Interactions Between Opioids and Dextroamphetamine on Locomotor Activity: Influence of an Opioid's Relative Efficacy at the Mu Receptor

Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the behavioral effects of stimulants, whereas opioid receptor antagonists generally attenuate the behavioral effects of stimulants; however, less is known regarding the interactions between stimulants and opioids possessing low to intermediate efficacy at the mu receptor. The purpose of this study was to examine the role of an opioid's relative efficacy at the mu receptor in altering the behavioral effects of dextro(d-)amphetamine. To this end, opioids possessing a range of relative efficacy at the mu receptor were examined alone and in combination with cumulative doses of d-amphetamine on a test of open-field, locomotor activity in male rats. Levorphanol, buprenorphine, butorphanol, nalbuphine, (-)-pentazocine, (-)-metazocine, (-)-cyclazocine, (-)-NANM, and nalorphine increased the locomotor effects of d-amphetamine in either an additive or greater-than-additive manner according to an effect-additive model. Only the selective, high-efficacy kappa agonist, spiradoline, and the non-selective opioid receptor antagonist, naloxone, failed to increase the effects of d-amphetamine under the conditions examined. These data indicate that opioids possessing a large range of relative efficacy at the mu receptor, including those possessing very low relative efficacy, significantly increase the locomotor effects of d-amphetamine.

COMPARATIVE ASSESSMENT OF FOSFOMYCIN AND NITROFURANTOIN THERAPY IN URINARY TRACT INFECTION DURING PREGNANCY.

Background: Urinary tract infections in pregnancy can be complications if the microbes causing it are proven to be resistant to standard use antibiotics. Routinely a multi-dose regimen of nitrofurantoin is used as a management protocol, however recent literatures have highlighted the relative efficacy of Fosfomycin in successful treatment. The present study was done to comparatively assess the efficacy of single dose Fosfomycin and standard dose nitrofurantoin in UTI among pregnant females, Methodology: Study employed a pool of 60 subjects divided equally in two groups. The groups were provided either with Fosfomycin or nitrofurantoin. Observations: Fosfomycin showed a lower rate of side effects and microbial resistance as compared to nitrofurantoin. The clinical and laboratory analysis revealed a statistically significant superiority of Fosfomycin in the selected study sample. Conclusion: Fosfomycin showed a better outcome compared to nitrofurantoin in the selected study sample. Keywords: Fosfomycin, Nitrofurantoin, Pregnancy, UTI

Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines

Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of two vaccine products. Estimates of rVE for enhanced influenza vaccines (eIV) vs. standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (e.g., all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (i.e., as compared with placebo) on the interpretation of rVE of eIV vs IIV. We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials.

A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan

Background. In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications’ relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. Methods. We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data. Results. The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours. Conclusion. Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.

Finding an effective way to create learning environments for didactic courses in a virtual classroom setting

Background: The COVID-19 pandemic forced college administrators to do virtual classes using Zoom webinars during the autumn of 2021. The study objective is to examine the relative efficacy of interactive vs non-interactive Zoom webinars in virtual classrooms during the COVID-19 era. Methods: These two modes of live Zoom webinars were used for Year 1 Pharmacy students. Two surveys were conducted among students for general feedback on teaching and their preferred type of virtual learning. Results: Amongst the 177 students present, 87 (49%) responded to the first survey, of whom 20 (23%) provided their feedback about the Zoom webinar. Amongst these responders, a relatively higher number of students preferred interactive Zoom webinars with student panellists. Also, of the 177 students, 118 (66.7%) students responded to the second survey on the mode of live Zoom webinars. Amongst the respondents, around 88-99 (74-84%) agreed or strongly agreed that a live Zoom webinar with interactive sessions is more effective than non-interactive sessions. Additionally, 73 (62%) of the respondents preferred five to ten students in the panel. Furthermore, the survey analysis suggested that the effectiveness of interactive sessions is the same irrespective of the instructors. Conclusion: The results concluded that the interactive live Zoom webinar with 5-10 student panellists is effective in creating a learning environment in virtual didactic courses.

Protocol for GET FIT Prostate: a randomized, controlled trial of group exercise training for fall prevention and functional improvements during and after treatment for prostate cancer

Background Many prostate cancer survivors are treated with androgen deprivation therapy (ADT), but these therapies may increase frailty, worsen physical functioning, and increase fall risk. While exercise may counter functional declines associated with ADT, no studies have tested whether and which type of exercise may reduce falls and frailty. The purpose of this trial is to compare the relative efficacy of strength training versus tai ji quan training against each other and to a stretching control group on falls, frailty, and physical functioning in men expose to ADT for prostate cancer. Methods Prostate cancer survivors treated with ADT (N = 360) who have fallen in the past year or are at risk of a fall based on validated risk factors will be recruited to participate in this single-blind, parallel group, randomized trial. Participants will be randomized to one of three supervised, group training programs: (i) strength training, (ii) tai ji quan training, or (iii) stretching (control), that train 3×/week for 6 months. Outcomes are assessed at baseline, 3 (mid-intervention), 6 (immediately post-intervention), and 12 (follow-up) months. The primary outcome is falls assessed by monthly self-report. Secondary outcomes include the following: frailty (low lean body mass (by bioelectrical impedance analysis), exhaustion (by SF-36 vitality scale), low activity (by CHAMPS physical activity survey), slowness (by 4 m usual walk speed), and weakness (by chair stand time)); objective and subjective measures of physical function will also be collected. Negative binomial regression models will be used to assess differences in falls between groups, while mixed effects modeling will be used to compare the relative efficacy of training group on secondary outcomes. Discussion Exercise represents a non-pharmacologic approach to mitigate the problem of falls experienced among men treated with ADT. By engaging in appropriate exercise, men may be able to avoid or delay falls, frailty, and disability associated with their cancer treatment. Findings of the trial are expected to inform clinical practice about how exercise could be prescribed as part of cancer care for prostate cancer survivors prescribed ADT. Trial registration ClinicalTrials.gov NCT03741335. Registered on November 18, 2018.

Relative Efficacy of Dry-Off Antimicrobial Treatments in Dairy Cattle to Cure Existing Intramammary Infections: A Systematic Review and Network Meta-Analysis

This systematic review and network meta-analysis aimed to estimate the relative efficacy of dry cow antimicrobial therapies, registered in Canada and/or the United States, to cure existing intramammary infections (IMI) in dairy cattle. The controlled trials examining all-cause cures of existing IMI present at dry-off were eligible. Five databases and four conference proceeding platforms were searched. The risk of bias at the level of the outcome was assessed using the Cochrane 2.0 risk of bias instrument (Cochrane, Denmark), and the overall confidence in the findings from the network meta-analysis was assessed using the Confidence in Network Meta-Analysis (CINeMA) platform. Of 3,743 articles screened for eligibility by the two independent reviewers, 58 trials were included in the Bayesian network meta-analysis for the all-cause cure of existing IMI from dry-off to calving. No antimicrobial treatment (non-active control) was associated with a decreased risk of a cure compared with all other currently labeled antimicrobials in Canada and the United States; however, lack of replication trials for some antimicrobial products created large credibility intervals and, therefore, we were unable to identify meaningful comparisons between the products. Poor reporting of trial features, heterogeneity in outcome measurements, and high risk of bias in some domains further contributed to this inability to compare antimicrobials. Continued improvement in the reporting of animal trials is required to make recommendations for antimicrobial products on the basis of efficacy.Systematic Review Registration:https://atrium.lib.uoguelph.ca/xmlui/bitstream/handle/10214/16236/Protocol_NMA_efficacy_dryoff_antibiotics_cure_IMI.pdf?sequence=3&isAllowed=y.