Safety and effectiveness of insulin lispro mix 25/75 among Filipino patients with type 1 or type 2 diabetes mellitus: A post-marketing surveillance study

BACKGROUND: Diabetes mellitus (DM) is a major cause of morbidity and mortality in the Philippines. Improvement in hemoglobin A1c (HbA1c) remains below recommended targets for Filipino patients. Safe and effective therapies are needed for this population.OBJECTIVE: To investigate treatment-emergent adverse events (TEAEs) and change in HbA1c among Filipino patients with DM treated with insulin lispro mix 25/75 in a real-world setting.MATERIALS AND METHODS: This was a prospective, non-interventional, post-marketing surveillance study among 459 Filipinos aged 18 years or older with type 1 or 2 DM. Patients were treated with insulin lispro mix 25/75 according to the approved label, as prescribed by the investigators, and observed for 12 weeks. Occurrence of all TEAEs and change in HbA1c from baseline to final visit were reported.RESULTS: Mean (SD) treatment duration was 12.93 (5.7) weeks, and mean total daily dose was 0.62 (0.29) units/kg. Eighteen patients (3.9%) experienced 23 TEAEs, the majority of which were mild. None were reported to be related to treatment. No serious TEAEs or hypoglycemic episodes were reported. Mean (95% confidence interval) HbA1c was significantly reduced by -2.03% (-2.19%, -1.87%), and 36.3% of patients achieved HbA1c CONCLUSION: In this observational study, no treatmentrelated safety signals using insulin lispro mix 25/75 were detected among Filipino diabetic patients. HbA1c was significantly reduced in Filipino patients with DM at 12 weeks.

Outreach in surgery at the undergraduate level: an opportunity to improve surgical interest among women?

Medical career choice is often formed at the premedical level, thus surgeons must reach out to undergraduates to enhance interest in surgery. Because there is a predominance of women among undergraduates (57%), this outreach also serves as an opportunity to introduce women to a surgical career. We developed an undergraduate course ("Surgery 99") offering course credit for participation in clinical research projects in surgery, shadowing surgeons in the operating room, and receiving mentorship for a surgical career. Six surgeons (50% women) served as course instructors. The final exam was a thesis with oral presentation. For enrollment, 132 students applied and 13 were accepted each quarter. Eleven students (85%) were women. None of the students had prior exposure to surgery. All but one student (93%) found the experience met or exceeded their expectations. Upon exit, knowledge attained was ranked highest, followed by observation in the operating room, and clinical research experience. All found that the course affirmed their decision to attend medical school and promoted their interest in surgery residency. We demonstrate a successful model for outreach in surgery at the undergraduate level that can positively influence interest in a surgical career, especially among women.

Expression of multiple artificial microRNAs from a chicken miRNA126-based lentiviral vector.

BACKGROUND: The use of RNAi in both basic and translational research often requires expression of multiple siRNAs from the same vector. METHODS/PRINCIPAL FINDINGS: We have developed a novel chicken miR126-based artificial miRNA expression system that can express one, two or three miRNAs from a single cassette in a lentiviral vector. We show that each of the miRNAs expressed from the same lentiviral vector is capable of potent inhibition of reporter gene expression in transient transfection and stable integration assays in chicken fibroblast DF-1 cells. Transduction of Vero cells with lentivirus expressing two or three different anti-influenza miRNAs leads to inhibition of influenza virus production. In addition, the chicken miR126-based expression system effectively inhibits reporter gene expression in human, monkey, dog and mouse cells. These results demonstrate that the flanking regions of a single primary miRNA can support processing of three different stem-loops in a single vector. CONCLUSIONS/SIGNIFICANCE: This novel design expands the means to express multiple miRNAs from the same vector for potent and effective silencing of target genes and influenza virus.

Drug delivery-mediated control of RNA immunostimulation.

RNA interference (RNAi) has generated significant interest as a strategy to suppress viral infection, but in some cases antiviral activity of unmodified short-interfering RNA (siRNA) has been attributed to activation of innate immune responses. We hypothesized that immunostimulation by unmodified siRNA could mediate both RNAi as well as innate immune stimulation depending on the mode of drug delivery. We investigated the potential of immunostimulatory RNAs (isRNAs) to suppress influenza A virus in vivo in the mouse lung. Lipidoid 98N12-5(1) formulated with unmodified siRNA targeting the influenza nucleoprotein gene exhibited antiviral activity. Formulations were optimized to increase antiviral activity, but the antiviral activity of lipidoid-delivered siRNA did not depend on sequence homology to the influenza genome as siRNA directed against unrelated targets also suppressed influenza replication in vivo. This activity was primarily attributed to enhancement of innate immune stimulation by lipidoid-mediated delivery, which indicates increased toll-like receptor (TLR) activation by siRNA. Certain chemical modifications to the siRNA backbone, which block TLR7/8 activation but retain in vitro RNAi activity, prevented siRNA-mediated antiviral activity despite enhanced lipidoid-mediated delivery. Here, we demonstrate that innate immune activation caused by unmodified siRNA can have therapeutically relevant effects, and that these non-RNAi effects can be controlled through chemical modifications and drug delivery.

Genetic strategy to prevent influenza virus infections in animals.

The natural reservoirs of influenza viruses are aquatic birds. After adaptation, avian viruses can acquire the ability to infect humans and cause severe disease. Because domestic poultry serves as a key link between the natural reservoir of influenza viruses and epidemics and pandemics in human populations, an effective measure to control influenza would be to eliminate or reduce influenza virus infection in domestic poultry. The development and distribution of influenza-resistant poultry represents a proactive strategy for controlling the origin of influenza epidemics and pandemics in both poultry and human populations. Recent developments in RNA interference and transgenesis in birds should facilitate the development of influenza-resistant poultry.

Tension pyopneumothorax in a child: a case report.

Pneumonia is an infection of the lung parenchyma that may result in pleural thickening, effusion, or an empyema. When there is air or gas in association with purulent exudate in the pleural cavity, a pyopneumothorax exists. The progression to pyopneumothorax under tension is extremely rare. We present a case of tension pyopneumothorax in a child.