Explore the vast range of titles available.

We investigated the efficacy and safety of dapagliflozin, a sodium–glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). Data for patients randomized to dapagliflozin 10mg or placebo with a history of HF were pooled from five clinical trials. HbA1c, weight and systolic blood pressure (SBP; two studies) were examined up to 52weeks using longitudinal repeated-measures models. Composite cardiovascular outcomes, hospitalizations for HF (HHF), and adverse events (AEs) were also assessed. Patients (mean age 64years, T2DM duration ~14years, HbA1c 8.2%, ~50% with New York Heart Association Class ≥II) received dapagliflozin (N=171) or placebo (N=149). Dapagliflozin produced clinically meaningful placebo-adjusted reductions in HbA1c (−0.55%; 95% confidence interval [CI]: −0.80, −0.30), weight (−2.67kg; 95% CI: −3.88, −1.47), and SBP (−2.05mmHg; 95% CI: −5.68, 1.57) over 52weeks. HHF was rare, but numerically lower with dapagliflozin (n=1 [0.6%]) vs placebo (n=7 [4.7%]). Point estimates for hazard ratios of composite cardiovascular outcomes favored dapagliflozin vs placebo, although 95% CIs crossed unity. Dapagliflozin produced clinically meaningful reductions in HbA1c, weight, and SBP in patients with T2DM and HF, and was well tolerated.

Background. Coma is a frequent presentation of severe malaria in adults and an important cause of death. The role of cerebral swelling in its pathogenesis, and the possible benefit of intravenous mannitol therapy to treat this, is uncertain. Methods. A computed tomographic (CT) scan of the cerebrum and lumbar puncture with measurement of cerebrospinal fluid (CSF) pressure were performed on admission for 126 consecutive adult Indian patients with cerebral malaria. Patients with brain swelling on CT scan were randomized to adjunctive treatment with intravenous mannitol (1.5 g/kg followed by 0.5 g/kg every 8 hours; n = 30) or no adjunctive therapy (n = 31). Results. On CT scan 80 (63%) of 126 patients had cerebral swelling, of whom 36 (29%) had moderate or severe swelling. Extent of brain swelling was not related to coma depth or mortality. CSF pressures were elevated (≥200 mm H 2 O) in 43 (36%) of 120 patients and correlated with CT scan findings (P for trend =.001). Mortality with mannitol therapy was 9 (30%) of 30 versus 4 (13%) of 31 without adjunctive therapy (hazard ratio, 2.4 [95% confidence interval, 0.8—7.3]; P =.11). Median coma recovery time was 90 hours (range, 22—380 hours) with mannitol versus 32 hours (range, 5—168 hours) without (P =.02). Conclusions. Brain swelling on CT scan is a common finding in adult patients with cerebral malaria but is not related to coma depth or survival. Mannitol therapy as adjunctive treatment for brain swelling in adult cerebral malaria prolongs coma duration and may be harmful.

Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli.

A 49-year-old woman with traumatic brain injury after an automobile accident is found to have raised intracranial pressure, and hyperosmolar therapy is recommended. Hyperosmolar therapy with either hypertonic saline or mannitol reduces intracranial pressure by reducing brain volume. Foreword This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the author's clinical recommendations. Stage A 49-year-old female passenger was thrown against the doorframe during an automobile accident. After being pulled from the car, she opened her eyes intermittently, moaned, and had flexion withdrawal of her limbs (Glasgow Coma Scale score, 8). Her pupils were 5 mm in diameter and reactive to light. Her blood pressure was 165/85 mm Hg, her heart rate 112 beats per minute, and her breathing regular. After her spine was stabilized, she was conveyed to an intensive care unit (ICU). In the ICU, she no longer opened her eyes, had flexion posturing of her arms, and made no verbal . . .

Mannitol is widely used for treating brain edema caused by various diseases, but it has been reported to cause acute kidney injury. However, the prognosis for patients with non-traumatic intracerebral hemorrhage who also have acute kidney injury and continue to receive mannitol has not yet been documented. This study presents a retrospective cohort analysis utilizing the MIMIC-IV (medical information mart for intensive care-IV) database. The study population comprised adult patients diagnosed with non-traumatic intracerebral hemorrhage (ICH) and concurrent acute kidney injury (AKI). Mannitol administration during the intensive care unit (ICU) stay was considered the exposure variable. The primary endpoint for analysis was 28-day all-cause mortality. To account for potential confounding factors, multivariable analytical methods were employed. The 28-day mortality rate within the total cohort was 25%. In the mannitol group, the 28-day mortality rate was 50.4% (58/115), compared to 21.9% (203/927) in the control group. Mannitol use was associated with a significantly higher 28-day all-cause mortality in both the multivariable analysis (HR 2.42; 95% CI 1.80–3.25; p  < 0.001) and the univariable analysis (HR 2.31; 95% CI 1.67–3.19; p  < 0.001). Other variables independently associated with mortality included higher heart rate, mean arterial pressure, respiratory rate, platelet count, sodium, chloride, lactate, urea nitrogen, creatinine, SAPSII, SOFA, GCS, and Charlson Index. The in-hospital mortality rate was 47.8% (55 out of 115) in the mannitol treatment group and 16.2% (150 out of 927) in the non-treatment group. Mannitol use was associated with higher 28-day all-cause mortality in patients with non-traumatic ICH and AKI. However, given the methodological limitations and incomplete confounder adjustment of this study, this finding should be interpreted with caution. Further research is needed to confirm this relationship and explore the underlying mechanisms.

Background This review article discusses a case of sodium imbalance and fluid dysregulation in a patient with traumatic brain injury (TBI), progressing through phases including mannitol-induced osmotic diuresis, arginine vasopressin deficiency (central diabetes insipidus), and syndrome of inappropriate antidiuresis (SIAD), before eventual resolution with euvolemia. The timeline of clinical interventions, laboratory trends, and diagnostic insights highlights the complexity of managing sodium and fluid balance in TBI patients. Objective To illustrate the diagnostic and management challenges of a pediatric TBI case complicated by the sequential development of osmotic diuresis, arginine vasopressin deficiency, syndrome of inappropriate antidiuretic hormone secretion (SIAD), and subsequent stabilization. Methods We present a detailed case report of a child with severe TBI who experienced multiple phases of sodium and fluid dysregulation, necessitating vigilant monitoring and dynamic management adjustments. Results The patient initially developed profound polyuria due to mannitol-induced osmotic diuresis, which obscured the emerging arginine vasopressin deficiency. The transition to SIAD further complicated management, requiring careful fluid and sodium correction. This case underscores the importance of close monitoring in post-TBI patients to detect evolving endocrine disturbances that necessitate timely interventions. Conclusion The sequential manifestation of osmotic diuresis, arginine vasopressin deficiency, SIAD, and eventual stabilization in a single patient is a rare and complex occurrence. This case emphasizes the need for dynamic fluid and electrolyte management, with ongoing assessment to tailor interventions appropriately. Our findings highlight the critical role of multidisciplinary teams in optimizing patient outcomes in pediatric TBI cases.

Background Mannitol is Food and Drug Administration-approved for the reduction of intracranial pressure associated with cerebral edema and the reduction of intraocular pressure and is a commonly used drug in clinical practice. Hypersensitivity to mannitol is rarely reported, and only nine cases have been documented in English since 1967, all of which exhibited a rapid onset. We report a case of delayed anaphylactic shock induced by mannitol, aiming to alert clinical practitioners to the potential occurrence of such rare and serious adverse drug reactions (ADRs). Case presentation A 62-year-old Asian Chinese male patient was administered mannitol to reduce intraocular pressure following eye trauma. He did not report any discomfort during the first five intravenous infusions of mannitol. However, upon the sixth administration, the patient presented with anaphylactic shock, characterized by an abrupt loss of consciousness and hypotension. In response, the intravenous infusion was promptly discontinued, and a balanced salt solution was administered for fluid replacement. Epinephrine was administered to elevate blood pressure, while dexamethasone was utilized for its properties of inhibiting allergic responses. Subsequently, the patient’s level of consciousness and blood pressure stabilized. Discussion We examined the correlation between anaphylactic shock in patients and mannitol, providing a concise summary of the characteristics noted in previous reports of mannitol-induced allergies. Additionally, we highlighted the distinctions of this particular case through a comprehensive literature review, as well as exploring the potential mechanisms behind delayed drug hypersensitivity reactions attributed to mannitol. Conclusion It is crucial to be aware of the delayed allergic reactions associated with mannitol. Further post-marketing surveillance studies are necessary to identify rare and unknown adverse drug reactions following therapy with mannitol.

Background Current guidelines state that osmotic therapy is reasonable in patients with clinical deterioration from cerebral infarction-related cerebral edema. However, there are limited data on the safety and efficacy of this therapy. We aimed to evaluate the effect of mannitol on the outcome of ischemic stroke-related cerebral edema. Methods and Results We prospectively studied 922 consecutive patients admitted with acute ischemic stroke. Patients who showed space-occupying brain edema with tissue shifts compressing the midline structures received mannitol. The outcome was assessed with dependency rates at discharge (modified Rankin Scale grade 2–5) and in-hospital mortality. Rates of dependency were higher in patients treated with mannitol ( n  = 86) than in those who were not (97.7 and 58.5%, respectively; p  < 0.001). Independent predictors of dependency were age, history of ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) score at admission. Rates of mortality were higher in patients treated with mannitol than in those who were not (46.5 and 5.6%, respectively; p  < 0.001). Independent predictors of in-hospital mortality were diastolic blood pressure [relative risk (RR) 1.05, 95% confidence interval (CI) 1.02–1.08, p  < 0.001], NIHSS score at admission (RR 1.19, 95% CI 1.14–1.23, p  < 0.001) and treatment with mannitol (RR 3.45, 95% CI 1.55–7.69, p  < 0.005). Conclusions Administration of mannitol to patients with ischemic stroke-related cerebral edema does not appear to affect the functional outcome and might increase mortality, independently of stroke severity.

Between December, 2011, and January, 2012, physicians at the Punjabi Institute of Cardiology in Lahore-a public facility serving mainly poor patients for free-reported unexpected deaths that the physicians linked to five locally manufactured heart drugs. In accordance with its constitution and global mandate, core functions of WHO include those that must be in place to ensure the integrity and functioning of health services. Since many member states spend 30% of their health budgets on medicines, and because faulty or badly used health goods injure patients, Oxfam used the example of the Essential Medicines Department as an important case study.