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Acta Veterinaria Scandinavica Dec 2021Primary immune thrombocytopenia (ITP) is a cause of severe thrombocytopenia in dogs. Immunosuppressive corticosteroid drugs are frequently used in the management of ITP,... (Review)
Review
Primary immune thrombocytopenia (ITP) is a cause of severe thrombocytopenia in dogs. Immunosuppressive corticosteroid drugs are frequently used in the management of ITP, but treatment failure may occur. Immunomodulatory and non-corticosteroid immunosuppressive drugs might improve outcomes from therapy either alone or in combination with corticosteroids. The objectives of this scoping review were (1) to evaluate the current evidence relating to immunomodulatory and immunosuppressive drug protocols in the treatment of canine ITP, and (2) to answer the clinical question, whether or not therapy with immunomodulatory or non-corticosteroid immunosuppressive drugs alone or in combination with corticosteroids could improve outcome, compared to therapy with corticosteroids alone. A literature search was performed in the electronic databases of Agricola, CAB Abstracts, Embase, Medline and Web of Science for publications in November 2019 and again February 1, 2021. Selection criteria were relatively strict and included peer-reviewed research papers reporting outcome measures from immunomodulatory and immunosuppressive drug protocols in the treatment of canine ITP with a pre-therapeutic mean or median platelet count < 50,000/µL as a strict criterion for inclusion. Studies were evaluated if they had an appropriate diagnostic work up to exclude underlying conditions. Outcome measures and adverse events were compared between drug protocols both within studies and between studies. The search identified 456 studies, with six studies being eligible for inclusion. The studies were mostly case series while two were randomized controlled trials. Level of evidence varied with an overall uncertain subject enrollment, small groups, inadequate description and variable use of drug protocols or outcome measures. For outcomes such as platelet recovery time and duration of hospitalization, an improvement was observed using adjunctive therapy (human intravenous immunoglobulin) compared to therapy with corticosteroids alone. For outcomes of complete platelet recovery time, survival (6-month), mortality and relapse, no improvement was observed using adjunctive drugs compared to corticosteroids alone. Specifically, therapy with mycophenolate mofetil alone and adjunctive azathioprine were associated with more severe adverse events compared to other drug protocols. Evidence relating to immunomodulatory and immunosuppressive drug protocols in the treatment of canine ITP was of variable quality. Future larger case-controlled trials are required for determination of optimal treatment protocols in canine ITP.
Topics: Animals; Blood Platelets; Dog Diseases; Dogs; Immunosuppressive Agents; Pharmaceutical Preparations; Platelet Count; Purpura, Thrombocytopenic, Idiopathic
PubMed: 34961516
DOI: 10.1186/s13028-021-00620-z -
Frontiers in Immunology 2022Allergic rhinitis is an important risk factor for bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treatment of allergic rhinitis,...
A recombinant pollen adjuvanted Art v 1 protein-based vaccine treats allergic rhinitis and bronchial asthma using pre- and co-seasonal ultrashort immunotherapy regimens in sensitized mice.
Allergic rhinitis is an important risk factor for bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treatment of allergic rhinitis, conjunctivitis, and asthma. A disadvantage of current ASIT methods is the length of therapy which requires numerous allergen administrations. The success of ASIT is determined by its schedule, which, depending on the vaccine and type of allergy, can be pre-seasonal (before the allergy season begins), combined pre/co-seasonal (during the allergy season) etc. The aim of the present study was to evaluate a vaccine based on recombinant pollen major Art v 1 protein formulated with ISA-51 adjuvant for therapy of allergic rhinitis and bronchial asthma in -sensitized mice in an ultrashort (4 subcutaneous injections at weekly intervals) pre- and co-seasonal ASIT regimen. To simulate co-seasonal ASIT in mice, mice were regularly challenged with intranasal and nebulized pollen extract at the same time as receiving subcutaneous ASIT. For comparison, we used a previous Art v 1 protein vaccine formulated with SWE adjuvant, which in this study was modified by adding CpG oligonucleotide (Th1-biasing synthetic toll-like receptor 9 agonist), and a commercial vaccine containing a modified extract with aluminum hydroxide adjuvant. The therapeutic potential of Art v 1 based vaccine formulations with different ASIT regimens was evaluated in high and low (10 times lower) dose regimens. The ISA-51-adjuvanted vaccine formulations were the only ones among those studied in the ultrashort pre- and co-seasonal ASIT regimens to provide significant reduction in both signs of allergic rhinitis and bronchial asthma in sensitized mice (vs. positive control). In the ISA-51 adjuvanted group, immune response polarization toward Th1/Treg was observed in pre-seasonal ASIT, as reflected in a significant decrease in the serum level of total and Art v 1-specific IgE and increased ratios of allergen-specific IgG2a/IgG1 and IFN-γ/IL-4. The high dose SWE-CpG-adjuvanted vaccine had similar efficacy to the ISA-51 adjuvanted groups whereas the commercial vaccine showed significantly less effectiveness. The findings support further preclinical safety studies of the Art v 1-based vaccine formulated with ISA-51 adjuvant.
Topics: Mice; Animals; Seasons; Pollen; Immunoglobulin E; Rhinitis, Allergic; Asthma; Allergens; Vaccines; Adjuvants, Immunologic; Desensitization, Immunologic; Adjuvants, Pharmaceutic; Artemisia; Immunoglobulin G; Plant Extracts
PubMed: 36439113
DOI: 10.3389/fimmu.2022.983621 -
BMC Health Services Research May 2023Phramongkutklao Hospital is one of the largest military hospitals in Thailand. Beginning in 2016, an institutional policy was implemented in which medication...
BACKGROUND
Phramongkutklao Hospital is one of the largest military hospitals in Thailand. Beginning in 2016, an institutional policy was implemented in which medication prescription length was increased from 30 to 90 days. However, there have been no formal investigations into how this policy has impacted medication adherence among patients in hospitals. As such, this study evaluated how prescription length impacted medication adherence among dyslipidemia and type-2 diabetes patients who were treated at Phramongkutklao Hospital.
METHODS
This pre-post implementation study compared patients who received prescription lengths of 30 and 90 days based on information recorded in the hospital database between 2014 and 2017. Therein, we used the medication possession ratio (MPR) to estimate patient adherence. Focusing on patients with universal coverage insurance, we employed the difference-in-difference method to examine changes in adherence from before and after policy implementation, then conducted a logistic regression to test for associations between the predictors and adherence.
RESULTS
We analyzed data from a total of 2,046 patients, with equal amounts of 1,023 placed into the control group (no change to 90-day prescription length) and intervention group (change from 30 to 90-day prescription length). First, we found that increased prescription length was associated with 4% and 5% higher MPRs among dyslipidemia and diabetes patients in the intervention group, respectively. Second, we found that medication adherence was correlated with sex, comorbidities, history of hospitalization, and the number of prescribed medications.
CONCLUSION
Increasing the prescription length from 30 to 90 days improved medication adherence in both the dyslipidemia and type-2 diabetes patients. This shows that the policy change was successful for patients in the hospital considered for this study.
Topics: United States; Humans; Thailand; Medication Adherence; Policy; Drug Prescriptions; Prescription Drugs; Diabetes Mellitus, Type 2; Hospitals, Military
PubMed: 37226134
DOI: 10.1186/s12913-023-09530-4 -
American Journal of Preventive Medicine Mar 2021In Massachusetts, recent outbreaks of HIV have been fueled by injection and sexual exposures among people who inject drugs. Understanding pre-exposure prophylaxis need,...
INTRODUCTION
In Massachusetts, recent outbreaks of HIV have been fueled by injection and sexual exposures among people who inject drugs. Understanding pre-exposure prophylaxis need, knowledge, and use among people who inject drugs will help inform and evaluate interventions.
METHODS
In 2019, investigators analyzed 2018 National HIV Behavioral Surveillance data from people who inject drugs in Boston, MA, who met eligibility criteria. Proportions of people who inject drugs with U.S. Preventive Services Task Force-based pre-exposure prophylaxis indication were estimated by types of HIV acquisition risk in the past year: injection exposure only, sexual exposure only, and overlapping injection and sexual exposures. Investigators then evaluated pre-exposure prophylaxis awareness, conversations with healthcare providers about pre-exposure prophylaxis, and self-reported pre-exposure prophylaxis use among those with and without pre-exposure prophylaxis indications.
RESULTS
The prevalence of pre-exposure prophylaxis indication was 92% overall (389/423), with 290 (69%) participants indicated for injection exposures only, 3 (<1%) indicated for sexual exposures only, and 96 (23%) indicated for both injection and sexual exposures. Among those indicated for pre-exposure prophylaxis (n=389), 152 (39%) reported being aware of pre-exposure prophylaxis, 41 (11%) had discussed pre-exposure prophylaxis with a healthcare provider, and 8 (2%) had used pre-exposure prophylaxis in the past year. There were no statistically significant differences between pre-exposure prophylaxis‒indicated and ‒nonindicated people who inject drugs with respect to pre-exposure prophylaxis awareness, discussion with a healthcare provider, and pre-exposure prophylaxis use.
CONCLUSIONS
Indication for pre-exposure prophylaxis was high, but awareness was low, conversations about pre-exposure prophylaxis with healthcare providers were uncommon, and pre-exposure prophylaxis use was extremely low. These findings highlight important areas for clinical and community-based interventions to improve pre-exposure prophylaxis uptake among and delivery to people who inject drugs.
Topics: Boston; HIV Infections; Humans; Massachusetts; Pharmaceutical Preparations; Pre-Exposure Prophylaxis; Prevalence; Substance Abuse, Intravenous
PubMed: 33229144
DOI: 10.1016/j.amepre.2020.09.011 -
Cancer Medicine Jun 2023Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment....
BACKGROUND
Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited.
METHODS
This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity.
RESULTS
Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy.
CONCLUSIONS
Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.
Topics: Child; Humans; Female; Methotrexate; Trimethoprim, Sulfamethoxazole Drug Combination; Cohort Studies; Osteosarcoma; Anti-Inflammatory Agents, Non-Steroidal; Proton Pump Inhibitors; Bone Neoplasms; Risk Factors; Chemical and Drug Induced Liver Injury; Disease Progression
PubMed: 37062070
DOI: 10.1002/cam4.5936 -
Advanced Drug Delivery Reviews Oct 2021Evaluation of orally ingestible devices is critical to optimize their performance early in development. Using animals as a pre-clinical tool can provide useful... (Review)
Review
Evaluation of orally ingestible devices is critical to optimize their performance early in development. Using animals as a pre-clinical tool can provide useful information on functionality, yet it is important to recognize that animal gastrointestinal physiology, pathophysiology and anatomy can differ to that in humans and that the most suitable species needs to be selected to inform the evaluation. There has been a move towards in vitro and in silico models rather than animal models in line with the 3Rs (Replacement, Reduction and Refinement) as well as the better control and reproducibility associated with these systems. However, there are still instances where animal models provide the greatest understanding. This paper provides an overview of key aspects of human gastrointestinal anatomy and physiology and compares parameters to those reported in animal species. The value of each species can be determined based upon the parameter of interest from the ingested device when considering the use of pre-clinical animal testing.
Topics: Administration, Oral; Animals; Dosage Forms; Drug Delivery Systems; Drug Evaluation, Preclinical; Gastrointestinal Tract; Humans; Models, Animal
PubMed: 34371085
DOI: 10.1016/j.addr.2021.113915 -
Molecules (Basel, Switzerland) May 2022Tree nuts are rich in polar (phenolic compounds) and non-polar (tocols) antioxidants, with recognized effects in the prevention of diseases such as cancer. These...
Tree nuts are rich in polar (phenolic compounds) and non-polar (tocols) antioxidants, with recognized effects in the prevention of diseases such as cancer. These biomolecules possess antiproliferative activity on cancer cells; however, the combined effect of both types of compounds has been scarcely studied, and this approach could give valuable information on the real anticancer potential of tree nuts. In the present study, the antiproliferative activity of pure tocols and phenolic compounds, tocol- and phenolic-rich extracts (TRE and PRE, respectively) from tree nuts and the extracts combinations, was evaluated in four cancer (HeLa, MCF7, PC3, A549) and one control () cell lines. The most sensible cell lines were HeLa and MCF7. TRE and PRE from nuts were chemically characterized; γ and δ tocopherols, total tocols, total tocopherols and total phenolic compounds were negatively correlated with cell viability in MCF7 cells. In HeLa cells, only δ and total tocopherols were negatively correlated with cell viability. TRE and PRE had a low effect in reducing cell viability of the cancer cell lines, the most effective extracts were those of emory oak acorn (EOA), pecan nut (PEC) and walnut (WAL), and these were further studied for their pharmacological interactions, using the combination index and the isobologram methods. Combinations of both extracts showed a synergistic and strongly synergistic behavior in the three nuts (EOA, PEC and WAL), with combination indexes between 0.12 and 0.55. These results highlight the need to understand the interactions among components found in complex natural extracts or food products in order to fully understand their bioactivities.
Topics: HeLa Cells; Humans; Neoplasms; Nuts; Phenols; Plant Extracts; Tocopherols
PubMed: 35630629
DOI: 10.3390/molecules27103154 -
The Analyst Aug 2023We report a novel hydrogel for pre-concentration, fluorescent labelling, and light-triggered release of proteins for detection of low abundance biomarkers. The hydrogel...
We report a novel hydrogel for pre-concentration, fluorescent labelling, and light-triggered release of proteins for detection of low abundance biomarkers. The hydrogel was a co-polymer of acrylamide/bisacrylamide and methacrylamide attached to fluorescein isothiocyanate a light cleavable bond and a poly(ethylene glycol) spacer arm of molecular weight of 3400 g mol. Unlike previous work, proteins were captured by an irreversible chemical reaction rather than by non-covalent affinity binding or physical entrapment. Because the protein-reactive group was attached to fluorescein, which in turn was coupled to the hydrogel by a photocleavable bond, on release the protein was labelled with fluorescein. Our hydrogel offered a pre-concentration factor of up to 236 for a model protein, streptavidin. Each protein molecule was labelled with 85 fluorescein molecules, and 50% of the proteins in the hydrogel were released after UV exposure for ∼100 s. The proteins released from the hydrogel were captured in biotinylated microtitre plates and detected by fluorescence, allowing measurement of at least 0.01 ppm (or ∼166 pM) of protein in sample solutions. The reported hydrogel is promising for detection of low abundance proteins while being less laborious than enzyme-linked immunosorbent assay and less affected by changes in environmental conditions than label-free biosensors.
Topics: Hydrogels; Delayed-Action Preparations; Polyethylene Glycols; Polymers; Fluoresceins
PubMed: 37493470
DOI: 10.1039/d3an00811h -
Applied Health Economics and Health... Sep 2023The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are...
OBJECTIVES
The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are conducted based on evidence-based medical benefit assessments using data from prior clinical trials. Although the act does not explicitly set a willingness-to-pay (WTP) threshold, the process itself implicitly establishes a WTP for health improvement. We evaluated the implicit WTP for prescription pharmaceuticals post-AMNOG in the German healthcare system from the decision-maker/payer perspective.
METHODS
We extracted data on patient-group-specific annual treatment costs and endpoints from 2011 to 2021 from the dossiers assessed by the German Federal Joint Committee (FJC; Gemeinsamer Bundesausschuss). Using incremental cost-effectiveness ratios (ICERs), we calculated a WTP for the indications (I) diabetes, (II) cardiovascular disease, and (III) psoriasis weighted according to patient group size, first from the perspective of the decision-maker (approach A), and second from the perspective of the industry (approach B). To put clinical outcome measures into relation to one another, minimum clinically important differences (MCIDs) were derived from the literature and compared.
RESULTS
The annual treatment costs of newly authorized drugs were substantially higher (both pre- and post-negotiation) than that of their comparators (e.g., psoriasis, pre-negotiation: €20,601.59, post-negotiation: €16,763.57; comparators: €5178.00). However, although newly launched drugs were more expensive than their comparators, they brought greater medical benefits and were more aligned with value (r = 0.59, P < 0.001) than older drugs. We estimated WTP to vary widely by indication group [€33,814.08 per 1 percentage point hemoglobin A1c (HbA1c) reduction for diabetes, €10,970.83 per life year gained for cardiovascular disease, and €663.46 per 1% PASI decrease for psoriasis; approach A]. WTP was converted to MCID thresholds: diabetes: €16,907.04; cardiovascular drugs: no MCID existent to convert; and psoriasis: €33,173.00. WTP remained constant over time for diabetes and cardiovascular drugs but increased for psoriasis drugs.
CONCLUSION
This paper is one of the first to estimate the implicit WTP for prescription pharmaceuticals post-AMNOG and suggests that the WTP may vary between different therapeutic areas. Additionally, making different assumptions (approach A versus approach B) with regard to the assumed effectiveness in indication areas that had been declared as having no additional benefit by the FJC may explain the different perspectives of decision-makers and of the pharmaceutical industry on the value of a pharmaceutical.
Topics: Humans; Cardiovascular Diseases; Delivery of Health Care; Germany; Health Care Costs; Pharmaceutical Preparations; Cost-Benefit Analysis
PubMed: 37249741
DOI: 10.1007/s40258-023-00815-7 -
World Journal of Gastroenterology Jul 2021Gastroesophageal reflux disease (GERD) has a high prevalence worldwide, and its incidence is increasing annually. Modified Xiaochaihu Decoction (MXD) could relieve the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Gastroesophageal reflux disease (GERD) has a high prevalence worldwide, and its incidence is increasing annually. Modified Xiaochaihu Decoction (MXD) could relieve the symptoms of GERD, but the effects of MXD on GERD manifestations and relapse prevention need to be further explained. Therefore, we performed a prospective, double-blind, and double-simulation study.
AIM
To verify the efficacy of MXD for GERD and its effect on esophageal motility.
METHODS
Using randomization, double-blinding, and a simulation design, 288 participants with GERD were randomized to the treatment group and control group and received herbs (MXD) plus omeprazole simulation and omeprazole plus herbs simulation, respectively, for 4 wk. The GERD-Q scale score and esophageal manometry were measured at baseline, after treatment, and at 1 mo and 3 mo follow-up visits when medication was complete to evaluate recurrence indicators.
RESULTS
The GERD-Q scale score in both groups decreased significantly compared to those before treatment ( < 0.01). However, no significant difference was observed between the two groups ( > 0.05). Esophageal manometry showed that participants with lower esophageal sphincter pressure reduction and the proportion of ineffective swallowing (more than 50%) improved in both groups from baseline ( < 0.01), especially in the treatment group ( < 0.05). The percentage of small intermittent contractions, large intermittent contractions, and increased pre-phase contractions in the treatment group significantly improved compared with baseline ( < 0.05) but did not improve in the control group ( > 0.05). There was no significant difference between the groups after treatment ( > 0.05). The percentage of weak esophageal contractility (distal contractile integral < 450 mmHg·s·cm), improved in both groups ( < 0.01), but no significant difference was observed between the groups after treatment ( > 0.05). The relapse rate in the treatment group was lower than that in the control group at the 1 mo ( < 0.01) and 3 mo follow-up ( < 0.05).
CONCLUSION
MXD has a similar therapeutic effect to omeprazole in mild-to-moderate GERD. The therapeutic effect may be related to increased pressure in the lower esophageal sphincter and reduced ineffective swallowing.
Topics: Drugs, Chinese Herbal; Esophageal Sphincter, Lower; Gastroesophageal Reflux; Humans; Manometry; Prospective Studies
PubMed: 34366631
DOI: 10.3748/wjg.v27.i28.4710