Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

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LOW-DOSE HEPATITIS B IMMUNOGLOBULIN GIVEN “ON DEMAND” IN COMBINATION WITH LAMIVUDINE: A HIGHLY COST-EFFECTIVE APPROACH TO PREVENT RECURRENT HEPATITIS B VIRUS INFECTION IN THE LONG-TERM FOLLOW-UP AFTER LIVER TRANSPLANTATION

Transplantation Journal ◽

10.1097/01.tp.0000118904.63669.eb ◽

2004 ◽

Vol 77 (8) ◽

pp. 1203-1208 ◽

Cited By ~ 45

Author(s):

Daniele Di Paolo ◽

Giuseppe Tisone ◽

Paola Piccolo ◽

Ilaria Lenci ◽

Settimio Zazza ◽

...

Keyword(s):

Hepatitis B ◽

Low Dose ◽

Cost Effective ◽

Recurrent Hepatitis ◽

Cost Effective Approach ◽

B Virus ◽

Long Term Follow Up ◽

Hepatitis B Immunoglobulin

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Very-low-dose aspirin and surveillance colonoscopy is cost-effective in secondary prevention of colorectal cancer in individuals with advanced adenomas: network meta-analysis and cost-effectiveness analysis

BMC Gastroenterology ◽

10.1186/s12876-021-01715-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sajesh K. Veettil ◽

Siang Tong Kew ◽

Kean Ghee Lim ◽

Pochamana Phisalprapa ◽

Suresh Kumar ◽

...

Keyword(s):

Colorectal Cancer ◽

Cost Effectiveness ◽

Secondary Prevention ◽

Low Dose ◽

Meta Analysis ◽

Cost Effective ◽

Cost Effectiveness Analysis ◽

Surveillance Colonoscopy ◽

Combination Strategy ◽

Effectiveness Analysis

Abstract Background Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC). Methods Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk–benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained. Results According to NMA, the risk–benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective. Conclusion ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.

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Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2006.06.004 ◽

2006 ◽

Vol 66 (2) ◽

pp. 560-567 ◽

Cited By ~ 50

Author(s):

Meritxell Arenas ◽

Fèlix Gil ◽

Meritxell Gironella ◽

Víctor Hernández ◽

Sandra Jorcano ◽

...

Keyword(s):

Experimental Model ◽

Systemic Inflammation ◽

Low Dose ◽

Low Dose Radiotherapy ◽

Anti Inflammatory

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The Cost-effectiveness of Celecoxib versus Non-steroidal Anti-inflammatory Drugs plus Proton-pump Inhibitors for Treating Osteoarthritis in Algeria

Journal of Health Economics and Outcomes Research ◽

10.36469/9865 ◽

2013 ◽

Vol 1 (2) ◽

pp. 184-199 ◽

Cited By ~ 1

Author(s):

Nadir Hammoumraoui ◽

Sid Ahmed Kherraf ◽

Joaquin Mould-Quevedo ◽

Tarek A. Ismail

Keyword(s):

Cost Effectiveness ◽

Adverse Events ◽

Proton Pump ◽

Cost Effective ◽

Private Clinic ◽

Effective Treatment Option ◽

Life Years ◽

Cost Effective Treatment ◽

Inflammatory Drugs ◽

Anti Inflammatory

Background: Cyclooxygenase-2 inhibitors such as celecoxib are as effective as non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) in the treatment of osteoarthritis (OA), have fewer gastrointestinal side effects, but are more expensive. Objective: To evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib versus ns-NSAIDs, with/without proton-pump inhibitor (PPI) co-therapy, for treating OA in Algeria. Methods: The National Institute for Health and Clinical Excellence (NICE) health economic model from UK, updated with relative risks of adverse events using CONDOR trial data, was adapted for costeffectiveness analysis in OA patients aged ≥65 years. Patients could initiate treatment with celecoxib or ns-NSAIDs with/without omeprazole. Conditional probabilities were obtained from published clinical trials; effectiveness measure was quality-adjusted life years (QALYs) gained/patient. The analysis was conducted from a healthcare payer’s perspective. The average daily treatment costs and frequencies of resource use for adverse events were based on data collected in August 2011 from a private clinic located in Cheraga, Algiers, Algeria. Probabilistic sensitivity analysis (PSA) was performed to construct cost-effectiveness acceptability curves (CEACs). Results: QALYs gained/patient over a 6-month horizon were higher with celecoxib (0.368) and celecoxib+PPI (0.40) versus comparators. The lowest expected cost/patient was associated with ibuprofen (US$134.76 versus US$175.67 with celecoxib+PPI, and US$177.57 with celecoxib). Celecoxib+PPI was the most cost-effective drug treatment, with an ICER of US$584.43, versus ibuprofen. Treatment with celecoxib alone showed an ICER of US$1,530.56 versus diclofenac+PPI. These ICERs are <1 gross domestic product per capita in Algeria (US$7,500). Over 1-year, 3-year and 5-year horizons, celecoxib with/without PPI co-therapy showed higher QALYs/patient versus comparators, and decreasing ICERs. The ICER of celecoxib+PPI was lower than that of comparators over all time horizons. These findings were confirmed with CEACs generated via PSA. Conclusion: Using data from a single private clinic in Cheraga, Algiers, Algeria, and after considering new adverse event risks, we showed that celecoxib with/without PPI co therapy is more cost-effective than ns-NSAID+PPI for treating OA patients aged ≥65 years. Celecoxib+PPI remains dominant over a 5-year horizon, making it the most cost-effective treatment option for medium- and long-term use.

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Reversion of antibiotic resistance in drug-resistant bacteria using non-steroidal anti-inflammatory drug benzydamine

10.1101/2021.05.07.443075 ◽

2021 ◽

Author(s):

Yuan Liu ◽

Ziwen Tong ◽

Jingru Shi ◽

Tian Deng ◽

Ruichao Li ◽

...

Keyword(s):

Cost Effective ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Inflammatory Drug ◽

Development Of Resistance ◽

Drug Resistant Bacteria ◽

Metabolic States ◽

Anti Inflammatory ◽

Approved Drugs

Antimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimen. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing previously approved drugs as potent antibiotic adjuvants offers a cost effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad spectrum antibiotic tetracyclines activity against a panel of clinical important resistant pathogens, including MRSA, VRE, MCRPEC and tet (X)-positive Gram negative bacteria. Further mechanistically experiments showed that benzydamine dissipated membrane potential (ΔΨ) in both Gram positive and negative bacteria, which in turn upregulated the transmembrane proton gradient (ΔpH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline benzydamine combination against different metabolic states of bacteria including persister cells. As a proof of concept, the in vivo efficacy of this combination therapy was evidenced in multiple animal infection models. These findings revealed that benzydamine is a promising tetracycline antibiotics adjuvant and has the potential to address life threatening infections by MDR bacteria.

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Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0251348 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251348

Author(s):

Tiankui Shuai ◽

Chuchu Zhang ◽

Meng Zhang ◽

Yalei Wang ◽

Huaiyu Xiong ◽

...

Keyword(s):

Low Dose ◽

Hospitalization Rate ◽

Current Evidence ◽

Cochrane Library ◽

Chronic Obstructive ◽

Exacerbation Rate ◽

Histone Deacetylase 2 ◽

Copd Patients ◽

Anti Inflammatory ◽

Inflammatory Effect

Background A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity. Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant. Method We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies. Stata/SE 15.0 was used to perform all data analysis. Result A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816. Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%). Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%). Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial. Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group. Conclusion Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate. Instead, the hospitalization rate and mortality increased with theophylline. Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients. Trial registration PROSPERO Registration CRD42021224952.

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Low-dose methotrexate: anti-inflammatory or immunosuppressive?

Cleveland Clinic Journal of Medicine ◽

10.3949/ccjm.57.3.245 ◽

1990 ◽

Vol 57 (3) ◽

pp. 245-246 ◽

Cited By ~ 2

Author(s):

N. Olsen

Keyword(s):

Low Dose ◽

Dose Methotrexate ◽

Anti Inflammatory

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Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration

Cell & Bioscience ◽

10.1186/s13578-019-0369-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Yong Xie ◽

Meng Pan ◽

Yanpan Gao ◽

Licheng Zhang ◽

Wei Ge ◽

...

Keyword(s):

Bone Formation ◽

Bone Remodeling ◽

Low Dose ◽

High Dose ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Dose Dependent ◽

High Dose Aspirin

AbstractThe failure of remodeling process that constantly regenerates effete, aged bone is highly associated with bone nonunion and degenerative bone diseases. Numerous studies have demonstrated that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their constituent progenitor cells located around the remodeling area. These cells contribute to a complex metabolic scenario, resulting in degradative or synthetic functions for bone mineral tissues. The spatiotemporal effects of aspirin and NSAIDs in the bone remodeling are controversial according the specific therapeutic doses used for different clinical conditions. Herein, we review in vitro, in vivo, and clinical studies on the dose-dependent roles of aspirin and NSAIDs in bone remodeling. Our results show that low-dose aspirin (< 100 μg/mL), which is widely recommended for prevention of thrombosis, is very likely to be benefit for maintaining bone mass and qualities by activation of osteoblastic bone formation and inhibition of osteoclast activities via cyclooxygenase-independent manner. While, the roles of high-dose aspirin (150–300 μg/mL) and other NSAIDs in bone self-regeneration and fracture-healing process are difficult to elucidate owing to their dual effects on osteoclast activity and bone formation of osteoblast. In conclusion, this study highlighted the potential clinical applications of low-dose aspirin in abnormal bone remodeling as well as the risks of high-dose aspirin and other NSAIDs for relieving pain and anti-inflammation in fractures and orthopedic operations.

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