bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-epileptic Drugs Use and Increased Risk of Stroke: A Systematic Review
Authors: Prasad Gajurel Bikram , Kharel Sanjeev , Bhagat Riwaj , Ghimire Rakesh , Bhusal Kiran , Rijal Divas
Published: January 2024

Background

Antiepileptic drugs (AEDs), the predominant treatment for epilepsy, are also utilised for migraine, neuropathic pain, and bipolar disorders, accounting for 1% of usage among the common population. There is a greater risk of stroke, heart attack, and arrhythmia among AED users particularly those with enzyme-inducing properties.

This systematic review aimed to look into the ischemic stroke risk among AED users, particularly in patients who had never had a cerebrovascular accident before. English-language literature was searched in the databases of PubMed, EMBASE, and Google Scholar between 2000 and 2021. Studies should report the association between AEDs and the ischemic stroke risk. The outcomes for assessing efficacy and safety were: event ratio, hazard ratio, odds ratio, and risk ratio. Seven of the eight studies showed an increased risk of ischemic stroke associated with AEDs among individuals without a history of cardiovascular accidents Phenytoin, sodium valproate, oxcarbamazepine, levetiracetam, phenobarbital, and carbamazepine were all linked to an increased risk of stroke. Adequate data on the association between the duration of AED exposure and stroke was missing.

Key message

Not all AEDs are enzyme inducers. We conclude significant stroke risk with AEDs (mainly enzyme inducers), and dose dependency need to be assessed. The risks and benefits of AEDs should be weighed among the patients, especially with vascular risk factors to limit the risk of ischemic stroke.
Subacute Oral Toxicity Studies of Pankajakasthuri Orthoherb Tablets Formulated for Managing Pain and Inflammation of Joints
Authors: Nair J Hareendran , Nair A Kasthuri , MS Sithara , Sasidharan Shan
Published: January 2024

Objectives

The objective of this investigation was to assess the subacute oral toxicity of the Pankajakasthuri Orthoherb Tablets, a polyherbal formulation used to manage pain and inflammation due to various pathological reasons, including osteoarthrosis, polyarthritis, rheumatoid arthritis, and other chronic degenerative disorders.

Materials and Methods

The subacute toxicity studies of Pankajakasthuri Orthoherb Tablets were conducted using Wistar albino rats of both sexes, according to Organization for Economic Cooperation and Development-approved procedures. In this study, rats were orally administered Pankajakasthuri Orthoherb Tablets daily at doses of 250, 500, and 1000 mg/kg body weight for 28 days. Throughout the study period, general behavior, mortality, and adverse effects were recorded. Body weight, selected hematological and clinical chemistry parameters were determined at the end of the investigation period. Finally, histopathological analysis was performed to determine whether the study drug was inducing any alternations in the vital organs.

Results

Daily administration of Pankajakasthuri Orthoherb Tablets for a continuous 28 days did not record any major toxicity indications. Additionally, no significant variation in food and water consumption, body weight, relative organs and hematology and clinical chemistry parameters was recorded in both sexes compared to the control. Histopathological investigation of the vital organs also revealed normal architecture, which suggests no morphological alterations after the administration of Pankajakasthuri Orthoherb Tablets.

Conclusion

The outcomes of this investigation confirmed that Pankajakasthuri Orthoherb Tablets did not have the potential to induce toxicity signs in the experimental rats. The No observed Adverse Effect Level (NOAEL) for female and male rats of Pankajakasthuri Orthoherb Tablets under these experimental conditions was 500 mg/kg body weight. Based on the NOAEL, the human equivalent dose of the Pankajakasthuri Orthoherb Tablet was calculated at 5.195 g/day.
A Narrative Review of Autism Spectrum Disorder in the Indian Context
Authors: Srivastava Manushi , Srivastava Pradyumn , Dubey Arun Kumar , Srivastava Priya
Published: January 2024

Autism is called “spectrum” disorder because there is a wide variation in the type and the severity of symptoms that people experience. India has a vast population, diverse cultures, and multiple languages, making it crucial to under- stand the unique challenges faced by individuals with autism spectrum disorder in the Indian context. This narrative review explores the current state of knowledge about autism spectrum disorder in the Indian context. Databases such as PubMed, Google Scholar, Sage journals, and other sources were searched with relevant terms for preparing this review. All published literature till January 2023 was studied and those which met the inclusion criteria were included. The resources included were original research articles, review articles, web pages, and book chapters addressing the purpose of the paper. Forty-eight such studies which met the inclusion criteria were included in the study. Results showed that the prevalence of autism varied across different studies in India. The study found advanced paternal age, fetal distress, gestational respiratory infections, labor complications, preterm birth, neonatal jaundice, delayed birth cry, birth asphyxia, late initiation of breastfeeding, neonatal seizures, use of maternal hormonal intervention, and consanguinity as some of the identified risk factors of autism spectrum disorder. Parents and families of children with autism have to go through a complex negative experience, both in the family and the community. This negative experience is further compounded by the lack of awareness and access to appropriate professional help and resources. It can be concluded that there is an urgent need for services that help parents cope with the stress of parenting a child with autism.
Examining Psychological Moderators on Factors Affecting Consumers’ Impulse Buying in Organised Retail Stores
Authors: Singh Deependra , Bajpai Naval , Khandelwal Utkal
Published: January 2024

This research study focuses on examining the role of in-store elements for impelling consumers’ impulse buying in organised retail stores with the presence of consumers’ psychological moderators. The conceptual framework is developed by exploring the theoretical foundations for impulse buying behaviour. For testing the proposed hypotheses, confirmatory factor analysis–structural equation modelling is utilised. This study explains that each predicting factor positively influences consumers’ impulse buying in organised retail stores. This study is a valuable step to analyse consumers’ impulse buying behaviour in organised retail stores through in-store dimensions and consumers’ psychological moderators.
Informing the development of a scoring system for National Health Service Clinical Impact Awards; a Delphi process and simulated scoring exercise
Authors: Abel Gary , Froud Rob , Pitchforth Emma , Treadgold Bethan , Hocking Lucy , Sussex Jon , Elliott Marc , Campbell John
Published: January 2024

Objectives

To establish principles informing a new scoring system for the UK's Clinical Impact Awards and pilot a system based on those principles.

Design

A three-round online Delphi process was used to generate consensus from experts on principles a scoring system should follow. We conducted a shadow scoring exercise of 20 anonymised, historic applications using a new scoring system incorporating those principles.

Setting

Assessment of clinical excellence awards for senior doctors and dentists in England and Wales.

Participants

The Delphi panel comprised 45 members including clinical excellence award assessors and representatives of professional bodies. The shadow scoring exercise was completed by 24 current clinical excellence award assessors.

Main outcome measures

The Delphi panel rated the appropriateness of a series of items. In the shadow scoring exercise, a novel scoring system was used with each of five domains rated on a 0–10 scale.

Results

Consensus was achieved around principles that could underpin a future scoring system; in particular, a 0–10 scale with the lowest point on the scale reﬂecting someone operating below the expectations of their job plan was agreed as appropriate. The shadow scoring exercise showed similar levels of reliability between the novel scoring system and that used historically, but with potentially better distinguishing performance at higher levels of performance.

Conclusions

Clinical excellence awards represent substantial public spending and thus far the deployment of these funds has lacked a strong evidence base. We have developed a new scoring system in a robust manner which shows improvements over current arrangements.
Expanding Women’s Land Rights: Can MGNREGA Help?
Authors: Abraham Dimple Tresa , Neetha N.
Published: January 2024

Expanding women’s ownership of land has remained a challenge despite amendment to inheritance laws towards gender equality on account of gender bias, originating from entrenched patriarchy, hereditary customs and sociocultural norms. This may never change without political will and support from executive arms of related government departments, but innovative interventions may help. The article recommends one such measure drawing upon a multi-state evaluation study, wherein type and proportion of works completed on private lands under the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) were examined with respect to land ownership of beneficiary household by gender. The study found inequality in terms of both number and type of works completed on land owned by women, which largely may be attributable to comparatively lower proportion of women having land in their name. The article advocates affirmative action with respect to MGNREGA works on private lands, which could be a proactive policy push towards expanding women’s land rights.
Social Platform: Key to Market Innovation for Indian Artisans—A Case Study of Chanderi Cluster
Authors: Sharma Anu , Tiwari Ashima , Singh Neha
Published: January 2024

India is a vast country with diverse cultures and crafts. The artisan in this country forms the base of the Indian industry. From the clothes we wear to lifestyle products we use; the artisans play a vital role in our lives. This article talks about the influence of COVID-19 on the Chanderi artisans’ community and how the community survived through pandemic using various digital platforms. The artisans’ behaviour of adapting the new technology for not only selling their products but also to gain knowledge is the core concept of this article.
Co-creation of Value and Social Marketing: Systematic Literature Review and Future Research Agenda
Authors: Azzari Vitor , Mainardes Emerson Wagner , Cristo-Andrade Silveli , Durans Amilson de Araujo , Vale Carliene do , Macedo Carlos Jorge Taborda
Published: January 2024

The objective of this study was to develop a systematic literature review (SLR) on value co-creation and social marketing and propose an agenda for future research. We searched for articles related to the themes of value co-creation and social marketing in Scopus and Web of Science databases. After analysing the articles, we found that an SLR was performed with 19 articles using bibliometric techniques. Three thematic groupings emerged: engagement, cooperation between stakeholders and value co-creation at different levels. In addition, 15 research questions were proposed within these three themes. The findings present a new way of verifying the impacts of social marketing strategies through the value co-creation among the stakeholders involved in the process, benefiting society. Considering that the literature addresses related topics, such as the creation and destruction of value in social marketing, this study sought to develop an SLR on the connection between social marketing and value co-creation.
Analysis of material removal mechanism in nanoscale machining of copper
Authors: Sharma Anuj , Ranjan Prabhat , Roy Tribeni , Shukla Vivekanand
Published: January 2024

In the current study, molecular dynamics modeling and simulation are carried out to analyse mechanisms in tool-workpiece interaction in nanoscale cutting. Various combinations of a/ r ratios for constant r ( r = tool edge radius and a = uncut chip thickness) are considered and different crystal orientations of the workpiece specimen are employed in the nanoscale cutting model. From the simulation, material anisotropy behavior is observed during the nanoscale cutting of copper material. Analysis at the molecular scale reveals that the crystal orientations family {1 1 0}<1 0 0> is hard to machine and the family of crystal planes {1 1 1}<1 1 0> is easiest to cut. While comparing in different crystal planes and directions, it was noticed that the material deformation in nanoscale machining takes place only in slip directions, that is, <1 1 0> family of directions. It is also found that as the uncut chip thickness is decreased, the cutting mechanism changes from shear plane cutting to plowing to sliding in Cu.
Sociodemographic and Clinical Correlates of Subjects Presenting with Complaint of Premature Ejaculation
Authors: Dwivedi Suyash , Tripathi Adarsh , Kar Sujita Kumar , Suvirya Swastika , Nischal Anil , Dalal PK
Published: January 2024

Background:

Premature ejaculation (PE) is a common sexual disorder. The profile of subjects seeking treatment of PE in India has not been reported earlier.

Objective:

To study the sociodemographic and clinical profile of subjects presenting with the complaint of PE.

Material and Methods:

The subjects presenting with the complaints of PE were recruited from a specialty psychosexual OPD in the department of psychiatry of a tertiary care center in North India. The subjects were assessed on semistructured proforma, MINI-International Neuropsychiatric Interview, version 7.0, the Diagnostic and Statistical Manual of Mental Disorders, Premature Ejaculation Diagnostic Tool, Arizona Sexual Experience Scale, Hamilton Rating Scale for Depression, and Hamilton Rating Scale Anxiety, Sexual Health Inventory for Men, and Short Form-36 Health Questionnaire.

Results:

A total of 102 subjects were selected after screening 148 cases attending OPD with the complaints of PE after applying selection criteria. The mean age of the sample was 32.17 years (± 8.11). Most of the subjects were married (80.4%), cohabitating with partners (70.6%) and living in the rural area (53.9%). The mean age of onset was 28.29 years (± 7.83, range 17–53), and the mean duration of illness was 3.87 years (± 5.49, range 0.5–31). Prevalence of sexual, psychiatric, and medical comorbidities was 60.8%, 16.7%, and 29.5%, respectively. Emotional role functioning, energy, and general health were the most adversely affected domains of health-related quality of life.

Conclusion:

Most of the men in this study of PE subjects seeking treatment were married young adults. The individuals typically had moderate to severe PE. Comorbidities are prevalent, and roughly two-thirds of people have another medical, psychiatric, or sexual dysfunction.
Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial
Authors: Luvira Viravarn , Schilling William H. K. , Jittamala Podjanee , Watson James A. , Boyd Simon , Siripoon Tanaya , Ngamprasertchai Thundon , Almeida Pedro J. , Ekkapongpisit Maneerat , Cruz Cintia , Callery James J. , Singh Shivani , Tuntipaiboontana Runch , Kruabkontho Varaporn , Ngernseng Thatsanun , Tubprasert Jaruwan , Abdad Mohammad Yazid , Keayarsa Srisuda , Madmanee Wanassanan , Aguiar Renato S. , Santos Franciele M. , Hanboonkunupakarn Pongtorn , Hanboonkunupakarn Borimas , Poovorawan Kittiyod , Imwong Mallika , Taylor Walter R. J. , Chotivanich Vasin , Chotivanich Kesinee , Pukrittayakamee Sasithon , Dondorp Arjen M. , Day Nicholas P. J. , Teixeira Mauro M. , Piyaphanee Watcharapong , Phumratanaprapin Weerapong , White Nicholas J. ,   the PLATCOV Collaborative Group
Published: January 2024

Brief summary

In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance.

Background

Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries.

Methods

In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021.

Results

In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated.

Interpretation

Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.
Factors associated with SARS-CoV-2 infection in unvaccinated children and young adults
Authors: Silverberg Sarah L. , Shulha Hennady P. , McMillan Brynn , He Guanyuhui , Lee Amy , Márquez Ana Citlali , Bartlett Sofia R. , Gill Vivek , Abu-Raya Bahaa , Bettinger Julie A. , Cabrera Adriana , Coombs Daniel , Gantt Soren , Goldfarb David M. , Sauvé Laura , Krajden Mel , Morshed Muhammad , Sekirov Inna , Jassem Agatha N. , Sadarangani Manish
Published: January 2024

Background and objectives

Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC).

Methods

We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity.

Results

A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups).

Conclusions

SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.
Characterisation, symptom pattern and symptom clusters from a retrospective cohort of Long COVID patients in primary care in Catalonia
Authors: Torrell Gemma , Puente Diana , Jacques-Aviñó Constanza , Carrasco-Ribelles Lucia A. , Violán Concepció , López-Jiménez Tomás , Royano Veronica , Cantón Alba Molina , Medina-Perucha Laura , Rodríguez-Giralt Israel , Berenguera Anna
Published: January 2024

Background

Around 10% of people infected by SARS-COV-2 report symptoms that persist longer than 3 months. Little has been reported about sex differences in symptoms and clustering over time of non-hospitalised patients in primary care settings.

Methods

This is a descriptive study of a cohort of mainly non-hospitalized patients with a persistence of symptoms longer than 3 months from the clinical onset in co-creation with the Long Covid Catalan affected group using an online survey. Recruitment was from March 2020 to June 2021. Exclusion criteria were being admitted to an ICU, < 18 years of age and not living in Catalonia. We focused on 117 symptoms gathered in 18 groups and performed cluster analysis over the first 21 days of infection, at 22–60 days, and ≥ 3 months.

Results

We analysed responses of 905 participants (80.3% women). Median time between symptom onset and the questionnaire response date was 8.7 months. General symptoms (as fatigue) were the most prevalent with no differences by sex, age, or wave although its frequency decreased over time (from 91.8 to 78.3%). Dermatological (52.1% in women, 28.5% in men), olfactory (34.9% women, 20.9% men) and neurocognitive symptoms (70.1% women, 55.8% men) showed the greatest differences by sex. Cluster analysis showed five clusters with a predominance ofTaste & smell(24.9%) andMultisystemicclusters (26.5%) at baseline and_Multisystemic (34.59%)andHeterogeneous (24.0%)at ≥3 months. TheMultisystemiccluster was more prevalent in men. TheMenstrualcluster was the most stable over time, while most transitions occurred from theHeterogeneouscluster to theMultisystemiccluster and fromTaste & smelltoHeterogeneous.

Conclusions

General symptoms were the most prevalent in both sexes at three-time cut-off points. Major sex differences were observed in dermatological, olfactory and neurocognitive symptoms. The increase of theHeterogeneouscluster might suggest an adaptation to symptoms or a non-specific evolution of the condition which can hinder its detection at medical appointments. A carefully symptom collection and patients’ participation in research may generate useful knowledge about Long Covid presentation in primary care settings.
A randomised phase II trial of temozolomide with or without cannabinoids in patients with recurrent glioblastoma (ARISTOCRAT): protocol for a multi-centre, double-blind, placebo-controlled trial
Authors: Bhaskaran Divyalakshmi , Savage Joshua , Patel Amit , Collinson Fiona , Mant Rhys , Boele Florien , Brazil Lucy , Meade Sara , Buckle Peter , Lax Siân , Billingham Lucinda , Short Susan C.
Published: January 2024

Background

Glioblastoma (GBM) is the most common adult malignant brain tumour, with an incidence of 5 per 100,000 per year in England. Patients with tumours showing O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation represent around 40% of newly diagnosed GBM. Relapse/tumour recurrence is inevitable. There is no agreed standard treatment for patients with GBM, therefore, it is aimed at delaying further tumour progression and maintaining health-related quality of life (HRQoL). Limited clinical trial data exist using cannabinoids in combination with temozolomide (TMZ) in this setting, but early phase data demonstrate prolonged overall survival compared to TMZ alone, with few additional side effects. Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray containing a blend of cannabis plant extracts, that we aim to assess for preliminary efficacy in patients with recurrent GBM.

Methods

ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to assess cannabinoids in patients with recurrent MGMT methylated GBM who are suitable for treatment with TMZ. Patients who have relapsed ≥ 3 months after completion of initial first-line treatment will be randomised 2:1 to receive either nabiximols or placebo in combination with TMZ. The primary outcome is overall survival time defined as the time in whole days from the date of randomisation to the date of death from any cause. Secondary outcomes include overall survival at 12 months, progression-free survival time, HRQoL (using patient reported outcomes from QLQ-C30, QLQ-BN20 and EQ-5D-5L questionnaires), and adverse events.

Discussion

Patients with recurrent MGMT promoter methylated GBM represent a relatively good prognosis sub-group of patients with GBM. However, their median survival remains poor and, therefore, more effective treatments are needed. The phase II design of this trial was chosen, rather than phase III, due to the lack of data currently available on cannabinoid efficacy in this setting. A randomised, double-blind, placebo-controlled trial will ensure an unbiased robust evaluation of the treatment and will allow potential expansion of recruitment into a phase III trial should the emerging phase II results warrant this development.

Trial registration

ISRCTN: 11460478. ClinicalTrials.Gov: NCT05629702.
Novel model integrating computed tomography-based image markers with genetic markers for discriminating radiation pneumonitis in patients with unresectable stage III non-small cell lung cancer receiving radiotherapy: a retrospective multi-center radiogenomics study
Authors: Li Jiaran , Li Li , Tang Shanshan , Yu Qingxi , Liu Wenju , Liu Ning , Yang Fengchang , Zhang Dexian , Yuan Shuanghu
Published: January 2024

Background

Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC.

Methods

In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively.

Results

The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram.

Conclusion

Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.
Biochemical profiles and organ dysfunction in neonates with hypoxic-ischemic encephalopathy post-hoc analysis of the THIN trial
Authors: Francke Karen Haugvik , Støen Ragnhild , Thomas Niranjan , Aker Karoline
Published: January 2024

Background

Therapeutic hypothermia for infants with moderate to severe hypoxic-ischemic encephalopathy is well established as standard of care in high-income countries. Trials from low- and middle-income countries have shown contradictory results, and variations in the level of intensive care provided may partly explain these differences. We wished to evaluate biochemical profiles and clinical markers of organ dysfunction in cooled and non-cooled infants with moderate/severe hypoxic-ischemic encephalopathy.

Methods

This secondary analysis of the THIN (Therapeutic Hypothermia in India) study, a single center randomized controlled trial, included 50 infants with moderate to severe hypoxic-ischemic encephalopathy randomized to therapeutic hypothermia (n = 25) or standard care with normothermia (n = 25) between September 2013 and October 2015. Data were collected prospectively and compared by randomization groups. Main outcomes were metabolic acidosis, coagulopathies, renal function, and supportive treatments during the intervention.

Results

Cooled infants had lower pH than non-cooled infants at 6–12 h (median (IQR) 7.28 (7.20–7.32) vs 7.36 (7.31–7.40), respectively, p = 0.003) and 12–24 h (median (IQR) 7.30 (7.24–7.35) vs 7.41 (7.37–7.43), respectively, p < 0.001). Thrombocytopenia (< 100 000) was, though not statistically significant, twice as common in cooled compared to non-cooled infants (4/25 (16%) and 2/25 (8%), respectively, p = 0.67).

No significant difference was found in the use of vasopressors (14/25 (56%) and 17/25 (68%), p = 0.38), intravenous bicarbonate (5/25 (20%) and 3/25 (12%), p = 0.70) or treatment with fresh frozen plasma (10/25 (40%) and 8/25 (32%), p = 0.56)) in cooled and non-cooled infants, respectively. Urine output < 1 ml/kg/h was less common in cooled infants compared to non-cooled infants at 0–24 h (7/25 (28%) vs. 16/23 (70%) respectively, p = 0.004).

Conclusions

This post hoc analysis of the THIN study support that cooling of infants with hypoxic-ischemic encephalopathy in a level III neonatal intensive care unit in India was safe. Cooled infants had slightly lower pH, but better renal function during the first day compared to non-cooled infants. More research is needed to identify the necessary level of intensive care during cooling to guide further implementation of this neuroprotective treatment in low-resource settings.

Trial registration

Data from this article was collected during the THIN-study (Therapeutic Hypothermia in India; ref. CTRI/2013/05/003693 Clinical Trials Registry – India).
The role of cadre in the community on diabetic retinopathy management and its challenges in low-middle income countries: a scoping review
Authors: Sadikin Irma Suwandi , Lestari Yeni Dwi , Victor Andi Arus
Published: January 2024

Introduction

Diabetes is a serious public health problem, with low- and middle-income countries (LMICs) bearing over 80% of the burden. Diabetic retinopathy (DR) is one of the most prevalent diabetic microvascular problems, and early diagnosis through eye screening programs for people with diabetes is critical to prevent vision impairment and blindness. Community-based treatments, including non-physician cadres have been recommended to enhance DR care.

Methods

The review protocol was determined and scoping review was conducted.The population, concept, and context were “cadre”, “role of cadre in the management of DR”, and LMICs”. Data were collected from databases and searches, including grey literature.

Results

Cadre can motivate people to attend a diabetic eye screening event when the rate of eye examinations is about six times higher than before the start of the intervention. Health education is a possible area for task sharing, and the cadre reported could also perform the task of vision testing. The cadre could be a good supporter and a good reminder for society. However, several challenges have been faced in this study and inadequate infrastructure is the foremost challenge found in this study. Other challenges encountered in the studies include poverty, lack of community awareness, trust issues, and low education levels contributing to poor health.

Conclusion

The current study highlighted significant gaps in the literature, which focus on the role of cadre as a community-based intervention in managing DR in LMICs. Further research is needed to develop evidence to support cost-effective screening services and cadre-related policy development in LMICs.
Gender differences in long term sickness absence
Authors: Timp Sheila , van Foreest Nicky , Roelen Corné
Published: January 2024

Purpose

Sickness absence is a major public health problem, given its high cost and negative impact on employee well-being. Understanding sickness absence duration and recovery rates among different groups is useful to develop effective strategies for enhancing recovery and reducing costs related to sickness absence.

Methods

Our study analyzed data from a large occupational health service, including over 5 million sick-listed employees from 2010 to 2020, out of which almost 600,000 cases were diagnosed by an occupational health physician. We classified each case according to diagnosis and gender, and performed descriptive statistical analysis for each category. In addition, we used survival analysis to determine recovery rates for each group.

Results

Mean sickness duration and recovery rate both differ significantly among groups. Mental and musculoskeletal disorders had the longest absence duration. Recovery rates differed especially during the first months of sickness absence. For men the recovery rate was nearly constant during the first 1.5 year, for women the recovery rate was relatively low in the first three months, and then stayed nearly constant for 1.5 year.

Conclusion

Across almost all diagnostic classes, it was consistently observed that women had longer average sickness absence durations than to men. Considering mental disorders and diseases of the musculoskeletal system, women had relatively lower recovery rates during the initial months compared to men. As time progressed, the recovery rates of both genders converged and became more similar.
Frequency and risk of SARS-CoV-2 reinfections in Norway: a nation-wide study, February 2020 to January 2022
Authors: Bøås Håkon , Storm Margrethe Larsdatter , Tapia German , Kristoffersen Anja Bråthen , Løvlie Astrid Louise , Størdal Ketil , Lyngstad Trude Marie , Bragstad Karoline , Hungnes Olav , Veneti Lamprini
Published: January 2024

Background

SARS-CoV-2 reinfection rates have been shown to vary depending on the circulating variant, vaccination status and background immunity, as well as the time interval used to identify reinfections. This study describes the frequency of SARS-CoV-2 reinfections in Norway using different time intervals and assesses potential factors that could impact the risk of reinfections during the different variant waves.

Methods

We used linked individual-level data from national registries to conduct a retrospective cohort study including all cases with a positive test for SARS-CoV-2 from February 2020 to January 2022. Time intervals of 30, 60, 90 or 180 days between positive tests were used to define potential reinfections. A multivariable Cox regression model was used to assess the risk of reinfection in terms of variants adjusting for vaccination status, demographic factors, and underlying comorbidities.

Results

The reinfection rate varied between 0.2%, 0.6% and 5.9% during the Alpha, Delta and early Omicron waves, respectively. In the multivariable model, younger age groups were associated with a higher risk of reinfection compared to older age groups, whereas vaccination was associated with protection against reinfection. Moreover, the risk of reinfection followed a pattern similar to risk of first infection. Individuals infected early in the pandemic had higher risk of reinfection than individuals infected in more recent waves.

Conclusions

Reinfections increased markedly during the Omicron wave. Younger individuals, and primary infections during earlier waves were associated with an increased reinfection risk compared to primary infections during more recent waves, whereas vaccination was a protective factor. Our results highlight the importance of age and post infection waning immunity and are relevant when evaluating vaccination polices.
Between now and later: a mixed methods study of HPV vaccination delay among Chinese caregivers in urban Chengdu, China
Authors: Yim Vivian Wan-Cheong , Wang Qianyun , Li Yifan , Qin Chuanyun , Tang Weiming , Tang Shenglan , Jit Mark , Smith Jennifer S. , Larson Heidi J. , Tucker Joseph D. , Li Jing , Lin Leesa , Wu Dan
Published: January 2024

Background

Adolescent girls in China have a low HPV vaccination rate. Although vaccination is recommended by the Chinese health authorities, the cost is not covered by the national immunisation programme. Vaccination delay, among other reasons such as supply shortage and poor affordability, may contribute to low uptake. This sequential mixed methods study aimed to identify potential factors of delayed HPV vaccination among Chinese adolescent girls.

Methods

Quantitative data about the attitudes and perceptions of HPV vaccination were collected from 100 caregivers of 14–18-year-old girls using an online survey in Chengdu, China. The survey data informed a subsequent qualitative study using four focus group discussions. We conducted a descriptive analysis of the survey data and a thematic analysis of the qualitative data. The findings were interpreted using a health behaviour model adapted from the Health Belief Model and the Andersen’s Behavioural Model for Health Services Use.

Results

A total of 100 caregivers – 85 were mothers and 15 were fathers – participated in the survey; 21 caregivers joined focus group discussions. When asked about their intended course of action if the 9vHPV vaccine was out-of-stock, 74% chose to delay until the 9vHPV vaccine is available while 26% would consider 2vHPV or 4vHPV vaccines or seek alternative ways to procure the vaccine. Qualitative results confirmed that caregivers preferred delaying HPV vaccination for adolescent girls. The intent to delay was influenced by systemic barriers such as supply shortage and individual-level factors such as a preference for the 9vHPV vaccine, safety concerns, inadequate health communication, and the belief that adolescents were unlikely to be sexually active.

Conclusion

In urban areas, Chinese caregivers’ intent to delay vaccination in favour of 9vHPV vaccine over receiving the more accessible options was influenced by a mix of individual and contextual factors. Focussed health communication strategies are needed to accelerate HPV vaccination among adolescents.
Understanding nursing perspective towards barriers to the optimal delivery of enteral nutrition in intensive care settings
Authors: Zaher Sara , Sumairi Futoon AL. , Ajabnoor Sarah M.
Published: January 2024

Background

The management process of Enteral Nutrition (EN) typically involves the interaction between a team of health care practitioners. Nurses being the closest to the patients, have crucial responsibilities and play a major role in feeding delivery along with other medical treatments. This study was conducted to investigate the perception of the nurses working in adult and paediatric intensive care Units (ICUs) regarding the EN barriers and identify the factors that influenced their perception.

Methods

The data in this cross-sectional study was collected via online survey between 15 October 2021 and January 2022. All nurses working in adult or paediatric ICUs across Saudi Arabia were eligible to participate. The tool used for the data collection was adapted from Cahill et al. (2016) and then reviewed and modified by the researchers. The survey collected information about the demographics of the nurses, and it included 24 potential EN barriers where the participants were asked to rate their importance on a scale from 1 to 5. Descriptive statistics were performed to describe the variables, univariant analysis were performed to compare the perceptions of the nurses regarding the EN barriers based on their characteristics followed by stepwise linear regression analysis.

Results

A total of 136 nurses working in adult and paediatric ICUs were included in this study. The results showed that the most important barriers as perceived by the nurses was “Frequent displacement of feeding tube, requiring reinsertion” [3.29 ± 1.28], “Delays in initiating motility agents in patients not tolerating enteral nutrition” [3.27 ± 1.24] and “Enteral formula not available on the unit”. [3.27 ± 1.24]. Our results showed that the responses of the participants statistically varied based on their work settings, gender, region, and educational level for some items in the survey (P-value ≤ 0.05). In the regression analysis, gender was the only variable statistically influenced the total Likert rating scores of the participants (r = -0.213, p-value = 0.013).

Conclusion

This study identified several barriers that exist in the nursing practice of EN in critical care settings. There are distinct differences in the perception of the nurses to these barriers based on their characteristics. Understanding such differences is important for implementing future strategies for units that needed the most help in prioritizing EN delivery.
Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis
Authors: Totoki Takaaki , Makino Yuto , Yamakawa Kazuma , Koami Hiroyuki , Wada Takeshi , Ito Takashi , Iba Toshiaki
Published: January 2024

Background

Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model.

Method

We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study.

Results

We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43–1.05], OR 0.73 [0.45–1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity.

As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55–2.23], I2 value 55%).

Conclusions

Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results.

Trial registration

This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
Authors: Villacampa Alicia , Alfaro Enrique , Morales Cristina , Díaz-García Elena , López-Fernández Cristina , Bartha José Luis , López-Sánchez Francisco , Lorenzo Óscar , Moncada Salvador , Sánchez-Ferrer Carlos F. , García-Río Francisco , Cubillos-Zapata Carolina , Peiró Concepción
Published: January 2024

Background

Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells.

Methods

In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence.

Results

S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC.

Conclusion

S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element.