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Chest Sep 2023In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy.
RESEARCH QUESTION
Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma?
STUDY DESIGN AND METHODS
This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV area under the curve from 0 to 6 h (FEV AUC) over 12 weeks (assessing albuterol effect) and trough FEV at week 12 (assessing budesonide effect).
RESULTS
Of 1,001 patients randomized, 989 were ≥ 12 years old and evaluable for efficacy. Change from baseline in FEV AUC over 12 weeks was greater with albuterol-budesonide 180/160 μg vs budesonide 160 μg (least-squares mean [LSM] difference, 80.7 [95% CI, 28.4-132.9] mL; P = .003). Change in trough FEV at week 12 was greater with albuterol-budesonide 180/160 and 180/80 μg vs albuterol 180 μg (LSM difference, 132.8 [95% CI, 63.6-201.9] mL and 120.8 [95% CI, 51.5-190.1] mL, respectively; both P < .001). Day 1 time to onset and duration of bronchodilation with albuterol-budesonide were similar to those with albuterol. The albuterol-budesonide adverse event profile was similar to that of the monocomponents.
INTERPRETATION
Both monocomponents contributed to albuterol-budesonide lung function efficacy. Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel rescue therapy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov; No.: NCT03847896; URL: www.
CLINICALTRIALS
gov.
Topics: Humans; Child; Budesonide; Formoterol Fumarate; Metered Dose Inhalers; Administration, Inhalation; Asthma; Albuterol; Double-Blind Method; Bronchodilator Agents; Treatment Outcome
PubMed: 37003355
DOI: 10.1016/j.chest.2023.03.035 -
ELife Jul 2023Genomic analysis has shed light on how hadal snailfish have adapted to living at depths of several thousand metres.
Genomic analysis has shed light on how hadal snailfish have adapted to living at depths of several thousand metres.
Topics: Adaptation, Physiological; Perciformes; Animals
PubMed: 37436434
DOI: 10.7554/eLife.90216 -
Ugeskrift For Laeger Nov 2023Hydrofluorocarbons, the propellants used in metered dose inhalers, are powerful greenhouse gases. However, this review investigates the use of metered dose inhalers... (Review)
Review
Hydrofluorocarbons, the propellants used in metered dose inhalers, are powerful greenhouse gases. However, this review investigates the use of metered dose inhalers which continue to be on the rise in Denmark despite evidence that most patients are treated equally well with dry powder inhalers. If the use of metered dose inhalers in Denmark were reduced to approximately the level seen in Sweden it would lead to a reduction in CO2e comparable with the emissions from the electricity used in 16,500 typical Danish households.
Topics: Humans; Asthma; Nebulizers and Vaporizers; Metered Dose Inhalers; Dry Powder Inhalers; Respiration Disorders; Respiratory Tract Diseases; Administration, Inhalation
PubMed: 37987432
DOI: No ID Found -
Journal of Aerosol Medicine and... May 2024Standard nebulizers are intended for general purpose use and typically are continuously operated jet or ultrasonic nebulizers. Evolutionary developments such as... (Review)
Review
Standard nebulizers are intended for general purpose use and typically are continuously operated jet or ultrasonic nebulizers. Evolutionary developments such as breath-enhanced and breath-triggered devices have improved delivery efficiency and ease of use, yet are still suitable for delivery of nebulized medications approved in this category. However, recent developments of vibrating membrane or mesh nebulizers have given rise to a significant increase in delivery efficiency requiring reformulation of former drug products or development of new formulations to match the enhanced delivery characteristics of these new devices. In addition, the electronic nature of the new devices enables tailoring to specific applications and patient groups, such as guiding or facilitating optimal breathing and improving adherence to the therapeutic regimen. Addressing these patient needs leads to new nebulization technologies being embedded in devices with fundamentally distinct functionality, modes of operation and patient interfaces. Therefore, new generation nebulizers can no longer be regarded as one category with fairly similar performance characteristics but must be clinically tested and approved as drug/device combinations together with the specific drug formulation, similar to the approval of pressurized metered-dose inhalers and dry powder inhalers. From a regulatory viewpoint, it is required that drug and device are associated with each other as combinations by clear, mutually conforming labels or, even more desirably, by distinct container-closure systems (closed system nebulizer).
PubMed: 38768422
DOI: 10.1089/jamp.2024.29116.mk -
Ugeskrift For Laeger Sep 2023Palatal tremor (PT) is a rare cause of objective tinnitus. Symptomatic PT is caused by injuries of the Guillain-Mollaret triangle with contraction of levator veli...
Palatal tremor (PT) is a rare cause of objective tinnitus. Symptomatic PT is caused by injuries of the Guillain-Mollaret triangle with contraction of levator veli palatini. Essential PT causes are unknown and is produced by contraction of tensor veli palatini, with pathognomonic audible ear click. This is a case report of a 36-year-old female, who developed bilateral objective tinnitus, as well as vertigo, blepharospasm, and neck tension after a free fall trauma 30 metres in the net. She was diagnosed with essential PT and treated with botulinum neurotoxin injections in the soft palate.
Topics: Female; Humans; Adult; Tinnitus; Tremor; Palatal Muscles; Palate, Soft; Myoclonus
PubMed: 37767868
DOI: No ID Found -
Journal of Aerosol Medicine and... Dec 2023Dry powder inhaler products have played an important role in the treatment and prevention of asthma and more recently chronic obstructive pulmonary disease. The... (Review)
Review
Dry powder inhaler products have played an important role in the treatment and prevention of asthma and more recently chronic obstructive pulmonary disease. The considerations that go into formulation development to support these products cover a unique range of disciplines including analytical and physical chemistry, aerosol physics, device technology, process engineering and industrial design. An enormous research effort has been expended in the last half century to provide understanding of this complex dosage form. The guiding principles in considering the development of dry powder inhaler products encompass requirements for disease therapy, advantages and limitations of adopting certain technological approaches, and desirable features to facilitate patient use, which are all embodied in the target product profile.
Topics: Humans; Dry Powder Inhalers; Administration, Inhalation; Respiratory Aerosols and Droplets; Asthma; Pulmonary Disease, Chronic Obstructive
PubMed: 38016133
DOI: 10.1089/jamp.2023.29104.ajh -
MMW Fortschritte Der Medizin Mar 2024
Topics: Humans; Spain; Metered Dose Inhalers
PubMed: 38453875
DOI: 10.1007/s15006-024-3707-8 -
JPMA. the Journal of the Pakistan... Jul 2023Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority...
Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority of cases despite patients' late presentation. The objective of the study was to determine the frequency of postoperative complications of perforated duodenal ulcer, conducted in the Surgery Department, Jinnah Postgraduate Medical Centre, Karachi, from March 20, 2018 to September 20, 2018. The study was a descriptive case series of 108 patients of both genders with perforated duodenal ulcer > 1 week old with ASA score I & II. Patients with trauma and comorbidities were excluded. The patients underwent laparotomy and peritoneal toilet, and after noting the site of perforation indirect Graham's Omentopexy was performed. Complications like duodenal fistula, peritonitis, and paralytic ileus, and patient's death within 10 days of surgery were noted. Age ranged from 18 to 50 years with mean age of 35.027±5.13 years, mean weight 71.120±12.77 kg, mean height 1.541 ±0.09 metres, mean BMI 29.975±4.99 kg/m2, and the mean duration of complaint was 4.194±1.30 weeks. Male predominance in 75 (69.4%) patients. Duodenal fistula was seen in 10 (9.3%) patients, peritonitis 12 (11.1%), paralytic ileus 14 (13%) and mortality was in 11 (10.2%) patients.
Topics: Humans; Male; Female; Adult; Infant; Duodenal Ulcer; Risk Factors; Peptic Ulcer Perforation; Peritonitis; Fistula
PubMed: 37469068
DOI: 10.47391/JPMA.4768