The evolution of mean arterial pressure in critically ill patients on vasopressors before and during a trial comparing a specific mean arterial pressure target to usual care

Background In randomized clinical controlled trials, the choice of usual care as the comparator may be associated with better clinician uptake of the study protocol and lead to more generalizable results. However, if care processes evolve to resemble the intervention during the course of a trial, differences between the intervention group and usual care control group may narrow. We evaluated the effect on mean arterial pressure of an unblinded trial comparing a lower mean arterial pressure target to reduce vasopressor exposure, vs. a clinician-selected mean arterial pressure target, in critically ill patients at least 65 years old. Methods For this multicenter observational study using data collected both prospectively and retrospectively, patients were recruited from five of the seven trial sites. We compared the mean arterial pressure of patients receiving vasopressors, who met or would have met trial eligibility criteria, from two periods: [1] at least 1 month before the trial started, and [2] during the trial period and randomized to usual care, or not enrolled in the trial. Results We included 200 patients treated before and 229 after trial initiation. There were no differences in age (mean 74.5 vs. 75.2 years; p = 0.28), baseline Acute Physiology and Chronic Health Evaluation II score (median 26 vs. 26; p = 0.47) or history of chronic hypertension (n = 126 [63.0%] vs. n = 153 [66.8%]; p = 0.41). Mean of the mean arterial pressure was similar between the two periods (72.5 vs. 72.4 mmHg; p = 0.76). Conclusions The initiation of a trial of a prescribed lower mean arterial pressure target, compared to a usual clinician-selected target, was not associated with a change in mean arterial pressure, reflecting stability in the net effect of usual clinician practices over time. Comparing prior and concurrent control groups may alleviate concerns regarding drift in usual practices over the course of a trial or permit quantification of any change.

Antimicrobial Formulation of Chrysopogon zizanioides Essential Oil in an Emulsified Lotion for Acne

Acne is a skin condition arising from excess sebum production and microbial overgrowth within the pilosebaceous unit. Several commercial essential oils have shown promising activity against acne-related pathogens. Due to their volatility and thermal instability, the formulation of essential oils into commercial products remains a pharmaceutical challenge. Thus, this study aimed to develop a viable anti-acne topical treatment as an oil-in-water emulsified lotion to overcome these challenges. Chrysopogon zizanioides (vetiver) displayed noteworthy antimicrobial activity with a mean minimum inhibitory concentration of 0.14 mg/mL against Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. Emulsified lotions containing C. zizanioides were developed through the hydrophilic-lipophilic balance approach. At tested hydrophilic-lipophilic balance values of 8, 9, and 10, C. zizanioides emulsified lotions displayed maximum stability at hydrophilic-lipophilic balance 9 with a minimum change in mean droplet size and polydispersity index of 20.61 and 33.33%, respectively, over 84 days. The C. zizanioides emulsified lotion at optimum hydrophilic-lipophilic balance 9 completely inhibited the growth of C. acnes and killed S. aureus, S. epidermidis, and S. pyogenes within 24 h. Additionally, the lotion retained antimicrobial activity against these test micro-organisms over the 84-day stability test period. Thus, the C. zizanioides emulsified lotion demonstrated physical stability and antimicrobial efficiency, making it an ideal natural product anti-acne treatment.

Comparison of Intravitreal Ranibizumab and Aflibercept for the Treatment of Diabetic Macular Edema: A Real-World Study

Purpose: To compare the visual and anatomic outcomes of intravitreal ranibizumab versus aflibercept in patients with diabetic macular edema (DME) in a real-world study.Methods: This is a single-center retrospective comparative study of treatment-naïve patients who received intravitreal ranibizumab or aflibercept administration for DME for at least 12 months on an as needed regimen following three-monthly loading doses. The primary outcomes of the study were the mean change in best-corrected visual acuity (BCVA), central macular thickness (CMT), central macular volume (CMV). Factors to potentially affect these parameters were also analyzed.Results: A total of 100 eyes (66 patients) were included in the study. Fifty two eyes received ranibizumab and 48 received aflibercept injections. While the decrease in mean CMT at the 4th-month visit was significantly higher in the aflibercept-treated group than in the ranibizumab-treated group (p=0.02), there was no difference between the two groups at the end of the one-year follow-up (p=0.25). There was no significant difference between the two groups in terms of change in mean CMV during the follow-up. (p=0.26, p=0.27 at 4 and 12 months, respectively). The mean number of injections were also similar between groups (4.5 ± 1 vs. 4.6 ± 1.1 respectively, p=0.63).Conclusion: In a real-world setting, ranibizumab and aflibercept were both found to be effective in the first-line treatment of DME. Patients with DME who received fewer injections in the real-world could achieve visual and anatomical results comparable to randomized controlled trials participants.

Effect of Duration of Silicone Oil Tamponade on Retinal Structure after Rhegmatogenous Retinal Detachment Surgery

<b><i>Purpose:</i></b> The aim of the study was to investigate the effect of tamponade duration on retinal changes induced by silicone oil (SO) in patients who underwent successful rhegmatogenous retinal detachment (RRD) surgery. <b><i>Methods:</i></b> Retrospective comparative case series of 68 patients who underwent SO tamponade for RRD. Patients were divided into 2 groups based on timing of SO removal: &#x3c;6 months (group 1, <i>n</i> = 34) versus ≥6 months (group 2, <i>n</i> = 34). The main outcome measure was the change in central macular, inner, and outer retinal layer thickness (CMT, IRLT, and ORLT) before and after SO removal (SOR). <b><i>Results:</i></b> The median tamponade duration was 4 [Clin Ophthalmol. 2016;10:471–6, Zhonghua Yan Ke Za Zhi. 1997 Jan;33(1):39–41] months in group 1 and 8 [Arch Ophthalmol. 1994 Jun;112(6):778–85, Retina. 2004 Dec;24(6):871–7] months in group 2 (<i>p</i> &#x3c; 0.001). The mean CMT significantly increased from 245.3 ± 22.2 μm and 238.8 ± 41.6 μm under SO to 281.3 ± 60.2 μm and 259.0 ± 43.5 μm after SOR in group 1 (<i>p</i> = 0.009) and in group 2 (<i>p</i> = 0.007), respectively. Automated segmentation measurement revealed a significant increase in mean IRLT (<i>p</i> = 0.014 and <i>p</i> = 0.013) but no change in mean ORLT (<i>p</i> = 0.080 and <i>p</i> = 0.257) in both groups. After adjustment, there was no difference between the 2 groups in terms of mean final CMT, IRLT, and ORLT and mean retinal thickness changes after SOR. There was also no correlation between the tamponade duration and macular microstructural changes or visual recovery. <b><i>Conclusion:</i></b> SO tamponade causes a thinning of all retinal layers, mainly affecting the inner retinal layer. However, these changes resolved following SO extraction and were not affected by longer tamponade duration.

Part Three: Biomarker Changes in Cigarette Smokers Switched to Vuse Solo or Abstinence: A Randomized, Controlled Study

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42–96% vs. 52–97% (non-nicotine constituents); 51% vs. 55% (blood carboxyhemoglobin); and 29% vs. 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.

Randomized trial of two artificial intelligence coaching interventions to increase physical activity in cancer survivors

Physical activity (PA) has numerous health benefits. Personalized coaching may increase adherence to PA recommendations, but it is challenging to deliver personalized coaching in a scalable manner. The objective of our study was to determine whether novel artificially intelligent (AI) coaching interventions increase PA among overweight or obese, physically inactive cancer survivors compared to a control arm that receives health information. We conducted a single-center, three-arm randomized trial with equal allocation to (1) voice-assisted AI coaching delivered by smart speaker (MyCoach), (2) autonomous AI coaching delivered by text message (SmartText), and (3) control. Data collection was automated via sensors and voice technology, effectively masking outcome ascertainment. The primary outcome was change in mean steps per day from baseline to the end of follow-up at 4 weeks. Of the 42 randomized participants, 91% were female, and 36% were Black; mean age was 62.1 years, and mean BMI was 32.9 kg/m2. The majority were breast cancer survivors (85.7%). At the end of 4 weeks follow-up, steps increased in the MyCoach arm by an average of 3618.2 steps/day; the net gain in this arm was significantly greater [net difference = 3568.9 steps/day (95% CI: 1483–5655), P value <0.001] compared to control arm, and [net difference = 2160.6 steps/day (95% CI: 11–4310), P value 0.049] compared to SmartText. In conclusion, AI-based voice-assisted coaching shows promise as a practical method of delivering scalable, individualized coaching to increase physical activity in sedentary cancer survivors. Additional research is needed to replicate these findings in a broader population of cancer survivors and to investigate the effects of these interventions in the general population.ClinicalTrials.gov Identifier: NCT03212079, July 11, 2017, https://clinicaltrials.gov/ct2/show/NCT03212079.

Investigation of atovaquone-induced spatial changes in tumour hypoxia assessed by hypoxia PET/CT in non-small cell lung cancer patients

Background Tumour hypoxia promotes an aggressive tumour phenotype and enhances resistance to anticancer treatments. Following the recent observation that the mitochondrial inhibitor atovaquone increases tumour oxygenation in NSCLC, we sought to assess whether atovaquone affects tumour subregions differently depending on their level of hypoxia. Methods Patients with resectable NSCLC participated in the ATOM trial (NCT02628080). Cohort 1 (n = 15) received atovaquone treatment, whilst cohort 2 (n = 15) did not. Hypoxia-related metrics, including change in mean tumour-to-blood ratio, tumour hypoxic volume, and fraction of hypoxic voxels, were assessed using hypoxia PET imaging. Tumours were divided into four subregions or distance categories: edge, outer, inner, and centre, using MATLAB. Results Atovaquone-induced reduction in tumour hypoxia mostly occurred in the inner and outer tumour subregions, and to a lesser extent in the centre subregion. Atovaquone did not seem to act in the edge subregion, which was the only tumour subregion that was non-hypoxic at baseline. Notably, the most intensely hypoxic tumour voxels, and therefore the most radiobiologically resistant areas, were subject to the most pronounced decrease in hypoxia in the different subregions. Conclusions This study provides insights into the action of atovaquone in tumour subregions that help to better understand its role as a novel tumour radiosensitiser. Trial registration: ClinicalTrials.gov, NCT0262808. Registered 11th December 2015, https://clinicaltrials.gov/ct2/show/NCT02628080

Comparison of three neuraxial anesthesia approaches in parturient women with obesity and pregnancy-induced hypertension who underwent cesarean section

Objective To compare the effectiveness of different approaches of neuraxial anesthesia in parturient women with obesity and pregnancy-induced hypertension (PIH) who undergo cesarean section (CS). Methods We retrospectively analyzed data from 108 parturient women with obesity and PIH who underwent CS. All women were divided into the following three groups according to the neuraxial anesthesia approach: spinal anesthesia (SA), epidural anesthesia (EA), and combined spinal–epidural anesthesia (CSE). Clinical variables were compared. Results The mean age of the patients was 27.3 ± 2.2 years. Women in the CSE group had a longer duration from puncture to surgery, smaller intraoperative change in mean arterial pressure, higher Apgar scores at 1 and 5 minutes, shorter surgery time, lower rates of nausea and vomiting, and lower rate of intraoperative hypotension compared with those in the SA and EA groups. Conclusion CSE takes longer to administer in parturient women with obesity and PIH who undergo CS compared with those who have SA or EA. However, CSE has several advantages over SA or EA, including a shorter surgery time, more stable intraoperative mean arterial pressure, lower rates of nausea, vomiting, and intraoperative hypotension, and better Apgar scores at 1 and 5 minutes.

The ability of a submaximal cycle ergometer test to detect longitudinal changes in VO2max

Background The purpose of the present study was to examine the ability of a submaximal cycling test to detect longitudinal changes in maximal oxygen uptake (VO2max) and examine the conformity between changes in measured and estimated VO2max over a time span of 5–8 years. Methods A total of 35 participants (21 men and 14 women), aged 29 to 63 years, performed the Ekblom-Bak (EB) submaximal cycle test for estimation of VO2max and a maximal treadmill running test for direct measurement of VO2max. The baseline tests were conducted between 2009 and 2012, and the follow-up tests were completed 5 to 8 years later. Pearson’s coefficient of correlation (r) and paired sample t-test were used to analyse the association between change in measured and estimated VO2max. Random and systematic errors between the measured and estimated VO2max were evaluated using Bland-Altman plots. Repeated measures ANOVA were used to test differences between changes over time. Results There was no significant change in mean measured VO2max between baseline and follow-up (p = 0.91), however large individual variations were noted (− 0.78 to 0.61 L/min). The correlation between individual change in measured and estimated VO2max was r = 0.75 (p < 0.05), and the unstandardised B-coefficient from linear regression modelling was 0.88 (95% CI 0.61 to 1.15), i.e., for each litre of change in estimated VO2max, the measured value had changed 0.88 L. The correlation between baseline and follow-up errors (the difference between estimated-measured VO2max at each occasion) was r = 0.84 (p < 0.05). With regard to the testing procedure, repeated measures ANOVA revealed that there was no significant difference between the group who exercised at the same work rates at baseline and follow-up (n = 25), and those who required a change in work rate (n = 10). Conclusions The EB test detected a change in VO2max with reasonably good precision over a time span of 5–8 years. Further studies are needed to evaluate if the test can be used in clinical populations and in subjects with different medications.

Short-Term Cumulative Exposure to Ambient Traffic-Related Black Carbon and Blood Pressure: MMDA Traffic Enforcers’ Health Study

Exposure to traffic-related air pollution is linked with acute alterations in blood pressure (BP). We examined the cumulative short-term effect of black carbon (BC) exposure on systolic (SBP) and diastolic (DBP) BP and assessed effect modification by participant characteristics. SBP and DBP were repeatedly measured on 152 traffic enforcers. Using a linear mixed-effects model with random intercepts, quadratic (QCDL) and cubic (CCDL) constrained distributed lag models were fitted to estimate the cumulative effect of BC concentration on SBP and DBP during the 10 hours (daily exposure) and 7 days (weekly exposure) before the BP measurement. Ambient BC was related to increased BP with QCDL models. An interquartile range change in BC cumulative during the 7 days before the BP measurement was associated with increased BP (1.2% change in mean SBP, 95% confidence interval (CI), 0.1 to 2.3; and 0.5% change in mean DBP, 95% CI, −0.8 to 1.7). Moreover, the association between the 10-h cumulative BC exposure and SBP was stronger for female (4.0% change, 95% CI: 2.1–5.9) versus male and for obese (2.9% change, 95% CI: 1.0–4.8) vs. non-obese traffic enforcers. Short-term cumulative exposure to ambient traffic-related BC could bring about cardiovascular diseases through mechanisms involving increased BP.