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Previous observational studies of the diabetes drugs metformin vs. sulfonylureas have yielded mixed results about whether metformin reduces the risk of dementia, relative to the sulfonylureas. Here, the authors apply a novel competing risks approach to emulate dementia-related target trials in electronic health records of diabetic patients and a complementary systems pharmacology evaluation on human neural cells.

Assessing children's working memory capacity (WMC) can be challenging for a variety of reasons, including the rapid increase in WMC across early childhood. Here, we developed and piloted an adapted WMC task, which involved minimal equipment, could be performed rapidly, and did not rely on verbal production ability (to facilitate the use of the task with younger children). In our adaptation, we portrayed the events of the object-based Missing Scan Task (creatures hiding in and emerging from a house) in a touchscreen format. In the full experiment, 67 participants aged 23 to 90 months achieved the longest set size (LSS) scores that were distributed across the full range of possible scores. A comparison of these scores with those obtained using object-based formats indicated general agreement between the versions of the task. Scores were found to increase with child age. We propose this (freely available) touchscreen adaptation as a suitable WMC task for use with children aged 2 to 7 years.

Telemedicine has been an essential form of care since the onset of the COVID-19 pandemic. However, telemedicine may exacerbate disparities for populations with limited digital literacy or access, such as older adults, racial minorities, patients of low income, rural residences, or limited English proficiency. From March 2020 to March 2022, this retrospective cohort study analyzed the use of in-person, phone/message, and telemedical care at a single tertiary care center in an oncology department. We investigated the association between economic, racial, ethnic, socioeconomic factors and forms of care, including in-person visits, telemedicine-based visits, and telephone/messages. The study results show that telemedicine utilization is lower among patients 65 and older, female patients, American Indian or Alaska Native patients, uninsured patients, and patients who require interpreters during clinical visits. As a result, it is unlikely that telemedicine will provide equal access to clinical care for all populations. On the other hand, in-person care utilization remains low in low-income and rural-living patients compared to the general population, while telephone and message use remains high in low-income and rural-living patients. We conclude that telemedicine is currently unable to close the utilization gap for populations of low socioeconomic status. Patients with low socioeconomic status use in-person care less frequently. For the disadvantaged, unusually high telephone or message utilization is unlikely to provide the same quality as in-person or telemedical care. Understanding the causes of disparity and promoting a solution to improve equal access to care for all patients is critical.

Objectives While patient interest in telehealth increases, clinicians’ perspectives may influence longer-term adoption. We sought to identify facilitators and barriers to continued clinician incorporation of telehealth into practice.Methods A cross-sectional 24-item web-based survey was emailed to 491 providers with ≥50 video visits (VVs) within an academic health system between 1 March 2020 and 31 December 2020. We quantitatively summarised the characteristics and perceptions of respondents by using descriptive and test statistics. We used systematic content analysis to qualitatively code open-ended responses, double coding at least 25%.Results 247 providers (50.3%) responded to the survey. Seventy-nine per cent were confident in their ability to deliver excellent clinical care through VV. In comparison, 48% were confident in their ability to troubleshoot technical issues. Most clinicians (87%) expressed various concerns about VV. Providers across specialties generally agreed that VV reduced infection risk (71%) and transportation barriers (71%). Three overarching themes in the qualitative data included infrastructure and training, usefulness and expectation setting for patients and providers.Discussion As healthcare systems plan for future delivery directions, they must address the tension between patients’ and providers’ expectations of care within the digital space. Telehealth creates new friction, one where the healthcare system must fit into the patient’s life rather than the usual dynamic of the patient fitting into the healthcare system.Conclusion Telehealth infrastructure and patient and clinician technological acumen continue to evolve. Clinicians in this survey offered valuable insights into the directions healthcare organisations can take to right-size this healthcare delivery modality.

In an in/out referendum, held on 23 June 2016, the British electorate chose to leave the European Union. This paper uses the information and scientific outputs accumulated since the vote to explore and explain the deeper reasons behind Brexit. Key findings can be grouped in two categories. First of all, there are centuries long-standing endowments/factors – like history, geography, or differences in law or traditions, and, closely related to these, the legendary obsession with sovereignty and free trade – which have always been major drivers in influencing the British attitude towards Europe and have generally been reflected, in aspirations for a looser cooperation. Second, there are more recent factors – however, being around for the last 30-40 years – like changing balance of power (i.e., rising German influence) in the European institutions, or growing inequality in income, wealth, and opportunities, which may have been pushing some voters towards rejecting the status quo and embracing disruption as occasion emerged

Abstract Osteonecrosis in antiphospholipid syndrome is a diagnostic challenge for clinicians. Early diagnosis and intervention are important for better prognosis.

Abstract We should keep in mind slowly growing malignancies when the lesion is located close to the synovial regions of the extremities. The diagnosis of certainty of myxofibrosarcoma is histological and is based on the demonstration of the myxoid matrix, fibroblastic cells with a curvilinear arrangement of the vessels.

Although telemedicine has been an important conduit for clinical care during the COVID-19 pandemic, not all patients have been able to meaningfully participate in this mode of health care provision. Challenges with accessing telemedicine using consumer technology can interfere with the ability of patients and clinicians to meaningfully connect and lead to significant investments in time by clinicians and their staff. In this narrative case, we identify issues related to patients’ use of technology, make comparisons between telehealth adoption and the deployment of electronic health records, and propose that building intuitive and supported digital care experiences for patients is required to make virtual care sustainable.

The aim of this study was to determine the prevalence and the etiologic profile of hypertension (HTN) in systemic lupus erythematosus (SLE). A retrospective analysis was performed on 153 patients with SLE who attended our center for 16 years from January 2000 to December 2016. The diagnosis of SLE was established according to the classification criteria of the American College of Rheumatology in 1990. The prevalence of HTN in patients with SLE was 26.1% (40/153)' with an average delay of appearance of 21 months. There were 37 women and three men with a mean age of 46’ eight years (20–70). HTN was associated with lupus nephritis (n = 8)' other renal impairments (n = 6)' and corticosteroid treatment (n = 20). Essential HTN was found in six cases. Cardiovascular factors associated with HTN were: diabetes (n = 14)' sedentary life (n = 15)' obesity (n = 12)' and dyslipidemia (n = 8). Main clinical manifestations associated with HTN were: arthralgia/arthritis (24 cases)' cutaneous involvement (22 cases)' and hematological manifestations (16 cases). Anti-phospholipid syndrome was found in 12 cases. Coronary artery disease’ arteritis of lower limb’ and transient ischemic attacks complicated the course of HTN in six patients. Angiotensin-converting-enzyme inhibitors were the most commonly used drug for treatment in this group. HTN was frequently associated with corticosteroid treatment in this study. We feel that the use of corticosteroids should be avoided as far as possible in all patients with SLE.

The World Health Organization (WHO) highlights that cardiovascular diseases (CVDs) are one of the leading causes of death globally, with an estimated rise to over 23.6 million deaths by 2030. This alarming trend can be attributed to our unhealthy lifestyles and lack of attention towards early CVD diagnosis. Traditional cardiac auscultation, where a highly qualified cardiologist listens to the heart sounds, is a crucial diagnostic method, but not always feasible or affordable. Therefore, developing accessible and user-friendly CVD recognition solutions can encourage individuals to integrate regular heart screenings into their routine. Although many automatic CVD screening methods have been proposed, most of them rely on complex prepocessing steps and heart cycle segmentation processes. In this work, we introduce a simple and efficient approach for recognizing normal and abnormal PCG signals using Physionet data. We employ data selection techniques such as kernel density estimation (KDE) for signal duration extraction, signal-to-noise Ratio (SNR), and GMM clustering to improve the performance of 17 pretrained Keras CNN models. Our results indicate that using KDE to select the appropriate signal duration and fine-tuning the VGG19 model results in excellent classification performance with an overall accuracy of 0.97, sensitivity of 0.946, precision of 0.944, and specificity of 0.946.

This paper, by presenting and analysing some recent phenomena – like Brexit, the income (or more generally: prosperity) gap both between Western and Eastern, and Northern and Southern European member states, tensions within the Euro system, or even the resolution of the Greek crisis – would like to point to a certain direction which is worth to be considered in relation to the future of the European Union. In contrast to the standard narrative, it argues that instead of ever more integration – i.e. consisting of forcing more and more dogmatic economic policy under German domination –, Europe would benefit from a looser, multi-tier integration, based on mutually advantageous cooperation of nations. Such a solution would not exclude the preservation of a hard core of countries with deepening integration amongst their economies, but would give countries of the periphery the opportunity to preserve their room for manoeuver, their chances of development, and ultimately their dignity.

The role of the prokineticin 2 pathway in human reproduction, olfactory bulb morphogenesis, and gonadotropin-releasing hormone secretion is well established. Recent studies have highlighted the implication of di/oligogenic inheritance in this disorder. In the present study, we aimed to identify the genetic mechanisms that could explain incomplete penetrance in hypogonadotropic hypogonadism (HH). This study involved two unrelated Tunisian patients with HH, which was triggered by identifying a homozygous p.(Pro290Ser) mutation in the PROKR2 gene in a girl (HH1) with Kallmann syndrome (KS). The functional effect of this variant has previously been well demonstrated. Unexpectedly, her unaffected father (HH1P) and brother (HH1F) also carried this genetic variation at a homozygous state. In the second family, we identified a heterozygous p.(Lys205del) mutation in PROKR2, both in a male patient with normosmic idiopathic IHH (HH12) and his asymptomatic mother. Whole-exome sequencing in the three HH1 family members allowed the identification of additional variants in the prioritized genes. We then carried out digenic combination predictions using the oligogenic resource for variant analysis (ORVAL) software. For HH1, we found the highest number of disease-causing variant pairs. Notably, a CCDC141 variant (c.2803C > T) was involved in 18 pathogenic digenic combinations. The CCDC141 variant acts in an autosomal recessive inheritance mode, based on the digenic effect prediction data. For the second patient (HH12), prediction by ORVAL allowed the identification of an interesting pathogenic digenic combination between DUSP6 and SEMA7A genes, predicted as “dual molecular diagnosis.” The SEMA7A variant p.(Glu436Lys) is novel and predicted as a VUS by Varsome. Sanger validation revealed the absence of this variant in the healthy mother. We hypothesize that disease expression in HH12 could be induced by the digenic transmission of the SEMA7A and DUSP6 variants or a monogenic inheritance involving only the SEMA7A VUS if further functional assays allow its reclassification into pathogenic. Our findings confirm that homozygous loss-of-function genetic variations are insufficient to cause KS, and that oligogenism is most likely the main transmission mode involved in Congenital Hypogonadotropic Hypogonadism.