Aerosol-Mediated Non-Viral Lung Gene Therapy: The Potential of Aminoglycoside-Based Cationic Liposomes

Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF.

Infectious complications related to radiofrequency ablation of liver tumors: The role of antibiotics

Background and aim Prophylactic administration of antibiotics within 24 hours of surgery is recommended to reduce the risk of infection. We conducted a prospective study to compare the efficacy of single administration of antibiotics with a historical control of continuous administration of antibiotics for radiofrequency ablation (RFA) of malignant liver tumors. Methods Between February 1, 1999 and November 30, 2010, a total of 6,763 RFA treatments were performed in 2,355 patients, using a protocol with continuous administration of prophylactic antibiotics. On December 1, 2010, we began using a revised protocol with a single administration of prophylactic antibiotics, while continuing to use the old continuous administration protocol for patients who declined the new protocol. Interim analysis was performed to assess the safety of the single administration protocol. Thereafter, from April 1, 2012, all patients were treated using the new protocol. Risk factors for infectious complications of RFA were assessed using logistic regression. Results From December 2010 to March 2012, 766 RFA treatments were performed in 663 patients using the new antibiotic protocol. Infectious complications were observed following 4 of these treatments (0.52%). As the upper limit of the confidence interval (CI) resulting from a one-sided binomial test was exactly the prespecified limit of 1.0%, from April 2012 onwards, we treated all patients using the new protocol with single administration of prophylactic antibiotics. A total of 3,547 RFA treatments were performed using the single administration protocol. Univariable logistic regression indicated that prior transcatheter arterial chemoembolization (TACE) and maximal tumor diameter were significant risk factors for infectious complications (P = 0.04 and P < 0.001, respectively). Multivariable analysis indicated that the adjusted hazard ratio of single vs. continuous administration of antibiotics was 1.20 (95% CI: 0.53–2.75; P = 0.66). Conclusions The rate of infectious complications related to RFA was acceptably low. Single administration of prophylactic antibiotics did not significantly increase the rate of infectious complications related to RFA, compared with a more intensive antibiotic protocol.

Mitochondrial Function Influences Expression of Methamphetamine-Induced Motor Sensitization

Repeated methamphetamine use leads to neuronal maladaptations resulting in addictions. Mechanisms that underpin such adaptations have high energy requirements, implicating mitochondria involvement in addiction-related processes. We pharmacologically explored this possibility in methamphetamine self-administering rats. Motor sensitization a readout that is thought to reflect brain maladaptations akin to those occurring in methamphetamine abusing humans. This was assessed to determine (i) if a short access self-administration protocol results in the expression of motor sensitization, (iii) if and when, mitochondrial function is critical for protracted maintenance and (iii) whether drug contingency influences motor sensitization. Rats self-administered iv methamphetamine for 3 hours per day for 14 days. Those with iv cannula that failed patency were redeployed as non-contingent methamphetamine-matched animals. At three different times during forced abstinence, mitochondrial function was impaired with a low dose of the toxin, rotenone (1mg/kg/day) via a osmotic minipump. Motor sensitization was determined during an acute treatment of methamphetamine (1.25mg/kg sc) on abstinence day 62. Methamphetamine self-administration was sufficient to induce motor sensitization. Rotenone administration prevented the expression of sensitization, but the profile depended on abstinence time exposure. Drug contingency also influenced sensitization profiles. Mitochondrial function underpins neuronal plasticity associated with maintenance of motor sensitization induced by methamphetamine self-administration.

Application of Pulsed Rhythmic Drug Administration to Ovulation Induction Therapy in PCOS Patients with Clomiphene-Resistance: a Retrospective Research

There is currently a dispute over the choice of ovulation induction treatment for infertile women with polycystic ovary syndrome (PCOS). The objective of this study is to compare the therapeutic effect of pulsed rhythmic administration protocol (PRAP) with conventional letrozole + human menopausal gonadotropin (HMG) in patients with clomiphene-resistance polycystic ovary syndrome (PCOS). A retrospective analysis of 821 intrauterine insemination (IUI) cycles between January 2015 and January 2020 was performed. Of these, 483 cycles were treated with a pulsed rhythmic administration protocol (PRAP), and 338 cycles were treated with conventional letrozole + HMG protocol (LHP). The therapeutic effect of the two protocols has been compared. The pregnancy rate was 18.07% in the LHP and 27.07% in the PRAP. The ongoing pregnancy rate in LHP was 14.46% and in PRAP was 22.73%. The research suggests that PRAP is more effective than LHP and could be an adequate ovulation induction strategy for the IUI cycle of patients with clomiphene-resistance PCOS.

Nurses’ Perceptions on the Implementation of a Safe Drug Administration Protocol and Its Effect on Error Notification

Patient safety and quality of care are fundamental pillars in the health policies of various governments and international organizations. The purpose of this study is to evaluate nurses’ perceptions on the degree of implementation of a protocol for the standardization of care and to measure its influence on notification of adverse events related to the administration of medications. This comparative study used data obtained from questionnaires completed by 180 nurses from medical and surgical units. Our analyses included analysis of variance and regression models. We observe that the responses changed unevenly over time in each group, finding significant differences in all comparisons. The mean response rating was increased at 6 months in the intervention group, and this level was maintained at 12 months. With the new protocol, a total of 246 adverse events and 481 incidents without harm was reported. Thus, actions such as the use of protocols and event notification systems should be implemented to improve quality of care and patient safety.

Analysis of intraoperative modifiable factors to prevent acute kidney injury after elective noncardiac surgery: intraoperative hypotension and crystalloid administration related to acute kidney injury

Background The optimal intraoperative blood pressure range and crystalloid administration protocol for the prevention of acute kidney injury (AKI) after elective noncardiac surgery remain unknown. Methods This single-center retrospective cohort study included 6296 patients aged ≥ 50 years who had undergone elective noncardiac surgery under general anesthesia. We evaluated the relationship between duration of intraoperative hypotension and AKI. To assess whether the effects of crystalloid administration differed according to baseline estimated glomerular filtration rate (eGFR), we examined the interaction between intraoperative crystalloid administration and eGFR. We calculated univariable and multivariable adjusted odds ratios (ORs) and their 95% confidence intervals (95% CIs) for the prevalence of AKI. Results AKI occurred in 431 (6.8%) patients and was associated with intraoperative hypotension. Effects of intraoperative crystalloid administration differed significantly according to baseline eGFR. Increased risk of AKI was noted in patients with eGFR ≤45 ml min−1 1.73m−2 who were managed with restrictive or liberal crystalloid administration [OR 4.79 (95% CI 3.10 to 7.32) and 6.43 (95% CI 2.23 to 16.03), respectively] as opposed to those with eGFR >45 ml min−1 1.73m−2 who were managed with moderately restrictive crystalloid administration. Conclusions Our findings suggest that anesthesiologists should avoid intraoperative hypotension as well as either restrictive or liberal (as opposed to moderately restrictive) crystalloid administration in patients with decreased eGFR. Intraoperative blood pressure and crystalloid administration protocol are major modifiable factors that must be optimized to prevent postoperative AKI.

Safety and Effectiveness of an Accelerated Intravenous Iron Administration Protocol in Hospitalized Patients With Heart Failure

Background: The ACC/AHA heart failure (HF) guidelines include a class IIb recommendation for intravenous (IV) iron replacement in patients with iron deficiency and New York Heart Association class II or III to improve functional status and quality of life. Several studies have addressed the use of IV iron formulations such as ferric carboxymaltose or iron sucrose in HF population; however, few studies focused on sodium ferric gluconate complex (SFGC). Objectives: To assess the safety and effectiveness of an IV SFGC administration protocol in patients hospitalized with HF. Methods: A retrospective cohort study was conducted. We included patients admitted to the HF service from September 2017 to March 2018. The primary outcome was the frequency of adverse reactions. The secondary outcome was the odds of HF readmissions between the 2 groups (IV SFGC vs. control). Results: Of the 123 patients, 70 received IV iron (SFGC group) and 53 did not receive IV iron (control group). Five (7%) patients of the 70 in the SFGC group experienced adverse events, which included hypotension (n = 2, 2.8%), fever (n = 2, 2.8%) and myalgia (n = 2, 2.8%). Nine (12.8%) and 18 (25.7%) were readmitted within 30 days and 6 months respectively. In the control arm, 5 (9.4%) and 14 (26.4%) were admitted within 30 days and 6 months respectively. The odds of HF readmission at 30 days [OR 1.4 (95% CI: 0.45, 4.5)] and at 6 months [OR 0.96 (95% CI: 0.43, 2.2)] were similar in those who did not receive IV iron compared to those who received IV iron. Conclusions: Sodium ferric gluconate complex given at an accelerated dosing schedule appears to provide a more efficient means to prescribe IV iron in the inpatient setting and is safe with a low frequency of hypotension, fevers, and myalgias.

Importance of gamma radiation using sodium pertecnetate (TC 99m) and iodine 131 as a suggestion in the treatment of COVID-19

Objective: to point out the importance of nuclear medicine for the diagnosis and therapy of COVID-19, in addition to reporting the efficacy of treatment with radioisotopes (sodium pertechnetate and iodine 131) in individuals infected with SARS-CoV-2 causing viral sterility and preventing its mutagenesis and ensuring the absence of adverse reactions. Methodology: This is a review of the narrative-type literature, prepared between June and September 2020, using the following databases: PubMed, SciELO and Lilacs. Thus, there was the inclusion of articles published between 1971 and 2020. Results and Discussion: The use of gamma and neutron radiation for the purpose of eliminating viral pathogens has been extensively researched in American studies, initially focusing on H1N1. The substance of Sodium Pertecnate, suggested in this study, and iodo 131 (designed to act as prevention in the cervical region) have the potential for satisfactory responses in the therapeutic treatment of COVID-19 due to the innocuous, painless and free of any effect methodology therefore, offering greater security to the treatment. Inferring in the replication of the coronavirus through the electrolysis of its fatty structure, since with the sterilization of its RNA molecule there will be no replication. Final Consideration: Based on the effectiveness of this method in sterilization protocols and action on various types of microorganisms, especially other viruses that affect the respiratory system, it is suggested as a safe, low-cost and low-dose radioactivity method for the patient, when used doses similar to those of the diagnostic and therapeutic practice in Nuclear Medicine. It should be noted that the administration protocol must be in accordance with the standard already recommended clinically, with full guarantee of the absence of associated effects. For better clarification, there is a need for more specific research within the scope of SARS-CoV-2.