Acceptability of “High sn-2” Infant Formula in Non-Breast Fed Healthy Term Infants Regarding Gastrointestinal Tolerability by Both Parents and Pediatrician: An Open-Label Pilot Study in the Gulf Cooperation Council (GCC) Countries

Recent studies have highlighted the positive impact of high sn-2 formulas on gastrointestinal (GI) tolerance. We assessed the GI tolerance, acceptability, and safety of high sn-2 infant formula among non-breastfed healthy term infants in the Gulf countries. A multicenter observational study was conducted on 227 healthy-term infants who were prescribed high sn-2 palmitate infant formula and received a minimum of two formula feedings per day for the past two weeks prior to the study’s initiation. The number of stools per day decreased significantly from a median of four (interquartile range [IQR] = 4) at baseline to 3.0 (2) stools per day at the end of follow-up (p = 0.015). The percentage of stool amount changed significantly, where 61.2% and 33.7% of the infants had an amount of 25–50% of the diaper and >50% of the diaper, respectively (p < 0.001) at the end of the follow-up. Similarly, the percentage of hard stool decreased significantly from 17.4% at baseline to 0.4% of the population at week 12 (p < 0.00). The prevalence of colic and abdominal distention declined from 21.4% and 39.9% at baseline to 2.9% and 9.4% at week 12, respectively (p < 0.05). The same decline was observed in abdominal distension and regurgitation score (p < 0.05).

GSK3640254 Is a Novel HIV-1 Maturation Inhibitor With an Optimized Virology Profile

HIV-1 maturation inhibitors (MIs) offer a novel mechanism of action and potential for use in HIV-1 treatment. Prior MIs displayed clinical efficacy but were associated with the emergence of resistance and some gastrointestinal tolerability events. Treatment with the potentially safer next-generation MI GSK3640254 (GSK’254) resulted in up to a 2-log 10 viral load reduction in a phase IIa proof-of-concept study. In vitro experiments have defined the antiviral and resistance profile for GSK’254. The compound displayed strong antiviral activity against a library of subtype B and C chimeric viruses containing Gag polymorphisms and site-directed mutants previously shown to affect potency of earlier-generation MIs, with a mean protein-binding adjusted 90% effective concentration of 33 nM. Furthermore, GSK’254 exhibited robust antiviral activity against a panel of HIV-1 clinical isolates, with a mean EC 50 of 9 nM. Mechanistic studies established that bound GSK’254 dissociated on average 7.1-fold more slowly from wild-type Gag virus-like particles (VLPs) compared with a previous-generation MI. In resistance studies, the previously identified A364V Gag region mutation was selected under MI pressure in cell culture and during the phase IIa clinical study. As expected, GSK’254 inhibited cleavage of p25 in a range of polymorphic HIV-1 Gag VLPs. Virus-like particles containing the A364V mutation exhibited a p25 cleavage rate 9.3 times faster than wild-type, providing a possible mechanism for MI resistance. The findings demonstrate that GSK’254 potently inhibits a broad range of HIV-1 strains expressing Gag polymorphisms.

Effects of Delayed-Release Olive Oil and Hydrolyzed Pine Nut Oil on Glucose Tolerance, Incretin Secretion and Appetite in Humans

Background: To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. Methods: Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At -30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. Results: PNO-FFA augmented GLP-1 secretion from 0–360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240–360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). Conclusions: In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial (NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m2) were randomized to consume a beverage containing 12.5 g (Days 0–7) and 25 g (Days 7–28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.

Tapentadol is effective in the management of moderate-to-severe cancer-related pain in opioid-naïve and opioid-tolerant patients: a retrospective study

Purpose Tapentadol is a dual-acting mu-opioid receptor agonist and noradrenaline reuptake inhibitor with non-inferior analgesic efficacy to oxycodone and better gastrointestinal tolerability than full mu-opioid receptor agonists. Tapentadol is approved for cancer pain in Japan; however, real-world evidence on tapentadol’s effectiveness and safety for cancer-related pain in Japan is limited. Methods This retrospective study evaluated the effectiveness, safety, and tolerability of tapentadol (by patient type—opioid-naïve and opioid-tolerant) in 84 patients with moderate-to-severe cancer pain at Ichikawa General Hospital between September 2014 and August 2016. Results Almost 93% of patients achieved clinically relevant pain relief within 4 days (median). Over 90% of patients with neuropathic pain or mixed pain and all patients with nociceptive pain were responders. Pain intensity significantly decreased from baseline through to the end of maintenance period in opioid-naïve and opioid-tolerant patients. No patients discontinued tapentadol due to serious adverse events. No opioid-naïve patients experienced nausea or vomiting during tapentadol treatment. Only three opioid-tolerant patients experienced nausea which was considered to be related to tapentadol. Conclusion Tapentadol is effective and well tolerated in opioid-naïve and opioid-tolerant patients with cancer pain of varying pathophysiology, including those with nociceptive and/or neuropathic components. Tapentadol may be considered for first-line use in moderate-to-severe cancer-related pain.