Meta-Analysis of Carbohydrate Solution Intake during Prolonged Exercise in Adults: From the Last 45+ Years’ Perspective

Carbohydrate (CHO) supplementation during prolonged exercise postpones fatigue. However, the optimum administration timing, dosage, type of CHO intake, and possible interaction of the ergogenic effect with athletes’ cardiorespiratory fitness (CRF) are not clear. Ninety-six studies (from relevant databases based on predefined eligibility criteria) were selected for meta-analysis to investigate the acute effect of ≤20% CHO solutions on prolonged exercise performance. The between-subject standardized mean difference [SMD = ([mean post-value treatment group–mean post-value control group]/pooled variance)] was assessed. Overall, SMD [95% CI] of 0.43 [0.35, 0.51] was significant (p < 0.001). Subgroup analysis showed that SMD was reduced as the subjects’ CRF level increased, with a 6–8% CHO solution composed of GL:FRU improving performance (exercise: 1–4 h); administration during the event led to a superior performance compared to administration before the exercise, with a 6–8% single-source CHO solution increasing performance in intermittent and ‘stop and start’ sports and an ~6% CHO solution appearing beneficial for 45–60 min exercises, but there were no significant differences between subjects’ gender and age groups, varied CHO concentrations, doses, or types in the effect measurement. The evidence found was sound enough to support the hypothesis that CHO solutions, when ingested during endurance exercise, have ergogenic action and a possible crossover interaction with the subject’s CRF.

Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects.

Evaluation of medication administration timing variance using information from a large health system’s clinical data warehouse

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose An analysis to determine the frequency of medication administration timing variances for specific therapeutic classes of high-risk medications using data extracted from a health-system clinical data warehouse (CDW) is presented. Methods This multicenter retrospective, observational analysis of 1 year of medication administration data from 14 hospitals was conducted using a large enterprise health-system CDW. The primary objective was to assess medication administration timing variance for focused therapeutic classes using medication orders and electronic medication administration records data extracted from the electronic health record (EHR). Administration timing variance patterns between standard hospital staffing shifts, within therapeutic drug classes, and for as-needed (PRN) medications were also studied. Calculated variables for delayed medication administration (ie, administration time variance) were created for documented administration time intervals of 30-59, 60-120, and more than 120 minutes before or after medication orders. Results A total of 5,690,770 medication administrations (3,418,275 scheduled and 2,272,495 PRN) were included in the normalized data set. Scheduled medications were frequently subject to delays of ≥60 minutes (15% of administrations, n = 275,257) when scheduled for administration between 9-10 AM and between 9-10 PM. By therapeutic drug class, scheduled administrations of insulins, heparin products, and platelet aggregation inhibitors (most commonly heparin flushes and line-management preparations) were the most commonly delayed. For PRN medications, medications in the anticoagulant and antiplatelet agent class were most likely to be administered early (&lt;60 minutes from the scheduled time of first administration). Conclusion The findings of this study assist in understanding patterns of delayed medication administration. Medication class, time of day of scheduled administration, and frequency were factors that influenced medication administration timing variance.

Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing and Osseointegration: the Need for large Scale Human Clinical Trials

This article revisits the topic whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect bone healing and osseointegration. An understanding on this topic is crucial for clinicians to make evidence-based decisions to ensure patient safety and long-term success of implants. Based on authors’ systematic search, a limited number of articles were found to merit another systematic review. The understanding on the effects of NSAIDs on bone, specifically in human subjects, and the underlying biochemical mechanism, remain limited, owing to design variations in limited published studies. Some studies may suggest NSAIDs have no adverse,if not protective effects. One can suggest that a combination of certain NSAID type, dosage, administration timing and duration may adversely affect bone. Authors would like to raise awareness and highlight the need of collective efforts and further studies with standardised quantitative measurements to help our understanding of the effects of this commonly used line of treatment

Decreased Immune Response to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases Treated with Anti TNFα

Background: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear. Aim: to assess immune responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC). Methods: Prospective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike (S) antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly. Results: Overall 258 subjects: 185 IBD (67 treated with anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while some patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-S levels were significantly lower in anti-TNFα treated compared to untreated patients, and HC (p<0.001; p<0.001, respectively). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared to untreated patients, and HC (p<0.03; p<0.0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-S levels. Infection rate (~2%) and AEs were comparable in all groups. IBD activity did not change in response to BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment all patients mounted an immune response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine immune response longevity in this group may be limited, vaccine booster dose should be considered.

Methylene blue is not contraindicated to treat hemodynamic instability in pediatric and neonate patient

: The present review was carried out to describe publications on the use of methylene blue (MB) in pediatrics and neonatology, discussing dose, infusion rate, action characteristics and possible benefits for a pediatric patient group. The research was performed on the data sources PubMed, BioMed Central, and Embase (updated on Aug 31, 2020) by two independent investigators. The selected articles included human studies that evaluated MB use in pediatric or neonatal patients with vasoplegia due to any cause, regardless of the applied methodology. The MB use and 0 to18-years-old patients with vasodilatory shock were the adopted criteria. Exclusion criteria were the use of MB in patients without vasoplegia and patients ≥ 18-years-old. The primary endpoint was the increase in mean arterial pressure (MAP). Side effects and dose were also evaluated. Eleven studies were found of which 10 were case reports and 1 was a randomized clinical study. Only two of these studies were with neonatal patients (less than 28 days-old), reporting a small number of cases (1 and 6). All studies described positive action of MB on MAP, allowing the decrease of vasoactive amines in several of them. No severe side effects or death related to the use of the medication was reported. The maximum dose used was 2 mg/kg, but there was no consensus on the infusion rate and drug administration timing. Finally, no theoretical or experimental basis sustains the decision to avoid MB in children claiming it can cause pulmonary hypertension. The same goes for the concern of a possible deleterious effect on inflammatory distress syndrome.

Levothyroxine Administration Timing in Hypothyroidism Patients

Levothyroxine is a synthetic T4 hormone that is biochemically and physiologically identical to the natural hormone, and it is used when the body is deficient in the natural hormone. This study was conducted to summarize the current evidence that compare evidence supporting morning dose to evening dose of levothyroxine in patients with hypothyroidism‎. A simple systematic review was carried out, searching databases PubMed, Google Scholar, and EBSCO. The authors extracted the needed data. There is conflicting data regarding effectiveness of morning dose versus evening dose in management of levothyroxine. More studies reported effectiveness of bedtime dose more than breakfast dose in hypothyroidism management. Numerous studies reported effectiveness of bedtime dose more than breakfast dose in hypothyroidism management. The most resent evidences recommended that, if possible, L‐T4 be consistently taken either 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal), for optimal, consistent absorption.

A retrospective study on the therapeutic effects of sodium bicarbonate for adult in-hospital cardiac arrest

To investigate whether the effects of sodium bicarbonate (SB) during cardiopulmonary resuscitation (CPR) would be influenced by blood pH and administration timing. Adult patients experiencing in-hospital cardiac arrest (IHCA) from 2006 to 2015 were retrospectively screened. Early intra-arrest blood gas data were obtained within 10 min of CPR. Multivariable logistic regression analysis and generalised additive models were used for effect estimation and data exploration, respectively. A total of 1060 patients were included. Only 59 patients demonstrated favourable neurological status at hospital discharge. Blood pH ≤ 7.18 was inversely associated with favourable neurological outcome (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11–0.52; p value < 0.001) while SB use was not. In the interaction analysis for favourable neurological outcome, significant interactions were noted between SB use and time to SB (SB use × time to SB ≥ 20 min; OR 6.16; 95% CI 1.42–26.75; p value = 0.02). In the interaction analysis for survival to hospital discharge, significant interactions were noted between SB use and blood pH (Non-SB use × blood pH > 7.18; OR 1.56; 95% CI 1.01–2.41; p value = 0.05). SB should not be empirically administered for patients with IHCA since its effects may be influenced by blood pH and administration timing.

Modeling the Effect of Subcutaneous Lixisenatide on Glucoregulatory Endocrine Secretions and Gastric Emptying in Type 2 Diabetes to Simulate the Effect of iGlarLixi Administration Timing on Blood Sugar Profiles

Background: As type 2 diabetes (T2D) progresses, intensification to combination therapies, such as iGlarLixi (a fixed-ratio GLP-1 RA and basal insulin combination), may be required. Here a simulation study was used to assess the effect of iGlarLixi administration timing (am vs pm) on blood sugar profiles. Methods: Models of lixisenatide were built with a selection procedure, optimizing measurement fits and model complexity, and were included in a pre-existing T2D simulation platform containing glargine models. With the resulting tool, a simulated trial was conducted with 100 in-silico participants with T2D. Individuals were given iGLarLixi either before breakfast or before an evening meal for 2 weeks and daily glycemic profiles were analyzed. In the model, breakfast was considered the largest meal of the day. Results: A similar percentage of time within 24 hours was spent with blood sugar levels between 70 to 180 mg/dL when iGlarLixi was administered pre-breakfast or pre-evening meal (73% vs 71%, respectively). Overall percent of time with blood glucose levels above 180 mg/dL within a 24-hour period was similar when iGlarLixi was administered pre-breakfast or pre-evening meal (26% vs 28%, respectively). Rates of hypoglycemia were low in both regimens, with a blood glucose concentration of below 70 mg/dL only observed for 1% of the 24-hour time period for either timing of administration. Conclusions: Good efficacy was observed when iGlarlixi was administered pre-breakfast; however, administration of iGlarlixi pre-evening meal was also deemed to be effective, even though in the model the size of the evening meal was smaller than that of the breakfast.