Severe Hypernatremia During Hydatid Cyst Surgery: An Anusual Cause Of Acute Abdomen.

Treatment of liver hydatid cysts is still in most cases surgical. To avoid the recurrence of hydatid cysts injection of scolicidal products inside the cystic cavity is an important step in the surgical procedure. Many scolicidal solutions are used. Hypertonic Saline Solution (HSS) is widely used by surgeons; however, there is a risk of hypertonic saline resorption and acute hypernatremia. Iatrogenic hypernatremia can be life-threatening. We report three cases of hypernatremia secondary to HSS injection for hydatid cyst disease treatment. The objective of this study was to discuss the clinical features, and treatment of this rare complication.

Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder.

BACKGROUND AND OBJECTIVE: Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. In two phase III, 12-week studies in patients with insomnia disorder, daridorexant improved sleep and daytime functioning while maintaining a favorable safety profile. The objective of this 40-week extension study was to assess the long-term safety and tolerability of daridorexant. METHODS: Adults with insomnia disorder who completed the 12-week studies were invited to enroll in this double-blind extension study. Patients originally randomised to daridorexant (10 mg/25 mg/50 mg) remained on their respective treatments; patients randomised to placebo were re-randomised to daridorexant 25 mg or placebo. The 40-week treatment period was followed by a 7-day placebo run-out. The primary objective was to assess safety/tolerability. Exploratory objectives were to evaluate the efficacy of daridorexant on sleep (self-reported total sleep time) and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire). RESULTS: In total, 804 patients were enrolled in the study, of whom 801 received at least one dose of the study treatment and 550 patients (68.4%) completed the study. Overall incidence of treatment-emergent adverse events was similar across groups (35-40%). Daridorexant did not induce next-morning sleepiness and no withdrawal-related symptoms or rebound were observed after treatment discontinuation. Improvements in sleep and daytime functioning were maintained through to the end of the study and were most pronounced with daridorexant 50 mg. Daridorexant 50 mg, compared with placebo, increased self-reported total sleep time by a least-squares mean of 20.4 (95% confidence interval [CI] 4.2, 36.5), 15.8 (95% CI - 0.8, 32.5) and 17.8 (95% CI - 0.4, 35.9) minutes and decreased (i.e., improved) Insomnia Daytime Symptoms and Impacts Questionnaire total scores by a least-squares mean of - 9.3 (95% CI - 15.1, - 3.6), - 9.5 (95% CI - 15.4, - 3.5) and - 9.1 (95% CI - 15.6, - 2.7), at weeks 12, 24 and 36 of the extension study, respectively. CONCLUSIONS: Treatment with daridorexant, for up to 12 months, was generally safe and well tolerated. Exploratory efficacy analyses suggest that the sustained improvements in sleep and daytime functioning with daridorexant 50 mg support its use for long-term treatment of insomnia disorder, without concerns of new safety signals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03679884) [first posted: 21 September, 2018], https://clinicaltrials.gov/ct2/show/NCT03679884 .

Insomnia disorder is the long-term inability to fall asleep or stay asleep with a significant impact on daily life. Left inadequately treated, this disorder may increase the risk of other health problems. For patients with insomnia disorder who require a sleep medication, many drugs are not recommended for long-term use and there is an unmet need for one that can be used safely and effectively over the long term. Daridorexant is a new insomnia treatment that was approved for adults following positive results in two 12-week clinical studies. Both studies showed that, in patients with insomnia disorder, daridorexant improved night-time sleep and patients' ability to function during the day, while avoiding major safety concerns. Patients who completed these two studies could continue into a 40-week extension study enabling the safety and tolerability of daridorexant to be investigated for up to 1 year. Treatment remained double blind for the entire 1-year period. The extension study showed that daridorexant, at all doses studied (10 mg, 25 mg, 50 mg), continued to be generally safe and well tolerated. Patients showed no signs of tolerance, physical dependence, rebound nor any excessive daytime sleepiness. Exploratory efficacy analyses suggest that improved night-time and daytime symptoms of insomnia were sustained, in particular with the highest approved dose, 50 mg, and there were no signs that the benefits of the drug were wearing off at the end of the 1 year. These results support the use of daridorexant 50 mg for the long-term treatment of insomnia disorder in adults.

Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial.

BACKGROUND: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. METHODS: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. FINDINGS: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p<0·0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12·5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment. INTERPRETATION: In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40. FUNDING: Idorsia Pharmaceuticals and Janssen Biotech.

Les médicaments qui interfèrent avec les bilans biologiques : revue de la littérature.

BACKGROUND: Biological assessment is an integral part of the diagnostic process that guides therapeutic management decisions. However, these analyses remain subject to interference from endogenous or exogenous factors, which may alter the results. OBJECTIVE: To provide an up-to-date and comprehensive overview of the most commonly documented types of interference attributable to medications, to ensure reliable interpretation of test results and better management of patients. DATA SOURCES: This comprehensive systematic review of the literature was carried out in 2018. The bibliographic search was carried out in various online databases, specifically PubMed, ScienceDirect and Google Scholar. STUDY SELECTION: Only publications in French or English concerning medicinal products for human use were retained. The investigators' examination of drug-related interference with laboratory tests was limited to blood assays (serum or plasma). DATA EXTRACTION: An Excel spreadsheet was used to analyze the results. A total of 82 articles were selected. The interferences studied affected 47 biological parameters corresponding to various types of assessment: hormonal, hepatic, and renal. DATA SYNTHESIS: The mechanisms reported in the literature identified were analytical (56.9%), physiological (17.82%), and pharmacological (20.11%). The remainder of the mechanisms (5.17%) were not defined. CONCLUSIONS: Clinicians should be vigilant in validating and interpreting laboratory test results for patients receiving these types of drugs. Dialogue between clinicians and biological scientists is the best way to avoid unnecessary additional testing, which is often cumbersome and costly.

[Pain management in cancer patients in a Tunisian hospital]. / La gestion de la douleur chez les patients atteints du cancer dans un hôpital tunisien.

Pain is a common symptom in cancer patients. It is subjective and difficult to communicate. It continues to be outsourced and often overlooked despite the existence of multiple recommendations. The objective of this study is to describe pain management in cancer patients in a Tunisian hospital. This is a prospective study, conducted over one month at the maternity centre of Monastir by an intern in pharmacy using a questionnaire. Of 128 patients assessed, 50 were algic. Twenty-six percent of algic patients were not treated. The neuropathic component of pain was present in 30 % of cases but under treatment. Relief opioids were prescribed in 43 % of cases to relieve pain. Paracetamol was prescribed in 26 % of cases. Ten percent of patients use paracetamol self-medication. Sixteen percent of patients have tried non-pharmacological means, of which 62 % consume plants. To optimise the management of pain at our centre, the available analgesic sheets have been developed, validated by the medical staff and disseminated in the departments of carcinology and oncohematology. Therapeutic education sessions were also scheduled to warn patients about the risks of self-medication and misuse of medicinal plants. Pain management is complex. It requires respect for international recommendations, but especially for the efforts made by all stakeholders.