Systematic review and meta-analysis of efficacy and safety of combinational therapy with metformin and dipeptidyl peptidase-4 inhibitors

AbstractCombinational therapies are often required in the management of type 2 diabetes mellitus (T2DM). Among the important candidates, dipeptidyl peptidase-4 inhibitors (DPPIs) and metformin combination (DPPI-MET) have shown promising endeavors. In order to examine the efficacy and safety of such a combination therapy in T2DM patients finding inadequate control with metformin, this systematic review and meta-analysis has been conducted. Literature search was made in multiple electronic databases. Inclusion criteria included; RCTs examining the efficacy and safety of DPPI-MET against placebo-MET or MET-only groups of T2DM patients by observing changes in disease endpoints including HbA1c and FPG, and the length of trial be at least 12weeks. Mean differences based meta-analyses were performed and heterogeneity assessment was carried out. Nineteen studies were selected and included in the meta-analyses. DPPI-MET significantly improved all disease endpoints and the difference could be noticed up to 2years in the majority of outcome measures. In comparison with PBO-MET, the DPPI-MET combinational therapy resulted in the percent HbA1c changes from baseline with a mean difference [95% CI] of −0.77 [−0.86, −0.69] in 3-month (P<0.00001), −0.67 [−0.76, −0.59] in 6-month (P<0.00001), −0.67 [−0.88, −0.47] in 1-year (P<0.00001) and −0.36 [−0.53, −0.20] in 2-year trials (P<0.0003). Reduction in body weight and safety profile in the treated and control groups were not different. A combinational therapy with DPPI and metformin significantly improves diabetes clinical indicators and this effect has been observed for up to 2years herein. Safety and tolerability of DPPI-MET combination have been found well-manageable with a very similar adverse event profile in both treated and control groups

The role of nutraceuticals in the management of autism

AbstractAutism and related disorders are increasingly prevalent behavioral syndromes of impaired verbal and nonverbal communication and socialization owing to neurodevelopmental abnormalities. The most recent estimate for the prevalence of autistic disorders is about 1% on a global scale. Etiology of autism is multifactorial and multidimensional that makes therapeutic intervention even harder. Heterogeneity of genetic factors, oxidative stress, autoimmune mechanism, and epigenetic mechanisms complicate the nature of pathogenesis of the disease. Nutraceutical approach to treat this disease is a promising strategy, especially in some areas, it is more attractive than others. This review critically analyzes the roles of vitamins and cofactors, dietary modifications and gut abnormalities, probiotics and prebiotics, phytochemicals, and environmental factors in order to determine the state of evidence in nutraceutical-based autism management practices. This article presents a systematic review of randomized- and placebocontrolled trials to examine the evidence supports the use of autism nutraceu10.1016/j.jsps.2012.10.001ticals. The results will be discussed in the light of all relevant evidence generated from other clinical and exploratory studies

Synthesis, Antiviral, and Antimicrobial Evaluation of Benzyl Protected Diversified C-nucleosides

Formyl glycals are the versatile synthetic intermediates and can serves as precursor for the synthesis of various C and N-nucleosides. Due to the presence of electron donating and electron withdrawing character on formyl sugars which makes the molecule more susceptible to nucleophilic attack. Utilizing same strategy, we propose the synthesis of diversified C-nucleosides (3-14) by reaction with N,N dinucleophiles. These nucleoside analogs were than tested against viral, bacterial and fungal strains

Ketamine-based sedation use in mechanically ventilated critically ill patients with COVID-19: A multicenter cohort study

Backgrounds: Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) patients with COVID-19. Methods: Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 hours of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria. Results: In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): −0.26 (−0.45, −0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): −1.55 (−2.42, −0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality. Conclusions: Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients

Role of L- glutamine and crizanlizumab in sickle cell anaemia painful crisis reduction

BackgroundPatients with sickle cell disease, frequently ‎ suffer from intense painful episodes. Till recently hydroxyurea was the only available medical therapy that approved for reduction of painful episodes.AimsTo summarize the available data from randomized controlled trials that aim to evaluate the efficacy of newly approved L-‎glutamine‎ (alters redox state of red blood cells ‎‎[RBCs]) ‎and ‎crizanlizumab (‎(anti-P-selectin)‎)‎ ‎on vaso-occlusive episodes in Sickle cell disease ‎ patients.Methods PubMed, ‎Google Scholar, and EBSCO ‎ databases were ‎‎systematically search for relevant articles. The terms ‎ ‎ ‎ L-glutamine, sickle cell disease, sickle cell ‎anaemia,‎ ‎‎crizanlizumab ‎and vaso-occlusive episodes‎ were used.Results Out of Four-hundred seventy-two records, only three fulfilled the inclusion criteria. Two trials were aimed to evaluate the efficacy of L-glutamine therapy on the frequency of painful crises in sickle cell anaemia patients. Both studies showed that L-glutamine therapy significantly reduce the frequency of VOEs. Only one trial examined the ability of crizanlizumab on VOEs reduction, and showed crizanlizumab successful reduce the occurrence of VOEs.‎ConclusionNewer agent ‎with different mechanism of action, such as ‎L-glutamine, ‎and crizanlizumab may consider if ‎hydroxyurea not effective or not ‎tolerable

Effect of growth techniques on the structural, optical and electrical properties of indium doped TiO2thin films

We have investigated the effect of the growth techniques on the structural, the electrically and optically active defects in Indium doped TiO2 thin films grown by pulsed laser deposition (PLD) and sputtering techniques. X-ray diffraction (XRD) and Raman spectroscopy patterns revealed both rutile and anatase phases for the sputtering samples. On the other hand, only the anatase phase was observed for the PLD samples. The photoluminescence (PL) spectra have unveiled several peaks which were explained by defect related optical transitions. Particularly, the PL bands are fully consistent with anatase/rutile TiO2 phases and the formation of In2O3 during the preparation of our samples. It was also observed that at −4 V reverse bias, the PLD samples have lower leakage currents (∼1.4 × 10−7 A) as compared to the sputtering samples (∼5.9 × 10−7 A). In addition, the PLD samples exhibited lower ideality factors and higher barrier heights as compared to those grown by sputtering. Finally, the Deep Level Transient Spectroscopy (DLTS) measurements have shown only one defect in the PLD samples whereas five defects have been detected in the sputtering samples. Therefore, our results provide strong evidence that the PLD technique is better suited for the growth of In-doped TiO2 thin films

Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19—A multicenter cohort study

BackgroundDespite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients.MethodsA multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate.ResultsA total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87–1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00–0.47), p = 0.05 and beta coefficient 0.16 (95% CI −0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03].ConclusionThe use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding

Methods for Ultrasound Imaging of Multi- Layered Objects Based on Collimated Beam Systems

Non-destructive characterization of multi-layered structures that can be accessed from only a single side is important for applications such as well-bore integrity inspection. Collimated beam ultrasound systems are a technology for imaging inside multi-layered structures such as geothermal wells. These systems work by using a collimated narrow-band ultrasound transmitter that can penetrate through multiple layers of heterogeneous material. A series of measurements can then be made at multiple transmit frequencies. However, commonly used reconstruction algorithms such as Synthetic Aperture Focusing Technique (SAFT) tend to produce poor quality reconstructions for these systems both because they do not model collimated beam systems and they do not jointly reconstruct the multiple frequencies. In this thesis, we first propose a multi-frequency ultrasound model-based iterative reconstruction (UMBIR) algorithm designed for multi-frequency collimated beam ultrasound systems. The combined system targets reflective imaging of heterogeneous, multi-layered structures. For each transmitted frequency band, we introduce a physics-based forward model to accurately account for the propagation of the collimated narrow-band ultrasonic beam through the multi-layered media. We then show how the joint multi-frequency UMBIR reconstruction can be computed by modeling the direct arrival signals, detector noise, and incorporating a spatially varying image prior. We also propose a ringing artifact reduction method for ultrasound image reconstruction that uses a multi-agent consensus equilibrium (RARE-MACE) framework. Our approach integrates a physics-based forward model that accounts for the propagation of a collimated ultrasonic beam in multi-layered media, a spatially varying image prior, and a denoiser designed to suppress the ringing artifacts that are characteristic of reconstructions from high-fractional bandwidth ultrasound sensor data. Results using both simulated and experimental data indicate that multi-frequency UMBIR reconstruction yields much higher reconstruction quality than either single frequency UMBIR or SAFT. In addition, our results demonstrate the capability of our RARE-MACE method to suppress ringing artifacts and substantially improve the image quality over single frequency UMBIR and SAFT

Pharmaceutical care in the community pharmacies of Saudi Arabia: Present status and possibilities for improvement

Pharmaceutical care can be given in all settings: The community, hospitals, long-term care, and the clinic. However, published literature indicates that there is a substantial barrier to implementing pharmaceutical care programs in community pharmacies. This review was conducted to discover gaps and limitations in pharmaceutical care services in community pharmacies in the Kingdom of Saudi Arabia (KSA). We searched PubMed and other available scientific website databases using the following key words to retrieve the relevant articles: Community Pharmacy, Healthcare System, Pharmaceutical Care, KSA. Two authors independently screened the titles and abstracts of promising articles. They discarded irrelevant studies and retained studies, and reviews that held the promise of relevant data or information. The review revealed that only one out of the four studies conducted in KSA retrieved by the authors reported pharmaceutical care service other than dispensing. The same results were reported in other studies conducted in some developing countries. All pharmaceutical care services were reported in studies conducted in Europe. The authors came to the conclusion that in KSA, dispensing of medicines is the dominant service provided by community pharmacists and that there was very limited if not a total absence of other pharmaceutical care services

Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model

Tivozanib is a triple vascular endothelial growth factor receptor inhibitor, recently approved for the treatment of refractory advanced renal cell carcinoma. Clinical studies showed that around 46% of patients who received tivozanib suffer from hypertension in all grades. Thus, the present study was conducted to identify the role of angiotensin-II (AngII) in the mechanism underlying tivozanib-induced vascular toxicity and hypertension. C57BL/6 male mice received tivozanib (1 mg/kg) with or without losartan (10 or 30 mg/kg) for 3 weeks. Blood pressure was recorded every 3 days, and proteinuria was measured every week. On day 21, all mice were euthanized, and samples were harvested for further analysis. Tivozanib elevated blood pressure until systolic blood pressure reached 163 ± 6.6 mmHg on day 21 of treatment with low urination and high proteinuria. AngII and its receptors, endothelin-1, and oxidative stress markers were significantly increased. While nitric oxide (NO) levels were reduced in plasma and aortic tissues. AngII type 1 receptor blockade by losartan prevented these consequences caused by tivozanib and kept blood pressure within normal range. The results showed that AngII and ET-1 might be potential targets in the clinical studies and management of hypertension induced by tivozanib