Therapeutic Controversies in the Treatment of Asthma

1994 ◽  
Vol 28 (7-8) ◽  
pp. 904-914 ◽  
Author(s):  
Alan K. Kamada
Keyword(s):  
Adverse Effects ◽  
Systemic Absorption ◽  
Systemic Effects ◽  
High Dose ◽  
Adrenergic Agonists ◽  
Risk Of Death ◽  
Increased Risk ◽  
Metered Dose ◽  
Systemic Glucocorticoids ◽  
Inhaled Glucocorticoids

OBJECTIVE: To introduce readers to the current controversial topics in the area of asthma therapy. Background is provided such that clinicians are aware of these issues and can make rational decisions. DATA SOURCES: Pertinent articles were individually identified and reviewed from each journal. STUDY SELECTION: Relevant studies, determined by topic and other specific criteria, e.g., testing methodology, were included. DATA SYNTHESIS: Further investigation is required in the areas discussed. Systemic effects, specifically growth suppression (in children), adrenal suppression, and osteoporosis, have been demonstrated with high-dose inhaled glucocorticoids; however, the clinical relevance of such intravenous glucocorticoid formulations via nebulizer have not been demonstrated. Likewise, data on the equivalence of the inhaled glucocorticoids, with regard to efficacy and potential systemic effects, and the differences between metered-dose inhalers and dry powder inhalers, with regard to aerosol characteristics and drug delivery, are unclear. Theophylline, when used with inhaled β-adrenergic agonists and systemic glucocorticoids for the treatment of acute asthma, as not been shown to provide clear benefit and may result in increased adverse effects. The use of regular (vs. “as needed” or prn) inhaled β-adrenergic agonists, although shown in two studies to be detrimental to the control of asthma and result in an increased risk of death or near death caused by asthma, has not been conclusively demonstrated to be harmful. CONCLUSIONS: Monitoring for adverse effects and the use of techniques to minimize systemic absorption (spacers and mouth rinsing) are recommended when high-dose inhaled glucocorticoid therapy is used. Intranasal and intravenous glucocorticoid products are not recommended for administration via nebulizer because of safety concerns. Until further data are available, inhaled glucocorticoids are thought to be equivalent on a μg-per-μg basis rather than an actuation-per-actuation basis. Theophylline is no longer recommended for treatment of acute exacerbations in nonhospitalized patients not already receiving the medication, and the link between deterioration of asthma control (and the risk for death) and regular inhaled beta-adrenergic agonists appears weak.

Reasons for discontinuing clozapine: matched, case–control comparison with risperidone long-acting injection

2009 ◽  
Vol 194 (2) ◽  
pp. 165-167 ◽  
Author(s):  
David M. Taylor ◽  
Petrina Douglas-Hall ◽  
Banke Olofinjana ◽  
Eromona Whiskey ◽  
Arwel Thomas
Keyword(s):  
Adverse Effects ◽  
Control Group ◽  
Clinical Environment ◽  
Risk Of Death ◽  
Increased Risk ◽  
Common Causes ◽  
Control Comparison ◽  
Mortality Ratio ◽  
Matched Case ◽  
Long Acting

BackgroundClozapine has a range of serious adverse effects that may give rise to an increased risk of death.AimsTo compare reasons for discontinuation of clozapine with reasons for discontinuation of risperidone long-acting injection in age-matched individuals treated in the same clinical environment.MethodComparison of patients receiving clozapine and an age-matched control group receiving risperidone injection.ResultsWe established outcome for 529 consecutive patients receiving clozapine and 250 receiving risperidone (161 discontinuers from each group were compared). Adverse effects (odds ratio OR=2.19, 95% CI 1.31–3.67) and death (OR=7.0, 95% CI 2.09–23.5) were more commonly observed as reasons for discontinuation of clozapine than of risperidone. Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01–0.14). Standardised mortality ratio (SMR) was significantly raised for patients receiving clozapine (SMR=4.17, 95% CI 2.78–6.26). Pneumonia was the most common single cause of death.ConclusionsClozapine use in patients with severe mental illness was associated with a significantly increased risk of death compared with that for the general population. Causation could not be established. Adverse effects and death are common causes of clozapine discontinuation.

scholarly journals Risks associated with tiotropium in chronic obstructive pulmonary disease: overview of the evidence to date

2012 ◽  
Vol 3 (3) ◽  
pp. 123-131 ◽  
Author(s):  
Yoon K. Loke ◽  
Sonal Singh
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Drug Delivery ◽  
Adverse Effects ◽  
Pulmonary Disease ◽  
Urinary Retention ◽  
Mortality Data ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Risk Of Death ◽  
Increased Risk

Tiotropium is a long-acting inhaled anticholinergic agent that is widely used in the treatment of chronic obstructive pulmonary disease (COPD). It was initially launched as the tiotropium HandiHaler formulation, but this was followed by a newer version based on a potentially more efficient drug delivery device, known as Respimat. This Respimat formulation is available worldwide but has not yet succeeded in gaining regulatory approval in the USA. In the past few years, the adverse effects profile of tiotropium has come under close scrutiny owing to concerns about the possibility of urinary and cardiovascular adverse effects. These concerns appeared to have been alleviated following the publication of data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, which was a large trial of 4 years’ duration. This trial did not show any excess myocardial infarction, renal or urinary adverse events with tiotropium compared with placebo. However, the risk of urinary retention has been in the spotlight again following publication of two observational studies reporting a significantly increased risk of urinary retention in men recently started on inhaled anticholinergics, especially when prostatic hyperplasia coexists. More recently, a meta-analysis of mortality data for the tiotropium Respimat formulation raised the possibility of an increased risk of death, including death from cardiovascular causes. It is unclear if the more efficient drug delivery offered by the Respimat device is hitting a different part of the dose-toxicity curve. In the absence of any evidence of superior clinical efficacy with tiotropium Respimat compared with tiotropium HandiHaler, some experts have argued that there is no compelling reason to choose the Respimat formulation given the new uncertainties about its safety profile.

Long-term outcomes of survivors of autologous hematopoietic-cell transplantation for refractory and relapsed Hodgkin’s Disease

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6554-6554
Author(s):  
K. A. Goodman ◽  
V. Serrano ◽  
E. R. Riedel ◽  
S. Gulati ◽  
C. H. Moskowitz ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Risk Of Death ◽  
Increased Risk

6554 Background: With improvements in survival among refractory/relapsed Hodgkin’s Lymphoma (HL) patients after high-dose chemo-radiotherapy and autologous hematopoietic-cell transplant (AHCT), it is important to evaluate risk of late complications in this heavily treated population. Methods: From 1985–1998, 218 refractory/relapsed HL patients were treated on high dose chemo-radiotherapy and AHCT salvage protocols. 153 (70%) surviving ≥2 years after AHCT were analyzed. All received either radiotherapy with initial therapy or total lymphoid irradiation and involved field boost with the conditioning regimen (43%). Information from surviving patients was obtained through a self-administered questionnaire. The NDI was queried to determine vital status and cause of death. Primary endpoint was non-HL mortality, defined as mortality due to cardiac causes, infection or second malignancy (SM). Competing risk methods were used to calculate cause-specific mortality rates and examine its predictors. All events were calculated from 2 years post-AHCT to date of death/last follow-up. Results: Median follow-up time was 11 years. There have been 51 deaths, 32 due to HL and 19 due to other causes. Eleven deaths were due to SM: AML (3), MDS (2), NHL (2), NSCLC (2), gastric and colon cancer. There were 8 non-SM deaths: cardiac toxicity (4), infection, aplastic anemia, suicide, unknown causes (1 each). The 10 and 15-year overall survival (OS) rates are 64% and 57%, respectively. The 10-year cumulative incidence of death from HL and from non-HL causes were 22% and 13.5% ( table ). By univariate analysis, increased risk of death due to SM was associated only with higher age at AHCT (p=0.02). Conclusions: While HL initially accounts for the majority of deaths among patients surviving high-dose therapy, the HL mortality rate plateaus and risk of death from non-HL mortality increases after 5 years. Yet, even at 15-years, SM risk does not exceed that observed in patients treated with standard regimens. [Table: see text] No significant financial relationships to disclose.

Abstract 14626: Propofol and Dexmedetomidine Related Transient High-grade Symptomatic Av Block

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Usama Talib ◽  
Lakshman Sneha ◽  
Anneris Estevez
Keyword(s):  
Mechanical Ventilation ◽  
Adverse Effects ◽  
Sinus Bradycardia ◽  
Systolic Pressure ◽  
High Dose ◽  
High Grade ◽  
Av Block ◽  
Mechanical Ventilation Duration ◽  
Increased Risk ◽  
Life Threatening

Introduction: Dexmedetomidine and propofol are both associated with risk of sinus bradycardia and hypotension. High grade AV block has rarely been reported with these medications. We present a case of high grade AV block (Mobitz II) in the setting of co administration of dexmedetomidine and propofol resulting in hypotension, that resolved with discontinuation of propofol. Case: 85 year old female with history significant for hypertension and CLL was admitted to the ICU with ARDS secondary to COVID-19 requiring mechanical ventilation. Along with management of ARDS, dexmedetomidine and propofol were administered for adequate sedation while trying to limit high dose of propofol. On day one of administration of the combination (16 mcg/kg/min propofol and 0.6 mcg/kg/hr dexmedetomidine), patient developed Mobitz II AV block associated with hypotension with systolic pressure in 60s. Propofol was discontinued and AV block and hypotension resolved. Patient continued to improve and was eventually extubated and transferred to the telemetry floor. Her telemetry during hospital course did not reveal any further high grade AV block and thus patient did not require placement of a pacemaker. Discussion: Optimizing sedation in intubated patients and knowledge of associated adverse effects is warranted to minimize mechanical ventilation time and prevent life threatening complications. Dexmedetomidine has been associated with a reduction in mechanical ventilation duration but an increased risk of bradycardia and hypotension as compared to midazolam and propofol. (1) Hypotension is common with propofol but sinus bradycardia and arrythmias have also been reported. (2) Rarely propofol can precipitate high grade AV block that can be life threatening if not promptly addressed. (3) Co administration of dexmedetomidine and propofol can be associated with exaggeration of individual side effects. Mindfulness of such adverse effects can not only help prevent life threatening complications but also decrease chances of unnecessary pacemaker placements. Conclusion: Propofol though associated with sinus bradycardia, may result in high grade AV block when co-administered with dexmedetomidine that is usually reversible with discontinuation of the offending drug.

scholarly journals Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review

2020 ◽  
Vol 7 (1) ◽  
pp. e000756
Author(s):  
Roshni Patel ◽  
Sumrah A Naqvi ◽  
Chris Griffiths ◽  
Chloe I Bloom
Keyword(s):  
Adverse Effects ◽  
Observational Studies ◽  
Respiratory Infections ◽  
Bone Fractures ◽  
Risk Of Bias ◽  
Systemic Effects ◽  
Inhaled Corticosteroid ◽  
Mineral Density ◽  
Increased Risk ◽  
Ocular Disorders

BackgroundOral corticosteroid use increases the risk of systemic adverse effects including osteoporosis, bone fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if inhaled corticosteroid (ICS) use in asthma is also associated with increased risk of systemic effects.MethodsMEDLINE and Embase databases were searched to identify studies that were designed to investigate ICS-related systemic adverse effects in people with asthma. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia or mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and Risk of Bias In Non-randomised Studies of Interventions-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies reporting each outcome.ResultsThirteen studies met the inclusion criteria, 2 trials and 11 observational studies. Study numbers by outcome were: six BMD, six respiratory infections (four pneumonia, one tuberculosis (TB), one non-TB mycobacteria), one ocular disorder (cataracts) and no diabetes. BMD studies found conflicting results (three found loss of BMD and three found no loss), but were limited by study size, short follow-up and lack of generalisability. Studies addressing infection risk generally found positive associations but suffered from a lack of power, misclassification and selection bias. The one study which assessed ocular disorders found an increased risk of cataracts. Most studies were not able to fully adjust for known confounders, including oral corticosteroids.ConclusionThere is a paucity of studies assessing systemic adverse effects associated with ICS use in asthma. Those studies that have been carried out present conflicting findings and are limited by multiple biases and residual confounding. Further appropriately designed studies are needed to quantify the magnitude of the risk for ICS-related systemic effects in people with asthma.

scholarly journals High-dose opioid utilization and mortality among individuals initiating hemodialysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Matthew Daubresse ◽  
G. Caleb Alexander ◽  
Deidra C. Crews ◽  
Dorry L. Segev ◽  
Krista L. Lentine ◽  
...  
Keyword(s):  
United States ◽  
Cumulative Incidence ◽  
The United States ◽  
High Dose ◽  
Opioid Use ◽  
Opioid Prescription ◽  
Average Percentage ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Increased Risk

Abstract Background Individuals undergoing hemodialysis in the United States frequently report pain and receive three-fold more opioid prescriptions than the general population. While opioid use is appropriate for select patients, high-dose utilization may contribute to an increased risk of death due to possible accumulation of opioid metabolites. Methods We studied high-dose opioid utilization (≥120 morphine milligram equivalents [MME] per day) among adults initiating hemodialysis in the United States between 2007 and 2014 using national registry data. We calculated the cumulative incidence (%) of high-dose utilization and depicted trends in the average percentage of days individuals were exposed to opioids. We used adjusted Cox proportional hazards models to identify which opioid doses were associated with mortality. Results Among 327,344 adults undergoing hemodialysis, the cumulative incidence of high-dose utilization was 14.9% at 2 years after initiating hemodialysis. Among patients with ≥1 opioid prescription during follow-up, the average percentage of days exposed to high-dose utilization increased from 13.9% in 2007 to 26.1% in 2014. Compared to 0MME per day, doses < 60MME were not associated with an increased risk of mortality, but high-dose utilization was associated with a 1.63-fold (95% CI, 1.57, 1.69) increased risk of mortality. The risk of mortality associated with opioid dose was highest in the first year after hemodialysis initiation. Conclusions The risk of mortality associated with opioid utilization among individuals on hemodialysis increases as doses exceed 60MME per day and is greatest during periods of high-dose utilization. Patients and clinicians should carefully weigh the risks and benefits of opioid doses exceeding 60MME per day.

scholarly journals Erythropoietin Induced Erythroid Precursor Pool Depletion Causes Erythropoietin Hyporesponsiveness

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5156-5156
Author(s):  
Xiaoyu Yan ◽  
Sihem Ait-Oudhia ◽  
Wojciech Krzyzanski
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Age Distribution ◽  
Clinical Importance ◽  
Precursor Cells ◽  
High Dose ◽  
Erythroid Precursor ◽  
Precursor Pool ◽  
Risk Of Death ◽  
Increased Risk

Abstract Abstract 5156 Background: Erythropoietin (EPO) hyporesponsiveness is demonstrated by a persistence of anemia despite high dose of recombinant human erythropoietin (rHuEPO) or requirement of large doses to maintain the target hemoglobin concentration. The purpose of this study is to demonstrate that the bone marrow depletion induced by rHuEPO treatment may another contributing factor to hyporesponsiveness. Methods: Healthy Wistar rats were given single dose (SD) or multiple doses (MD) of rHuEPO. In MD study, animals were challenged with thrice-weekly (100 IU/kg) over two weeks and the pharamcodynamic biomarkers included reticulocyte (RET) and red blood cells (RBC) counts, and hemoglobin (HGB) concentrations. In SD study, in addition to the biomarkers in the peripheral blood, the erythropoietic responses in bone marrow and spleen were also quantified using a flow cytometric immunophenotyping technique. The total marrow and spleen cellularity was quantitatively assessed using flow cytometry. A mathematical approach involving measuring RET age distribution was developed to evaluate the RET loss due to neocytolysis. The pharmacokinetics of rHuEPO was assessed by measuring serum concentrations over time using ELISA. Result: In MD study, a slow and oscillatory decline of RET response was observed before the administration of the last dose on day 11. The RET kept decreasing below the baseline and reached a nadir on day 22, followed by a slow return to the baseline on day 28. These observations demonstrated the tolerance and rebound phenomena. In SD study, the RET decreased below the baseline after day 6. A depletion of the bone marrow erythroid precursor cells was also observed. Meanwhile, neocytolysis of RET was only observed from day 3–5 after rHuEPO injection. These results suggested that the reduced levels of RET after day 6 resulted from the depletion in the erythroid precursor cells in bone marrow induced by rHuEPO treatment. Conclusion: The EPO hyporesponsiveness is of clinical importance because it is associated with an increased risk of death or cardiovascular events. The findings in this study demonstrate that EPO-induced erythroid precursor depletion may contribute to the rHuEPO hyporesponsiveness. When the erythroid precursor cells are depleted, an increase of rHuEPO dose would not show much benefit, due to the smaller number of cells present to initiate the erythropoiesis. These findings provide additional justification for reducing the doses of erythropoietin stimulating agents in anemic patients demonstrating hyporesponsiveness. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Application of polymeric nanoparticles in oral delivery of recombinant human erythropoietin: A review

2019 ◽  
Vol 9 (1-s) ◽  
pp. 403-407
Author(s):  
Pankaj Rajendra Dhapake ◽  
Jasmine G Avari
Keyword(s):  
Side Effects ◽  
Drug Release ◽  
Oral Delivery ◽  
Recombinant Human Erythropoietin ◽  
Dosage Form ◽  
The Body ◽  
High Dose ◽  
Risk Of Death ◽  
Human Erythropoietin ◽  
Increased Risk

Recombinant Human Erythropoietin drugs are known as erythropoietin stimulating agents which stimulate the bone marrow to produce more red blood cells in the body. It is used an antianemic in the treatment of renal anemia and chemotherapy induced anemia. It also use in treatment of HIV, cerebral malaria and neurological disease like schizophrenia. The recombinant human erythropoietin dosage form currently available in the market is parenteral dosage form that is ready for injection liquid vial (syringe), which is usually administered 2-3 times weekly. To achieve a therapeutic effect of parenterally administered EPO, cumulative doses are required that significantly exceed levels of endogenous EPO. These high serum levels result in prolonged circulation times of EPO and unspecific binding to non-targeted tissue, which may lead to severe undesired side effects i.e. growth of tumor and also increased risk of death. By using the nanotechnology, side effects and toxicity related to high dose of erythropoietin should be reduces and prolong drug release. this will achieve by reducing administration frequency and lowering dosage of erythropoietin. Keywords: Recombinant Human Erythropoietin, Nanoparticle, Prolong drug release, Anemia

scholarly journals Revisiting the Safety of Vaccination against the Flu in Elderly Patients

2018 ◽  
Vol 6 (4) ◽  
pp. 155-161
Author(s):  
O. N. Tkacheva ◽  
A. P. Pereverzev ◽  
N. K. Runikhina ◽  
Yu. V. Kotovskaya
Keyword(s):  
Elderly Patients ◽  
Age Groups ◽  
Clinical Manifestations ◽  
Influenza Vaccines ◽  
High Dose ◽  
Post Vaccination ◽  
Risk Of Death ◽  
Younger Age ◽  
Increased Risk ◽  
Potential Risks

Abstract. Elderly patients are at higher risk of developing infectious diseases that might have more severe progression than those of younger age groups, accompanied by an increased risk of death. These medical conditions in elderly may also present difficulties for diagnosis due to a «blurred» clinical picture. By WHO recommendations the vaccination against influenza is one of the most effective ways to prevent this type of infection in elderly patients. However the use of vaccines may be associated with a risk of adverse drug reactions. In most cases, they have subclinical manifestations and/or non-severe clinical manifestations (adverse reactions), but in a relatively small percentage of cases, the use of vaccines may be associated with a risk of developing serious post-vaccination complications (anaphylaxis, Guillain-Barre syndrome etc.). This article represents data on the safety of influenza vaccines in patients over 60 years old, with due regard to immunosenescence. According to the authors opinion, this will improve the safety of vaccination against influenza patients 60 years and older. At the end of the article, the authors conclude that despite the potential risks, the by the benefits of the use of influenza vaccines continue to overweight potential risks and vaccination of elderly people is effective and safe way to prevent influenza. To improve the effectiveness of vaccination of patients 60 years and older the use of high dose vaccines and adjuvants can be recommended.

scholarly journals The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection

2021 ◽  
pp. 2100769
Author(s):  
Daniel Ward ◽  
Sanne Gørtz ◽  
Martin Thomsen Ernst ◽  
Nynne Nyboe Andersen ◽  
Susanne K. Kjær ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Calcineurin Inhibitors ◽  
Adjusted Relative Risk ◽  
Icu Admission ◽  
Risk Of Death ◽  
Relative Risks ◽  
Increased Risk ◽  
Systemic Glucocorticoids ◽  
Interleukin Inhibitors ◽  
Log Linear

BackgroundImmunosuppression may worsen SARS-CoV-2 infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark.MethodsWe identified all SARS-CoV-2 test-positive patients from February to October 2020 and linked health care data from nationwide registers, including prescriptions for the exposure, immunosuppressant drugs. We estimated relative risks of hospital admission, intensive care unit (ICU) admission, and death (each studied independently up to 30 days from testing) with a log linear binomial regression adjusted for confounders using a propensity score-based matching weights model.ResultsA composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1·56 [95% confidence interval 1.10–2.22]). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (aRR 2.38 [95% CI 1.72–3.30]), which were also associated with an increased risk of hospital admission (aRR 1.34 [95% CI 1.10–1.62]), but not ICU admission (aRR 1.76 [95% CI [0.93–3.35]); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors, or interleukin inhibitors, was not associated with an increased risk of hospitalisation, ICU admission, or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine, or chloroquine.ConclusionsExposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of COVID-19 in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.

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