Early Morning Symptoms Research Articles

Colon-Specific Delivery of Naproxen Pellets for Rheumatoid Arthritis: Development, Optimization, and Evaluation Using a 3-Level Randomized Full Factorial Design

Rheumatoid arthritis (RA) is characterized by increased joint pain and stiffness, particularly in the morning, which requires medication for treatment. Our research described here was aimed to develop, evaluate, and optimize coated naproxen pellets for colon-specific delivery using the carboxymethyl Leucaena leucocephala gum for the chronotherapy of RA. The extrusion-spheronization process was used for the preparation of the pellets followed by coating in a fluidized bed processor with materials such as Eudragit® S 100 and L 100. An 11-run, 2-factor, 3-level, randomized full factorial design was used to analyze the impact on the responses by varying the levels of independent factors to obtain the optimized formulation. The drug release of all the formulation batches at the 4th hour varied from 1.24 to 17.22% in the upper gastrointestinal (GI) tract; while the release of the drug at the 10th hour varied from 76.87 to 98.39% at the colonic pH. Furthermore, it was observed that the optimized formulation exhibited an increased release of naproxen in the presence of cecal matter collected from rats. We suggest that the prepared optimized formulation of the coated pellets of naproxen shows promise for the chronotherapeutic treatment of early morning symptoms associated with RA.

Oral pH triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part I: Optimization, in-vitro, and ex-vivo characterization

The primary goal of this research was to investigate pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLM) using Eudragit S-100 as a pH-dependent polymer. The formulation was optimized using the Box-Behnken design. The suggested C-SKLM formulation with the amount of ketoprofen = 189.09 mg, the amount of Eudragit-100 = 600 mg, and the paddle speed = 400 rpm showed a considerable particle size (106 µm), drug encapsulation efficacy (79.67%), and % cumulative drug release at 5th hr (8.62) and 10th hr (92.62) for oral administration. Microphotographs of scanning electron microscopy indicated that the optimized C-SKLM was smooth and spherical. The differential scanning calorimetry and X-ray powder diffraction studies have shown that ketoprofen was dispersed in the polymer in its optimized C-SKLM formulation, and the spectra from the Fourier transform infrared study have shown no significant drug-polymer interaction. Ex-vivo permeation studies on isolated rat gastro-intestinal segments revealed that the maximum amount of ketoprofen permeated after 2 h through the isolated stomach (0.559 ± 0.049 mg), small intestine (1.36 ± 0.226 mg), and colon (0.972 ± 0.068 mg) was observed for ketoprofen pure. In contrast, a significantly lesser amount of the drug was permeated through the stomach (0.1 ± 0.025 mg) and small intestine (0.28 ± 0.1 mg) than the colon (0.697 ± 0.23 mg) from the ketoprofen-loaded microspheres formulation. In-vitro and ex-vivo permeation studies suggest that the developed C-SKLM could be helpful for the effective management of early morning symptoms due to rheumatoid arthritis by delaying the release by targeting the colon.

DUAL RELEASE CHRONOTHERAPEUTIC SYSTEM OF POORLY WATER SOLUBLE ANTIHYPERTENSIVE DRUG CARVEDILOL: DESIGN, DEVELOPMENT AND IN VITRO CHARACTERIZATION

The current research investigation’s goal was to design a core-in-cup type pulsatile system of an antihypertensive drug (carvedilol phosphate) to reduce the evening and early-morning symptoms of hypertension. An inclusion complex of this drug was prepared with hydroxyl propyl beta cyclodextrin to increase carvedilol solubility. Using direct compression method, various batches of core tablets were formulated using Croscarmellose sodium as a superdisintegrant. Core tablets of the optimized formulation were press coated with backing layer and release-retarding plug layer. An in vitro release research was performed after evaluating the physicochemical characteristics of the core in cup design tablets. Based on the lag time of 8 h between the first and second pulse releases, a batch containing sodium alginate (100 mg) and hydroxypropyl methylcellulose K4M (100 mg) was chosen as the optimum batch. Thus, the dual-release core-in-cup pulsatile tablets may be utilized for managing the hypertension symptoms appearing in chronological order.

Perspectives of colon-specific drug delivery in the management of morning symptoms of rheumatoid arthritis.

Rheumatoid arthritis is a chronic condition that is characterized by joint pain and inflammation. It is an autoimmune disorder in which the body tissues are erroneously attacked by the immune system of the host itself. It has been evident that rheumatoid arthritis symptoms follow a 24h circadian rhythm and exhibit high thresholds of pain, functional disability, and stiffness predominantly early in the morning. Colon-specific drug delivery systems can be utilized in the formulations to be used in the treatment of rheumatoid arthritis. The colon-specific drug delivery system has shown promising results in the treatment of different diseases at the colonic site like Crohn's disease, ulcerative colitis, colon cancer, etc. The colon-specific drug delivery is capable of delivering the formulation at the predetermined location and predetermined time. The early morning symptoms of rheumatoid arthritis like pain and inflammation can be treated using the various approaches of the colon-specific drug delivery system because it will lead to patient compliance as the patient will not require administering the formulation immediately after waking up in the morning. This review also explains the immunological factors which may trigger rheumatoid arthritis in human beings. It further explores conventional approaches like pH-dependant, microorganisms-driven, pressure-controlled, and time-dependant formulations. By employing two or more conventional approaches given above the various novel approaches have been designed to eliminate the drawbacks of individual techniques.

Cross-linked Alginate Beads of Montelukast Sodium Coated with Eudragit for Chronotherapy: Statistical Optimization, In vitro and In vivo Evaluation.

Chronotherapy is the administration of medication according to the biological rhythm to maximize pharmacological effects and minimize side effects. The objective of the current investigation is to prepare delayed-release beads (DRBs) containing montelukast sodium (MKS) for chronotherapy of asthma. Delayed-release beads of alginate were prepared using a simple method, i.e., ionotropic gelation. The effect of cross-linking agents (zinc or calcium ions) and the concentration of chitosan on the properties of the beads were investigated. The prepared beads were coated by a polymer having pHindependent solubility, i.e., Eudragit RSPO and Eudragit RLPO in different ratios to achieve the desired lag time of 4-5 h. Beads were evaluated for surface morphology, practical yield, encapsulation efficiency, XRD, and in vitro release study. The pharmacokinetic study was carried out on New Zealand white male rabbits. No major differences in the drug release profile were observed between Ca++ and Zn++ crosslinked beads. However, a slight slow release was seen in the case of chitosan-reinforced beads. MKS released from cross-linked alginate beads was slightly altered with sodium alginate concentration, crosslinking time, and talc. At a higher alginate concentration, slow drug release was observed, whereas the addition of talc to alginate increased the release rate. The in vitro release study showed that the optimal formulation of DRBs has a lag time of 4.5 h, and the release at 6 h was found to be 74.9%. In vivo pharmacokinetic study of the beads showed Tmax at 7 h with an initial lag time of 4 h. When dosed at sleep time, the prepared cross-linked beads may deliver montelukast sodium required to relieve early morning symptoms in asthmatic patients.

Association between sleep apnea severity and symptoms of depression and anxiety among individuals with obstructive sleep apnea

ObjectiveWe determined whether the severity of sleep apnea is associated with symptoms of depression and anxiety in patients with obstructive sleep apnea (OSA) and whether symptoms of OSA, other than respiratory events, are associated with depression and anxiety symptoms. MethodsDepressive and anxiety symptoms were defined as a Patient Health Questionnaire-9 score of ≥10 and a Generalized Anxiety Disorder-7 score of ≥8, respectively. Sleep apnea severity and rapid eye movement-related OSA were evaluated using the apnea-hypopnea index (AHI). Subjective symptoms of OSA were assessed using the Sleep Apnea Severity Questionnaire (SASQ). We conducted multivariate logistic regression analyses. ResultsWe included 1390 adult patients with OSA (80.4% men) and 125 control subjects with primary snoring. Symptoms of depression and anxiety were present in 15.5% and 14.4% of patients with OSA, respectively. The prevalence of depressive and anxiety symptoms did not differ between OSA and control subjects after controlling for age and sex. Severe OSA, defined as an AHI score of ≥30, was significantly less likely than mild OSA to be associated with the presence of depression and anxiety symptoms in both the unadjusted and adjusted models (models were adjusted by age, sex, medical comorbidities, history of psychiatric disorders, and daytime sleepiness). By contrast, OSA symptoms assessed using the SASQ were positively correlated with the presence of depression and anxiety symptoms in both the unadjusted and adjusted models. Specifically, nocturnal awakening and morning waking symptoms, but not nocturnal breathing difficulties, were positively correlated with the presence of depression and anxiety symptoms. Subjects with rapid eye movement-related OSA were more likely to have depressive symptoms, but not anxiety, than those without. ConclusionsSymptoms of depression and anxiety were negatively correlated with the severity of sleep apnea but positively correlated with nocturnal awakening and early morning symptoms of OSA.

Exploration of Parteck® SRP 80 and Hypromellose for Chronomodulated Release of LTD4 Receptor Antagonist and Statistical Optimization Using Central Composite Design.

To manage early morning symptoms of nocturnal bronchial asthma, a chronotherapeutic drug delivery system (ChrDDS) of montelukast sodium was designed and developed utilizing non-saccharide, fully synthetic Parteck® SRP 80, and hydrophilic cellulose derivative hydroxypropyl methylcellulose (HPMC). Recurrent lag phase, each followed by the release of a fraction of the drug dose, can be achieved by formulating a "tablets in a capsule" system containing more than one compressed coated tablet encapsulated in an enteric-coated capsule. Lag time in this study was controlled by the compressed coating of HPMC K4M and a blend of ethyl cellulose and Carbopol polymer. Assembly of the system includes two compressed coated tablets encapsulated in a capsule which was further proceeded for enteric coating in a conventional, a novel wax-based, and a Eudracap™ enteric-coated capsule. The optimized formulation of directly compressed tablets of Parteck ® SRP 80 showed a hardness of 8.8 kg/cm2 which is 1.25-fold higher than wet granulated tablets of HPMC. In vitro release data of matrix tablets of Parteck® SRP 80 demonstrated controlled release of drug for a duration of up to 10.8-11 h with changing ratio of polymer and filler. Eudracap™ capsule showed a minimum acid uptake value of 1.75%. The current approach can open a path for the time-regulated release of montelukast that may be beneficial for individuals with episodes of asthma attacks mostly in the early morning.

A Real-World Study on the Day and Night-Time Symptoms Among Greek COPD Patients Who Recently Initiated Treatment with Dual Bronchodilation: The DANICO Study.

PurposeThe rationale of this study was to investigate the prevalence of daily and night symptoms and quality of sleep in Greek COPD patients as a means to evaluate their response to treatment with the fixed dose combination of aclidinium/formoterol (administered through the Genuair® device).Patients and MethodsThis study was a multicenter, nationwide, non-interventional, observational study in 2105 patients suffering from COPD, who have recently started treatment with aclidinium/formoterol. Patients were attending to two visits, one baseline and a final visit, 3 months later. Different variables have been collected on either the baseline or the final visit or both: demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, COPD assessment test (CAT), COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach proposed by the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD treatment report, and severity of early-morning, daytime and night-time COPD-related symptoms. Reasons for prescribing aclidinium/formoterol, satisfaction of patients to the treatment, as well as their compliance have also been recorded.ResultsAfter 3 months on aclidinium/formoterol, 50.1% of the patients experienced an improvement in their early-morning symptoms. Furthermore, 49.9% of them experienced an improvement in their daily symptoms, 44.9% improved their night-time symptoms and 43.2% reduced the frequency of overnight sleep disruptions due to COPD symptoms. These favorable outcomes apply mainly to GOLD Groups B–D. Treatment with aclidinium/formoterol improved on average the pre-bronchodilation FEV1% pred by 3.18%, the post-bronchodilation FEV1% pred by 2.78% and reduced CAT score by 5.22 points. Satisfaction with using aclidinium/formoterol across patients was high, as well as compliance to therapy.ConclusionAclidinium/formoterol provided significant benefits on the quality of life of COPD patients by reducing the morning, daytime and the night-time symptoms and symptom burden in GOLD Groups B–D, and activity impairment under real-life conditions in all GOLD ABCD groups.

Advances in study of early morning symptoms of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with diurnal variations in symptoms, among which morning symptoms are the most common, which have an important impact on patients' daily activities, quality of life and health, and the risk of exacerbations. This review focuses on the occurrence of morning symptoms of COPD, their impacts on patients with COPD, the tools used to assess morning symptoms, and the current treatment of morning symptoms.

Common factors reducing sleep quality of patients with Parkinson's disease in Kyrgyzstan

Patients with PD often suffer from sleep disorders, which may be caused by nocturnal symptoms, early morning symptoms, painful leg cramps, vivid dreams, nightmares,etc. Aim is to identify common factors that reduce sleep quality in patients with Parkinson's disease (PD) in Kyrgyzstan.

A Real-World Observational Study Examining the Impact of Aclidinium Bromide Therapy on the Quality of Life, Symptoms, and Activity Impairment of Patients with Chronic Obstructive Pulmonary Disease: The Greek ON-AIR Study.

PurposeThis multicenter, prospective, observational study aimed to supplement real-world evidence on the effects of aclidinium bromide on the quality of life (QoL), symptoms, and activity impairment of patients with COPD.Patients and MethodsEligible patients were ≥40 years of age, newly initiated on aclidinium bromide as monotherapy or add-on therapy according to the product’s approved label. Patient-reported COPD assessment test (CAT), the severity of symptoms and their impact on daily activities, and the features of the Genuair® inhaler device were assessed at enrollment and at 12 weeks post-treatment onset.ResultsBetween 13 March 2015 and 29 January 2016, 285 eligible consenting patients (76.3% males; median age: 69.0 years; 26.0% newly diagnosed with COPD) were enrolled by 15 hospital-based respiratory medicine specialists in Greece. Aclidinium bromide was initiated as add-on therapy to other inhaled maintenance medications in 73.1% of evaluable patients. The median (interquartile range [IQR]) baseline CAT score decreased from 14.0 (9.0–20.0) to 10.0 (6.0–15.0) points (p<0.001) after 12 weeks of treatment, with 76.5% of the patients achieving a ≥2-point decrease. The severity of night-time and early-morning symptoms, assessed using a 5-point Likert-type scale, decreased from a median (IQR) of 1.0 (0.0–2.0) to 0.0 (0.0–1.0), and from 2.0 (1.0–2.0) to 1.0 (1.0–2.0), respectively (p<0.001 for both). In patients with paired data, the prevalence of at least moderate night-time symptoms, early-morning symptoms, and daily activity impairment decreased from 28.2% to 19.1%, from 63.6% to 34.2%, and from 59.5% to 38.7%, respectively (p<0.001 for all). Inhaler device features were assessed as “very good”/“good” by more than 90% of the patients. The adverse drug reaction rate was 1.4%.ConclusionThe study provides real-world evidence on the beneficial effects of aclidinium bromide on the patients’ QoL, symptom severity, and daily activity impairment, which are complemented by a favorable safety profile and high patient satisfaction with the inhaler device.

BURDEN OF RESPIRATORY SYMPTOMS IN STABLE COPD PATIENTS FROM CENTRAL EASTERN EUROPE: RESULTS FROM A LARGE OBSERVATIONAL STUDY

SESSION TITLE: Wednesday Electronic Posters 2 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Since 2011, the Global Initiative for Obstructive Lung Disease (GOLD) has included symptom burden in the multidimensional assessment of patients with chronic obstructive pulmonary disease (COPD). The prevalence and severity of 24-hour respiratory symptoms in COPD patients from Central Eastern Europe (CEE) is less known. METHODS: This was a multinational cross-sectional study (NCT03031769) in stable COPD patients from 11 countries. Out of 2162 patients enrolled, 1422 were from 5 CEE countries: Romania (RO) n=406, Poland (PL) n=356, Serbia (SB) n=250, Bulgaria (BG) n=210, and Slovakia (SK) n=200. All patients had COPD with duration of at least 1 year. Stable disease was defined as no exacerbation history or changes in maintenance treatment in the last 2 months before enrolment. Respiratory symptoms over the last 24 hours were evaluated using specific questionnaires: Night-time Symptoms of COPD Instrument-NiSCI, Early Morning Symptoms of COPD Instrument-EmSCI and the derivative questionnaire for stable patients from Evaluating Respiratory Symptoms in COPD (E-RS™:COPD) for daytime symptoms. COPD Assessment Test (CAT) was also used. RESULTS: The percentages of patients reporting at least one respiratory symptom in each period of the day in each country were as follows. Night-time (NT) symptoms: BG 84.8%, PL 61.8%, RO 71.4%, SK 77.5%, SB 66.8%; early morning (EM) symptoms: BG 93.8%, PL 89.6%, RO 87.7%, SK 92.0%, SB 80.4%; day-time (DT) symptoms: BG 99.5%, PL 94.7%, RO 92.6%, SK 95.5%, SB 90.8%. Across countries, mean severity scores between 0.6 and 1 for NT and between 0.8 and 1.1 for EM indicated mild symptoms. Mean severity scores for DT symptoms were: BG 14.7, PL 13.2, RO 12.5, SK 11.4 and SB 9.8 – out of a maximum of 40, with higher scores representing more severe symptoms. The impact of symptoms was most apparent for night awakenings (BG 39.5%, PL 28.7%, RO 36.0%, SK 34.0%, SB 27.2%) and tiredness during the day (BG 81.0%, PL 70.7%, RO 79.0%, SK 60.0%, SB 66.2%). Mean CAT scores ranged from 15 in SK and SB to almost 17 in PL, 19 in RO, and 19.2 in BG. The distribution of low burden (A/C) vs. high burden (B/D) symptom categories by GOLD 2017 report differed at country level: 27.2% vs. 72.8% in BG, 35.9% vs. 64.1% in PL, 27.6% vs. 72.4% in RO, 32.5% vs. 67.5% in SK and 48.4% vs. 51.6% in SB. The majority of patients received COPD maintenance treatment: 98.8% in PL and SB, 99% in RO and SK and 100% in BG. CONCLUSIONS: Despite regular treatment, symptoms place a high burden in stable COPD patients from CEE countries. Symptoms are variable and impact daily life of patients. CLINICAL IMPLICATIONS: Comprehensive assessment of respiratory symptoms can prove beneficial towards a more personalized treatment of patients with COPD. DISCLOSURES: Employee relationship with AstraZeneca Please note: $1001 - $5000 Added 03/10/2019 by Silviu Alecu, source=Web Response, value=Salary No relevant relationships by Adam Antczak, source=Web Response Employee relationship with AstraZeneca Please note: $1001 - $5000 Added 03/14/2019 by Yunqin Chen, source=Web Response, value=Salary No relevant relationships by Florin Mihaltan, source=Web Response No relevant relationships by Vesna Radulović, source=Web Response

Association between wheezing and sleep disturbance in Lebanese asthmatic school-aged children

Background: Asthma is the most common chronic illness in childhood, affecting approximately 7.53% of children in the Middle East. Symptoms that asthmatic children experience include coughing, chest tightness, dyspnea, and recurrent wheezing, with nightly and early morning symptoms being more prevalent. On the other hand, many studies have shown that children with insufficient, fragmented, or poor-quality sleep are prone to impulsivity, hyperactivity, and aggression, as well as problems with mood, academic performance, and neurocognitive functioning. Objective: To determine whether an association exists between wheezing as a symptom of asthma on one hand and disturbed sleep on the other hand in Lebanese children aged 5 to 15 years. Methods: This is a cross-sectional study done on school-aged children recruited in different schools across Lebanon. Two surveys were filled by their parents or guardians: the first one is the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to investigate wheezing and asthma, and the second is the Pediatric Sleep Questionnaire (PSQ) to evaluate sleep quality. Results: 235 children were enrolled from five different schools in two regions in Lebanon. Of those diagnosed with asthma according to their parents/guardian (n=32), 16 had 1 to 3 nocturnal wheezing attacks during the last 12 months, 7 had 4 to 12 nocturnal wheezing attacks and the remaining 9 experienced no wheezing attacks during the last year. Delayed sleep onset latency, night waking’s and restless sleep were found to be associated with nocturnal wheezing attacks. Conclusion: An increased number of nocturnal wheezing attacks in asthmatic children are related to sleep disturbance and poor sleep quality. Future trials on how asthma treatment could improve sleep behavior in children are needed in Lebanon.

An Indian perspective on dust mites

Dust mites are the most important group of indoor allergens. The dust mites have been classified as house dust mites and storage mites, however, with recent knowledge the different dust mite species are now labelled as “domestic mites.” The dust mites have been isolated at numerous Indian locations and their sensitization in Indian population has also been documented. In view of high sensitization in India, it is important to recognize the role of dust mites and their allergens in the precipitation of allergic diseases including allergic rhinitis and asthma. Allergies to dust mites can be confirmed by a classical clinical history of perennial, early morning and indoor symptoms substantiated by a positive skin prick test to these allergens. Further management of allergies to mites is possible using appropriate allergen avoidance measures and allergen immunotherapy. Multifaceted avoidance measures can be used, but, allergen avoidance by the means of an allergen impermeable bed encasings has the best evidence and is recommended in different guidelines. Allergen immunotherapy, the disease-modifying modality, has been proven to efficacious for house dust mite allergies.

New ADHD agent provides nighttime dosing for early-morning symptom control

New ADHD agent provides nighttime dosing for early-morning symptom control

Assessment of Different Cetirizine Dosing Strategies on Seasonal Allergic Rhinitis Symptoms: Findings of Two Randomized Trials.

BackgroundCetirizine has been shown to be effective for relief of seasonal allergic rhinitis (SAR) symptoms. Allergic rhinitis symptoms have been reported to have circadian variations, with symptoms tending to be most bothersome overnight and in the morning.ObjectiveTo evaluate the effects of different cetirizine dosing schedules in comparison to twice daily (BID) chlorpheniramine and placebo on SAR symptoms at 12 and 24 hours postdose.MethodsStudy 1 subjects received cetirizine 10-mg once daily in the morning (QAM), cetirizine 10-mg once daily at bedtime (QHS), cetirizine 5-mg twice daily, or placebo. Study 2 subjects received cetirizine 5-mg QAM, cetirizine 10-mg QHS, chlorpheniramine 8-mg BID, or placebo. The primary end point was total symptom severity complex (TSSC); TSSC was the sum of symptom severity ratings averaged over the 2-week study period. Post hoc analyses of reflective symptom severity assessed in the morning (TSSCAM) and in the evening (TSSCPM) were conducted to evaluate cetirizine’s effects at 12 and 24 hours postdose.ResultsIn study 1, subject- and investigator-assessed TSSC was significantly lower in all cetirizine groups versus placebo (P ≤ .003). In study 2, subject-assessed TSSC was significantly lower in all cetirizine groups versus placebo (P ≤ .04) and was numerically lower for investigator-assessed TSSC. Post hoc analyses demonstrated that cetirizine significantly improved TSSCAM at 12 and 24 hours postdose versus placebo in both studies regardless of dosing schedule. TSSCPM significantly improved at 12 and 24 hours postdose in all study 1 cetirizine groups versus placebo. In study 2, versus placebo, TSSCPM significantly improved at 12 hours postdose in cetirizine 5-mg QAM group and numerically improved at 24 hours postdose in cetirizine 10-mg QHS group.ConclusionRegardless of dosing regimen, cetirizine demonstrates effective 24-hour relief of SAR symptoms, particularly on TSSCAM, which assesses overnight and early morning symptom control.

The variability of respiratory symptoms and associated factors in COPD

Few studies have investigated the variability of COPD-related symptoms or factors related to symptom variability.This observational, prospective, multicentre study was conducted to describe the number and intensity of morning and night-time respiratory symptoms and their variability over one week using the Night-time and Early Morning Symptoms of COPD Instruments (NiSCI and EMSCI) to evaluate stable COPD patients. Logistic regression analyses were performed to investigate factors associated with symptom variability.A total of 2669 patients were evaluated (mean age, 67.7 years; 80.9% men; mean FEV1 50.6%). Of these, 48% reported night-time symptoms and 71% reported morning symptoms. Of the 2293 patients who completed the NiSCI and EMSCI, 90% showed variability in either symptom number (89.6%) or symptom intensity (15.8%). More severe dyspnoea, more exacerbations during the previous year and the exacerbator or mixed COPD-asthma phenotypes were associated with variability in symptom number or intensity. Anxiety was significantly associated with variability in symptom number and intensity.Most COPD patients showed symptom variability over a weeklong period, especially in terms of symptom number. Several COPD-related factors, mainly factors related to more severe disease and more frequent exacerbations, were associated with increased symptom variability.

EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis

BackgroundDuring the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce...

The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis.

BackgroundPatients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life. This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.MethodsData were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7. Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.ResultsData for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male). In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05). Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients. Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05). Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001). In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05). The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.ConclusionAclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used. Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms.

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use: Results from an Observational Study (ASSESS)

ABSTRACTThis observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p < 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p < 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p < 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.