L'efficacia dell'associazione budesonide e formeterolo nel controllo dell'asma in pazienti assegnati agli step di trattamento 2-4 secondo le linee guida GINA
This study analyzed data from over 12,000 patients in 5 clinical trials to compare the effectiveness of budesonide/formoterol maintenance and reliever therapy to other asthma treatments when introduced in patients at different treatment steps according to GINA guidelines. The results showed that budesonide/formoterol maintenance and reliever therapy achieved similar or higher rates of asthma control and lower rates of exacerbations compared to same or higher dose ICS/LABA treatments across all treatment steps. It was most effective in higher treatment steps. Budesonide/formoterol maintenance and reliever therapy may be a preferable treatment option for patients requiring more effective control across steps 2 to 4.
Safety a lungo termine della procedura di termoplastica bronchiale: i risulta...Merqurio
This study summarizes the long-term (5 year) safety results of bronchial thermoplasty (BT) from the Asthma Intervention Research (AIR) trial. 45 BT-treated patients and 24 control patients were followed for 5 and 3 years, respectively. The rates of respiratory adverse events were stable from years 2 to 5 post-BT. There were no increases in hospitalizations or emergency room visits for respiratory symptoms in years 2 through 5 compared to year 1. Lung function as measured by FVC and FEV1 showed no deterioration over the 5-year period in the BT group. The results support the long-term safety of BT out to 5 years.
This document provides guidelines for managing acute asthma exacerbations in children aged 0-18 years in emergency department and inpatient settings. It recommends obtaining a brief focused history and physical exam including onset of symptoms, medications, risk factors and triggers. It recommends monitoring response to therapy including clinical exam, asthma score, oxygen saturation and lung function. Initial treatment should include supplemental oxygen if saturation is below 91% and inhaled short-acting beta-2 agonists such as albuterol every 10-20 minutes for a total of 3 doses. The guidelines provide recommendations on inhaler device selection, adjunctive therapies and criteria for admission or discharge.
Master thesis - Consensus procedure on Gaucher disease type 1Aline Kiewiet
This document summarizes a Delphi study conducted to develop a consensus set of management goals for type 1 Gaucher disease. A panel of 25 experts participated in 3 survey rounds. In the first round, the panel was presented with 64 potential management goals derived from literature review and patient input. Through 3 rounds of anonymous surveys and feedback, consensus was reached on 39 goals. The final goals included both traditional short-term goals as well as newly added goals focusing on long-term complications, associated conditions, and patient-reported outcomes. Developing an international consensus on management goals can help standardize and improve treatment guidelines for type 1 Gaucher disease.
This document discusses guidelines for pharmaceutical drugs. It explains that drugs are available either by prescription from a healthcare provider or over-the-counter without a prescription. Both routes are regulated by drug laws to ensure safety and effectiveness. It then discusses factors considered for determining if a drug can be sold over-the-counter, including if consumers can self-diagnose conditions and understand proper usage. The document also covers advantages and disadvantages of over-the-counter access for consumers as well as strategies to improve patient compliance with drug treatments.
This document summarizes a clinical trial that evaluated the safety and efficacy of patiromer for treating hyperkalemia in patients with chronic kidney disease receiving RAAS inhibitors. The trial had two phases - an initial 4-week treatment phase followed by an 8-week randomized withdrawal phase. Results showed that patiromer significantly reduced serum potassium levels and maintained normokalemia compared to placebo. The most common side effects were constipation and diarrhea. The authors concluded that patiromer was effective for treating hyperkalemia and allowing continued use of RAAS inhibitors in patients with chronic kidney disease.
Outcomes in Long-term Opioid Tapering and Buprenorphine Transition: A Retrosp...Paul Coelho, MD
This study analyzed outcomes for 240 patients with chronic pain who were prescribed long-term opioid therapy above 90 mg morphine-equivalent daily doses. Patients were offered an outpatient opioid taper or transition to buprenorphine if taper was not tolerated. 44.6% successfully tapered, 18.8% transitioned to buprenorphine, and 36.6% dropped out of treatment. Higher initial opioid doses predicted needing buprenorphine, and benzodiazepine/z-drug use predicted greater dropout. Pain intensity changes after treatment were mixed, with over half of tapered patients reporting increased pain and about half of transitioned patients reporting decreased pain.
Nada Alkis' Master Thesis, Novo Nordisk & University of CopenhagenNada Alkis
My master thesis consisted of two parts. The first part is based on the research question: Are the FDA and EMA aligned in their approval decisions regarding fixed dose combination (FDC) medical products? This question was explored by evaluating the labels of all the FDCs approved between: January 2000 – April 2017 within 5 chronic therapeutic areas: type-2 diabetes mellitus (T2DM), asthma, chronic obstructive pulmonary disease (COPD), hypertension, and human immunodeficiency virus (HIV). In fact, it was found that there were differences between the FDA and EMA approval decisions with regards to the approved and used in pre-defined sub-populations. Some of the reasons for these discrepancies are discussed.
The second part of this thesis attempts to apply for the conceptual issues addressed in the first part to a practical setting. Specifically, assessing the real-world patient reported outcomes (PROs) for patients switched to a certain FDC product, Xultophy. And how the PROs collected from this real-world use might compare to the clinical trial PROs used to support labelling claims. It was found that real-world data, in the form of PROs collected in a community pharmacy setting, is a novel and interesting approach to gathering important information and could be explored further in future research.
FDA 2013 Clinical Investigator Training Course: Clinical pharmacology 2: Clin...MedicReS
FDA 2013 Clinical Investigator Training Course: Clinical pharmacology 2: Clinical Considerations During Phase 2 and Phase 3 of Drug Development
Kellie Reynolds, Pharm.D.,(CDER)
Safety a lungo termine della procedura di termoplastica bronchiale: i risulta...Merqurio
This study summarizes the long-term (5 year) safety results of bronchial thermoplasty (BT) from the Asthma Intervention Research (AIR) trial. 45 BT-treated patients and 24 control patients were followed for 5 and 3 years, respectively. The rates of respiratory adverse events were stable from years 2 to 5 post-BT. There were no increases in hospitalizations or emergency room visits for respiratory symptoms in years 2 through 5 compared to year 1. Lung function as measured by FVC and FEV1 showed no deterioration over the 5-year period in the BT group. The results support the long-term safety of BT out to 5 years.
This document provides guidelines for managing acute asthma exacerbations in children aged 0-18 years in emergency department and inpatient settings. It recommends obtaining a brief focused history and physical exam including onset of symptoms, medications, risk factors and triggers. It recommends monitoring response to therapy including clinical exam, asthma score, oxygen saturation and lung function. Initial treatment should include supplemental oxygen if saturation is below 91% and inhaled short-acting beta-2 agonists such as albuterol every 10-20 minutes for a total of 3 doses. The guidelines provide recommendations on inhaler device selection, adjunctive therapies and criteria for admission or discharge.
Master thesis - Consensus procedure on Gaucher disease type 1Aline Kiewiet
This document summarizes a Delphi study conducted to develop a consensus set of management goals for type 1 Gaucher disease. A panel of 25 experts participated in 3 survey rounds. In the first round, the panel was presented with 64 potential management goals derived from literature review and patient input. Through 3 rounds of anonymous surveys and feedback, consensus was reached on 39 goals. The final goals included both traditional short-term goals as well as newly added goals focusing on long-term complications, associated conditions, and patient-reported outcomes. Developing an international consensus on management goals can help standardize and improve treatment guidelines for type 1 Gaucher disease.
This document discusses guidelines for pharmaceutical drugs. It explains that drugs are available either by prescription from a healthcare provider or over-the-counter without a prescription. Both routes are regulated by drug laws to ensure safety and effectiveness. It then discusses factors considered for determining if a drug can be sold over-the-counter, including if consumers can self-diagnose conditions and understand proper usage. The document also covers advantages and disadvantages of over-the-counter access for consumers as well as strategies to improve patient compliance with drug treatments.
This document summarizes a clinical trial that evaluated the safety and efficacy of patiromer for treating hyperkalemia in patients with chronic kidney disease receiving RAAS inhibitors. The trial had two phases - an initial 4-week treatment phase followed by an 8-week randomized withdrawal phase. Results showed that patiromer significantly reduced serum potassium levels and maintained normokalemia compared to placebo. The most common side effects were constipation and diarrhea. The authors concluded that patiromer was effective for treating hyperkalemia and allowing continued use of RAAS inhibitors in patients with chronic kidney disease.
Outcomes in Long-term Opioid Tapering and Buprenorphine Transition: A Retrosp...Paul Coelho, MD
This study analyzed outcomes for 240 patients with chronic pain who were prescribed long-term opioid therapy above 90 mg morphine-equivalent daily doses. Patients were offered an outpatient opioid taper or transition to buprenorphine if taper was not tolerated. 44.6% successfully tapered, 18.8% transitioned to buprenorphine, and 36.6% dropped out of treatment. Higher initial opioid doses predicted needing buprenorphine, and benzodiazepine/z-drug use predicted greater dropout. Pain intensity changes after treatment were mixed, with over half of tapered patients reporting increased pain and about half of transitioned patients reporting decreased pain.
Nada Alkis' Master Thesis, Novo Nordisk & University of CopenhagenNada Alkis
My master thesis consisted of two parts. The first part is based on the research question: Are the FDA and EMA aligned in their approval decisions regarding fixed dose combination (FDC) medical products? This question was explored by evaluating the labels of all the FDCs approved between: January 2000 – April 2017 within 5 chronic therapeutic areas: type-2 diabetes mellitus (T2DM), asthma, chronic obstructive pulmonary disease (COPD), hypertension, and human immunodeficiency virus (HIV). In fact, it was found that there were differences between the FDA and EMA approval decisions with regards to the approved and used in pre-defined sub-populations. Some of the reasons for these discrepancies are discussed.
The second part of this thesis attempts to apply for the conceptual issues addressed in the first part to a practical setting. Specifically, assessing the real-world patient reported outcomes (PROs) for patients switched to a certain FDC product, Xultophy. And how the PROs collected from this real-world use might compare to the clinical trial PROs used to support labelling claims. It was found that real-world data, in the form of PROs collected in a community pharmacy setting, is a novel and interesting approach to gathering important information and could be explored further in future research.
FDA 2013 Clinical Investigator Training Course: Clinical pharmacology 2: Clin...MedicReS
FDA 2013 Clinical Investigator Training Course: Clinical pharmacology 2: Clinical Considerations During Phase 2 and Phase 3 of Drug Development
Kellie Reynolds, Pharm.D.,(CDER)
The document discusses the application of pharmacokinetics in clinical situations. It describes how pharmacokinetics is used to select drugs, design dosage regimens, evaluate patient responses, determine when to measure serum drug concentrations, perform assays to measure drug levels, evaluate pharmacokinetic data, and adjust dosage regimens if needed based on monitoring drug concentrations. The goals are to enhance efficacy and decrease toxicity for individual patients.
This article reviews standard therapies used to treat pulmonary arterial hypertension (PAH), including oxygen supplementation, calcium channel blockers, diuretics, digoxin, and anticoagulation. While these therapies are commonly used, the evidence supporting their use is limited as large prospective clinical trials have not been conducted. Oxygen supplementation in hypoxemic patients with COPD has shown improved survival in some studies, but its value for patients with PAH specifically has not been well evaluated. Calcium channel blockers are effective for some acute responders, but long-term success rates are low. More research is still needed to fully understand the risks and benefits of standard therapies for PAH.
This document provides an overview of gastroretentive drug delivery systems (GR-DDS). GR-DDS are designed to prolong the gastric residence time of drugs to increase absorption in the upper gastrointestinal tract. The document discusses factors that influence gastric emptying and various approaches to increasing gastric retention time, including floating, swelling/expanding, mucoadhesive, magnetic, and high density systems. Key advantages of GR-DDS include prolonged drug release, increased bioavailability, and reduced drug fluctuations.
This document discusses therapeutic drug monitoring (TDM), which refers to measuring drug concentrations in biological fluids to optimize drug therapy. TDM aims to maintain drug levels within the therapeutic window to maximize efficacy and minimize toxicity. It is useful for drugs with a narrow therapeutic index, large inter-individual variability, or in patients with organ dysfunction. Common drugs monitored include digoxin, aminoglycosides, phenytoin, and lithium. Factors like absorption, distribution, metabolism, excretion, drug interactions, and compliance can impact drug levels and require consideration during TDM interpretation. The document outlines the need, suitable/unsuitable drugs, therapeutic ranges, testing methods, and factors affecting TDM.
Hyperbaric oxygen therapy (HBOT) facilitated healing of chronic foot ulcers in patients with diabetes according to a randomized controlled trial. In the trial, 94 patients with diabetic foot ulcers of at least 3 months duration were assigned to receive either HBOT or a placebo treatment of hyperbaric air over 40 sessions. At 1-year follow-up, complete healing of the index ulcer occurred in 52% of patients receiving HBOT compared to 29% of patients receiving the placebo air, a statistically significant difference. Fewer major amputations also occurred in the HBOT group compared to the placebo group. The study provides evidence that HBOT can help facilitate healing of chronic diabetic foot ulcers when used as an adjunct to standard
The presentation is about the dose selection for laboratory animal toxicology drug testing, explaining staged and staggered approach of dose selection.
P02.167. Long term evaluation of homeopathy on post treatment impairment of p...home
Significant improvement was observed with the homeopathy
treatment in FEV1 (p<0.001),><0.001), /><0.001).><0.0001),><0.05)><0.01)><0.001)><0.0001).
Conclusion
Homeopathy is effective in improving lung capacity and
health status. Benefits remain evident after a year. This
suggests that homeopathy could make an important
contribution to post treatment tuberculosis pulmonary
impairment.
The document outlines five overarching principles and ten recommendations for managing hand osteoarthritis based on a systematic review and expert consensus. The principles focus on individualized treatment, education, and a multidisciplinary approach. The recommendations address non-pharmacological therapies, analgesics, injections, surgery, and follow-up based on levels of evidence and expert agreement.
Global Medical Cures™ | Nexium- Pediatric PostMarketing Adverse Event ReviewGlobal Medical Cures™
Global Medical Cures™ | Nexium- Pediatric PostMarketing Adverse Event Review
DISCLAIMER-
Global Medical Cures™ does not offer any medical advice, diagnosis, treatment or recommendations. Only your healthcare provider/physician can offer you information and recommendations for you to decide about your healthcare choices.
Outcome measures in cardiac rehabilitation Javidsultandar
This document discusses outcome measures used in cardiac rehabilitation programs. It defines four domains for measuring outcomes: clinical, behavioral, health, and service. The clinical domain includes physiological and psychological measurements. The behavioral domain involves lifestyle behaviors and self-management. The health domain captures overall health impacts. The service domain relates to patient satisfaction and program performance. The document provides examples of specific outcome measures that fall within each domain and discusses the purposes of measuring outcomes, including quality improvement.
This document describes a study that used action research to develop a feasible lifestyle intervention for patients with prediabetes in primary care settings. The study had two main goals: (1) determine the resources and competencies needed, and (2) identify effective intervention components. It involved two cycles with general practices. The first cycle explored various intervention options, and the second tested the intervention developed in cycle one. In total, 64 patients, 8 GPs, and 10 nurses participated. The study found an intervention involving six consultations over one year was feasible for practices. Nurses had the skills to deliver the core intervention. It led to clinical reductions in patients' BMI and HbA1c. The developed intervention showed potential for diabetes prevention
An observational clinical study on the effectiveness of the aqueous leaf extr...Alexander Decker
This study evaluated the effectiveness of an aqueous leaf extract of Lippia multiflora in reducing blood pressure in 28 hypertensive patients over 4 weeks. Participants prepared an infusion from 30g of dried leaves boiled in water, taken twice daily. Results showed a significant decline in both systolic and diastolic blood pressure, with mean reductions of 11.6 mmHg and 6.43 mmHg respectively. The extract demonstrated potential as an antihypertensive agent through properties like diuresis, smooth muscle relaxation, and lipid lowering effects. Further research is warranted to explore higher dosages or modified formulations.
This study compared the efficacy of once weekly exenatide to insulin glargine titrated to target glucose levels in patients with type 2 diabetes over 26 weeks. It found that exenatide once weekly resulted in greater reductions in HbA1c and body weight compared to insulin glargine. Exenatide also better controlled post-prandial glucose, while insulin glargine was better for fasting glucose levels. Hypoglycemic events were more common in the insulin glargine group. The study concluded that for patients concerned about hypoglycemia, weight gain and convenience, once weekly exenatide is preferable to insulin glargine.
Chu et al. (2015)
The study reviewed 14 clinical studies that used quantitative sensory testing to detect hyperalgesia in chronic pain patients on long-term opioids. Most sensory modalities tested, including cold, heat, pressure, electrical, ischemic, and injection pain, failed to demonstrate hypersensitivity to test stimuli. Heat pain sensitivity showed some promising results in detecting hyperalgesia, but none of the measures reviewed met the criteria as a definitive standard. Additional studies with improved designs are needed.
Inalazione di corpi_estranei_nei_bambini._meta_analisi_della_letteraturaMerqurio
Foreign body inhalation continues to be a cause of childhood morbidity and mortality, requiring prompt treatment. The document reviews several studies on foreign body inhalation in children. It summarizes epidemiological data from retrospective studies covering 3-10 years from single medical centers. It also reviews systematic data collected from multiple countries. The goal is to synthesize this data to better understand the distribution of foreign bodies inhaled by children and to improve prevention and treatment of these potentially life-threatening events.
The document discusses the application of pharmacokinetics in clinical situations. It describes how pharmacokinetics is used to select drugs, design dosage regimens, evaluate patient responses, determine when to measure serum drug concentrations, perform assays to measure drug levels, evaluate pharmacokinetic data, and adjust dosage regimens if needed based on monitoring drug concentrations. The goals are to enhance efficacy and decrease toxicity for individual patients.
This article reviews standard therapies used to treat pulmonary arterial hypertension (PAH), including oxygen supplementation, calcium channel blockers, diuretics, digoxin, and anticoagulation. While these therapies are commonly used, the evidence supporting their use is limited as large prospective clinical trials have not been conducted. Oxygen supplementation in hypoxemic patients with COPD has shown improved survival in some studies, but its value for patients with PAH specifically has not been well evaluated. Calcium channel blockers are effective for some acute responders, but long-term success rates are low. More research is still needed to fully understand the risks and benefits of standard therapies for PAH.
This document provides an overview of gastroretentive drug delivery systems (GR-DDS). GR-DDS are designed to prolong the gastric residence time of drugs to increase absorption in the upper gastrointestinal tract. The document discusses factors that influence gastric emptying and various approaches to increasing gastric retention time, including floating, swelling/expanding, mucoadhesive, magnetic, and high density systems. Key advantages of GR-DDS include prolonged drug release, increased bioavailability, and reduced drug fluctuations.
This document discusses therapeutic drug monitoring (TDM), which refers to measuring drug concentrations in biological fluids to optimize drug therapy. TDM aims to maintain drug levels within the therapeutic window to maximize efficacy and minimize toxicity. It is useful for drugs with a narrow therapeutic index, large inter-individual variability, or in patients with organ dysfunction. Common drugs monitored include digoxin, aminoglycosides, phenytoin, and lithium. Factors like absorption, distribution, metabolism, excretion, drug interactions, and compliance can impact drug levels and require consideration during TDM interpretation. The document outlines the need, suitable/unsuitable drugs, therapeutic ranges, testing methods, and factors affecting TDM.
Hyperbaric oxygen therapy (HBOT) facilitated healing of chronic foot ulcers in patients with diabetes according to a randomized controlled trial. In the trial, 94 patients with diabetic foot ulcers of at least 3 months duration were assigned to receive either HBOT or a placebo treatment of hyperbaric air over 40 sessions. At 1-year follow-up, complete healing of the index ulcer occurred in 52% of patients receiving HBOT compared to 29% of patients receiving the placebo air, a statistically significant difference. Fewer major amputations also occurred in the HBOT group compared to the placebo group. The study provides evidence that HBOT can help facilitate healing of chronic diabetic foot ulcers when used as an adjunct to standard
The presentation is about the dose selection for laboratory animal toxicology drug testing, explaining staged and staggered approach of dose selection.
P02.167. Long term evaluation of homeopathy on post treatment impairment of p...home
Significant improvement was observed with the homeopathy
treatment in FEV1 (p<0.001),><0.001), /><0.001).><0.0001),><0.05)><0.01)><0.001)><0.0001).
Conclusion
Homeopathy is effective in improving lung capacity and
health status. Benefits remain evident after a year. This
suggests that homeopathy could make an important
contribution to post treatment tuberculosis pulmonary
impairment.
The document outlines five overarching principles and ten recommendations for managing hand osteoarthritis based on a systematic review and expert consensus. The principles focus on individualized treatment, education, and a multidisciplinary approach. The recommendations address non-pharmacological therapies, analgesics, injections, surgery, and follow-up based on levels of evidence and expert agreement.
Global Medical Cures™ | Nexium- Pediatric PostMarketing Adverse Event ReviewGlobal Medical Cures™
Global Medical Cures™ | Nexium- Pediatric PostMarketing Adverse Event Review
DISCLAIMER-
Global Medical Cures™ does not offer any medical advice, diagnosis, treatment or recommendations. Only your healthcare provider/physician can offer you information and recommendations for you to decide about your healthcare choices.
Outcome measures in cardiac rehabilitation Javidsultandar
This document discusses outcome measures used in cardiac rehabilitation programs. It defines four domains for measuring outcomes: clinical, behavioral, health, and service. The clinical domain includes physiological and psychological measurements. The behavioral domain involves lifestyle behaviors and self-management. The health domain captures overall health impacts. The service domain relates to patient satisfaction and program performance. The document provides examples of specific outcome measures that fall within each domain and discusses the purposes of measuring outcomes, including quality improvement.
This document describes a study that used action research to develop a feasible lifestyle intervention for patients with prediabetes in primary care settings. The study had two main goals: (1) determine the resources and competencies needed, and (2) identify effective intervention components. It involved two cycles with general practices. The first cycle explored various intervention options, and the second tested the intervention developed in cycle one. In total, 64 patients, 8 GPs, and 10 nurses participated. The study found an intervention involving six consultations over one year was feasible for practices. Nurses had the skills to deliver the core intervention. It led to clinical reductions in patients' BMI and HbA1c. The developed intervention showed potential for diabetes prevention
An observational clinical study on the effectiveness of the aqueous leaf extr...Alexander Decker
This study evaluated the effectiveness of an aqueous leaf extract of Lippia multiflora in reducing blood pressure in 28 hypertensive patients over 4 weeks. Participants prepared an infusion from 30g of dried leaves boiled in water, taken twice daily. Results showed a significant decline in both systolic and diastolic blood pressure, with mean reductions of 11.6 mmHg and 6.43 mmHg respectively. The extract demonstrated potential as an antihypertensive agent through properties like diuresis, smooth muscle relaxation, and lipid lowering effects. Further research is warranted to explore higher dosages or modified formulations.
This study compared the efficacy of once weekly exenatide to insulin glargine titrated to target glucose levels in patients with type 2 diabetes over 26 weeks. It found that exenatide once weekly resulted in greater reductions in HbA1c and body weight compared to insulin glargine. Exenatide also better controlled post-prandial glucose, while insulin glargine was better for fasting glucose levels. Hypoglycemic events were more common in the insulin glargine group. The study concluded that for patients concerned about hypoglycemia, weight gain and convenience, once weekly exenatide is preferable to insulin glargine.
Chu et al. (2015)
The study reviewed 14 clinical studies that used quantitative sensory testing to detect hyperalgesia in chronic pain patients on long-term opioids. Most sensory modalities tested, including cold, heat, pressure, electrical, ischemic, and injection pain, failed to demonstrate hypersensitivity to test stimuli. Heat pain sensitivity showed some promising results in detecting hyperalgesia, but none of the measures reviewed met the criteria as a definitive standard. Additional studies with improved designs are needed.
Inalazione di corpi_estranei_nei_bambini._meta_analisi_della_letteraturaMerqurio
Foreign body inhalation continues to be a cause of childhood morbidity and mortality, requiring prompt treatment. The document reviews several studies on foreign body inhalation in children. It summarizes epidemiological data from retrospective studies covering 3-10 years from single medical centers. It also reviews systematic data collected from multiple countries. The goal is to synthesize this data to better understand the distribution of foreign bodies inhaled by children and to improve prevention and treatment of these potentially life-threatening events.
Similar to L'efficacia dell'associazione budesonide e formeterolo nel controllo dell'asma in pazienti assegnati agli step di trattamento 2-4 secondo le linee guida GINA
1) The study compared the efficacy of fluticasone propionate alone or in combination with salmeterol in achieving asthma control as defined by guidelines over 1 year in 3,421 patients with uncontrolled asthma.
2) Treatment was stepped up until total control was achieved or the maximum dose was reached, and significantly more patients achieved total and well-controlled asthma with salmeterol/fluticasone than with fluticasone alone.
3) The study confirms that guideline-defined asthma control can be achieved in the majority of patients through aggressive dose titration of controller medications.
Bronchial Asthma Management in Children GINA UpdatesShubhamPandit60
This document provides guidelines for the treatment and management of bronchial asthma. It discusses assessing asthma severity and control, patient education, controlling exacerbating factors, and pharmacological therapy. The key changes in GINA'23 include assessing asthma severity retrospectively based on treatment required for control rather than difficulty to treat. It emphasizes using the lowest effective maintenance treatment and adjusting therapy through a continual cycle based on periodic assessment and review.
This document summarizes the proceedings of the Small Airways Working Group Meeting held on September 9th, 2017 in Milan. It includes the agenda, list of attendees, and progress updates on several studies. Multiple studies comparing the effectiveness of extra-fine particle inhaled corticosteroids to fine particle ICS have been published or are underway. Preliminary results suggest extra-fine ICS may achieve better asthma control at lower doses and with fewer side effects like pneumonia. The group discussed potential future studies on flexible dosing strategies, metabolic effects of high dose ICS, and the impact of particle size in patients with obesity or GERD. Priority research areas and ongoing protocols were reviewed for continued relevance and feasibility.
Outcome study of pulmonary telerehab - respirehab for post COVID patientsSubodh Gupta
Respirehab's case paper of telerehab of post COVID patients for improving breathing capacity, physical endurance and patient well being. The online pulmonary rehab delivered excellent gains on various parameters like SGRQ, MMRC and SPO2. This would be very helpful for COPD patients suffering from shortness of breath (Dyspnea).
The Global Initiative for Asthma (GINA) is an independent organization established by the WHO and NHLBI in 1993 to increase awareness of asthma and improve asthma prevention and management worldwide through coordinated efforts. GINA publishes annual evidence-based strategy reports that provide practical guidance on asthma diagnosis and treatment, which have been downloaded over 500,000 times from 100 countries. The 2022 report includes updates to the diagnostic algorithm for asthma and treatment guidelines, such as emphasizing low-dose ICS-formoterol as the preferred reliever medication option.
The Global Initiative for Asthma (GINA) is an independent organization established by the WHO and NHLBI in 1993 to increase awareness of asthma and improve asthma prevention and management through coordinated global efforts. GINA publishes annual evidence-based strategy reports that provide practical guidance on asthma diagnosis and treatment that can be adapted for local health systems. The 2022 report includes updates to the diagnostic algorithm for asthma and introduces two treatment tracks - one using low-dose ICS-formoterol as reliever is preferred for reducing exacerbations, while the other using SABA as reliever is alternative.
The Global Initiative for Asthma (GINA) is an independent organization established by the WHO and NHLBI in 1993 to increase awareness of asthma and improve asthma prevention and management through coordinated global efforts. GINA publishes annual evidence-based strategy reports that provide practical guidance on asthma diagnosis and treatment that can be adapted for local health systems. The 2022 report includes updates to the diagnostic approach for patients taking controller treatment and emphasizes using low-dose ICS-formoterol as reliever therapy to reduce exacerbation risk compared to SABA relievers.
The Global Initiative for Asthma (GINA) is an independent organization established by the WHO and NHLBI in 1993 to increase awareness of asthma and improve asthma prevention and management through a coordinated global effort. GINA publishes annual evidence-based strategy reports for asthma management and prevention that can be adapted for local health systems. The 2022 report provides updated guidance on diagnosing asthma, assessing control, and treating asthma in two treatment tracks - one using low-dose ICS-formoterol as reliever and preferred, and one using SABA as reliever but less preferred due to higher risk of exacerbations.
This study compared the effectiveness of febuxostat and allopurinol in lowering serum urate levels using data from a large U.S. managed care organization. The study included over 16,000 patients taking febuxostat or allopurinol for gout. After matching patients based on demographics, clinical characteristics, and other factors, febuxostat was found to be more effective than allopurinol at reducing serum urate levels and achieving treatment targets. A higher proportion of febuxostat users reached targets of less than 6 mg/dL and less than 5 mg/dL, and they reached the targets faster than allopurinol users. Febuxostat was also more effective in overall
This study aimed to evaluate the efficacy of oral montelukast in acute asthma exacerbation. It was a randomized, double-blind, placebo-controlled trial conducted in a tertiary care hospital over 2 years. Patients presenting with acute asthma exacerbation were randomized to receive standard therapy with either montelukast or placebo. The primary outcomes of lung function, duration of hospital stay, and secondary outcomes showed no significant differences between the montelukast and placebo groups. The study concluded that montelukast provided no added benefit over standard therapy alone for acute asthma exacerbation. Larger multicenter trials are still needed.
The document summarizes the 2019 Global Initiative for Asthma (GINA) guidelines. Key changes from prior years include: (1) short-acting beta agonists alone are no longer recommended for initial treatment due to increased risk of severe exacerbations; (2) all adults and adolescents should receive low-dose inhaled corticosteroids to reduce exacerbation risk. The guidelines outline criteria for diagnosing asthma, assessing patients, developing treatment plans, adjusting medications based on control, and managing exacerbations. The overall goals of treatment are to reduce risks of death, exacerbations, airway damage and medication side effects.
Co-Chairs, Joseph K. Han, MD, and Seth J. Isaacs, MD, prepared useful Practice Aids pertaining to chronic rhinosinusitis with nasal polyps for this CME/MOC/CC/AAPA/IPCE activity titled “Biologics in CRSwNP: Putting a Paradigm Shift Into Practice.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3Tq6n1G. CME/MOC/CC/AAPA/IPCE credit will be available until May 6, 2025.
This review evaluated the efficacy and safety of using a single fixed-dose inhaler containing a fast-acting beta-2 agonist and inhaled corticosteroid (FABA/ICS) only as needed in people with mild asthma. The review found moderate to high certainty evidence that as-needed FABA/ICS is clinically effective for adults and adolescents with mild asthma, reducing exacerbations, systemic corticosteroid use, and healthcare visits compared to as-needed short-acting beta-2 agonists alone. As-needed FABA/ICS was also found to be as effective as regular inhaled corticosteroids at controlling asthma while reducing average daily corticosteroid exposure and with no increased adverse effects.
This document discusses the goals and management of asthma. The goals of asthma management are to achieve symptom control, prevent exacerbations, maintain normal pulmonary function, avoid adverse medication effects, and prevent mortality. Management involves both pharmacological and non-pharmacological approaches. Pharmacological management follows a stepwise treatment approach based on a scoring system, starting with reliever medication and increasing treatment up to six steps as needed to achieve symptom control.
Week 2 Discussion-2nd reply
Jessica Alper
Chief complaint
The chief complaint that this fifteen-year-old patient is complaining of is shortness of breath and nonproductive nocturnal cough.
Primary and differential diagnoses
The patient states that she typically only feels the stated symptoms after working out, but lately she has consistently felt that way. She denies symptoms related to upper respiratory system, gastrointestinal, or urinary. The objective findings reveal vital signs that are within normal limits and the patient is in no signs of respiratory distress. Assessment of head, eyes, ears, nose, and throat are not impressive, and the inspection of the anterior and posterior chest show no abnormalities. While auscultating the patient’s chest, decreased air movement and high-pitched whistling on expiration was observed. The lungs were also noted to be resonant upon percussion.
The primary diagnosis for this patient is severe persistent asthma. Asthma is defined as complex and it typically involves airway inflammation, intermittent airflow obstruction, as well as bronchial hyperresponsiveness. Symptoms usually involve wheezing, coughing, shortness of breath, as well as chest tightness and pain (Morris, 2022). The patient is feeling these same symptoms daily, multiple times a day, and throughout the night, with a nocturnal nonproductive cough, therefore this is the final diagnosis for this patient.
The first differential diagnosis is viral bronchiolitis, which is defined as “an acute inflammatory injury of the bronchioles that is usually caused by a viral infection” (Maraqa, 2021). Congestive heart failure is another differential diagnosis as well as chronic sinusitis. Congestive heart failure is a condition that causes pulmonary vessels and interstitial pulmonary edema, reducing the compliance of the lungs, therefore leading to a feeling of dyspnea and wheezing (Morris, 2022). Acute sinusitis is an “inflammatory process involving the paranasal sinus” (Brook, 2022), and it may be associated with allergies. It can lead to unproductive cough as well as exacerbation of asthma.
Treatment plan
The goal of asthma is to control it as best as possible. An ideal goal for a 15-year-old child is to have less than 2 days per week in which the patient will have an attack, along with less than twice per month of nightly awakenings. According to the symptoms, this patient should follow step 4 or step 5 of the guidelines. Step 4 would include a medium-dose inhaled corticosteroids, as well as long-acting beta agonist. If the patient did not respond to this treatment, an alternative plan including a medium-dose inhaled corticosteroid and a leukotriene receptor antagonist or Theophylline may be used. If both these treatments fail, then the patient should be moved to step 5 of treatment, which includes a high-dose inhaled corticosteroid and a long-acting beta agonist would be prescribed (Managing Asthma, 2022). It is also important to orde ...
The document discusses bioequivalence studies and their protocol. It defines bioequivalence as drug substances from two dosage forms reaching systemic circulation at the same rate and to the same extent. The objective is for drug bioavailability from test and reference products to not be statistically different when administered under similar conditions. Study designs commonly used include crossover, parallel group and replicate designs. Key aspects covered are analytical methods, subject selection, drug administration, sampling, data evaluation, and applications of pharmacokinetics in drug development and novel drug delivery systems.
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Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
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Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
তাই একজন নাগরিক হিসাবে এই তথ্য গুলো আপনার জানা প্রয়োজন ...।
বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
How to Build a Module in Odoo 17 Using the Scaffold Method
L'efficacia dell'associazione budesonide e formeterolo nel controllo dell'asma in pazienti assegnati agli step di trattamento 2-4 secondo le linee guida GINA
2. Bateman et al. Respiratory Research 2011, 12:38 Page 2 of 11
http://respiratory-research.com/content/12/1/38
adolescents and adults is the addition of a long-acting Studies and population
b2-agonist (LABA). At Step 4, an increase in ICS dose The clinical studies included in this retrospective analy-
or the addition of another controller medication (e.g. a sis involved >12000 patients from five double-blind, ran-
leukotriene modifier or sustained-release theophylline) domised, parallel-group trials (6-12 months’ duration)
is recommended in order to achieve control. However, with exacerbation as a primary variable. The trials inves-
in the significant proportion of patients in which con- tigated the efficacy of BUD/FORM maintenance and
trol is not achieved, Step 5 management may be consid- reliever therapy (Symbicort SMART ® Turbuhaler ® ,
ered, recognising that lack of control is associated with AstraZeneca AB, Lund, Sweden) versus comparator
a higher risk of exacerbations, poor quality of life and therapies which included: higher maintenance dose ICS
other adverse outcomes [2]. (budesonide) plus SABA as needed [3,4]; same mainte-
For patients whose asthma is uncontrolled on Step 2 nance dose ICS/LABA (BUD/FORM, Symbicort®, Astra-
or higher treatment, a recent strategy included in GINA Zeneca, Lund, Sweden) plus SABA as needed [3,7]; and
guidelines is the use of a combination inhaler containing higher maintenance dose ICS/LABA (BUD/FORM [5] or
budesonide and formoterol for both maintenance ther- salmeterol/fluticasone [Seretide™, GlaxoSmithKline,
apy and relief of symptoms (option for Steps 3-5). This Uxbridge, UK]) plus SABA as needed [5,6]. In all studies
approach has been shown in several large-scale rando- the SABA used was terbutaline (Bricanyl®, AstraZeneca,
mised controlled trials to achieve similar current clinical Sweden; 0.4 mg/inhalation) and all aforementioned
control of asthma and to be superior to comparators in drugs were administered via Turbuhaler® (AstraZeneca,
reducing asthma exacerbations [3-7]. These results have Lund, Sweden) except for salmeterol/fluticasone which
been achieved with the use of significantly lower doses was delivered via either Diskus™ or Evohaler™ (Glax-
of inhaled and systemic corticosteroids [3-6]. The com- oSmithKline, Uxbridge, UK).
parators in these studies have been either a two- to The methodologies of the five studies have been pub-
four-fold higher dose of budesonide (a Step 2-3 option) lished in detail previously [3-7]. Further details of each
[3,4], the same dose of ICS plus a LABA (a Step 3 of these studies are provided in the additional files (see
option) or a higher-dose ICS plus a LABA (a Step 4 Additional file 1, Table S1 of the additional files). All
treatment), together with a short-acting b 2 -agonist five studies were performed in accordance with the
(SABA) for as-needed relief of symptoms [3,5-7]. Recent Declaration of Helsinki and Good Clinical Practice
post hoc analyses of the results of these studies have guidelines and were approved by independent ethics
provided further insights into the relationship between committees. Written informed consent was obtained
levels of current asthma control achieved and “future from each adult patient; for patients under 18 years of
risk” [8-10]. From the clinician’s perspective, the deci- age, informed consent was obtained from both the
sion to consider a change in medication will usually be patient and his/her legal guardian. As this retrospective
prompted by a patient’s failure to achieve control on analysis is based on these five studies no additional
current treatment (Steps 2-4). It is therefore appropriate approvals were applied for.
to examine the relative benefit of introducing budeso- Stratification by GINA treatment step at entry
nide/formoterol (BUD/FORM) maintenance and reliever Patients with asthma at least 12 years of age who were
therapy in patients previously prescribed different GINA symptomatic during run-in were randomised. Data col-
steps of treatment. We report here a post hoc analysis of lected at study entry were used to classify each
the results of five clinical trials comparing BUD/FORM patient’s pre-study asthma medication as Step 2, 3 or 4
maintenance and reliever therapy with comparator treat- according to GINA classification based on ICS dose
ments when introduced in patients on different treat- and use of other controller medication. In all studies
ment steps (Steps 2-4) according to GINA guidelines at the regular use of ICS was an inclusion criterion but
study entry. use of systemic steroids within 30 days of study entry
was an exclusion criterion - thus patients on either
Methods Step 1 or Step 5 were excluded[3-7]. The GINA treat-
Objectives ment steps were defined as:
This pooled analysis describes the relative effect of
BUD/FORM maintenance and reliever therapy on cur- • Step 2 - low-dose ICS
rent asthma control and on exacerbation risk, compared • Step 3 - low-dose ICS plus at least one of a LABA,
with fixed-dose maintenance regimens of ICS or combi- a leukotriene receptor antagonist (LTRA) or
nation ICS/LABA, plus SABA as reliever, in patients xanthine, or medium- to high-dose ICS alone
with asthma stratified by GINA treatment step at study • Step 4 - medium- to high-dose ICS plus at least
entry. one of a LABA (including high-dose ICS/LABA
3. Bateman et al. Respiratory Research 2011, 12:38 Page 3 of 11
http://respiratory-research.com/content/12/1/38
combination), an LTRA or xanthine (Additional file adjustments performed for overdispersion if present.
1, Tables S2 and S3). Time to first exacerbation was described by Kaplan-
Meier plots stratified by treatment and GINA treatment
Assessments step and analysed in a Cox proportional hazard model
Asthma control as defined by GINA criteria with factors including treatment, GINA treatment step
Each patient’s asthma control, defined by GINA guide- and treatment-GINA treatment step at entry interac-
line-derived criteria (Controlled, Partly Controlled or tion, stratified by study. The same models were applied
Uncontrolled asthma) [2], was determined retrospec- to hospitalisations and ER treatments.
tively each week from diary data in the studies. In this The change in FEV1 as percentage of predicted nor-
report, we have considered only the results from the last mal, from randomisation to last visit on treatment, was
week of the run-in period and the last week of the study analysed using analysis of variance (ANOVA) with the
[9]. Where there was insufficient diary data to perform same factors as above and with the value at randomisa-
an assessment of control, the week was considered tion as a covariate. In calculating mean FEV1 over time
Uncontrolled. by GINA treatment step and treatment group the last
FEV1 observation carried forward principle was used to cor-
Forced expiratory volume in 1 second (FEV 1 ) was rect for missing values. In the plot of this data, as visits
recorded at clinic visits and the percentage of predicted occurred at different intervals in the studies, values were
normal was calculated. At the study entry visit pre- and positioned with the month nearest to the study visit.
post-bronchodilator FEV1 was recorded and for all sub- Thus the 1- and 3-month-visit data from the Bousquet
sequent visits patients were requested to take their et al. study were plotted with the 2- and 4-month-visit
morning study medication as usual. data from the Kuna et al. study, and the 4- and 8-
Reliever use month-visit data from the Rabe et al. study were plotted
Reliever use per patient per 24 hours was derived from with the 3- and 9-month data from the O’Byrne et al.
diary cards and summarised as mean over the last 10 and the Scicchitano et al. study, respectively [3-7]. In
days of run-in and over the study period. addition, a 6-month value was imputed for patients in
Exacerbations the Rabe et al. study as the mean of the 4- and 8-
Due to minor differences in the definition of exacerba- month-visit values [7].
tions across the original studies, the definition of exacer- Patient means of daily reliever use during the treat-
bations in this pooled analysis was standardised to a ment period were analysed using ANOVA analysis of
worsening of asthma symptoms requiring an oral steroid variance with the same factors as above and with mean
course of at least 3 days’ duration, an emergency room reliever use during run-in as a covariate.
(ER) visit or a hospitalisation for treatment of asthma.
For more details of the definitions of control and Results
exacerbations please refer to the additional files. GINA treatment steps at entry and demographics
A total of 12512 subjects were included in the analysis
Statistical methods described; only one patient included in the original trials
The main purpose of the analysis was to estimate the lacked data on pre-entry medication and was excluded
effect of BUD/FORM maintenance and reliever therapy from the analysis. The numbers of patients defined as
versus a comparator for each individual GINA treatment being at GINA treatment Steps 2, 3 or 4 at entry were
step at entry. P-values below 5% were regarded as indi- 1037, 6352 and 5123 respectively. All patients used ICS,
cating statistical significance. 45% used LABA, 5% used theophylline, 3% used LTRAs
The percentage of patients in each control state dur- and ≤ 2% used anticholinergics, cromones or oral b 2-
ing the last study week was presented by treatment and agonists (see Additional file 1, Table S3 in additional
GINA treatment step and analysed in two separate files).
logistic regression models - one for the odds of being Baseline characteristics were similar between compara-
Controlled and one for the odds of being at least Partly tor treatment groups in this pooled analysis (Table 1).
Controlled - both with factors including treatment, By categorising patients by their GINA treatment step at
GINA treatment step, treatment-GINA treatment step entry, some differences were evident between the steps
interaction and study. The number of exacerbations was for patient age and FEV 1 but mean total symptom
presented as yearly exacerbation rates by GINA treat- scores were similar.
ment step and treatment and analysed using a Poisson
model with factors including treatment, GINA treat- Asthma control defined by GINA criteria
ment step, treatment-GINA treatment step interaction In the final week of treatment, the proportion of
and study, and observation time as an offset, with patients with GINA-defined Controlled asthma and
4. Bateman et al. Respiratory Research 2011, 12:38 Page 4 of 11
http://respiratory-research.com/content/12/1/38
Table 1 Baseline characteristics of study subjects
Budesonide/formoterol maintenance and reliever therapy vs. higher maintenance dose ICS + SABA
Step 2 Step 3 Step 4
Higher BUD/FORM Higher BUD/FORM Higher BUD/FORM
maintenance ICS maintenance and maintenance ICS maintenance and maintenance ICS maintenance and
+ SABA reliever therapy + SABA reliever therapy + SABA reliever therapy
(N = 262) (N = 231) (N = 1013) (N = 1051) (N = 769) (N = 747)
Male, n (%) 123 (47) 104 (45) 399 (39) 433 (41) 318 (41) 315 (42)
Age, mean 30.6 32.2 39.5 37.5 42.6 42.0
ICS, n (%) Low 262 (100) 231 (100) 242 (24) 226 (22) 0 0
Medium 0 0 664 (66) 711 (68) 643 (84) 591 (79)
High 0 0 107 (11) 114 (11) 126 (16) 156 (21)
LABA use, 0 0 221 (22) 214 (20) 706 (92) 689 (92)
n (%)
Asthma 6.5 9 10 9 10 9
diagnosis,
median years
FEV1, % PN 74.3 74.5 72.5 72.8 71.2 72.3
As-needed use, 2.16 2.24 2.03 2.08 2.26 2.12
mean daily
Symptom 1.36 1.37 1.57 1.63 1.74 1.65
score, mean
total
Budesonide/formoterol maintenance and reliever therapy vs. same maintenance dose ICS/LABA + SABA
Step 2 Step 3 Step 4
Same BUD/FORM Same BUD/FORM Same BUD/FORM
maintenance ICS/ maintenance and maintenance ICS/ maintenance and maintenance ICS/ maintenance and
LABA + SABA reliever therapy LABA + SABA reliever therapy LABA + SABA reliever therapy
(N = 375) (N = 389) (N = 896) (N = 883) (N = 596) (N = 597)
Male, n (%) 157 (42) 170 (44) 389 (43) 391 (44) 274 (46) 250 (42)
Age, mean 35.3 34.7 39.4 37.7 42.6 43.4
ICS, n (%) Low 375 (100) 389 (100) 130 (15) 136 (15) 0 0
Medium 0 0 671 (75) 644 (73) 415 (70) 411 (69)
High 0 0 95 (11) 103 (12) 181 (30) 186 (31)
LABA use, 0 0 107 (12) 118 (13) 548 (92) 548 (92)
n (%)
Asthma 8 9 11 10 12 13
diagnosis,
median years
FEV1, % PN 72.5 73.7 71.9 72.1 70.8 70.3
As-needed use, 2.01 1.98 2.17 2.18 2.34 2.23
mean daily
Symptom 1.62 1.56 1.68 1.65 1.78 1.76
score, mean
total
Budesonide/formoterol maintenance and reliever therapy vs. higher maintenance dose ICS/LABA + SABA
Step 3* Step 4
Higher BUD/FORM Higher BUD/FORM
maintenance ICS/ maintenance and maintenance ICS/ maintenance and
LABA + SABA reliever therapy LABA + SABA reliever therapy
(N = 1786) (N = 1203) (N = 1585) (N = 1051)
Male, n (%) 716 (40) 498 (41) 654 (41) 420 (40)
Age, mean 36.2 36.3 40.9 41.7
ICS, n (%) Low 124 (7) 139 (12) 0 0
Medium 1424 (80) 918 (76) 1283 (81) 876 (83)
5. Bateman et al. Respiratory Research 2011, 12:38 Page 5 of 11
http://respiratory-research.com/content/12/1/38
Table 1 Baseline characteristics of study subjects (Continued)
High 238 (13) 146 (12) 302 (19) 175 (17)
LABA use, n 119 (7) 138 (11) 1527 (96) 1004 (96)
(%)
Asthma 11 11 10 12
diagnosis,
median years
FEV1, % PN 72.7 71.9 71.4 70.4
As-needed use, 2.28 2.26 2.34 2.27
mean daily
Symptom 1.95 1.91 1.88 1.88
score, mean
total
BUD/FORM = budesonide/formoterol; FEV1 = forced expiratory volume in 1 second; ICS = inhaled corticosteroid; LABA = long-acting b2-agonist; PN = predicted
normal; SABA = short-acting b2-agonist.
*Seven Step 2 classified patients were pooled with Step 3.
GINA steps were assigned according to treatment at study entry.
Controlled or Partly Controlled asthma decreased with increased during treatment, with a tendency to reach a
increasing GINA treatment step, irrespective of study plateau earlier in higher GINA treatment steps. BUD/
treatment (Figures 1A and 1B). The proportion of FORM maintenance and reliever therapy gave a signifi-
patients with Controlled asthma was higher for all cantly larger increase in FEV 1 for all GINA treatment
GINA treatment steps when BUD/FORM maintenance steps compared with higher maintenance dose ICS +
and reliever therapy was compared with higher mainte- SABA (mean FEV1 80.0-88.5 vs. 76.8-86.4) and for Steps
nance dose ICS + SABA (13-23% vs. 9-16%, respectively) 3 and 4 when compared with the same maintenance
and was statistically significant for GINA treatment ICS/LABA + SABA group (mean FEV 1 85.1-88.4 vs.
Steps 2 (P = 0.03) and 3 (P < 0.01). The proportion of 82.9-85.9). Mean FEV1 was similar in the BUD/FORM
patients with Controlled asthma was similar for all maintenance and reliever therapy group and the higher
GINA treatment steps when BUD/FORM maintenance maintenance dose ICS/LABA + SABA group at the end
and reliever therapy was compared with same mainte- of the study (84.8-89.1 vs. 84.7-89.1) (Figure 2).
nance dose ICS/LABA + SABA (16-22% vs. 14-21%) and
higher maintenance dose ICS/LABA + SABA (16-20% Reliever use
vs. 16-21%) (Figure 1A). Patients in the higher GINA treatment steps at entry
The proportion of patients with Controlled or Partly used more reliever medication (SABA or ICS/LABA as
Controlled asthma was significantly higher for all GINA reliever) on average during the study than those in
treatment steps when BUD/FORM maintenance and lower GINA treatment steps. Mean reliever use was sig-
reliever therapy was compared with higher maintenance nificantly lower in patients receiving BUD/FORM main-
dose ICS + SABA (49-61% vs. 37-53% of patients; P < tenance and reliever therapy compared with higher
0.05). The proportion of patients with Controlled or maintenance dose ICS + SABA (0.737-1.165 vs. 1.100-
Partly Controlled asthma was at least similar for all 1.734; P < 0.001) and same maintenance dose ICS/
treatment steps when BUD/FORM maintenance and LABA + SABA (0.924-1.195 vs. 1.119-1.502; P < 0.001)
reliever therapy was compared with same maintenance at all GINA treatment steps apart from the Step 2 sub-
dose ICS/LABA + SABA (52-61% vs. 45-63%) and was group comparison with same maintenance dose ICS/
significantly higher for GINA treatment Step 4 patients LABA + SABA (0.834 vs. 0.928). When BUD/FORM
(P = 0.011). When compared with higher maintenance maintenance and reliever therapy was compared with
dose ICS/LABA + SABA the proportion of patients with higher maintenance dose ICS/LABA + SABA there were
Controlled or Partly Controlled asthma was similar for no differences between study treatments in reliever use
BUD/FORM maintenance and reliever therapy for both in either of the GINA treatment steps (0.874-1.105 vs.
GINA treatment steps assessed (50-59% vs. 51-58%) 0.889-1.143) (Additional file 1, Figure S1).
(Figure 1B).
Exacerbations
FEV1 The rate of exacerbations during study treatment gener-
On average, higher GINA treatment steps at entry were ally increased with increasing GINA treatment step at
associated with a lower FEV1 both before and during entry (Figure 3). BUD/FORM maintenance and reliever
study treatment. Following randomisation, mean FEV1 therapy significantly reduced the rate of exacerbations in
6. Bateman et al. Respiratory Research 2011, 12:38 Page 6 of 11
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Figure 1 Proportion of Controlled or Partly Controlled asthma patients in final week of treatment by study treatment and GINA
treatment step at entry. BUD/FORM = budesonide/formoterol; ICS = inhaled corticosteroid; LABA = long-acting b2-agonist; OR = odds ratio;
SABA = short-acting b2-agonist.
patients in GINA treatment Steps 3 and 4 at entry com- statistical significance (GINA treatment Step 2 patients
pared with higher maintenance dose ICS + SABA (0.177 vs. higher maintenance dose ICS + SABA [0.144 vs.
and 0.303 vs. 0.411 and 0.486) in all GINA treatment 0.174], and GINA treatment Step 3 patients vs. higher
steps compared with same maintenance dose ICS/LABA maintenance dose ICS/LABA + SABA [0.198 vs. 0.250])
+ SABA (0.141-0.276 vs. 0.254-0.532) and in GINA (Figure 3).
treatment Step 4 patients compared with higher mainte- In all three comparisons, fewer patients receiving
nance dose ICS/LABA + SABA (0.313 vs. 0.470) (Figure BUD/FORM maintenance and reliever therapy experi-
3). In the remaining two groups, although exacerbations enced a severe exacerbation compared with the fixed-
were numerically lower with BUD/FORM maintenance dose controller regimens plus SABA: BUD/FORM main-
and reliever therapy the differences did not reach tenance and reliever therapy vs. higher maintenance
7. Bateman et al. Respiratory Research 2011, 12:38 Page 7 of 11
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Figure 2 Mean FEV1 by visit and GINA step at study entry. BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS +
SABA, difference at last visit as percentage predicted normal, adjusted for FEV1 at randomisation visit (95% confidence interval): Step 2, 2.18 (0.22,
4.14); Step 3, 3.58 (2.29, 4.87); Step 4, 3.83 (2.25, 5.40). BUD/FORM maintenance and reliever therapy vs. same maintenance dose ICS/LABA +
SABA, difference at last visit as percentage predicted normal, adjusted for FEV1 at randomisation visit (95% confidence interval): Step 2, 1.29
(-1.29, 3.88); Step 3, 2.50 (1.25, 3.76); Step 4, 2.70 (1.24, 4.17). BUD/FORM maintenance and reliever therapy vs. higher maintenance dose ICS/LABA
+ SABA, difference at last visit as percentage predicted normal, adjusted for FEV1 at randomisation visit (95% confidence interval): Step 3, 0.22
(-0.82, 1.26); Step 4, 0.53 (-0.57, 1.64).
dose ICS + SABA, 241 patients (12.9%) vs. 391 patients LABA + SABA, 202 patients (9.0%) vs. 394 patients
(20.9%), respectively [3,4]; BUD/FORM maintenance (11.7%), respectively [5,6].
and reliever therapy vs. same maintenance dose ICS/ In general, higher GINA treatment steps were asso-
LABA + SABA, 247 patients (12.2%) vs. 437 patients ciated with a shorter time to first event for all treatment
(21.4%), respectively [3,7]; and BUD/FORM maintenance groups (Figure 4). Within each GINA treatment step,
and reliever therapy vs. higher maintenance dose ICS/ the BUD/FORM maintenance and reliever therapy
8. Bateman et al. Respiratory Research 2011, 12:38 Page 8 of 11
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combinations plus SABA when introduced in patients
previously prescribed treatments at Steps 2, 3 or 4 in
the GINA report.
Satisfactory control, defined as Controlled or Partly
Controlled asthma in the GINA report, was achieved in
at least as many, or, for some comparisons and treat-
ment steps, in a higher proportion of patients treated
with BUD/FORM maintenance and reliever therapy
compared with other fixed-dose maintenance regimens
+ SABA. For most comparisons, this was achieved with
a lower mean dose of ICS and was associated with a
lower risk of exacerbations (future risk). From the pri-
Figure 3 Exacerbation rate by study treatment and GINA mary analyses of each of these trials, it is clear that
treatment step at study entry. BUD/FORM = budesonide/ lower exacerbation rates also resulted in significantly
formoterol; ICS = inhaled corticosteroid; LABA = long-acting b2- lower requirements for short courses of oral corticoster-
agonist; SABA = short-acting b2-agonist BUD/FORM maintenance
and reliever therapy vs. higher maintenance dose ICS + SABA,
oids [3-7].
exacerbation rate ratio (95% confidence interval): Step 2, 0.829 The superiority of BUD/FORM maintenance and relie-
(0.570, 1.207); Step 3, 0.431 (0.353, 0.526); Step 4, 0.624 (0.512, 0.761). ver therapy over higher maintenance dose ICS alone
BUD/FORM maintenance and reliever therapy vs. same maintenance with SABA as reliever in achieving satisfactory control
dose ICS/LABA + SABA, exacerbation rate ratio (95% confidence (defined as Controlled or Partly Controlled by GINA)
interval): Step 2, 0.583 (0.389, 0.874); Step 3, 0.455 (0.371, 0.558); Step
4, 0.519 (0.434, 0.620). BUD/FORM maintenance and reliever therapy
for patients previously prescribed Step 2 treatment is an
vs. higher maintenance dose ICS/LABA + SABA, exacerbation rate important observation. This analysis suggests that using
ratio (95% confidence interval): Step 3, 0.795 (0.631, 1.002); Step 4, BUD/FORM both as maintenance and reliever for
0.665 (0.549, 0.807). patients not controlled at this treatment step offers sig-
nificant benefit. Secondly, BUD/FORM maintenance and
reliever therapy at Steps 3 and 4 is also superior to
group showed a significantly prolonged time to first fixed-dose ICS/LABA given at the same maintenance
event compared with all three comparator fixed-dose dose of ICS in achieving reductions in exacerbations,
maintenance regimens + SABA. although it is only in patients at Step 4 that a statisti-
Relatively few events (<5% of patients) required hospi- cally significant advantage is seen in current clinical
tal treatment or an ER visit during the study period in control. Finally, BUD/FORM maintenance and reliever
all groups, except among patients classified as GINA therapy achieves only similar levels of current clinical
treatment Step 4 receiving same or higher maintenance control to a higher maintenance dose of ICS/LABA but
dose ICS/LABA + SABA, for which 7.8% and 6.0% of retains its advantage in reducing exacerbations (only sta-
patients required hospitalisation or an ER visit, respec- tistically significant in patients on Step 4), making it an
tively. However, most comparisons (rate and time to attractive option in patients on this step for reducing
first exacerbation) favoured the BUD/FORM mainte- exposures to inhaled and systemic corticosteroids.
nance and reliever therapy group (Additional file 1, These results are supported by the changes in FEV 1
Table S4). and as-needed use of reliever medication. Improvements
in FEV 1 were significantly greater with BUD/FORM
Discussion maintenance and reliever therapy for all comparisons
For ease of use, pharmacotherapy in asthma guidelines other than at Step 2 when compared with same mainte-
is arranged in treatment steps. Increasing treatment in nance dose ICS/LABA + SABA and with a higher main-
patients who require additional treatment medication tenance dose of ICS/LABA + SABA. The reduction in
involves selecting an option from among the treatments reliever use was significant in the comparison with a
on the same or a higher step. Treatments are stratified higher maintenance dose ICS + SABA in Steps 2-4 and
on the basis of randomised trials comparing their effi- Steps 3 and 4 when compared with same maintenance
cacy in patients qualifying for that treatment step with dose ICS/LABA + SABA.
due regard to their therapeutic index, that is, weighing A further finding of the analysis is the relationship
up benefit and safety. The results of this post hoc analy- between treatment step and other indicators of asthma
sis of five large clinical studies provides clinically useful severity. A recent American Thoracic Society/European
information on the relative efficacy and benefits of Respiratory Society Task Force Report on asthma sever-
BUD/FORM maintenance and reliever therapy com- ity and control states that the level of treatment
pared with high-dose ICS or fixed-dose ICS/LABA required to achieve and/or maintain control is the most
9. Bateman et al. Respiratory Research 2011, 12:38 Page 9 of 11
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Figure 4 Time to first severe exacerbation by GINA treatment step at study entry. BUD/FORM = budesonide/formoterol; ICS = inhaled
corticosteroid; LABA = long-acting b2-agonist; SABA = short-acting b2-agonist P-values refer to Cox model. BUD/FORM maintenance and
reliever therapy vs. higher maintenance dose ICS + SABA, hazard ratio (95% confidence interval): Step 2, 0.545 (0.341, 0.870); Step 3, 0.507 (0.401,
0.642); Step 4, 0.701 (0.546, 0.900). BUD/FORM maintenance and reliever therapy vs. same maintenance dose ICS/LABA + SABA, hazard ratio (95%
confidence interval): Step 2, 0.467 (0.268, 0.814); Step 3, 0.516 (0.406, 0.656); Step 4, 0.561 (0.449, 0.700). BUD/FORM maintenance and reliever
therapy vs. higher maintenance dose ICS/LABA + SABA, hazard ratio (95% confidence interval): Step 3, 0.726 (0.554, 0.950); Step 4, 0.773 (0.620,
0.965).
10. Bateman et al. Respiratory Research 2011, 12:38 Page 10 of 11
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consistent indicator of severity [11]. In our analysis, effective option for patients requiring treatment adjust-
patients on higher treatment steps at entry were older ments across Steps 2 to 4 in the GINA treatment guide-
(less than 10 years’ mean difference between Steps 2 lines. The as-needed use of BUD/FORM for relief is
and 4), possibly indicating increasing treatment require- obviously of greatest benefit to patients in each treatment
ments associated with lifelong asthma, and there was a step whose asthma control is not optimal, either because
trend towards lower FEV1 and higher symptom scores they are undertreated or because their asthma is more
during run-in. Consistent with this, the proportion of refractory (severe). The reduction in such patients’ rates of
patients with GINA-defined Controlled asthma and asthma exacerbations, with attendant reduction in need
Controlled or Partly Controlled asthma at study end for systemic corticosteroids, is a useful advantage and,
decreased with increasing GINA treatment step at entry, although not examined in this analysis, might be asso-
irrespective of study treatment. These results are also ciated with reductions in risk of adverse effects of treat-
consistent with those of the Gaining Optimal Asthma ment, particularly in the long term.
Control (GOAL) study in which the proportion of
patients achieving target levels of control decreased with Additional material
increasing severity of asthma categorised according to
prior treatment. This was in spite of escalation of ICS Additional file 1: Overall asthma control achieved with budesonide/
or fixed-dose ICS/LABA to maximum recommended formoterol maintenance and reliever therapy for patients on
different treatment steps - additional data Additional information
levels for a prolonged period [12]. providing supplementary trial details, hospitalisation and ER rates and
The limitations of this study include that it is a post hoc reliever use data
analysis; patients were not randomised according to
GINA treatment step in each study. The assessment of
GINA-defined asthma control was also post hoc and Acknowledgements
based upon data derived from patient diary cards; how- We thank Dr Jonathan Brennan from MediTech Media Ltd, who provided
ever, the method that was employed and its usefulness medical writing assistance on behalf of AstraZeneca. The analysis was
sponsored by AstraZeneca, Lund, Sweden.
have been discussed in a previous report [9]. A further
limitation is that, although in all the studies asthma Author details
symptoms and reliever use during run-in confirmed that 1
Division of Pulmonology, Department of Medicine, University of Cape
patients were uncontrolled at entry, in three of the five Town, Cape Town, South Africa. 2Nottingham Biomedical Research Unit, City
Hospital Campus, Nottingham University, Nottingham, UK. 3Department of
studies some medications had been withdrawn during Allergy, Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain.
this phase, resulting in worse control than at recruitment. 4
Clinical Management Group, Woolcock Institute of Medical Research,
While this will have served to emphasise the benefits of Sydney, Australia. 5Pulmonary Department, Mainz University Hospital, Mainz,
Germany. 6Université Paris-Sud 11, Centre National de Référence de
subsequent treatments, it would not have favoured any of L’Hypertension Artérielle Pulmonaire, Service de Pneumologie et
the treatments. In only one study was the control state Réanimation Respiratoire, Hôpital Antoine-Béclère, Clamar Cedex, France.
7
known prior to run-in, and in this study the five-item AstraZeneca Research and Development, Lund, Sweden. 8Michael G
DeGroote School of Medicine, Faculty of Health Sciences, McMaster
Asthma Control Questionnaire score was higher than University, Hamilton, Ontario, Canada. 9Department of Respiratory Medicine
2.1, confirming that the majority of those recruited were and Allergology, University Hospital, Lund, Sweden.
uncontrolled [7]. Furthermore, the numbers of patients
Authors’ contributions
on Step 2 treatment and the relatively low exacerbation All authors read and approved the final manuscript. EDB was an investigator in
rates in this subgroup weakens the confidence of the esti- three of the clinical trials, and was involved in the study design, analysis and
mate. Finally, because of the relatively short duration of interpretation of data and the lead in drafting the manuscript. TH contributed
to the design, interpretation of results and drafting the manuscript. SQ has
the studies (6-12 months), we have not attempted to participated in planning and discussion of the manuscript. HR participated in
study other aspects of future risk such as lung function the study design, analysis and interpretation of data and the writing of the
decline or the adverse effects of treatment. However, a manuscript. RB contributed to the planning of the analyses, commented on the
data/results of the analyses and provided input to the interpretation of the data
recent combined analysis of these five and one additional and also contributed to the final manuscript. MH contributed to data analysis
study comparing BUD/FORM maintenance and reliever and approved the manuscript. CJ participated in the study design, analysis and
therapy with fixed-dose alternatives confirmed that the interpretation of data and the writing of the manuscript. SP and OÖ
contributed to the statistical analysis plan, performed the statistical analyses and
former was associated with fewer asthma-related serious contributed to the writing of the manuscript. PO’B contributed to the
adverse events and discontinuations during the studies development of the research strategy, evaluation and analysis of the data and
and with no increased risk of deaths or cardiac-related to the writing of the manuscript. MRS participated in data evaluation, editing of
draft manuscripts, and approval of the final manuscript. GSE was involved in
serious adverse events [13]. the study design, analysis and interpretation of data and the drafting of the
manuscript.
Conclusions
Conflicts of interests
In summary, this analysis confirms that the BUD/FORM EDB has received honoraria for consulting, speaking at scientific meetings
maintenance and reliever therapy approach is a highly and participating in advisory boards for AstraZeneca. His institution has
11. Bateman et al. Respiratory Research 2011, 12:38 Page 11 of 11
http://respiratory-research.com/content/12/1/38
received grants for participation in clinical trials. TH has received honoraria 9. Bateman ED, Reddel HK, Eriksson G, Peterson S, Ostlund O, O’Byrne PM:
from AstraZeneca for advisory work and presentations. SQ has been on Overall asthma control - the relationship between current control and
advisory boards for and has received speaker’s honoraria from AstraZeneca, future risk. J Allergy Clin Immunol 2010, 125:600-608.
GlaxoSmithKline, MSD, Novartis, Almirall, Altana, Chiesi and Pfizer. HR has 10. Bateman ED, Bousquet J, Busse WW, Clark TJ, Gul N, Gibbs M, Pedersen S:
been on advisory boards for AstraZeneca, GlaxoSmithKline and Novartis, has Stability of asthma control with regular treatment: an analysis of the
received speaker’s honoraria from GlaxoSmithKline, AstraZeneca, Merck and Gaining Optimal Asthma controL (GOAL) study. Allergy 2008, 63:932-938.
Getz Pharma, has provided consultancy services for Biota and 11. Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW,
GlaxoSmithKline, and has received research funding from GlaxoSmithKline Casale TB, Chanez P, Enright PL, Gibson PG, De Jongste JC, Kerstjens HA,
and AstraZeneca. RB has received reimbursement for attending scientific Lazarus SC, Levy ML, O’Byrne PM, Partridge MR, Pavord ID, Sears MR,
conferences and/or fees for speaking and/or consulting from AstraZeneca, Sterk PJ, Stoloff SW, Sullivan SD, Szefler SJ, Thomas MD, Wenzel SE: An
Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Nycomed and Pfizer. official American Thoracic Society/European Respiratory Society
The Pulmonary Department at Mainz University Hospital received financial statement: asthma control and exacerbations: standardizing endpoints
compensation for services performed during participation in clinical trials for clinical asthma trials and clinical practice. Am J Respir Crit Care Med
organised by various pharmaceutical companies. MH has relationships with 2009, 180:59-99.
drug companies including AstraZeneca, Chiesi, GlaxoSmithKline, MSD, 12. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA,
Novartis, Nycomed and Pfizer. In addition to being investigator in trials Pedersen SE: Can guideline-defined asthma control be achieved? The
involving these companies, relationships include consultancy services and Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004,
membership of scientific advisory boards. CJ is employed by the Woolcock 170:836-844.
Institute of Medical Research. The Institute receives funding for its ongoing 13. Sears MR, Radner F: Safety of budesonide/formoterol maintenance and
education and research programs from AstraZeneca and GlaxoSmithKline reliever therapy in asthma trials. Respir Med 2009, 103:1960-1968.
and conducts clinical trials for these and other pharmaceutical companies
under contract. She receives no monies directly through these sources or doi:10.1186/1465-9921-12-38
funding through the Co-operative Research Centre for Asthma, a Cite this article as: Bateman et al.: Overall asthma control achieved with
collaborative research programme funded jointly by the Australian budesonide/formoterol maintenance and reliever therapy for patients
Government and Industry partners. In the last 3 years CJ has received on different treatment steps. Respiratory Research 2011 12:38.
reimbursement for Advisory Board Membership, consultancy and speakers
fees in from Altana, Astra Zeneca, GlaxoSmithKline, Hunter Immunology,
Novartis, Nycomed and Tyrian Diagnostics. PO’B has been on advisory
boards for AstraZeneca, GlaxoSmithKline, Merck, Nycomed, Topigen and
Wyeth and has received lecture fees from these and other pharmaceutical
companies including Chiesi and Ono Pharma. In addition, he has received
grants for research studies from AstraZeneca, Genentech, GlaxoSmithKline,
MedImmune, Merck, Pfizer, Topigen and Wyeth. MRS holds an Endowed
chair in Respiratory Epidemiology jointly endowed by AstraZeneca and
McMaster University. He has received research funding from pharmaceutical
companies including Merck Sharp Dome and AstraZeneca. He has acted as
a consultant or advisory board member to Merck Sharp Dome, Novartis, and
AstraZeneca. OÖ, SP, GSE are employed by AstraZeneca and own shares in
AstraZeneca.
Received: 11 November 2010 Accepted: 4 April 2011
Published: 4 April 2011
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