High prevalence with no gender difference of likely eating disorders in type 1 mellitus diabetes on insulin pump.

AIM: The aim of this study was to determine the prevalence of likely eating disorders and insulin misuse in a prospective cohort of adults with type 1 diabetes mellitus (T1DM) treated with insulin pump therapy. METHODS: This prospective study was held at the participants' home. The participants completed the SCOFF questionnaire as well as a question related to insulin misuse. Information about lifestyle, medical history, insulin pump and Continuous Glucose Monitoring (CGM) data were collected. RESULTS: The analysis covered 198 participants with a median age of 51 [95% CI 38; 62] years. The prevalence of likely eating disorders was 21.7% (95% CI 16.3; 28.2) in the study population and 20.6% (95% CI 14.3; 28.6) and 24.2% (95% CI 14.6; 37.0) in males and females respectively. The prevalence of insulin misuse was 39.0% (95% CI 30.8; 47.7). There was no significant difference in prevalence between males and females for likely eating disorders and insulin misuse. The analysis of CGM data revealed no factors related to glycaemic control associated with likely eating disorders. CONCLUSION: The results of this study indicate that the prevalence of likely eating disorders is high even in a middle-aged population with a T1DM and satisfactory glucose control.

Peer-driven intervention to help patients resume CPAP therapy following discontinuation: a multicentre, randomised clinical trial with patient involvement.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is one of the most common chronic diseases. It may be associated with symptoms of excessive daytime sleepiness and neurocognitive and cardiovascular complications. First line therapy for OSAS involves home continuous positive airway pressure (CPAP), however, nearly half of patients do not adhere with this treatment over the long term. Cognitive-behavioural interventions that include health professionals and patient and public involvement are increasingly advocated in the fields of education and research. We hypothesise that a peer-driven intervention could help patients with OSAS to resume CPAP use after discontinuation. METHODS AND ANALYSIS: We have designed a prospective, multicentre randomised, controlled trial that will be coconducted by health professionals, a home provider of CPAP and patients as experts or peers or participants. The primary aim is to evaluate the impact of a 6-month, peer-driven intervention to promote the resumption of CPAP after discontinuation. We anticipate that 20% of patients in the intervention group will reuse CPAP as compared with 6% in control group, thus, 104 patients must be included in each group. The secondary aims are (1) to evaluate the impact of the peer-driven intervention on adherence to CPAP compared with the control group (mean adherence and percentage of nights with at least 4 hours' use/night for 70% of nights); (2) to determine factors associated with resumption of CPAP; (3) to assess patient satisfaction with the peer-driven intervention at 6 months; (4) to evaluate the feasibility and the execution of the peer-driven intervention and peer satisfaction. Adult outpatients with an established diagnosis of severe OSA (Apnoea-Hypopnoea Index >30 events/hour) that have stopped using CPAP within 4-12 months after initiation will be recruited. The peers who will perform the intervention will be patients with OSAS treated with CPAP with good adherence (at least 4 hours/night, 70% of nights) and trained in motivational enhancement and cognitive-behavioural therapies. Trained peers will conduct three interviews within 6 months with participants. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the French Regional Ethics Committee CPP Ouest II-Angers, (IRB 21.02.25.68606 (2021/2025)). All participants will sign written informed consent. The results will be presented at conferences and published in peer-reviewed journals as well as public media. TRIAL REGISTRATION NUMBER: NCT04538274.

Detecting COVID-19 and other respiratory infections in obstructive sleep apnoea patients through CPAP device telemonitoring.

OBJECTIVE: The earliest possible detection of individuals with COVID-19 has been essential to curb the spread of infection. Existing digital tools have been scaled up to address this issue. Every night telemonitoring data on continuous positive airway pressure (CPAP) device use, the first-line therapy for obstructive sleep apnoea (OSA), is collected worldwide. We asked whether the changes in CPAP adherence patterns of might constitute an alert for COVID-19. METHODS: We analysed preliminary results of telemonitoring data, recorded between February 1 and April 30, 2020, on OSA patients followed by our sleep clinics and diagnosed with COVID-19. RESULTS: CPAP telemonitoring data from the first 19 patients diagnosed with COVID-19 showed a clear decrease or halt in adherence in the 20 days immediately preceding COVID-19 diagnosis compared to an earlier period (p < 0.01). CONCLUSION: Patterns of continuous positive airway pressure device use by obstructive sleep apnoea patients collected through telemonitoring can indicate the onset of COVID-19 symptoms. Existing telemonitoring platforms could be immediately used to screen for COVID-19, and for other respiratory infections, in this large at-risk population.

Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial.

BACKGROUND: Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. METHODS: In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11 000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified ß-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. FINDINGS: Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified ß-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p<0·0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90·5 mL/min (IQR 76·6-94·0) to 71·8 mL/min (59·0-89·0) was observed in islet recipients who had not previously received a kidney graft and from 63·0 mL/min (55·0-71·0) to 57·0 mL/min (45·5-65·1) in islet recipients who had previously received a kidney graft. INTERPRETATION: For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. FUNDING: Programme Hospitalier de Recherche Clinique grant from the French Government.

Antituberculosis Drug-Associated DRESS: A Case Series.

BACKGROUND: Although antituberculosis drug-associated drug reaction with eosinophilia and systemic symptoms (DRESS) is rarely reported, its diagnosis should not be dismissed. Its management implies an early withdrawal of suspected drugs. OBJECTIVE: The objective of this study was to describe the characteristics of antituberculosis drug-associated DRESS and to identify the most likely involved drugs. METHODS: We searched for potential cases of DRESS with rifampicin, isoniazid, pyrazinamide, and ethambutol reported from January 1, 2005, to July 30, 2015, in the French pharmacovigilance database. A literature review was also performed. RESULTS: Sixty-seven cases of antituberculosis drug-associated DRESS were analyzed (40 women and 27 men, median age of 61 years). Liver and kidneys were the most frequently involved organs. Two patients died from DRESS. Skin tests were performed in 11 patients and were positive in 8 cases. Discrepancies between epicutaneous tests and reintroduction of the culprit drugs were observed for 2 patients with a premature reintroduction of antituberculosis drugs in 1 case. Antituberculosis drugs were the only suspects in 20 cases. As for the literature data, rifampicin was the most suspected drug because of its larger indications, but in case of tuberculosis infections, isoniazid was the most suspected drug. CONCLUSIONS: We described the largest case series of first-line antituberculosis drug-associated DRESS in the literature. All antituberculosis drugs pose a risk of DRESS. An early withdrawal of the culprit drugs is essential. A drug allergy evaluation must be performed to optimize the second-line treatment of tuberculosis infection.

[Pharmacokinetic drug interaction between miconazole mucoadhesive tablet and tacrolimus: About 3 case-reports in transplant patients]. / Interaction pharmacocinétique entre la forme mucoadhésive de miconazole et le tacrolimus : à propos de 3 observations cliniques chez des patients greffés.

Loramyc® is a mucoadhesive tablet of miconazole, indicated for the treatment of oropharyngeal candidiasis in immunocompromised patients. Miconazole, as others azole antifungals, is known for its potent inhibitory properties of cytochromes P450 enzymes and P-glycoprotein (P-gp). Inhibition of cytochromes P450 enzymes and P-gp can produce pharmacokinetic drug interaction. Immunosuppressive agents, such as calcineurin inhibitors (tacrolimus, cyclosporine) are substrates of cytochromes P450 3A4 and P-gp. Nevertheless, the impact of systemic absorption of miconazole mucoadhesive tablet has not been investigated by the laboratory before regulatory approval. No recommendation currently exists in case of co-prescription of Loramyc® and immunosuppressive agents which are counter-indicated as a matter of principle. Herein, we present 3 cases of transplanted patients, requiring miconazole mucoadhesive tablet, who presented a tacrolimus overdose. These cases illustrate that of therapeutic drug monitoring is feasible in order to prevent the occurrence of overdoses and adverse reactions related.

Serotonin Syndrome: Analysis of Cases Registered in the French Pharmacovigilance Database.

BACKGROUND: More information would be required for a better understanding of the actual circumstances of serotonin syndrome (SS) occurrence in routine clinical practice. AIM: The objective of the study was to analyze characteristics of SS French pharmacovigilance reports, especially involved drugs and nature of drug-drug interactions (DDIs). METHOD: We performed a retrospective analysis of SS registered in the French pharmacovigilance database between January 1, 1985 and May 27, 2013. Only cases whose clinical symptoms fulfilled Sternbach, Radomski, or Hunter SS diagnostic criteria were retained for the analysis. RESULTS: Most of the 125 (84.0%) analyzed cases were associated with a recent change in a serotonergic drug (introduction, increasing the dose or overdose). Antidepressants were the most often involved serotonergic drugs, mostly serotonin reuptake inhibitors (SRIs, 42.1%) and to a lesser extent serotonin-noradrenalin reuptake inhibitors (9.1%, mainly venlafaxine), tricyclic antidepressants (8.6%, mainly clomipramine), and some monoamine oxidase inhibitors (6.2%, mainly moclobemide). Nonpsychotropic medications were also involved, generally opioids (14.8%, mainly tramadol). Most of the cases (59.2%) resulted from pharmacodynamic DDIs, most often involving SRIs + opioids (mostly paroxetine + tramadol). However, SS also occurred with a single serotonergic drug in a significant number of cases (40.8%), most often SRIs (mainly fluoxetine) or venlafaxine at usual doses. Lastly, a major pharmacokinetic DDI could have played a role in 1/5 (20.8%) of cases. CONCLUSIONS: This is the first study about SS based on a large pharmacovigilance database and published in English. Our results reveal not only the frequent involvement of antidepressants and tramadol, the importance of DDIs (both pharmacodynamic and pharmacokinetic), but also the significant risk of SS even with a single serotonergic drug used at normal dose.

[Drug-drug interaction with telaprevir or boceprevir in liver transplant patients: about four cases]. / Interactions avec télaprévir ou bocéprévir chez des patients greffés hépatiques: à propos de 4 cas cliniques.

Boceprevir and telaprevir are both direct-acting antivirals indicated, as part of combination therapy for the management of chronic hepatitis C virus (HCV) genotype 1 infection. Transplanted patients treated with anticalcineurines (tacrolimus and cyclosporine) are confronted with major risks of interactions. Indeed, these antiviral are strong inhibitors of the enzyme cytochrome 3A4/A5, responsible for the metabolisme of ciclosprine and tacrolimus. The literature gives evidence of the dangerousness of this drug-drug interaction. We report four clinical cases illustrating the dosage adaptations at liver transplant patients and treated by telaprevir or boceprevir. To protect the immunosuppressive efficiency, a multidisciplinary care and narrow monitoring of the interaction between immunosuppressing agents and protease inhibitors were necessary.

[Dysthyroidism with anti-VEGF treatment, a class effect? about one case report]. / Dysthyroidie sous anti-VEGF, effet indésirable de classe ? à propos d'un cas.

Tyrosine-kinase inhibitors are recent therapy used in different neoplastic diseases. Dysthyroidism seems to be a class effect of these drugs with a potentially cross cumulative effect. We describe here the case of a man who first developed dysthyroidism with sunitinib, then a deep and permanent hypothyroidism when axitinib was introduced.

[Treatment with erlotinib after gefitinib induced hepatotoxicity: literature review and case report]. / Traitement par erlotinib après une toxicité hépatique induite par le géfitinib : revue de la littérature à propos d'une observation.

Gefitinib and erlotinib are selective epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor. They are approved for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR-TK. We report the case of a hepatitis cytolytic during gefitinib treatment with a positive rechallenge. A relay by erlotinib has been initiated and doesn't give recurrence of hepatotoxicity. From a literature review and this observation, arguments have been provided to justify erlotinib as a safe and well-tolered alternative for patients who have to stop gefitinib after a severe hepatotoxicity.

[Not Available]. / Dysthyroidie sous anti-VEGF, effet indésirable de classe ? À propos d'un cas.

Tyrosine-kinase inhibitors are recent therapy used in different neoplastic diseases. Dysthyroidism seems to be a class effect of these drugs with a potentially cross cumulative effect. We describe here the case of a man who first developed dysthyroidism with sunitinib, then a deep and permanent hypothyroidism when axitinib was introduced.