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Annals of the American Thoracic Society Oct 2023It can be challenging for healthcare professionals (HCPs) to prescribe inhaled therapy for patients with chronic obstructive pulmonary disease (COPD) because of the... (Review)
Review
It can be challenging for healthcare professionals (HCPs) to prescribe inhaled therapy for patients with chronic obstructive pulmonary disease (COPD) because of the multiple individual and combinations of inhaled medications available in numerous delivery systems. Guidance on the selection of an inhaled delivery system has received limited attention compared with the emphasis on prescribing the class of the inhaled molecule(s). Although numerous recommendations and algorithms have been proposed to guide the selection of an inhaled delivery system for patients with COPD, no specific approach has been endorsed in COPD guidelines/strategies or by professional organizations. To provide recommendations for an inhaler selection strategy at initial and follow-up appointments, we examined the impact of patient errors using handheld inhalers on clinical outcomes and performed a focused narrative review to consider patient factors (continuity of the inhaled delivery system, cognitive function, manual function/dexterity, and peak inspiratory flow) when selecting an inhaled delivery system. On the basis of these findings, five questions are proposed for HCPs to consider in the initial selection of an inhaler delivery system and three questions to consider at follow-up. We propose that HCPs consider the inhaled medication delivery system as a unit and to match appropriate medication(s) with the unique features of the delivery system to individual patient factors. Assessment of inhaler technique and adherence together with patient outcomes/satisfaction at each visit is essential to determine whether the inhaled medication delivery system is providing benefits. Continued and repeated education on device features and correct technique is warranted to optimize efficacy.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Nebulizers and Vaporizers; Pharmaceutical Preparations; Patient Satisfaction; Administration, Inhalation; Bronchodilator Agents
PubMed: 37499210
DOI: 10.1513/AnnalsATS.202304-384CME -
Endocrine Practice : Official Journal... Oct 2023To evaluate the discriminant and convergent validities of the Hypoglycemia Awareness Questionnaire Impaired Awareness (HypoA-Q IA) subscale and establish a diagnostic...
OBJECTIVE
To evaluate the discriminant and convergent validities of the Hypoglycemia Awareness Questionnaire Impaired Awareness (HypoA-Q IA) subscale and establish a diagnostic threshold for the classification of impaired awareness of hypoglycemia (IAH) in adults with type 1 diabetes (T1D).
METHODS
Twenty-one adults with T1D (male, 48%; median age, 36 years; and T1D duration, 21 years) completed the HypoA-Q IA subscale, Clarke, and hypoglycemia severity (HYPO) scores, continuous glucose monitoring, and hyperinsulinemic hypoglycemic clamp testing. Those with IAH defined by a Clarke score of ≥4 (n = 10) and who experienced severely problematic hypoglycemia and/or marked glycemic lability started automated insulin delivery as part of an 18-month intervention study with the 6-monthly paired assessment of the HypoA-Q IA subscale, Clarke score, HYPO score and continuous glucose monitoring, and hypoglycemic clamp testing at baseline and 6 and 18 months.
RESULTS
The HypoA-Q IA subscale discriminated between those with and without IAH defined by the Clarke score (W = 110.5; P <.001). During intervention, the HypoA-Q IA subscale demonstrated convergent validity via significant relationships with the Clarke (r = 0.72; P <.001) and HYPO (r = 0.60; P <.001) scores; hypoglycemia exposure below 70 (r = 0.53; P <.01), 60 (r = 0.50; P <.01), and 54 (r = 0.48; P <.01) mg/dL; and autonomic symptom (r = -0.53; P <.05), epinephrine (r = -0.68; P <.001), and pancreatic polypeptide (r = -0.52; P <.05) responses to insulin-induced hypoglycemia. The receiver operating characteristic curve analysis revealed that the HypoA-Q IA subscale was an excellent predictor of an abnormal symptom response to insulin-induced hypoglycemia (area under the curve, 0.86) with a score of 12, which was the optimal threshold for IAH classification (sensitivity, 83%; specificity, 80%).
CONCLUSION
These findings support the validity of the HypoA-Q IA subscale and propose a HypoA-Q IA diagnostic threshold to identify IAH in both clinical and research settings.
Topics: Adult; Humans; Male; Diabetes Mellitus, Type 1; Blood Glucose; Blood Glucose Self-Monitoring; Hypoglycemia; Hypoglycemic Agents; Surveys and Questionnaires; Insulin
PubMed: 37611750
DOI: 10.1016/j.eprac.2023.08.004 -
Indian Journal of Ophthalmology Jul 2024To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric...
PURPOSE
To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric cataract surgery.
METHODS
Consecutive children aged ≤12 years planned for cataract surgery were recruited. A commercially available premixed combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) was injected at the beginning of surgery without any topical/infusion drugs for mydriasis. Pupil sizes at various points of surgery were studied.
RESULTS
We recruited 75 patients with a mean age of 24.3 ± 33.4 months (range: 1 month-11 years). Adequate mydriasis with a single injection was achieved in 93.5% (n = 73 eyes of 70 patients) without additional pharmacotherapy or intervention. The mean pupillary diameter increased from 1.8 ± 0.79 to 6.1 ± 1.4 mm after injection (mean change of 4.2 ± 1.25 mm from baseline). The mean variability in pupillary diameter was 0.73 ± 1.3 mm. In five eyes, good dilatation was not possible even after repeat injection.
CONCLUSION
Fixed-dose premixed intracameral injection is effective in pupil dilatation. It alleviates the need for any topical dilators or additional intraoperative supplementation for pediatric cataract surgery.
Topics: Humans; Mydriatics; Child, Preschool; Male; Infant; Female; Cataract Extraction; Pupil; Child; Tropicamide; Phenylephrine; Lidocaine; Anterior Chamber; Cataract; Prospective Studies; Follow-Up Studies; Ophthalmic Solutions; Dose-Response Relationship, Drug
PubMed: 38454863
DOI: 10.4103/IJO.IJO_2628_23 -
The efficacy of aprepitant for the prevention of postoperative nausea and vomiting: A meta-analysis.Medicine Jul 2023Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs suggest that aprepitant has the strongest antiemetic effect of any single drug. This meta-analysis aimed to explore the efficacy of aprepitant for preventing PONV based on the existing literature.
METHODS
To identify RCTs investigating the use of aprepitant for PONV prevention, we searched PubMed, Embase, and Cochrane Library databases for articles published prior to March 20, 2022. Seventeen RCTs were identified, with 3299 patients, meeting the inclusion criteria. PONV incidence, complete response, 80 mg aprepitant combined with dexamethasone and ondansetron, vomiting, nausea, and analgesic dose-response were the main outcomes measured.
RESULTS
Compared with the control group, PONV incidence was significantly reduced among those receiving aprepitant (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.26, 0.44; P < .0001), with a more complete response (OR: 1.35; 95% CI: 1.14, 1.59; P = .0004). Supplementation of 80 mg aprepitant in combination with dexamethasone and ondansetron substantially improved the effects of PONV (OR: 0.36; 95% CI: 0.16, 0.82; P = .01). Further, administration of 80 mg aprepitant was better at preventing vomiting than nausea (OR: 8.6; 95% CI: 3.84, 19. 29; P < .00001). No statistically significant difference between the dose-response of analgesics was identified (mean difference: -1.09; 95% CI: -6.48, 4.30; P = .69). The risk of bias was assessed independently by paired evaluators.
CONCLUSION
Aprepitant effectively reduces the incidence of PONV; however, the effects of postoperative analgesia require further exploration.
Topics: Humans; Aprepitant; Postoperative Nausea and Vomiting; Ondansetron; Morpholines; Antiemetics; Vomiting; Dexamethasone
PubMed: 37478247
DOI: 10.1097/MD.0000000000034385 -
JCO Global Oncology Jan 2024The effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) is not known.
METHODS
This was a double-blind, phase III trial designed to show the noninferiority of a DEX-free regimen (olanzapine, palonosetron, and fosaprepitant [OPF]) compared with the DEX-containing regimen (olanzapine, palonosetron, and DEX [OPD]). Chemotherapy-naïve patients age 18-80 years receiving single-day HEC were randomly assigned 1:1 to receive either the OPD regimen or the OPF regimen. The primary objective was to compare complete response (CR) rates for vomiting during the overall period (start of chemotherapy to 120 hours). Secondary objectives included CR for vomiting during the acute period (0-24 hours) and delayed period (24-120 hours), CR for nausea, and comparison of toxicities and patient-reported outcomes.
RESULTS
Three hundred forty-six patients received the study interventions, 174 in the OPD arm and 172 in the OPF arm. The DEX-free OPF arm had significantly higher CR rates for vomiting compared with the DEX-containing OPD arm in acute (94.7% 85.6%; < .004), delayed (81.9% 50.5%; < .001), and overall (79.6% 48.8%; < .001) periods. For nausea, CR rates in the OPF arm were higher in delayed (53.4% 39.6%; = .009) and overall (50.5% 39.1%; = .031) periods but not in the acute period (77.9% 81.6%; = .39). Fatigue ( = .009) and drowsiness ( = .002) were more in the OPF arm in the acute period and insomnia ( < .001) in the OPD arm in the overall period.
CONCLUSION
This study shows that a DEX-free OPF regimen is efficacious and should be considered a standard option for acute and delayed CINV prophylaxis for HEC.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Antiemetics; Palonosetron; Olanzapine; Vomiting; Nausea
PubMed: 38237092
DOI: 10.1200/GO.23.00301 -
Scientific Reports Oct 2023Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association...
Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and 818 plasma metabolites in middle-aged subjects from the general population. We included 3803 out of 6251 subjects (mean age, 57 years; 52% women) from the Malmö sub-cohort of The Swedish CardioPulmonary bioImage Study with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses were determined using multivariable linear regression analysis and p values were corrected using the Bonferroni method. Six amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics were associated with orthostatic blood pressure after adjusting for age, gender and systolic blood pressure. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic. Twenty-two out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease.
Topics: Middle Aged; Humans; Female; Male; Blood Pressure; Hypotension, Orthostatic; Antihypertensive Agents; Diabetes Mellitus; Metabolome; Amino Acids; Lipids
PubMed: 37880314
DOI: 10.1038/s41598-023-44226-z -
Journal of Neurology Aug 2023Small fiber neuropathy (SFN) affects unmyelinated and thinly myelinated nerve fibers causing neuropathic pain with distal distribution and autonomic symptoms. In...
Small fiber neuropathy (SFN) affects unmyelinated and thinly myelinated nerve fibers causing neuropathic pain with distal distribution and autonomic symptoms. In idiopathic SFN (iSFN), 30% of the cases, the underlying aetiology remains unknown. Gadolinium (Gd)-based contrast agents (GBCA) are widely used in magnetic resonance imaging (MRI). However, side-effects including musculoskeletal disorders and burning skin sensations were reported. We investigated if dermal Gd deposits are more prevalent in iSFN patients exposed to GBCAs, and if dermal nerve fiber density and clinical parameters are likewise affected. 28 patients (19 females) with confirmed or no GBCA exposure were recruited in three German neuromuscular centers. ISFN was confirmed by clinical, neurophysiological, laboratory and genetic investigations. Six volunteers (two females) served as controls. Distal leg skin biopsies were obtained according to European recommendations. In these samples Gd was quantified by elemental bioimaging and intraepidermal nerve fibers (IENF) density via immunofluorescence analysis. Pain phenotyping was performed in all patients, quantitative sensory testing (QST) only in a subset (15 patients; 54%). All patients reported neuropathic pain, described as burning (n = 17), jabbing (n = 16) and hot (n = 11) and five QST scores were significantly altered. Compared to an equal distribution significantly more patients reported GBCA exposures (82%), while 18% confirmed no exposures. Compared to unexposed patients/controls significantly increased Gd deposits and lower z-scores of the IENF density were confirmed in exposed patients. QST scores and pain characteristics were not affected. This study suggests that GBCA exposure might alter IENF density in iSFN patients. Our results pave the road for further studies investigating the possible role of GBCA in small fiber damage, but more investigations and larger samples are needed to draw firm conclusions.
Topics: Female; Humans; Contrast Media; Gadolinium; Epidermis; Nerve Fibers; Skin; Neuralgia; Biopsy
PubMed: 37138180
DOI: 10.1007/s00415-023-11740-z -
Thorax Oct 2023Estimating the causal effect of an intervention at individual level, also called individual treatment effect (ITE), may help in identifying response prior to the...
RATIONALE
Estimating the causal effect of an intervention at individual level, also called individual treatment effect (ITE), may help in identifying response prior to the intervention.
OBJECTIVES
We aimed to develop machine learning (ML) models which estimate ITE of an intervention using data from randomised controlled trials and illustrate this approach with prediction of ITE on annual chronic obstructive pulmonary disease (COPD) exacerbation rates.
METHODS
We used data from 8151 patients with COPD of the Study to Understand Mortality and MorbidITy in COPD (SUMMIT) trial (NCT01313676) to address the ITE of fluticasone furoate/vilanterol (FF/VI) versus control (placebo) on exacerbation rate and developed a novel metric, Q-score, for assessing the power of causal inference models. We then validated the methodology on 5990 subjects from the InforMing the PAthway of COPD Treatment (IMPACT) trial (NCT02164513) to estimate the ITE of FF/umeclidinium/VI (FF/UMEC/VI) versus UMEC/VI on exacerbation rate. We used Causal Forest as causal inference model.
RESULTS
In SUMMIT, Causal Forest was optimised on the training set (n=5705) and tested on 2446 subjects (Q-score 0.61). In IMPACT, Causal Forest was optimised on 4193 subjects in the training set and tested on 1797 individuals (Q-score 0.21). In both trials, the quantiles of patients with the strongest ITE consistently demonstrated the largest reductions in observed exacerbations rates (0.54 and 0.53, p<0.001). Poor lung function and blood eosinophils, respectively, were the strongest predictors of ITE.
CONCLUSIONS
This study shows that ML models for causal inference can be used to identify individual response to different COPD treatments and highlight treatment traits. Such models could become clinically useful tools for individual treatment decisions in COPD.
Topics: Humans; Administration, Inhalation; Lung; Pulmonary Disease, Chronic Obstructive; Androstadienes; Benzyl Alcohols; Chlorobenzenes; Bronchodilator Agents; Drug Combinations; Double-Blind Method; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37012070
DOI: 10.1136/thorax-2022-219382 -
Cancer Medicine Aug 2023Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0-120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long-lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post-chemotherapy. In this post-hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention.
METHODS
This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1-3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1-4. Patients were chemotherapy-naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0-144 h) phase.
RESULTS
The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012).
CONCLUSION
A single dose of NEPA, administered on day 1 only, was more effective than a 3-day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors.
Topics: Humans; Male; Female; Aprepitant; Antiemetics; Vomiting; Prospective Studies; Isoquinolines; Quinuclidines; Drug Combinations; Nausea; Cyclophosphamide; Anthracyclines; Antineoplastic Agents; Dexamethasone
PubMed: 37537943
DOI: 10.1002/cam4.6121 -
International Journal of Chronic... 2023Clinically important deterioration (CID) is a composite endpoint developed to quantify the impact of pharmacological treatment in clinical trials for Chronic Obstructive... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Clinically important deterioration (CID) is a composite endpoint developed to quantify the impact of pharmacological treatment in clinical trials for Chronic Obstructive Pulmonary Disease (COPD), also showing a prognostic value. CID is defined as any of the following condition: forced expiratory volume in 1 s decrease ≥100 mL from baseline, and/or St. George's Respiratory Questionnaire total score increase ≥4-unit from baseline, and/or the occurrence of a moderate-to-severe exacerbation of COPD. Although most COPD patients experience a clinical worsening as they get older, to date, no specific studies assessed the correlation between ageing and CID in COPD. Therefore, the aim of this study was to investigate the impact of ageing on CID in COPD patients.
PATIENTS AND METHODS
Data obtained from 55219 COPD patients were extracted from 17 papers, mostly post-hoc analyses. A pairwise meta-analysis and a meta-regression analysis were performed according to PRISMA-P guidelines to quantify the impact of pharmacological therapy on CID and to determine whether ageing might modulate the risk of CID in COPD patients.
RESULTS
Inhaled treatments resulted generally effective in reducing the risk of CID in COPD (relative risk: 0.81, 95% confidence interval 0.79-0.84; P < 0.001). The meta-regression analysis indicated a trend toward significance (P = 0.063) in the linear relationship between age and the risk of CID. Of note, age significantly (P < 0.05) increased the risk of CID when associated with lower post-bronchodilator FEV. These results were not affected by a significant risk of bias.
CONCLUSION
This quantitative synthesis suggests that inhaled therapy is effective in reducing the risk of CID in COPD, although such a protective effect may be affected in older patients with impaired lung function. Further studies specifically designed on CID in COPD are needed to confirm these results.
Topics: Aged; Humans; Aging; Bronchodilator Agents; Forced Expiratory Volume; Meta-Analysis as Topic; Pulmonary Disease, Chronic Obstructive; Systematic Reviews as Topic; Treatment Outcome; Clinical Deterioration
PubMed: 37841747
DOI: 10.2147/COPD.S396945