Zhou Wanping , Qin Yiming , Lu Meihua , Lv Haitao
Published: November 2023

Background

Coronary status at one month after Kawasaki disease (KD) onset had a great significance. The present study aimed to establish a prediction model for coronary artery aneurysms (CAA) at one month in children with KD.

Methods

Patients with a diagnosis of KD between May 2017 and Dec 2018 were enrolled as the development cohort to build a prediction model. The model was validated by internal and external validation. Patients between Jan 2019 and Dec 2019 were enrolled as the validation cohort. The adaptive least absolute shrinkage and selection operator (LASSO) was used to select the possible predictors. Receiving operating characteristic curve (ROC), calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. The performance of the Son score was also assessed.

Results

LASSO regression demonstrated that age, sex, and CALs in the acute stage were predictors for CAA at one month. The area under the ROC (AUC) was 0.946 (95% confidence interval: 0.911–0.980) with a sensitivity of 92.5% and a specificity of 90.5%. The calibration curve and the DCA showed a favorable diagnostic performance. The internal and external validation proved the reliability of the prediction model. The AUC of our model and the Son score were 0.941 and 0.860, respectively (P < 0.001).

Conclusion

Our prediction model for CAA at one month after disease onset in KD had an excellent predictive utility.
How is overall survival assessed in randomised clinical trials in cancer and are subsequent treatment lines considered? A systematic review
Authors: Royle Kara-Louise , Meads David , Visser-Rogers Jennifer K. , White Ian R. , Cairns David A.
Published: November 2023

Background

Overall survival is the “gold standard” endpoint in cancer clinical trials. It plays a key role in determining the clinical- and cost-effectiveness of a new intervention and whether it is recommended for use in standard of care. The assessment of overall survival usually requires trial participants to be followed up for a long period of time. In this time, they may stop receiving the trial intervention and receive subsequent anti-cancer treatments, which also aim to extend survival, during trial follow-up. This can potentially change the interpretation of overall survival in the context of the clinical trial. This review aimed to determine how overall survival has been assessed in cancer clinical trials and whether subsequent anti-cancer treatments are considered.

Methods

Two searches were conducted using MEDLINE within OVID© on the 9th of November 2021. The first sought to identify papers publishing overall survival results from randomised controlled trials in eight reputable journals and the second to identify papers mentioning or considering subsequent treatments. Papers published since 2010 were included if presenting or discussing overall survival in the context of treating cancer.

Results

One hundred and thirty-four papers were included. The majority of these were presenting clinical trial results (98, 73%). Of these, 45 (46%) reported overall survival as a (co-) primary endpoint. A lower proportion of papers including overall survival as a (co-) primary endpoint compared to a secondary endpoint were published in recent years. The primary analysis of overall survival varied across the papers. Fifty-nine (60%) mentioned subsequent treatments. Seven papers performed additional analysis, primarily when patients in the control arm received the experimental treatment during trial follow-up (treatment switching).

Discussion

Overall survival has steadily moved from being the primary to a secondary endpoint. However, it is still of interest with papers presenting overall survival results with the caveat of subsequent treatments, but little or no investigation into their effect. This review shows that there is a methodological gap for what researchers should do when trial participants receive anti-cancer treatment during trial follow-up. Future research will identify the stakeholder opinions, on how this methodological gap should be addressed.
Relationship of triglyceride-glucose index with cardiometabolic multi-morbidity in China: evidence from a national survey
Authors: Zhang Zenglei , Zhao Lin , Lu Yiting , Meng Xu , Zhou Xianliang
Published: November 2023

Background

Cardiometabolic multi-morbidity (CMM) is emerging as a global healthcare challenge and a pressing public health concern worldwide. Previous studies have principally focused on identifying risk factors for individual cardiometabolic diseases, but reliable predictors of CMM have not been identified. In the present study, we aimed to characterize the relationship of triglyceride-glucose (TyG) index with the incidence of CMM.

Methods

We enrolled 7,970 participants from the China Health and Retirement Longitudinal Study (CHARLS) and placed them into groups according to quartile of TyG index. The endpoint of interest was CMM, defined as the presence of at least two of the following: stroke, heart disease, and diabetes mellitus. Cox regression models and multivariable-adjusted restricted cubic spline (RCS) curves were used to evaluate the relationship between TyG index and CMM.

Results

In total, 638 (8.01%) incident cases of CMM were recorded among the participants who did not have CMM at baseline (2011) during a median follow-up of 84 months (interquartile range, 20‒87 months). The incidences of CMM for the participants in quartiles (Q) 1–4 of TyG index were 4.22%, 6.12%, 8.78%, and 12.60%, respectively. A fully adjusted Cox model showed that TyG index was closely associated with the incidence of CMM: the hazard ratio (HR) [95% confidence interval (CI)] for each 1.0-unit increment in TyG index for CMM was 1.54 (1.29–1.84); and the HRs (95% CIs) for Q3 and Q4 (Q1 as reference) of the TyG index for CMM were 1.41 (1.05–1.90) and 1.61 (1.18–2.20), respectively. The association of TyG index with the incidence of CMM was present in almost all the subgroups, and persisted in the sensitivity analyses and additional analyses. Multivariable-adjusted RCS analysis revealed a significant dose-response relationship of TyG index with the risk of CMM (overall P < 0.001; non-linear P = 0.129).

Conclusions

We found that a high TyG index is associated with a higher risk of incident CMM. This finding may have significance for clinical practice and facilitate the creation of a personalized prevention strategy that involves monitoring the TyG index.

Graphical Abstract
Epidemiological manifestations and impact of healthcare-associated infections in Libyan national hospitals
Authors: Daw Mohamed Ali , Mahamat Mahamat Hassabarassoul , Wareg Said Emhamed , El-Bouzedi Abdallah H , Ahmed Mohamed Omar
Published: November 2023

Background

Healthcare-associated infection is a serious global problem, particularly in developing countries. In North African countries, comprehensive research on the incidence and effects of such infections is rare. This study evaluated the epidemiology and determined the impact of healthcare-associated infections in Libyan national teaching hospitals.

Methods

A prospective longitudinal study was carried out in Libya’s four largest teaching and referral hospitals (Tripoli Medical Center, Tripoli-Central Hospital, Benghazi Medical Center, and Sabha Medical Center) from November 1, 2021, to October 31, 2022. The epidemiological events and the parameters incorporated in this study were based on the data published by the Libyan Centers for Disease Control. The surveillance was carried out on all patients admitted to the wards of medicine, surgery, intensive care, gynecology & obstetrics, and pediatrics in all four hospitals. Trained staff reviewed the medical records and compared the percentages of patients with healthcare-associated infections. Bio-statistical and multivariable logistic regression analyses were carried out to test the variables associated with healthcare-associated infections and the resulting deaths.

Results

A total of 22,170 hospitalized patients in four hospitals were included in the study. Hospital-acquired infection was reported in 3037 patients (13.7%; 95% CI: 12.9–14.4%). The highest incidence was in Benghazi Medical Center (17.9%; 95% CI: 16.9–18.7%), followed by Sabha Medical Center (14.8%; 95% CI:14.9-16.51%). Surgical site infection was the most prevalent (31.3%), followed by ventilator-associated pneumonia (29.3%), urinary tract infection (26.8%), and bloodstream infection (12.6%). Patients with healthcare-associated infections experienced severe morbidity requiring intervention. New antimicrobial regimens were needed for 1836 patients (93%), and 752 patients (34%) required admission to intensive care. Surgical intervention, respiratory support, and inotropes were also needed as a consequence of HAI events.

Conclusions

The high incidence of healthcare-associated infections in Libyan hospitals should be considered a major problem and a serious burden. This should alert healthcare authorities at the national and hospital levels to the urgent need for preventive and control strategies to combat hospital-acquired infections.
Dengue virus serotype did not contribute to clinical severity or mortality in Taiwan’s largest dengue outbreak in 2015
Authors: Tsai Jih-Jin , Chang Ko , Chen Chun-Hong , Liao Ching-Len , Chen Liang-Jen , Tsai Yan-Yi , Tsai Ching-Yi , Lin Ping-Chang , Hsu Miao-Chen , Liu Li-Teh
Published: November 2023

Background

Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan.

Methods

We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality.

Results

The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death.

Conclusions

Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death.
Blood manganese and non-alcoholic fatty liver disease in a high manganese exposure area in China
Authors: Wu Liping , Lan Yanqi , Yu Ze , Wang Yanhong , Liao Wei , Zhang Guoqiang , Wang Li
Published: November 2023

Background and aims

Manganese (Mn) deficiency and intoxication may affect nonalcoholic fatty liver disease (NAFLD) risk differently. We aimed to explore the association between blood Mn and NAFLD in an area with high Mn exposure in drinking water.

Methods

We conducted a case–control study among 1407 patients with NAFLD and 1774 sex- and age-matched healthy controls in a physical examination population in Zhoushan hospital, Zhejiang province in China. We used the restricted cubic splines method to investigate the dose–response relationship. Logistic regression models were applied to determine the risk of NAFLD, and severity of NAFLD.

Results

The blood Mn concentration was higher in the NAFLD group than in the control group in women (16.1 ± 6.2 μg/L vs. 14.7 ± 6.4 μg/L, P = 0.022) and men (14.5 ± 6.3 μg/L vs. 13.6 ± 6.8 μg/L, P < 0.001). We found an inverted L shape relationship between blood Mn and NAFLD in both women and men. Compared to the lowest quartile, the adjusted odds ratio (OR) and 95% confidence interval (CI) of NAFLD for the highest quartile group was 1.646(1.222,2.217), 1.494(1.082,2.061), and 3.146(1.285,7.701) for the total population, men, and women. The positive relationship was only observed in those with fibrosis-4 score < 1.30 and normal alanine transaminase. Stratified analysis showed an interaction between smoking (P = 0.073), alcohol drinking (P = 0.013), and Mn, with a more prominent effect on the NAFLD in the never-smokers (OR = 2.153, 95% CI 1.408–3.290) and drinkers (OR = 2.596, 95% CI 1.608–4.191).

Conclusion

Higher blood Mn is associated with an elevated NAFLD risk in the high Mn exposure areas, especially in nonsmokers and drinkers. Further studies are needed to verify this result in the areas with high Mn exposure.
Have the psychiatric needs of people seeking gender reassignment changed as their numbers increase? A register study in Finland
Authors: Kaltiala Riittakerttu , Holttinen Timo , Tuisku Katinka
Published: November 2023

Background

The number of people seeking gender reassignment (GR) has increased everywhere and these increases particularly concern adolescents and emerging adults with female sex. It is not known whether the psychiatric needs of this population have changed alongside the demographic changes.

Methods

A register-based follow-up study of individuals who contacted the nationally centralized gender identity services (GIS) in Finland in 1996–2019 (gender dysphoria [GD] group, n = 3665), and 8:1 age and sex-matched population controls (n = 29,292). The year of contacting the GIS was categorized to 5-year intervals (index periods). Psychiatric needs were assessed by specialist-level psychiatric treatment contacts in the Finnish Care Register for Hospital Care in 1994–2019.

Results

The GD group had received many times more specialist-level psychiatric treatment both before and after contacting specialized GIS than had their matched controls. A marked increase over time in psychiatric needs was observed. Among the GD group, relative risk for psychiatric needs after contacting GIS increased from 3.3 among those with the first appointment in GIS during 1996–2000 to 4.6 when the first appointment in GIS was in 2016–2019. When index period and psychiatric treatment before contacting GIS were accounted for, GR patients who had and who had not proceeded to medical GR had an equal risk compared to controls of needing subsequent psychiatric treatment.

Conclusion

Contacting specialized GIS is on the increase and occurs at ever younger ages and with more psychiatric needs. Manifold psychiatric needs persist regardless of medical GR.
Systemic Therapy Update on
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Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update
Authors: Garje Rohan , Rumble R. Bryan , Parikh Rahul A. ,   for the Systemic Therapy Update onLutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer Guideline Expert Panel, Garje Rohan , Rumble R. Bryan , Parikh Rahul , Basu Arnab , Beckemann Katy , Bodei Lisa , Borno Hala , Carducci Michael Anthony , Celano Paul , Emamekhoo Hamid , Hamilton Robert , Herchenhorn Daniel , Hope Thomas A. , Hotte Sebastian J. , Kungel Terry , Loblaw Andrew , Taplin Mary-Ellen , Vapiwala Neha , Wang Peng , Williams James , Wulff-Burchfield Elizabeth , Zhang Tian
Published: November 2023

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the

ASCO Guideline Methodology Manual

. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (
Appendix 1
and
Appendix 2
, online only).
Machine Learning in Spine Surgery: A Narrative Review
Authors: Adida Samuel , Legarreta Andrew D. , Hudson Joseph S. , McCarthy David , Andrews Edward , Shanahan Regan , Taori Suchet , Lavadi Raj Swaroop , Buell Thomas J. , Hamilton D. Kojo , Agarwal Nitin , Gerszten Peter C.
Published: November 2023

Artificial intelligence and machine learning (ML) can offer revolutionary advances in their application to the field of spine surgery. Within the past 5 years, novel applications of ML have assisted in surgical decision-making, intraoperative imaging and navigation, and optimization of clinical outcomes. ML has the capacity to address many different clinical needs and improve diagnostic and surgical techniques. This review will discuss current applications of ML in the context of spine surgery by breaking down its implementation preoperatively, intraoperatively, and postoperatively. Ethical considerations to ML and challenges in ML implementation must be addressed to maximally benefit patients, spine surgeons, and the healthcare system. Areas for future research in augmented reality and mixed reality, along with limitations in generalizability and bias, will also be highlighted.
COVID-19 anxiety and uncertainty of classes: Devastating effect on students’ academic behavior and performance
Authors: Kulal Abhinandan , Rahiman Habeeb Ur
Published: November 2023

Background: The second wave of coronavirus disease 2019 (COVID-19) upsurged the level of anxiety among students and in addition to this, frequent closure of class, switching of teaching and learning to virtual added more agony to academic life. This study aimed to assess the impact of COVID-19 anxiety and uncertainty in class on academic performance moderated through academic behavior. Methods: A structured questionnaire was developed to collect primary data and was distributed to 480 students using a systematic sampling technique. A structured equation model was developed and tested with a few hypotheses to answer the research objectives. A conceptual model was developed with the help of literature in order to understand causal relationship between study variables and tested with the help of the structured equation model. Results: The study results showed that COVID-19 anxiety and uncertainty in classes negatively impacted students’ academic behaviour, which lead to students’ poor performance. The study identified that COVID-19 anxiety and uncertainty of class do not have a direct impact on academic performance; it only has an indirect negative impact on academic performance. Conclusions: It can be concluded that uncertainty of classes during lockdown increased anxiety among students and it negatively impacted the academic behaviour of the students which lead to poor academic performance. The study helps the policymakers of the education sector to uplift the spirit of students in this pandemic situation and motivate the students to keep hope in their future careers; therefore, this study helps to fill that gap by contributing a working model
Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol
Authors: Navti Prerana D. , Fernandes Gasper , Soman Soji , Nikam Ajinkya N. , Kulkarni Sanjay , Birangal Sumit R , Dhas Namdev , Shenoy Gautham G. , Rao Vinay , Koteshwara Kunnatur Balasundara , Mutalik Srinivas
Published: November 2023

Background: In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. Methods: In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Results: Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. Conclusions: TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS.
Exploring students’ performance using lingua franca in science education: a study of grade ten students in Capiz, Philippines
Authors: Diestro Dirk
Published: November 2023

Background Currently global competitiveness is the main thrust of the country’s education department, raising the quality of education in the Philippines has become a priority for government officials, who see it as one way to address other teaching and learning challenges. Hence, this quasi-experimental research aimed to determine the influence of lingua franca-based and English-based instruction on the science performance of Grade ten students. Methods The respondents of this study were forty-six Grade ten students out of the total population of fifty-three. Out of the forty-six respondents, twenty-three students were assigned to the experimental group and were taught using lingua franca-based instruction, and the remaining twenty-three were taught using English-based instruction. A researcher-made test was prepared and underwent validity and reliability tests. Mean was used to determine the science performance of the students, t-Test was used to test the significant difference between the students’ science performance before and after teaching using lingua franca-based instruction and English-based instruction, and Cohen’s d was used to compare two means in determining the effect size. Results It was found that both groups exhibited fairly satisfactory science performance in the pre-test, and in the post-test, the control group reveals satisfactory Science performance while the experimental group shows very satisfactory science performance. No significant difference was determined between the pre-tests of both groups and significant differences were determined between the pre-test and post-test of both groups, and in the post-test of both groups, a large size effect was obtained in using the lingua franca-based medium of instruction on the science performance of the students. Conclusions Hence, the practice of Lingua Franca-based instruction exhibits positive and desirable results in improving the performance of the students.