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Francesco Giorgino,1 Alfred Penfornis,2 Valeria Pechtner,3 Raffaella Gentilella,4 Antonella Corcos4 1Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy; 2Service d’Endocrinologie, Diabétologie, et Maladies Métaboliques, Centre Hospitalier Sud-Francilien de Corbeil-Essonnes, Université Paris-Sud, Orsay, France; 3Lilly Diabetes, Eli Lilly & Company, Neuilly-sur-Seine, France; 4Eli Lilly Italia, Sesto Fiorentino, Italy Abstract: Adherence to antihyperglycemic medications is often suboptimal in patients with type 2 diabetes, and this can contribute to poor glycemic control, increased hospitalization, and the development of diabetic complications. Reported adherence rates to antihyperglycemics vary widely among studies, and this may be related to differences in methodology for measuring adherence, patient populations, and other factors. Poor adherence may occur regardless of the specific regimen used and whether therapy is oral or injectable, and can be especially common in chronic, asymptomatic conditions, such as type 2 diabetes. More convenient drug-administration regimens and advances in formulations and delivery devices are among strategies shown to improve adherence to antihyperglycemic therapy, especially for injectable therapy. This is exemplified by technological developments made in the drug class of glucagon-like peptide 1-receptor agonists, which are a focus of this narrative review. Dulaglutide, albiglutide, and prolonged-release exenatide have an extended duration of action and can be administered once weekly, whereas such agents as liraglutide require once-daily administration. The convenience of once-weekly versus once-daily administration is associated with better adherence in real-world studies involving this class of agent. Moreover, provision of a user-friendly delivery device has been shown to overcome initial resistance to injectable therapy among patients with type 2 diabetes. This suggests that recent innovations in drug formulation (eg, ready-to-use formulations) and delivery systems (eg, single-dose prefilled pens and hidden, ready-attached needles) may be instrumental in encouraging patient acceptance. For physicians who aim to improve their patients’ adherence to antihyperglycemic medications, it is thus important to consider the patient’s therapeutic experience (treatment frequency, drug formulation, delivery device). Better adherence, powered by recent technological advances in the delivery of glucagon-like peptide 1-receptor agonists, may thus lead to improved clinical outcomes in type 2 diabetes. Keywords: type 2 diabetes mellitus, adherence, compliance, glucagon-like peptide 1-receptor agonists

Alfred Penfornis,1 Béatrice Fiquet,2 Jean Frédéric Blicklé,3 Sylvie Dejager2,4 1Department of Endocrinology and Diabetology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes Cedex, France; 2Clinical Affairs, Novartis Pharma SAS, Rueil-Malmaison, France; 3Department of Internal Medicine and Diabetology, Strasbourg University Hospital, Strasbourg, France; 4Department of Diabetology, Metabolism and Endocrinology, Pitié-Salpétrière Hospital, Paris, France Background: Few data exist examining the management of elderly patients with type 2 diabetes mellitus and renal impairment (RI). This observational study assessed the therapeutic management of this fragile population. Methods: Cross-sectional study: data from 980 diabetic patients ≥75 years with renal disease are presented. Results: Patients had a mean age of 81 years (range 75–101) with long-standing diabetes (15.4 years) often complicated (half with macrovascular disease). Mean estimated glomerular filtration rate was 43 mL/min/1.73 m2 and 20% had severe RI. Mean hemoglobin A1c was 7.4%. Anti-diabetic therapy was oral based for 51% of patients (60% $2 oral anti-diabetic drugs [OAD]) and insulin based for 49% (combined with OAD in 59%). OAD included metformin (47%), sulfonylureas (26%), glinides (19%), and DPP-4 inhibitors (31%). Treatments were adjusted to increasing RI, with less use of metformin, sulfonylureas, and DPP-4 inhibitors, and more glinides and insulin in severe RI. In all, 579 (60%) of these elderly patients with comorbidities had hemoglobin A1c

Alfred Penfornis,1 Jean Frédéric Blicklé,2 Béatrice Fiquet,3 Stéphane Quéré,4 Sylvie Dejager3 1Department of Endocrinology-Metabolism and Diabetology-Nutrition, Jean Minjoz Hospital, University of Franche-Comté, Besançon, France; 2Department of Internal Medicine and Diabetology, Strasbourg University Hospital, Strasbourg, France; 3Clinical Affairs, Novartis Pharma SAS, Rueil-Malmaison, France; 4BioStatistics, Novartis Pharma SAS, Rueil-Malmaison, France Background and aim: Chronic kidney disease (CKD) is frequent in type 2 diabetes mellitus (T2DM), and therapeutic management of diabetes is more challenging in patients with renal impairment (RI). The place of metformin is of particular interest since most scientific societies now recommend using half the dosage in moderate RI and abstaining from use in severe RI, while the classic contraindication with RI has not been removed from the label. This study aimed to assess the therapeutic management, in particular the use of metformin, of T2DM patients with CKD in real life. Methods: This was a French cross-sectional observational study: 3,704 patients with T2DM diagnosed for over 1 year and pharmacologically treated were recruited in two cohorts (two-thirds were considered to have renal disease [CKD patients] and one-third were not [non-CKD patients]) by 968 physicians (81% general practitioners) in 2012. Results: CKD versus non-CKD patients were significantly older with longer diabetes history, more diabetic complications, and less strict glycemic control (mean glycated hemoglobin [HbA1c] 7.5% versus 7.1%; 25% of CKD patients had HbA1c ≥8% versus 15% of non-CKD patients). Fifteen percent of CKD patients had severe RI, and 66% moderate RI. Therapeutic management of T2DM was clearly distinct in CKD, with less use of metformin (62% versus 86%) but at similar mean daily doses (~2 g/d). Of patients with severe RI, 33% were still treated with metformin, at similar doses. For other oral anti-diabetics, a distinct pattern of use was seen across renal function (RF): use of sulfonylureas (32%, 31%, and 20% in normal RF, moderate RI, and severe RI, respectively) and DPP4-i (dipeptidyl peptidase-4 inhibitors) (41%, 36%, and 25%, respectively) decreased with RF, while that of glinides increased (8%, 14%, and 18%, respectively). CKD patients were more frequently treated with insulin (40% versus 16% of non-CKD patients), and use of insulin increased with deterioration of RF (19%, 39%, and 61% of patients with normal RF, moderate RI, and severe RI, respectively). Treatment was modified at the end of the study-visit in 34% of CKD patients, primarily to stop or reduce metformin. However, metformin was stopped in only 40% of the severe RI patients. Conclusion: Despite a fairly good detection of CKD in patients with T2DM, RI was insufficiently taken into account for adjusting anti-diabetic treatment. Keywords: therapeutic management, metformin, sulfonylureas, renal disease, type 2 diabetes

Field trials (FTs) are a necessary step towards future commercialization of biotech crops and products thereof, whether for research and development or cultivation approval. A total of 187 FTs in 30 countries have been compiled for 2022 and 2023 using a survey and intergovernmental databases. FTs have been classified according to methods, crops and traits. Compiled FTs are mostly conducted by the public sector on eight plant species with improved stress resistance, industrial application, yield, and quality. Regarding genome editing (GenEd), 23 FTs (12% of total) are carried out in 6 countries, on 10 crops. Regulations were examined in 141 countries to discuss why in some countries FTs are not performed, although basic biotech research is carried out. The EU particularly is compared to the rest of the world. Regarding the new proposal in the EU for GenEd product classification, it was found that all recent FTs of such products fall in the category that the EU would consider as ‘equivalent to conventional plants’ (NGT-1). We also studied current cultivation approvals to highlight differences with crops tested in the field and those may be approved in the future.

Abstract Background Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care. Methods DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316), or follow-up without screening (N = 315). The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented. Results The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5%) patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71). The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint. Conclusions These results suggest that the systematic detection of silent ischemia in high-risk asymptomatic patients with diabetes is unlikely to provide any major benefit on hard outcomes in patients whose cardiovascular risk is controlled by an optimal medical treatment. Trial registration ClinicalTrials.gov: NCT00627783

Abstract Background To identify demographic and clinical factors associated with psychological and behavioral functioning (PBF) in people with type 2 diabetes living in France. Methods In March 2002, approximately 10,000 adults, who had been reimbursed for at least one hypoglycemic treatment or insulin dose during the last quarter of 2001, received a questionnaire about their health status and PBF (3,646 responders). For this analysis, the 3,090 persons with type 2 diabetes, aged 18-85 years old were selected. PBF was measured with the adapted version of the Diabetes Health Profile for people with type 2 diabetes. This permitted the calculation of three functional scores - psychological distress (PD), barriers to activity (BA), and disinhibited eating (DE) - from 0 (worst) to 100 (best). Results Major negative associations were observed with PBF for microvascular complications (a difference of 6.7 in the BA score between persons with and without microvascular complications) and severe hypoglycemia (difference of 7.9 in the BA score), insulin treatment (-8.5 & -9.5 in the PD & BA scores respectively, as compared to treatment with oral hypoglycemic agents), non-adherence to treatment (-12.3 in the DE score for persons forgetting their weekly treatment), increasing weight (-8.5 & -9.7 in the PD & DE scores respectively, as compared to stable weight), at least one psychiatrist visit in 2001 (-8.9 in the DE score), and universal medical insurance coverage (-7.9 in the PD score) (due to low income). Conclusion Prevention and management of microvascular complications or adherence to treatment (modifiable factors) could be essential to preserving or improving PBF among people with type 2 diabetes. A specific approach to type 2 diabetes management may be required in groups with a low socioeconomic profile (particularly people with universal medical insurance coverage), or other non modifiable factors.

Tailored motivational messages are helpful to motivate people in eHealth applications for increasing physical activity, but it is not sufficiently clear how such messages can be effectively generated in advance. We, therefore, put forward a theory-driven approach to generating tailored motivational messages for eHealth applications for behavior change, and we examine its feasibility by assessing how motivating the resulting messages are perceived. For this, we designed motivational messages with a specific structure that was based on an adaptation of an existing ontology for tailoring motivational messages in the context of physical activity. To obtain tailored messages, experts in health psychology and coaching successfully wrote messages with this structure for personas in scenarios that differed with regard to the persona’s mood, self-efficacy, and progress. Based on an experiment in which 60 participants each rated the perceived motivational impact of six generic and six tailored messages based on scenarios, we found credible support for our hypothesis that messages tailored to mood, self-efficacy, and progress are perceived as more motivating. A thematic analysis of people’s free-text responses about what they found motivating and demotivating about motivational messages further supports the use of tailored messages, as well as messages that are encouraging and empathetic, give feedback about people’s progress, and mention the benefits of physical activity. To aid future work on motivational messages, we make our motivational messages and corresponding scenarios publicly available.

Summary: Background: Two randomised controlled trials (RCTs) have previously shown that telemedical monitoring of diabetic foot ulcer (DFU) reduces the number of visits to the outpatient clinic, without losing treatment efficacy or increasing costs. Here we present the results of an open-label, randomised controlled trial designed to investigate whether telemonitoring, provided by an expert nurse (with extensive experience in DFU and trained in remote monitoring), reduces the hospital stay and the associated costs for a patient with DFU (TELEPIED trial). Methods: Eligible patients (n = 180) were randomly allocated to: (i) a control group, in which they received standard care, and (ii) an intervention group, in which they received asynchronous telemedicine follow-up by the expert nurse. The primary outcome was the cumulative hospital days over 12 months. The main secondary outcomes were (i) direct healthcare costs (estimated in a collective perspective), (ii) wound healing and (iii) amputation rates. ITT (intention-to-treat) population was analysed. Findings: In the ITT population, cumulative hospital days were significantly higher in the control group (13.4 days [95% CI 9.0–17.8]) than in the intervention group (7.1 days [2.8–11.5]) (p = 0.0458, ANCOVA model). Cumulative direct costs over 12 months were 7185 € (95% CI 5144–9226) in the control group and 3471 € (95% CI 1430–5512) in the intervention group (p = 0.0120). The percentage of wounds healed and amputation rate were not significantly different between groups. Similar results were found with the PP population. Interpretation: The implementation of a telemedical intervention with an expert nurse could lead to a length of hospitalization and direct costs that were two times lower compared to conventional follow-up. This lower medical and economic burden was obtained without losing effectiveness on the rate of healing, nor increasing the amputation rate. Additional studies are required to confirm these findings. Funding: This study was designed, funded and conducted by CERITD (Study and Research Centre for Intensification of Diabetes Treatment, Evry, France), Genopole GIP, 20 rue Henri Desbruères, 91030 EVRY Cedex and Laboratoires URGO, 15 Avenue d’Iéna, 75116 Paris Cedex, France. The findings and conclusions in this study are those of the authors and do not necessarily represent the views of the sponsor. The corresponding author (DD) certify that authors were not precluded from accessing data in the study, and they accept responsibility to submit for publication.

Summary: Background: Type 1 diabetes is a complex heterogenous autoimmune disease without therapeutic interventions available to prevent or reverse the disease. This study aimed to identify transcriptional changes associated with the disease progression in patients with recent-onset type 1 diabetes. Methods: Whole-blood samples were collected as part of the INNODIA study at baseline and 12 months after diagnosis of type 1 diabetes. We used linear mixed-effects modelling on RNA-seq data to identify genes associated with age, sex, or disease progression. Cell-type proportions were estimated from the RNA-seq data using computational deconvolution. Associations to clinical variables were estimated using Pearson's or point-biserial correlation for continuous and dichotomous variables, respectively, using only complete pairs of observations. Findings: We found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Significant associations of the gene expression changes were found with ZnT8A autoantibody positivity. Rate of change in the expression of 16 genes between baseline and 12 months was found to predict the decline in C-peptide at 24 months. Interestingly and consistent with earlier reports, increased B cell levels and decreased neutrophil levels were associated with the rapid progression. Interpretation: There is considerable individual variation in the rate of progression from appearance of type 1 diabetes-specific autoantibodies to clinical disease. Patient stratification and prediction of disease progression can help in developing more personalised therapeutic strategies for different disease endotypes. Funding: A full list of funding bodies can be found under Acknowledgments.

BackgroundFor patients with type 2 diabetes (T2D), calculating the daily dose of basal insulin may be challenging. Insulia is a digital remote monitoring solution that uses clinical algorithms to recommend basal insulin doses. A predecessor device was evaluated in the TeleDiab-2 randomized controlled trial, showing that a higher percentage of patients using the app achieved their target fasting blood glucose (FBG) level compared to the control group, and insulin doses were adjusted to higher levels without hypoglycemia. ObjectiveThis study aims to analyze how the glycemic control of Insulia users has evolved when using the app in a real-life setting in France. MethodsA retrospective observational analysis of data collected through the device in adult French patients with T2D treated with basal insulin and oral antihyperglycemic agents using the system for ≥6 months was conducted. Analyses were descriptive and distinguished the results in a subpopulation of regular and compliant users of the app. Glycemic outcomes were estimated considering the percentage of patients who achieved their individualized FBG target between 5.5 and 6 months following the initiation of device use, the frequency of hypoglycemia resulting in a treatment change over the 6-month period of exposure, and the evolution of the average hemoglobin A1c (HbA1c) level over the same period. ResultsOf the 484 users, 373 (77.1%) performed at least one dose calculation. A total of 221 (59.2%) users were men. When app use started, the mean age, BMI, HbA1c, and basal insulin dose were 55.8 (SD 11.9) years, 30.6 (SD 5.9) kg/m2, 10.1% (SD 2.0%), and 25.5 (SD 15.8) IU/day, respectively. Over a median use duration of 5.0 (95% CI 3.8-5.7) months, patients used the system 5.8 (SD 1.6) times per week on average, and 73.4% of their injected doses were consistent with the app’s suggested doses. Among regular and compliant user patients (n=91, ≥5 measurements/week and ≥80% adherence to calculated doses), 60% (55/91) achieved the FBG target (±5%) at 6 months (5.5-6 months) versus 51.5% (145/282) of the other patients (P=.15). There was an increase in the proportion of patients achieving their target FBG for regular and compliant users (+1.86% every 2 weeks) without clear improvement in other patients. A logistic model did not identify the variables that were significantly associated with this outcome among regular and compliant users. In the overall population, the incidence of reported hypoglycemia decreased simultaneously (–0.16%/month). Among 82 patients, the mean HbA1c decreased from 9.9% to 7.2% at 6 months. ConclusionsAn improvement in glycemic control as measured by the percentage of patients reaching their FBG individualized target range without increasing hypoglycemic risk was observed in patients using the Insulia app, especially among regular users following the dose recommendations of the algorithm.

BackgroundWe assessed the performance and patient satisfaction of a new insulin patch pump, the A7+TouchCare (Medtrum), compared with the Omnipod system.MethodsThis multicenter, randomized, open-label, controlled study enrolled 100 adult patients with type 1 or type 2 diabetes mellitus (A1C ≥ 6.5% and ≤ 9.5%, i.e., 48 to 80 mmol/mol) who were assigned with the Omnipod or with the A7+TouchCare pump for 3 months. The primary study outcome was the glucose management indicator (GMI) calculated with continuous glucose monitoring (CGM).ResultsPremature withdrawals occurs respectively in 2 and 9 participants in the Omnipod and TouchCare groups. In the Per Protocol analysis, the difference in GMI between groups was 0.002% (95% confidence interval -0.251; 0.255). The non-inferiority was demonstrated since the difference between treatments did not overlap the pre-defined non-inferiority margin (0.4%). There was no significant difference in CGM parameters between groups. On average, patients in both groups were satisfied/very satisfied with the insulin pump system. Patients preferred Omnipod as an insulin management system and especially the patch delivery system but preferred the A7+TouchCare personal diabetes manager to control the system.ConclusionsThis study showed that the A7+TouchCare insulin pump was as efficient as the Omnipod pump in terms of performance and satisfaction.Clinical trail registrationThe study was registered in the ClinicalTrials.gov protocol register (NCT04223973).

Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic hyperglycemia, although this correction, if obtained rapidly in people living with severe chronic hyperglycemia, can paradoxically interfere with the disease or even induce complications. We reviewed the literature describing the impact of the rapid and intense treatment of hyperglycemia on diabetic complications. The literature review showed that worsening complications occurred significantly in diabetic microangiopathy with the onset of specific neuropathy induced by the correction of diabetes. The results for macroangiopathy were somewhat mixed with the intensive and rapid correction of chronic hyperglycemia having a neutral impact on stroke and myocardial infarction but a significant increase in cardiovascular mortality. The management of diabetes has now entered a new era with new therapeutic molecules, such as gliflozin for patients living with type 2 diabetes, or hybrid insulin delivery systems for patients with insulin-treated diabetes. Our manuscript provides evidence in support of these personalized and progressive algorithms for the control of chronic hyperglycemia.

Background Despite their increasing prevalence and potential, eHealth applications for behavior change suffer from a lack of adherence and from dropout. Advances in virtual coach technology provide new opportunities to improve this. However, these applications still do not always offer what people need. We, therefore, need a better understanding of people’s needs and how to address these, based on both actual experiences of users and their reflections on envisioned scenarios. Methods We conducted a longitudinal study in which 671 smokers interacted with a virtual coach in five sessions. The virtual coach assigned them a new preparatory activity for quitting smoking or increasing physical activity in each session. Participants provided feedback on the activity in the next session. After the five sessions, participants were asked to describe barriers and motivators for doing their activities. In addition, they provided their views on videos of scenarios such as receiving motivational messages. To understand users’ needs, we took a mixed-methods approach. This approach triangulated findings from qualitative data, quantitative data, and the literature. Results We identified 14 main themes that describe people’s views of their current and future behaviors concerning an eHealth application. These themes relate to the behaviors themselves, the users, other parties involved in a behavior, and the environment. The most prevalent theme was the perceived usefulness of behaviors, especially whether they were informative, helpful, motivating, or encouraging. The timing and intensity of behaviors also mattered. With regards to the users, their perceived importance of and motivation to change, autonomy, and personal characteristics were major themes. Another important role was played by other parties that may be involved in a behavior, such as general practitioners or virtual coaches. Here, the themes of companionableness, accountability, and nature of the other party (i.e., human vs AI) were relevant. The last set of main themes was related to the environment in which a behavior is performed. Prevalent themes were the availability of sufficient time, the presence of prompts and triggers, support from one’s social environment, and the diversity of other environmental factors. We provide recommendations for addressing each theme. Conclusions The integrated method of experience-based and envisioning-based needs acquisition with a triangulate analysis provided a comprehensive needs classification (empirically and theoretically grounded). We expect that our themes and recommendations for addressing them will be helpful for designing applications for health behavior change that meet people’s needs. Designers should especially focus on the perceived usefulness of application components. To aid future work, we publish our dataset with user characteristics and 5,074 free-text responses from 671 people.

Since aerobic glycolysis was first observed in tumors almost a century ago by Otto Warburg, the field of cancer cell metabolism has sparked the interest of scientists around the world as it might offer new avenues of treatment for malignant cells. Our current study claims the discovery of gnetin H (GH) as a novel glycolysis inhibitor that can decrease metabolic activity and lactic acid synthesis and displays a strong cytostatic effect in melanoma and glioblastoma cells. Compared to most of the other glycolysis inhibitors used in combination with the complex-1 mitochondrial inhibitor phenformin (Phen), GH more potently inhibited cell growth. RNA-Seq with the T98G glioblastoma cell line treated with GH showed more than an 80-fold reduction in thioredoxin interacting protein (TXNIP) expression, indicating that GH has a direct effect on regulating a key gene involved in the homeostasis of cellular glucose. GH in combination with phenformin also substantially enhances the levels of p-AMPK, a marker of metabolic catastrophe. These findings suggest that the concurrent use of the glycolytic inhibitor GH with a complex-1 mitochondrial inhibitor could be used as a powerful tool for inducing metabolic catastrophe in cancer cells and reducing their growth.

The rate of recurrence for diabetic foot ulcer (DFU) is 50% at 2 years Armstrong DG, 2017. International recommendations call for regular monitoring to prevent DFU recurrence. We aim to investigate the relation between post-healing follow-up and recurrence rates. The study will begin in November 2021 and end in April 2022; final study results are scheduled for December 2022. The purpose of the study is to evaluate the benefit of the multidisciplinary follow-up of healed DFU patients at the rate of two annual consultations and its impact on foot wound recurrence.

Background: Iodine supplementation is indicated by the French National Authority for Health (HAS) and the World Health Organization (WHO) during pregnancy. This study investigates whether this supplementation is consistently prescribed in line with WHO recommendations in pregnant women diagnosed with gestational diabetes mellitus. Method: A total of 99 women with a diagnosis of gestational diabetes were included in the study and were all closely monitored. Results: Only 17 (17.2%) patients received the recommended iodine supplementation. The follow-up, whether conducted by a gynecologist or midwife, did not influence the prescription of iodine supplements. By contrast, 72 (72.7%) of patients received folic acid supplementation. Conclusions: The prescription of iodine supplementation for the pregnant women included in our study is insufficient. Few practitioners seem aware of the recommendations, even when the pregnancy is complicated by gestational diabetes.

Charcot neuroarthropathy (CN) is a destructive complication of the joints in patients with diabetes and should be managed from the onset of the first symptoms to avoid joint deformity and the risk of amputating the affected joint. Here, we describe the case of a young 24-year-old patient living with type I diabetes who developed active bilateral CN in both tarsal joints. This case of neuroarthropathy was uncommon due to the bilateral presentation at the same level of the joint. Despite the patient consulting from the beginning of the symptoms, none of the physicians suspected or diagnosed CN, leading to a delay in management and the aggravation of bone destruction by CN. This highlights the importance of early management of CN with the need to refer people with suspected CN to specialised diabetic foot care centres.

BackgroundIndividuals frequently turning to social media to discuss medical conditions and medication, sharing their experiences and information and asking questions among themselves. These online discussions can provide valuable insights into individual perceptions of medical treatment, and increasingly, studies are focusing on the potential use of this information to improve health care management. ObjectiveThe objective of this infodemiology study was to identify social media posts mentioning paracetamol-containing products to develop a better understanding of patients’ opinions and perceptions of the drug. MethodsPosts between January 2003 and March 2019 containing at least one mention of paracetamol were extracted from 18 French forums in May 2019 with the use of the Detec’t (Kap Code) web crawler. Posts were then analyzed using the automated Detec’t tool, which uses machine learning and text mining methods to inspect social media posts and extract relevant content. Posts were classified into groups: Paracetamol Only, Paracetamol and Opioids, Paracetamol and Others, and the Aggregate group. ResultsOverall, 44,283 posts were analyzed from 20,883 different users. Post volume over the study period showed a peak in activity between 2009 and 2012, as well as a spike in 2017 in the Aggregate group. The number of posts tended to be higher during winter each year. Posts were made predominantly by women (14,897/20,883, 71.34%), with 12.00% (2507/20,883) made by men and 16.67% (3479/20,883) by individuals of unknown gender. The mean age of web users was 39 (SD 19) years. In the Aggregate group, pain was the most common medical concept discussed (22,257/37,863, 58.78%), and paracetamol risk was the most common discussion topic, addressed in 20.36% (8902/43,725) of posts. Doliprane was the most common medication mentioned (14,058/44,283, 31.74%) within the Aggregate group, and tramadol was the most commonly mentioned drug in combination with paracetamol in the Aggregate group (1038/19,587, 5.30%). The most common unapproved indication mentioned within the Paracetamol Only group was fatigue (190/616, with 16.32% positive for an unapproved indication), with reference to dependence made by 1.61% (136/8470) of the web users, accounting for 1.33% (171/12,843) of the posts in the Paracetamol Only group. Dependence mentions in the Paracetamol and Opioids group were provided by 6.94% (248/3576) of web users, accounting for 5.44% (342/6281) of total posts. Reference to overdose was made by 245 web users across 291 posts within the Paracetamol Only group. The most common potential adverse event detected was nausea (306/12843, 2.38%) within the Paracetamol Only group. ConclusionsThe use of social media mining with the Detec’t tool provided valuable information on the perceptions and understanding of the web users, highlighting areas where providing more information for the general public on paracetamol, as well as other medications, may be of benefit.