Search Results for: Screening per la tubercolosi

Background
The growing global burden of diabetes suggests a currently unrealised growth in prevalence of eye disease. This prospective observational study addresses gaps in evidence of blood sugar control as a risk factor for the diagnosis of glaucoma, diabetic eye disease, macular degeneration and cataract using waves 2–9 (2004–2019) of the English Longitudinal Study of Ageing.

Methods
Logistic regression modelling is used to predict the probability of self-reported diagnosis of four eye conditions separately over a 14-year period in a community-dwelling sample in England. Analysis of approximately 29 000 person observations over eight study waves from around 5600 participants for each eye disease is conducted with an average of 5.7 waves per participant. Participants’ baseline blood sugar control is categorised as non-diabetic (diabetes not previously diagnosed and glycated haemoglobin (HbA1c)

Introduction
Sepsis-induced left ventricular (LV) dysfunction participates in cardiovascular dysfunction and associated organ failure in patients with septic shock. The tested hypothesis is that dobutamine will reduce tissue hypoperfusion and secondary organ dysfunction in increasing oxygen delivery in fluid-filled patients with septic shock and associated symptomatic septic cardiomyopathy with documented low-flow state.

Methods and analysis
ADAPT–Dobutamine is a blinded, two parallel group, add-on, multicentre, randomised 1:1 and placebo-controlled trial. Patients will be included if hospitalised in the intensive care unit with septic shock (Sepsis-3 definition) and septic cardiomyopathy, identified using echocardiography (LV ejection fraction ≤40% and LV outflow tract velocity–time integral 130 bpm, severe ventricular arrhythmia, obstructive cardiomyopathy, severe aortic stenosis, ongoing acute coronary syndrome and indication for extracorporeal life support. Primary outcome will be the evolution of a modified Sequential Organ Failure Assessment score (excluding the neurologic system) during the initial intensive care unit stay encompassing screening (before randomisation), and from Day 1 to 3 after randomisation. Randomisation will be stratified on participating centres and previously documented heart failure (ejection fraction ≤40%). The use of open-labelled Dobutamine as a rescue therapy will be allowed in refractory shock based on strict clinical requirements. The use of alternative inotropes will not be allowed.

Ethics and dissemination
Approved by the Comité de Protection des Personnes Nord-Ouest IV from Lille (France) on 19 December 2019 (approval reference #19.04.05.36321). The results will be published in a peer-reviewed journal and presented in various congresses.

Trial registration number
NCT04166331.

Introduction
Haemostasis, a process involving platelet activation, platelet aggregation and coagulation, poses intricate clinical challenges for clinicians. There remains significant national variability in thromboprophylaxis protocols, which are used in 77–82% of surgical cases in Australia. There is also increasing concern focused on the development of antiplatelet resistance. Given an apparent lack of standardised approaches to haemostasis, these decisions frequently require clinician discretion and can result in suboptimal outcomes. To optimise patient management, all available therapeutic agents should be considered. Current standards may need to be revised accordingly.
Dextrans are polysaccharides with perioperative significance in haemostasis. Although the proposed mechanisms of dextran action are multifactorial, these agents may have a significant impact in cases of trauma, reconstructive surgery, transplantation and vascular surgery. However, a suspected deficit in the quality of the literature, and therefore clinical standardisation, raises concerns for optimal incorporation into practice.
Accordingly, we plan to examine both peer-reviewed articles and ‘grey’ literature that considers the indications, efficacy and complications associated with the clinical use of dextrans to promote haemostasis. The primary objective of this scoping review will be to analyse and map the existing literature on the use of dextrans in both operative and non-operative settings and provide insight that will bridge the current knowledge gap and guide future research initiatives.

Methods and analysis
The study and literature search will be performed in accordance with recommendations adapted for scoping reviews in alignment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews standards. A thorough and systematic investigation will be undertaken across several electronic databases, including EMBASE, the Cochrane Library and MEDLINE; additional studies will be accessed and examined by reference tracking. All relevant research published before 11 March 2024 will be reviewed for appropriateness of inclusion. Two researchers will perform data screening and extraction of relevant information. Study observations will be presented in a descriptive manner using a mixed methods and narrative approach.

Ethics and dissemination
Ethics approval was not required for this study. The results will be disseminated through publication in open-access peer-reviewed journals, established professional networks and conference presentations.

Positività 0,97% e 2,8%, ma va confermata. Verso test nazionale

Positività 0,97% e 2,8%, ma va confermata. Verso test nazionale

Introduction
Though prior trials have shown the effectiveness of community-based hypertension detection and care delivery models, their adoption and translation to practice has been slow. In this study, we will develop and test strategies for the implementation and scale-up of a proven multicomponent hypertension intervention (MCHI) in Pakistan that comprises health education, blood pressure (BP) monitoring and referrals by lady health workers (LHWs) and hypertension management by physicians in primary care settings.

Methods and analysis
In this 24-month hybrid type III implementation-effectiveness cluster-randomised controlled trial, we will recruit 3000 adult hypertensive patients from two rural districts of Pakistan. We will engage public health sector managers, physicians and LHWs and use the Consolidated Framework for Implementation Research to identify barriers and facilitators to the implementation of an already proven-to-be-effective MCHI. Using Expert Recommendations for Implementing Change and the modified Delphi technique, a set of implementation strategies addressing barriers will be identified. The strategies will be categorised as level 1 (requiring a change in processes), level 2 (requiring a change in infrastructure) and level 3 (financial restructuring). Basic health units and 250–300 households from their catchment will be considered as clusters. Clusters will be randomised in a ratio of 1:1 to intervention and control. While MCHI will be offered in both trial arms (intervention and control), the aforementioned implementation strategies will be randomised to the intervention arm only, starting with level 1 and moving to levels 2 and 3 as needed. Baseline and 6-monthly follow-up surveys, each of 6 months duration, will be conducted to collect data from the recruited participants on sociodemographics, cardiovascular disease (CVD) risk factors, CVD-related expenses and quality of life. The primary outcome will be the mean difference in BP-lowering medications per participant between the intervention and control arms. The primary outcome will be analysed using a linear mixed model with fixed effects for baseline value of the outcome. Additional outcomes include implementation outcomes: proportion of LHWs conducting health education, BP screening and monitoring, facility referrals and proportion of physicians diagnosing and treating hypertensive patients; effectiveness outcomes: proportion of participants with controlled BP and improved EQ-5D-5L score.

Ethics and dissemination
Ethical approval has been obtained from the Ethics Review Committee of Aga Khan University Pakistan (ERC # 2023-9084-26739). Findings will be reported to: (1) study participants; (2) funding body and institutes collaborating and supporting the study; (3) provincial and district health departments to inform policy; (4) presented at local, national and international conferences and (5) disseminated by peer-review publications

Trial registration number
NCT06726057.

Introduction
Perinatal care continuity across the full continuum is essential for optimising maternal and infant health; however, a stark gap occurs post partum, with less than one half of Indian mothers receiving postpartum care due to significant logistical and sociocultural barriers, particularly for periurban and rural residents. To overcome these barriers and reduce women’s postpartum isolation, our international team of maternal and infant health clinicians and researchers developed and pilot-tested a culturally-tailored mobile interactive education and support group intervention, Kushal Maa (‘informed-mother’), confirming feasibility and acceptability and preliminary effectiveness. The current study seeks to estimate the effectiveness of the Kushal Maa intervention compared with standard care on maternal and neonatal health-related behaviours and health, characterise the mechanisms of intervention impact and evaluate the cost-effectiveness of the Kushal Maa intervention in improving postpartum maternal and neonatal health compared with the standard of care.

Methods and analysis
We will conduct a prospective, parallel block-randomised controlled trial with a 1:1 allocation ratio among 2100 pregnant women across three geographically diverse Indian states. Inclusion criteria for women: aged 18+years of age at enrolment, in the last trimester of pregnancy (30–33 weeks of gestation), with any parity, carrying single or multiple gestation (1-2), with knowledge of site-specific local language and had access to a mobile phone. Participants will be block-randomised in groups of 15. Intervention participants will receive 28 tailored education and support sessions weekly via audio/video conference facilitated by trained moderators (four prenatal and 24 weekly postpartum sessions through 6 months) and will be engaged in WhatsApp groups for health education videos and peer discussion via text chat. Control participants receive the standard of care. Data will be collected at four points: 30–33 weeks of pregnancy (enrolment), 6 weeks, 3 months and 6 months postpartum (endline). Investigators, outcome assessors and data analysts will be blinded to group allocation. Primary outcomes will be measured at 6 weeks, 3 months and 6 months post partum and include: postpartum depression (using Edinburgh Postnatal Depression Scale), exclusive breastfeeding and met need for postpartum family planning. Secondary outcomes include other maternal and child health knowledge, outcomes and maternal and newborn healthcare use indicators. We will use intention-to-treat analysis. Mixed-effects models will account for clustering due to the group-oriented delivery of the intervention and repeated measures.

Ethics and dissemination
This study has been approved by the Health Ministry Screening Committee, Government of India and approved by ethics boards at the Post-Graduate Institute for Medical Education and Research, Chandigarh (Ref:001208, IEC-06/2022–2471), Maharashtra University of Health Sciences (Ref: MUHS/EC/06/2024), Sangath (Ref: AB_2022_81) and the University of California, San Francisco (Ref: 21–35730). All research activities will be performed in accordance with the Declaration of Helsinki. On completion, findings will be disseminated to stakeholders through diverse strategies. Results will be published in academic journals and presented at conferences.

Trial registration number
ClinicalTrials.gov: NCT05268588 Clinical Trials Registry – India: CTRI/2022/07/043889.

Objectives
This scoping review aims to map existing evidence on knowledge, attitudes and practices (KAP) and barriers to preconception care in low- and middle-income countries. The primary objective is to identify key gaps and research priorities to guide future efforts to improve maternal and child health.

Design
This review followed Arksey and O’Malley’s scoping review framework, with a comprehensive search across Medline, EMBASE, CINAHL and Scopus from inception to May 2025. Eligible studies included original research on preconception care (PCC), KAP in low- and middle-income countries (LMICs) without date restrictions. Two independent reviewers conducted screening in Covidence. Findings were presented in graphical, tabular and narrative formats, adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Extension for Scoping Reviews (PRISMA-ScR) standard.

Setting
The review focused on PCC studies conducted in LMICs across various healthcare settings, emphasising primary and secondary levels of care. The geographical scope was global but limited to LMICs as defined by World Bank criteria.

Result
A total of 62 studies were included in the review. Of these, 42 employed quantitative methods, 18 used qualitative approaches and 2 used a mixed-methods design. Regarding focus areas, 25 studies assessed knowledge, 14 assessed practices, 12 studies assessed KAP comprehensively and 10 assessed attitudes. Participants were mainly women of reproductive age (44 studies), with only five studies including men. Among healthcare providers, KAP varied, with midwives being the most frequently studied group. Stakeholders such as policymakers were notably under-represented. Identified barriers included limited training, cultural beliefs and inadequate policies. Facilitators highlighted were targeted education, spousal support and policy advocacy, emphasising the need for gender-sensitive and systemic interventions.

Conclusion
LMICs face complex challenges in utilising PCC, influenced by socioeconomic, cultural, and healthcare system factors. To address these challenges, nuanced approaches incorporating intersectional perspectives and practical qualitative methodologies are essential for improving couples’ and child health outcomes.

Trial registration number
The study protocol was registered in the Open Science Framework (OSF) on December 23, 2022, with DOI: 10.17605/OSF.IO/H3MK6.

Objectives
This systematic review investigated available evidence on the stand-alone and incremental predictive performance of ophthalmic artery Doppler (OAD) for pre-eclampsia.

Design
Systematic review.

Data sources
We conducted a literature search from PubMed (Medline), the Cochrane CENTRAL, EMBASE and Scopus from inception to 8 April 2025.

Eligibility criteria
Studies eligible for inclusion were prospective or retrospective cohort studies, case-control studies or randomised controlled trials that reported on the predictive performance of OAD for pre-eclampsia in singleton pregnancies; and conducted in either high-income country (HIC) or low- and middle-income country (LMIC).

Data extraction and synthesis
Two reviewers independently screened and assessed articles for inclusion. One reviewer then extracted data using a standardised data extraction sheet, and any uncertainties were discussed with a second reviewer. The Prediction model Risk of Bias Assessment Tool was used for quality and risk of bias assessment. Findings were summarised and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and synthesised qualitatively.

Results
We identified and included 11 observational studies (3 from HIC and 8 from LMICs) with a total of 12 150 singleton pregnancies, of which 517 (4.3%) were complicated by pre-eclampsia at end of follow-up. The included studies were of varied quality, with three at low risk of bias, four at unclear risk and four at high risk. No interventional study was identified. Three studies (27.3%) recruited high-risk pregnancies (defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria as one or more of the following: chronic hypertension, personal or family history of pre-eclampsia, early (≤18 years) or late (≥40 years) first pregnancy, primipaternity, chronic kidney disease, increased body mass index >30 kg/m2, presence of diabetes mellitus prior to pregnancy, autoimmune disease and thrombophilia), while eight studies (72.7%) recruited undetermined risk pregnancies. Stand-alone performance of OAD (interpreted by area under the receiver operating curve at 95% CI) showed that in the first trimester, the peak systolic velocity (PSV) ratio demonstrated very good predictive ability (0.97, 95% CI 0.92 to 1.0) (n=1 study), and the second PSV (PSV2) demonstrated very good predictive ability (0.91, 95% CI 0.82 to 0.99) (n=1 study). Also, PSV2 demonstrated fair predictive ability (0.61, 95% CI 0.42 to 0.79; and 0.53, 95% CI 0.40 to 0.66) for early and late pre-eclampsia, respectively (n=1 study). In the second trimester, the PSV ratio demonstrated very good predictive ability (0.88, 95% CI 0.84 to 0.91) (n=1 study), and PSV2 demonstrated good predictive ability (0.73, 95% CI 0.66 to 0.81; and 0.76, 95% CI 0.71 to 0.81) for pre-eclampsia (n=2 studies). In the third trimester, the PSV ratio demonstrated good predictive ability (0.82, 95% CI 0.73 to 0.89; and 0.77, 95% CI 0.71 to 0.82) for preterm and term pre-eclampsia, respectively (n=1 study). Also, PSV2 demonstrated good predictive ability 0.70 (0.57 to 0.84) (n=1 study).
Subsequently, in the second trimester, PSV ratio demonstrated better incremental predictive performance than uterine artery pulsatility index for preterm pre-eclampsia, when added to maternal factors and mean arterial pressure (MAP) (56.1%–80.2% vs 56.1%–74.8% detection rate (DR) at 10% FPR) (n=1 study). Also in the third trimester, adding PSV ratio to maternal factors and MAP was superior to soluble fms-like tyrosine kinase-1/placental growth factor ratio in predicting pre-eclampsia at

Background
High blood pressure (BP) is a significant global health issue, with many treated patients failing to achieve BP control. The Triple Pill vs Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial evaluated the effectiveness, cost-effectiveness and acceptability of early use of low-dose triple fixed-dose combination of BP-lowering drugs (‘triple pill’) compared with usual care in the management of hypertension. The TRIUMPH trial showed superior BP control with the triple pill strategy compared with usual care. This process evaluation of the TRIUMPH trial aimed to explore the contextual factors that influenced the trial outcomes, implementation of the triple pill strategy, mechanisms of its effects and potential barriers and facilitators for implementing the triple pill strategy in routine practice.

Methods
Guided by the UK Medical Research Council’s framework, semistructured interviews were conducted with 23 patients and 13 healthcare providers involved in the TRIUMPH trial. Data were analysed using the framework analysis method in NVivo.

Results
Hypertension care in Sri Lanka was hindered by the absence of systematic screening and overcrowded public clinics. Despite free medication provision at public clinics, long waiting times and occasional stock-outs posed challenges. In the TRIUMPH trial, both intervention and usual care were delivered in the context of ‘better than usual’ care, including team-based management, reduced waiting times, monetary assistance for travel, routine adherence monitoring and intensive follow-up. The triple pill strategy provided a simplified regimen, better access to BP-lowering medications and better BP-lowering efficacy. Key barriers to implementation in routine practice included the triple pill’s large size, therapeutic inertia and restrictive regulatory policies regarding fixed-dose combinations.

Conclusions
Implementation of the triple pill strategy into routine practice requires health system strengthening, provider training and supportive policy measures to replicate its effectiveness seen in the trial.

Trial registration number
ACTRN12612001120864, SLCTR/2015/020.

Introduction
interRAI is a global collaboration of clinicians, researchers and policy-makers who have developed a suite of assessment tools to assess the health status and care needs of older adults in various settings (ie, home, long-term care, etc). We aim to determine how interRAI tools have been used as an intervention and to evaluate intervention efficacy in older adults (65+) across diverse healthcare settings. Importantly, given the deployment of interRAI primarily in high-income countries, we anticipate that the findings may have minimal relevance to low- and middle-income nations, where there is an immediate and urgent need for equity in geriatric assessment.

Methods and analysis
To be included, all studies must satisfy our inclusion criteria, outlined by the population (ie, older adults and/or individuals providing some element of care to older adults), intervention (ie, randomised or non-randomised), comparator (ie, with or without one) and outcome (ie, how the interRAI formed the basis of a study intervention). Our search strategy is based on previous reviews of interRAI tools, our research and clinical experience, and the expertise of a specialised librarian. In addition to PubMed, we will conduct our search without date or language restrictions in Scopus, Embase,Cumulative Index to Nursing and Allied Health Literature (CINAHL), Academic Search Premier and PsycInfo. Study screening will employ a team-based approach, with Kappa statistics >0.8 indicating ‘substantial’ agreement and an acceptable threshold. Data extraction will capture the study ID and design, as well as sample characteristics and outcomes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, with findings presented graphically and narratively.

Ethics and dissemination
Ethics approval is not required. Our knowledge dissemination strategies include traditional research avenues (ie, manuscript publications). We will also create an infographic to disperse widely and leverage existing partnerships to provide community presentations.

Registration details
https://doi.org/10.17605/OSF.IO/BGJKP

Screening della popolazione pediatrica. Il diabete è simile ai paesi Ue

Introduction
Type 1 diabetes (T1D) is associated with changes in brain structure, cognition, mental health, and functional outcomes. While these changes have been linked to dysregulated glycaemic control, findings are inconsistent, and their long-term impact remains unclear. Most evidence comes from cross-sectional or short-term longitudinal studies, limiting insights into causal associations. To address this, we aim to study individuals with T1D approximately 30 years after onset to assess how early dysglycaemic insults during neurodevelopment influence cognitive and functional outcomes in mid-adulthood.

Methods and analysis
This protocol paper outlines an observational, case/control, cross-sectional/longitudinal and descriptive study that follows up the original Royal Children’s Hospital (RCH) Diabetes Cohort Study. The initial study recruited children in Australia diagnosed with T1D between 1990 and 1992, conducting five waves of data collection. We now introduce the Cognition and Longitudinal Assessments of Risk Factors over 30 Years (CLARiFY) Diabetes Complications Study to assess brain, cognition and functional outcomes in mid-adulthood, approximately 30 years post-T1D onset. Both T1D participants from the original cohort and healthy controls will participate in semistructured interviews, neuroimaging and cognitive testing. T1D participants will also undergo complications screening. Data from this study and previous waves will be used to (Aim 1) explore cross-sectional and longitudinal impacts of T1D on brain health over 30 years. Linear regression will analyse cross-sectional outcomes, and multivariate analysis will assess cognitive variables jointly. Longitudinal outcomes will be examined using linear mixed-effects regression for IQ patterns, with secondary outcomes analysed via generalised linear models. Additionally, linear mixed-effects regression (Aim 2) will identify T1D-related metabolic factors affecting brain outcomes, with covariate selection informed by the construction of directed acyclic graphs (DAGs).

Ethics and dissemination
The study was approved by the Royal Children’s Hospital Human Research Ethics Committee (HREC 35 240F and 2019.065). The research findings will be disseminated through peer-reviewed publications, conference presentations, and print and social media. Participants will receive a summary of the study findings on its completion.

Purpose
Congenital cytomegalovirus (cCMV) is an important cause of long-term childhood disability. In Australia, the identification and treatment practices and the long-term clinical and neurodevelopmental outcomes of children with cCMV are unknown. The Australasian cCMV Register (ACMVR) is a longitudinal register and resource for research that aims to describe and explore, in Australian children with cCMV: (1) their clinical characteristics over time, (2) antiviral therapy use/prescribing up to 1 year of age and (3) risk factors and potential avenues for prevention of adverse sequelae of the virus.

Participants
Children

Introduction
In the Middle East and North Africa (MENA) region, changing demographic and epidemiological profiles have resulted in a diverse and shifting burden of disease (BoD). Disability-adjusted life years (DALYs), which combine years of life lost (YLL) due to premature mortality and years lived with disability (YLD), offer a valuable metric for assessing disease burden at the national level. While global burden of disease (GBD) estimates provide broad insights, national burden of disease (NBD) estimates offer country-specific data that can better inform tailored health policies and resource allocation. This systematic review protocol outlines our methodology for collating and analysing the NBD estimates in the MENA region using DALYs as the primary outcome measure.

Methods and analysis
This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will systematically search PubMed, Scopus, Web of Science and EMBASE for studies published from 1993 to 2024 that report national-level DALY estimates for diseases, injuries or risk factors in MENA countries. Eligible studies must report DALY estimates using national methodologies, while studies using exclusively GBD estimates will be excluded. Two independent reviewers will conduct title/abstract and full-text screening, data extraction and quality assessment using Standardised Reporting of Burden of Disease Studies (STROBOD), with disagreements resolved by a third reviewer when necessary.

Ethics and dissemination
Ethical approval is not required for this review as it involves analysis of previously published data. The findings will be disseminated through publication in a peer-reviewed journal and presented at relevant academic and policy forums.

Prospero Registration Number
PROSPERO CRD42024498688.

Introduction
Perioperative neurocognitive disorders (PNDs), a common postoperative complication associated with anaesthesia and surgical procedures, are characterised by impairments in memory, attention, language comprehension and social functioning. Accumulating evidence from clinical studies indicates that transcranial magnetic stimulation (TMS)—a non-invasive neuromodulatory modality capable of targeted cortical stimulation—may offer therapeutic promise for PND management. To comprehensively assess the intervention efficacy and safety parameters of TMS in mitigating postoperative cognitive decline, we propose conducting a systematic review and meta-analysis of randomised controlled trials adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Our findings aim to provide evidence-based insights into the neuroprotective potential of TMS for mitigating cognitive decline in surgical populations.

Methods and analysis
The investigation will implement a multifaceted search protocol encompassing international and Chinese scholarly resources. The search will be conducted in major databases, including Web of Science, Embase, PubMed, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database from inception to 31 March 2025. To capture the latest research trends, ongoing trials will be simultaneously searched in the WHO International Clinical Trial Registry Platform, ClinicalTrials.gov and the China Clinical Trial Registry. Grey literature will be supplemented through resources such as GreyNet International, OpenGrey and Google Scholar. The inclusion criteria for this review are restricted to randomised controlled trials investigating the application of TMS as an intervention for PND. Primary endpoints comprise clinically confirmed incidence rates of postoperative delirium and delayed neurocognitive recovery. Two researchers will independently perform literature screening, data extraction and risk of bias assessment. The risk of bias in included studies will be evaluated using the Cochrane Risk of Bias Tool 2.0. Evidence certainty will be appraised through the GRADE framework with explicit justification for downgrading decisions. Meta-analysis will be conducted using STATA V.15.1 statistical software. The data synthesis process will incorporate standardised methodologies, including heterogeneity testing, sensitivity analysis and assessment of publication bias.

Ethics and dissemination
This study will not involve the collection of biometric information or medical privacy data throughout the research process, thus complying with the exemption criteria outlined in the ‘Measures for Ethical Review of Biomedical Research Involving Human Subjects.’ The findings will adhere to academic standards and be submitted for publication in reputable international medical journals following a rigorous double-blind peer-review process.

Systematic review registration
The research protocol has been prospectively registered on the PROSPERO international prospective systematic review registration platform (registration number: CRD42025636978).