Evaluate the effectiveness and safety of proton pump inhibitors (PPIs) in the treatment of upper GIT disorders

Introduction: Proton pump inhibitors (PPIs) are most prescribed medication classes and have similar efficacy between generic and brand names. PPIs are used for treatment upper GIT disorders. The aim of the present study was to evaluate the effectiveness and safety of proton pump inhibitors (PPIs). Methods: A cross sectional study conducted randomly on pharmacies, patients and Doctors to collect a data regarding the effectiveness and safely use of PPI through predesigned questionnaire containing information about dosage, types, side effect, effectiveness and safety of PPIs. The collected data was analysis by using Chi-square for determine the significant differences at α < 0.05. Result: The result of present study revealed numbers of points in which the questionnaire were intended for pharmacies, patients and doctors knowledge, effectiveness and safety of PPIs. The data gathered from pharmacy shown PPI dispensed without prescription (P< 0.05) in dose of 20 mg of omeprazole and for treatment of gastritis, stomachache and on medication use (P< 0.05). No side effect or any problem, safe, and effective of PPIs was from patients seeking PPIs to the drug dispensers. Furthermore, questionnaire for patients whom seeking treatment shown some similarity to pharmacies answers, however lack the knowledge about side effect of PPIs, and PPIs withdraw among patients. PPIs was found to be used by patients due to the advices of friends (P< 0.05). The last part in this study was doctors involved in which some common similarity were also identified between doctors, patients and pharmacies responses. Although, Doctors responses were revealed that PPIs should be used by prescription in single dose of common types of PPIs (P< 0.05). Conclusion: Due to the short time use of PPIs have been reported. This study suggested that, even no side effect and highly effective of PPIs reported, the PPIs should be monitoring and use under prescription.

Similar Efficacy of Arthroscopy and Arthrotomy in Infection Eradication in the Treatment of Septic Knee: A Systematic Review and Meta-Analysis

Aim: To compare the arthroscopy vs. arthrotomy for the treatment of native knee septic arthritis.Methods: Electronic databases of PubMed, Embase and Cochrane Library were searched for eligible studies. Retrospective comparative studies comparing arthroscopy or arthrotomy for patients with septic arthritis of the native knee were eligible for this review. The primary outcome was recurrence of infection after first procedure. The secondary outcomes included hospital length of stay, operative time, range of motion of the involved knee after surgery, overall complications and mortality rate,Results: Thirteen trials were included in this study. There were a total of 2,162 septic arthritis knees treated with arthroscopic debridement and irrigation, and 1,889 septic arthritis knees treated with open debridement and irrigation. Arthroscopy and arthrotomy management of the knee septic arthritis showed comparable rate of reinfection (OR = 0.85; 95% CI, 0.57–1.27; P = 0.44). No significant difference was observed in hospital length of stay, operative time and mortality rate between arthroscopy and arthrotomy management group, while arthroscopy treatment was associated with significantly higher knee range of motion and lower complication rate when compared with arthrotomy treatment.Conclusion: Arthroscopy and arthrotomy showed similar efficacy in infection eradication in the treatment of native septic knee. However, arthroscopy treatment was associated with better postoperative functional recovery and lower complication rate.

Predicting County-Level Overdose Death Rates Amid the Escalating Overdose Crisis in the United States: A Statistical Modeling Approach Predicting Deaths Through 2022

Aims. U.S. overdose (OD) deaths continue to escalate but are characterized by geographic and temporal heterogeneity. We previously validated a predictive statistical model to predict county-level OD mortality nationally from 2013 to 2018. Herein, we aimed to: 1) validate our model’s performance at predicting county-level OD mortality in 2019 and 2020; 2) modify and validate our model to predict OD mortality in 2022.Methods. We evaluated our mixed effects negative binomial model’s performance at predicting county-level OD mortality in 2019 and 2020. Further, we modified our model which originally used data from the year X to predict OD deaths in the year X+1 to instead predict deaths in year X+3. We validated this modification for the years 2017 through 2019 and generated future-oriented predictions for 2022. Finally, to leverage available, albeit incomplete, 2020 OD mortality data, we also modified and validated our model to predict OD deaths in year X+2 and generated an alternative set of predictions for 2022.Results. Our original model continued to perform with similar efficacy in 2019 and 2020, remaining superior to a benchmark approach. Our modified X+3 model performed with similar efficacy as our original model, and we present predictions for 2022, including identification of counties most likely to experience highest OD mortality rates. There was a high correlation (Spearman’s ρ = 0.93) between the rank ordering of counties for our 2022 predictions using our X+3 and X+2 models. However, the X+3 model (which did not account for OD escalation during COVID) predicted only 62,000 deaths nationwide for 2022, whereas the X+2 model predicted over 87,000.Conclusion. We have predicted county-level overdose death rates for 2022 across the US. These predictions, made publicly available in our online application, can be used to identify counties at highest risk of high OD mortality and support evidence-based OD prevention planning.

Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium

The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.

Efficacy of front-line immunochemotherapy for follicular lymphoma: a network meta-analysis of randomized controlled trials

Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1–3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.

Effects and Safety of Allisartan Isoproxil Combined With Amlodipine or Indapamide in Patients With Hypertension Who Failed Allisartan Monotherapy

Background To primarily evaluate the effects and safety of a selective angiotensin II type 1 (AT1) receptor blocker (ARB) allisartan isoproxil combined with amlodipine or indapamide in the treatment of patients with essential hypertension who failed allisartan monotherapy. Methods Patients aged 18–75 years with mild-to-moderate essential hypertension [office systolic blood pressure (SBP) 140 to &lt;180 and/or office diastolic blood pressure (DBP) 90 to &lt;110 mm Hg] in 44 study centers between 2016 and 2018 were recruited. Allisartan isoproxil tablet 240 mg was administered per day for 4 weeks, and continued for 8 weeks if office blood pressure (BP) achieved the target of SBP/DBP &lt;140/90 mm Hg. The nonachievers were 1:1 randomly divided into allisartan isoproxil 240 mg + indapamide sustained-release tablet 1.5 mg, or allisartan isoproxil 240 mg + amlodipine besylate 5 mg groups for further 8 weeks of combined therapy. The BP target achieving rate, reduction of sitting BP from baseline, safety and compliance were evaluated as the primary efficacy endpoint. Results A total of 2,212 patients were enrolled, among them 2,126 patients were included in the efficacy analysis, with an average age of 55.1 ± 10.2 years. A total of 1,463 cases (68.8%) were effective after 4 weeks allisartan treatment, and the mean SBP and DBP were significantly decreased by 14.7 ± 12.2 and 8.0 ± 8.4 mm Hg compared with the baseline levels (all P &lt; 0.001). In nonachievers, allisartan combined with indapamide for 8 weeks significantly lowered the sitting BP (SBP/DBP) by 14.0 ± 12.2/8.3 ± 9.2 mm Hg, respectively, compared with 4 weeks monotherapy with allisartan with a BP targeting rate of 57.7% (169/293). In the allisartan + amlodipine group, the SBP/DBP were significantly decreased by (14.4 ± 12.1/8.2 ± 8.2) mm Hg, respectively, with a BP targeting rate of 62.8% (181/288). There was no statistical significance in BP reduction, targeting rate, or adverse reactions between the 2 combined therapies. Conclusions Allisartan isoproxil combined with indapamide or amlodipine can further improve the BP targeting rate when allisartan monotherapy failed in essential hypertension. The 2 combined therapies have similar efficacy and safety.

Effect of nebulised BromAc® on rheology of artificial sputum: relevance to muco-obstructive respiratory diseases including COVID-19

Respiratory diseases such as cystic fibrosis, COPD, bronchiectasis asthma and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Since earlier studies have shown success with BromAc as mucolytic agent for treating a rare disease known as pseudomyxoma peritonei (PMP), we tested the formulation on two gelatinous airway representative sputa models, in order to determine whether similar efficacy exist. The sputum (1.5 ml) lodged in an endotracheal tube was treated to aerosolised N-acetylcysteine, bromelain, or their combination (BromAc) using a nebuliser with 6.0 ml of the agents in phosphate buffer saline, over 25 min. Controls received phosphate buffer saline. The dynamic viscosity was measured before and after treatment using a capillary tube method, whilst the sputum flow (ml/sec) was assessed using a 0.5 ml pipette. Finally, the sequestered agents (concentration) in the sputa after treatment were quantified using standard bromelain and N-acetylcysteine chromogenic assays. Results indicated that bromelain and N-acetylcysteine affected both the dynamic viscosities and pipette flow in the two sputa models, with changes in the former parameter having immense effect on the latter. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, correlation was found between the rheological effects and the concentration of agents in the sputa. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretion, however further studies with patient sputum samples using aerosol BromAc is warranted.

Russian recombinant coagulation factors: the technological background and the results of clinical studies

The prolongation of survival and the improvement of quality of life in patients with hemophilia A and B are only possible if hemostatic disorders caused by coagulation factor VIII and IX deficiency are managed effectively. Recombinant coagulation factors are playing an ever-increasing role in the preventive care of affected patients. The development, production and use of domestic recombinant coagulation factors opened up new treatment opportunities and improved access to preventive care for hemophilia patients. The results of clinical studies on the efficacy and safety of the Russian recombinant factors showed that they had similar efficacy and safety compared to the plasma derived clotting factors.

Real-World Use of Clopidogrel and Ticagrelor in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries: Patient Characteristics and Long-Term Outcomes

Background: Current guidelines recommend ticagrelor as the preferred P2Y12 inhibitor on top of aspirin in patients after an acute coronary syndrome. Yet, the efficacy and safety of ticagrelor vs. clopidogrel in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remain uncertain.Methods: A total of 1,091 patients with MINOCA who received dual antiplatelet therapy were enrolled and divided into the clopidogrel (n = 878) and ticagrelor (n = 213) groups. The primary efficacy endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. The safety endpoint referred to bleeding events. The Kaplan-Meier, propensity score matching (PSM), and Cox regression analyses were performed.Results: The incidence of MACE was similar for clopidogrel- and ticagrelor-treated patients over the median follow-up of 41.7 months (14.3 vs. 15.0%; p = 0.802). The use of ticagrelor was not associated with a reduced risk of MACE compared with clopidogrel after multivariable adjustment in overall (HR = 1.25, 95% CI: 0.84–1.86, p = 0.262) and in subgroups of MINOCA patients. Further, there was no significant difference in the risk of bleeding between two groups (HR = 1.67, 95% CI: 0.83–3.36, p = 0.149). After PSM, 206 matched pairs were identified, and the differences between clopidogrel and ticagrelor for ischemic endpoints and bleeding events remained nonsignificant (all p &gt; 0.05).Conclusions: In this observational analysis of MINOCA patients, ticagrelor was not superior to clopidogrel in reducing ischemic events and did not cause a significant increase in bleeding, indicating a similar efficacy and safety between clopidogrel and ticagrelor. A randomized study of ticagrelor vs. clopidogrel in this specific population is needed.

Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases

Aim: This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]). Materials & methods: A total of 30 participants with primary immunodeficiency diseases aged ≥2 years sequentially received iv.Ig, sc.Ig and fsc.Ig during consecutive clinical studies. Results: For iv.Ig, sc.Ig and fsc.Ig, rates of validated acute serious bacterial infections/participant-year (0, 0.09 and 0.04, respectively) and all infections/participant year (4.17, 3.68 and 2.42, respectively) were similarly low; rates of systemic and local causally related adverse events/participant-year were 5.60, 1.93 and 0.88, respectively and 0.13, 0.92 and 1.57, respectively. Conclusion: fsc.Ig provided similar efficacy to iv.Ig and sc.Ig. Clinical Trial registration: NCT00546871 , NCT00814320 , NCT01175213 (ClinicalTrials.gov)