Δ9-Tetrahydrocannabinol (THC): A Critical Overview of Recent Clinical Trials and Suggested Guidelines for Future Research.

In this overview, we seek to appraise recent experimental and observational studies investigating THC and its potential role as adjunctive therapy in various medical illnesses. Recent clinical trials are suggestive of the diverse pharmacologic potentials for THC but suffer from small sample sizes, short study duration, failure to address tolerance, little dose variation, ill-defined outcome measures, and failure to identify and/or evaluate confounds, all of which may constitute significant threats to the validity of most trials. However, the existing work underscores the potential therapeutic value of THC and, at the same time, calls attention to the critical need for better-designed protocols to fully explore and demonstrate safety and efficacy. In the most general sense, the present brief review illuminates some intriguing findings about THC, along with the basic threats to the validity of the research that supports those findings. The intent is to highlight existing generic weaknesses in the existing randomized controlled trial literature and, most importantly, provide guidance for improved clinical research.

Physical and pharmacokinetic characterization of Soluvec™, a novel, solvent-free aqueous ivermectin formulation.

Purpose: To describe application of the Quicksol™ solvent-free approach to solubilize ivermectin (IVM). Methods: Lyophilized IVM complexed with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was resolubilized in aqueous polysorbate-80, generating Soluvec™. Lyophilizate was examined by Fourier-transform infrared spectroscopy and differential scanning calorimetry; Soluvec, by dynamic light scattering. Pharmacokinetics was evaluated in dogs allocated to subcutaneous (SC) or intramuscular (IM) Soluvec or oral IVM. Results: IVM in Soluvec was tightly bound by HPßCD, forming nearly monodisperse 28 nm particles with solubility ∼2500-times that of free IVM. SC and IM Soluvec increased IVM exposure, peak IVM and extended duration of IVM exposure, versus oral dosing. Conclusion: The Quicksol method generated Soluvec, a concentrated aqueous parenteral IVM formulation with pharmacokinetic properties suitable for veterinary or human use.

Ivermectin (IVM) kills insects and worms that cause disease. Because it doesn't dissolve well, blood IVM can be low. We found a new way to dissolve IVM, using simple, common materials. Dogs receiving our IVM (Soluvec™) had high blood IVM levels for longer, compared with tablet IVM. Next, we hope to learn the best ways to dose Soluvec in animals and people.

Self-medication dilemma in dengue fever.

This paper focuses on the trends of self-medication practices in treating symptoms that may lead to fatal complications in dengue. As dengue is a viral infection with increasing incidence, decision regarding its treatment is mostly affected by public health believes and practices to self-treat the condition by different home remedies, over-the-counter (OTC) drugs or using outdated prescription drugs that proved beneficial in the past experience. Poverty, lack of education, and poor access to health facilities pave the way for making such decisions. Future complications can be averted by raising awareness, counseling the patients and dispensing of pharmaceuticals with strict monitoring.

Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials.

INTRODUCTION: Insulin degludec (degludec) is a basal insulin with an ultra-long, stable action profile and reduced pharmacodynamic variability. Seven phase 3a trials compared degludec with insulin glargine (glargine). Patient-level meta-analyses were performed to obtain a comprehensive overview of differences between the insulin preparations, possible because consistent outcome definitions were utilized. METHODS: Three categories of trials were analyzed: basal-bolus-treated type 1 diabetes mellitus (T1DMB/B), insulin-naïve type 2 diabetes mellitus (T2DMinsulin-naïve), and basal-bolus-treated T2DM (T2DMB/B). Regression models were adjusted for baseline characteristics. Endpoints analyzed were glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), insulin dose and hypoglycemic rates analyzed in mutually exclusive groups: non-severe nocturnal, non-severe daytime, and severe. RESULTS: As with previous treat-to-target trials, reductions in HbA1c were similar between degludec and glargine. Reductions in FPG were significantly greater with degludec in T1DMB/B and T2DMinsulin-naïve. Total daily insulin dose was significantly lower with degludec in T1DMB/B and T2DMinsulin-naïve. Estimated hypoglycemia rate ratios for degludec/glargine were as follows for T1DMB/B, T2DMinsulin-naïve and T2DMB/B, respectively: non-severe nocturnal 0.83, 0.64, 0.75 (all P < 0.05); non-severe daytime 1.14 [not significant (ns)], 0.89 (ns), and 0.83 (P < 0.05). Rate ratios for severe events were 1.12 (ns) (T1DMB/B); 0.14 (P < 0.05) (T2DMinsulin-naïve); and not analyzed (T2DMB/B) due to too few events. CONCLUSIONS: Compared with glargine, degludec is associated with equivalent HbA1c control and significantly lower nocturnal hypoglycemia rates. In T1DMB/B and T2DMinsulin-naïve, degludec is also associated with significantly greater reductions in FPG and lower total doses of insulin versus glargine.

Adherence patterns in patients with type 2 diabetes on basal insulin analogues: missed, mistimed and reduced doses.

OBJECTIVE: To describe basal insulin analogue dosing irregularities, the effect of these events on patient functioning, well-being and diabetes management, and the identification of patients most at risk. RESEARCH DESIGN AND METHODS: The GAPP2 (Global Attitude of Patients and Physicians 2) study was an online multinational cross-sectional study of patients with type 2 diabetes currently treated with basal insulin, and healthcare professionals (HCPs) involved in the care of such patients. Basal insulin adherence patterns were evaluated with respect to three types of dosing irregularity: missed, mistimed [± 2 hours from prescribed time], and reduced dose over the last 30 days. RESULTS: A total of 3042 patients treated with basal insulin analogues and 1222 prescribers completed the full survey; 38% of patients reported any type of basal insulin dosing irregularity in the last 30 days. Patients reported missing (22% on 3 ± 0.16 occasions), mistiming (24% on 4.2 ± 0.21 occasions) or reducing (14% on 4.2 ± 0.24 occasions) basal insulin doses, with 15% of patients reporting multiple types of dosing irregularities. For most patients, missed (83%) and mistimed doses (82%) were unintentional, whereas the majority (87%) of patients reducing doses did so intentionally. Patients who intentionally missed or reduced a dose of basal insulin were significantly more likely to have performed this dosing irregularity on multiple occasions. Fifty-three percent of patients increased the frequency of blood glucose monitoring, and 17% of patients extended the duration of more frequent blood glucose monitoring by one or more days as a result of unintentional missed doses. Reduced dosing was highest in a subset of patients reporting self-treated hypoglycaemia. CONCLUSIONS: Basal insulin dosing irregularities including missed, mistimed and reduced doses are common. A significant proportion of patients also report undertaking these irregular dosing behaviours at a frequency that would be considered by prescribers to negatively impact diabetes management. This is despite the potential under-reporting due to recall or social bias that may be a limitation of a self-reported survey around these behaviours.

Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey in patients and physicians.

OBJECTIVES: The objectives were to estimate the prevalence of self-treated hypoglycaemia in patients using basal insulin analogues; identify demographic, treatment related and behavioural risk factors; and describe patient and physician responses to these events. RESEARCH DESIGN AND METHODS: The GAPP2 (Global Attitude of Patients and Physicians 2) study was an online multinational cross-sectional study of patients with type 2 diabetes currently treated with basal insulin, and healthcare professionals involved in the care of such patients. The primary variable of interest was self-treated hypoglycaemia within the last 30 days. RESULTS: A total of 3042 patients treated with basal insulin analogues and 1222 prescribers completed the full survey. Overall, 36% of patients had experienced self-treated hypoglycaemia during the previous 30 days. In response to self-treated hypoglycaemia, patients reported missing (7%), reducing (11%) or mistiming (4%) basal insulin doses, increasing the level of glucose monitoring (40%) or utilising healthcare resources (7%). Patients reporting irregular basal insulin dosing by missing, mistiming or reducing a dose were also significantly more likely to report an episode of self-treated hypoglycaemia in the same time period: 41% versus 34% (p = 0.004), 43% versus 33% (p < 0.001), and 56% versus 32% (p < 0.001) respectively. Nocturnal events worried significantly more patients than diurnal events (42% versus 23%, p < 0.001). Patient worry about hypoglycaemia, insulin regimen and reduced basal dosing were identified as the key differentiating variables associated with increased risk of self-treated hypoglycaemic events. Most prescribers (76%) believed that insulin analogues minimised the risk of nocturnal hypoglycaemia when compared to NPH insulin; 46% also reported being contacted at least once a month by insulin analogue patients after self-treated hypoglycaemic events. CONCLUSIONS: Self-treated hypoglycaemia is common in approximately one third of patients using insulin analogue regimens. Additionally, self-treated hypoglycaemia was found to be associated with clinically significant effects on patient well-being and functioning, patient and physician management and healthcare utilisation despite the potential limitations of an online self-complete survey such as the need to be topic focused, the potential for under-reporting and social bias.

Diffuse lamellar keratitis after laser in situ keratomileusis with the Moria LSK-One and Carriazo-Barraquer microkeratomes.

PURPOSE: To assess risk factors for and incidence of diffuse lamellar keratitis (DLK) and to investigate whether microkeratome design is associated with the incidence of DLK. SETTING: The Laser Eye Consultants of Boston, Boston and Waltham, Massachusetts, USA. METHODS: In a retrospective nonrandomized comparative study, 1122 consecutive primary laser in situ keratomileusis (LASIK) treatments (584 patients) were analyzed to determine the incidence of DLK using 2 different microkeratome designs (Moria LSK-One [LSK] and Moria Carriazo-Barraquer [C-B]). The incidence of DLK was as determined by clinical signs. RESULTS: The overall incidence of DLK was 2.23%. The incidence in the LSK and C-B groups was 1.09% and 4.38%, respectively, with a statistically significant difference in incidence between the 2 groups (P<.01). Epithelial irregularities increased the risk for DLK. There was no significant statistical difference in sex, age, operating room location, type of laser, or time of day the surgery was performed between the 2 groups or between eyes that had DLK and eyes without DLK. The incidence of DLK using the C-B microkeratome fell significantly after May 2000, when new cleaning methods for this device were introduced. CONCLUSIONS: Different microkeratomes and how they are maintained may influence the incidence of DLK. Diffuse lamellar keratitis is more common after LASIK in a setting of epithelial irregularities, whether or not an actual epithelial defect is created.

Understanding the accommodating intraocular lens.

PURPOSE: To review current accommodating intraocular lens (IOL) designs and introduce a new design consisting of a plus lens and a minus lens. SETTING: Cornea Consultants of Boston, Boston, Massachusetts, USA. METHODS: Computer simulation studies of a model eye calculated the pseudoaccommodation range with different powers of 1 IOL or of 2 IOLs acting as a doublet. RESULTS: The doublet consisting of a convex (plus) lens and a concave (minus) lens gave a greater range of power change than a single convex lens or a doublet consisting of 2 convex lenses. The greater range of power results from the plus lens moving forward. CONCLUSION: The results show that an IOL design consisting of positive and negative lenses that move closer or farther from each other offers a greater range of pseudoaccommodation than other designs.