New Onset Hypoglycemia in Non-diabetic Adult Patients: Where Do We Go from Here?

Background: Hypoglycemia is a commonly encountered metabolic state in the patient population. It can be medically defined as a blood sugar \u3c70mg/dL in a diabetic patient or \u3c50mg/dL in a non-diabetic patient. It is less frequently seen in non-diabetics due to the body’s ability to autoregulate insulin administration. Common symptoms are sweating, tremors, palpitations, dizziness, drowsiness, and confusion. If left untreated, these symptoms can progress to seizures, arrythmias, or other complications that ultimately lead to death. Objective: To highlight the possible causes of hypoglycemia and the appropriate work-up for normally euglycemic patients. Case Description: We herein report a case of hypoglycemia in a 36-year-old female with Lupus related end-stage renal disease on hemodialysis via Ash-catheter who presented with peritonitis due to a defunct peritoneal dialysis catheter. The patient was found to be bacteremic; therefore both catheters were removed and antibiotics were started. Repeat blood cultures showed no growth for 48 hours, so the patient was held fasting at midnight for placement of a new catheter. On the day of surgery, she registered multiple blood sugar readings as low as 15mg/dL. Her symptoms were limited to drowsiness and shortness of breath. She was given four D50 boluses, glucagon IV, and a D5 drip that was adjusted to a D15 drip to stabilize her blood sugar. It was discovered that at an admission two months ago, the patient had a few readings in the 30s. She denied any recollection of this and claimed to have been asymptomatic. She also denied a history of low blood sugars and a diagnosis of diabetes. In surgery that day, the patient went into cardiac arrest on the operating table after being sedated. She was resuscitated after one round of chest compressions, and her catheter was placed. During the episodes of low blood sugar, specific labs were drawn for the work-up of hypoglycemia (glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, insulin antibodies, and sulfonylurea/meglitinide screen), but results yielded inconclusive values that prevented a diagnosis. The patient’s blood sugars became steady once her diet was restarted, and she was discharged in stable condition to a rehab facility after cautionary counseling was given. Discussion: This case highlights an optimal way to work-up a patient with new onset hypoglycemia, focusing on patient history and drawing the appropriate labs during hypoglycemic episodes. The specific labs listed above can be used to differentiate between various causes of hypoglycemia (exogenous insulin administration, an insulin secreting tumor [insulinoma], insulin antibodies, insufficient cortisol or glucagon levels, or improper sulfonylurea/meglitinide use) by comparing them to standards. If labs are unable to be obtained, a 72-Hour Fast can be conducted to create a controlled environment, and a Glucagon Tolerance Test can further explore if the cause of hypoglycemia is insulin related. The goal of all of this testing is to be able to identify and treat the underlying cause of the hypoglycemia and prevent future episodes and the complications that accompany it

Liqui-pellet: the emerging next-generation oral dosage form which stems from liquisolid concept in combination with pelletization technology

In spite of the major advantages that the liquisolid technology offers, particularly in tackling poor bioavailability of poorly water-soluble drugs (i.e., BCS Class II drugs), there are a few critical drawbacks. The inability of a high liquid load factor, poor flowability, poor compactibility, and an inability to produce a high dose dosage form of a reasonable size for swallowing are major hurdles, hampering this technology from being commercially feasible. An attempt was therefore made to overcome these drawbacks whilst maintaining the liquisolid inherent advantages. This resulted in the emerging next generation of oral dosage forms called the liqui-pellet. All formulations were incorporated into capsules as the final product. Solubility studies of naproxen were conducted in different liquid vehicles, namely polyethylene glycol 200, propylene glycol, Tween 80, Labrafil, Labrasol, and Kolliphor EL. The scanning electron microscopy studies indicated that the liquid vehicle tends to reduce the surface roughness of the pellet. X-ray powder diffraction (XRPD) indicated no significant differences in the crystalline structure or amorphous content between the physical mixture and the liqui-pellet formulation. This was due to the presence of a high concentration of amorphous Avicel in the formulation which overshadowed the crystalline structure of naproxen in the physical mixtures. Flowability and dissolution tests confirmed that this next-generation oral dosage form has excellent flowability, whilst maintaining the typical liquisolid enhanced drug release performance in comparison to its physical mixture counterpart. The liqui-pellet also had a high liquid load factor of 1, where ~ 29% of the total mass was the liquid vehicle. This shows that a high liquid load factor can be achieved in a liqui-pellet without compromising flowability. Overall, the results showed that the poor flowability of a liquisolid formulation could be overcomed with the liqui-pellet, which is believed to be a major advancement into the commercial feasibility of the liquisolid concept

Optimising the release rate of naproxen liqui-pellet: a new technology for emerging novel oral dosage form

Liqui-pellet is a new dosage form stemming from pelletisation technology and concept from liquisolid technology. In spite of liqui- pellet overcoming a major hurdle in liquisolid technology through achieving excellent flow property with high liquid load factor, the formulation requires to be optimised in order to improve drug release rate. Liqui-pellets of naproxen containing Tween 80, Primojel, Avicel and Aerosil were extruded and spheronised. Flowability test confirmed that all liqui-pellet formulations have excellent-good flow property (Carr’s index between 3.9–11.17%), including liqui-pellets with a high liquid load factor of 1.52, where 38% of the total mass is co-solvent. This shows a relatively high liquid load factor can be achieved in liqui-pellet without compromising the flowability, which is one of the key novelty of this work. It was found that the improved drug release rate was due to the remarkably improved disintegration of the supposedly non-disintegrating microcrystalline-based pellet; the optimised liqui-pellet seems to explode into fragments in the dissolution medium. At pH 1.2, the optimised formulation had ~ 10% more drug release than non-optimised formulation after 2 h, and at pH 7.4, the drug release of the optimised pellet was nearing 100% at ~ 15 min, whereas the none- optimised pellet only achieved ~ 79% drug release after 2 h. DSC and XRPD indicated an increase in the dissolution rate could be due to molecularly dispersion of naproxen in the pellets. Overall results showed that liqui-pellet exhibited an enhanced drug release and the capacity for high liquid load factor whilst maintaining excellent flowability, rendering it a potentially commercially feasible drug delivery system

Comparative efficacy of escitalopram in the treatment of major depressive disorder

Mazen K Ali, Raymond W LamDepartment of Psychiatry, University of British Columbia, and Mood Disorders Centre, University of British Columbia Hospital, Vancouver, CanadaBackground: Escitalopram is an allosteric selective serotonin reuptake inhibitor (SSRI) with some indication of superior efficacy in the treatment of major depressive disorder. In this systematic review, we critically evaluate the evidence for comparative efficacy and tolerability of escitalopram, focusing on pooled and meta-analysis studies.Methods: A literature search was conducted for escitalopram studies that quantitatively synthesized data from comparative randomized controlled trials in MDD. Studies were excluded if they did not focus on efficacy, involved primarily subgroups of patients, or synthesized data included in subsequent studies. Outcomes extracted from the included studies were weighted mean difference or standard mean difference, response and remission rates, and withdrawal rate owing to adverse events.Results: The search initially identified 24 eligible studies, of which 12 (six pooled analysis and six meta-analysis studies) met the criteria for review. The pooled and meta-analysis studies with citalopram showed significant but modest differences in favor of escitalopram, with weighted mean differences ranging from 1.13 to 1.73 points on the Montgomery Asberg Depression Rating Scale, response rate differences of 7.0%–8.3%, and remission rate differences of 5.1%–17.6%. Pooled analysis studies showed efficacy differences compared with duloxetine and with serotonin noradrenaline reuptake inhibitors combined, but meta-analysis studies did not. The effect sizes of the efficacy differences increased in the severely depressed patient subgroups.Conclusion: Based on pooled and meta-analysis studies, escitalopram demonstrates superior efficacy compared with citalopram and with SSRIs combined. Escitalopram shows similar efficacy to serotonin noradrenaline reuptake inhibitors but the number of trials in these comparisons is limited. Efficacy differences are modest but clinically relevant, especially in more severely depressed patients.Keywords: escitalopram, depressive disorders, meta-analysis, pooled analysis, efficacy, antidepressant

Moser functions and fractional Moser-Trudinger type inequalities

We improve the sharpness of some fractional Moser-Trudinger type inequalities, particularly those studied by Lam-Lu and Martinazzi. As an application, improving upon works of Adimurthi and Lakkis, we prove the existence of weak solutions to the problem $(-\Delta)^\frac{n}{2}u=\lambda ue^{bu^2} \,\text{ in }\Omega,\, 00,$ with Dirichlet boundary condition, for any domain $\Omega$ in $\mathbb{R}^n$ with finite measure. Here $\lambda_1$ is the first eigenvalue of $(-\Delta)^\frac n2$ on $\Omega$

Study of the transformations of micro/nano-crystalline acetaminophen polymorphs in drug-polymer binary mixtures

This study elucidates the physical properties of sono-crystallised micro/nano-sized acetaminophen/paracetamol (PMOL) and monitors its possible transformation from polymorphic form I (monoclinic) to form II (orthorhombic). Hydrophilic Plasdone® S630 copovidone (S630), N-vinyl-2-pyrrolidone and vinyl acetate copolymer, and methacrylate-based cationic copolymer, Eudragit® EPO (EPO), were used as polymeric carriers to prepare drug/polymer binary mixtures. Commercially available PMOL was crystallised under ultra sound sonication to produce micro/nano-sized (0.2–10 microns) crystals in monoclinic form. Homogeneous binary blends of drug-polymer mixtures at various drug concentrations were obtained via a thorough mixing. The analysis conducted via the single X-ray crystallography determined the detailed structure of the crystallised PMOL in its monoclinic form. The solid state and the morphology analyses of the PMOL in the binary blends evaluated via differential scanning calorimetry (DSC), modulated temperature DSC (MTDSC), scanning electron microscopy (SEM) and hot stage microscopy (HSM) revealed the crystalline existence of the drug within the amorphous polymeric matrices. The application of temperature controlled X-ray diffraction (VTXRPD) to study the polymorphism of PMOL showed that the most stable form I (monoclinic) was altered to its less stable form II (orthorhombic) at high temperature (>112°C) in the binary blends regardless of the drug amount. Thus, VTXRD was used as a useful tool to monitor polymorphic transformations of crystalline drug (e.g. PMOL) to assess their thermal stability in terms of pharmaceutical product development and research

Correlation between ocular elasticity and intraocular pressure on optic nerve damages

Optic neuropathy in glaucoma causes visual field loss and blindness [1]. The optic nerve damage in the lamina cribrosa (LC) of the sclera, the primary site of glaucoma, is correlated with the intraocular pressure (IOP) [2]. Literature shows that the optic nerves are sheared at high IOP and the scleral biomechanical properties play an important role in the development and progression of glaucomatous damage to the LC and ganglion cell axons with the optic nerve head (ONH). The aim of this study is to determine and characterize the correlation between the corneal, scleral and ONH elasticity, and intraocular pressure on the optic nerve damages

Correlation between ocular elasticity and intraocular pressure on optic nerve damages

Optic neuropathy in glaucoma causes visual field loss and blindness [1]. The optic nerve damage in the lamina cribrosa (LC) of the sclera, the primary site of glaucoma, is correlated with the intraocular pressure (IOP) [2]. Literature shows that the optic nerves are sheared at high IOP and the scleral biomechanical properties play an important role in the development and progression of glaucomatous damage to the LC and ganglion cell axons with the optic nerve head (ONH). The aim of this study is to determine and characterize the correlation between the corneal, scleral and ONH elasticity, and intraocular pressure on the optic nerve damages