Search Results (411)

Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the clinical and endoscopic efficacy, patient-reported outcomes (PROs), and safety of upadacitinib in biologic-experienced patients with CD in a real-world setting. Methods: This prospective bi-centric real-world study enrolled 28 anti-TNF-experienced patients with CD receiving upadacitinib 45 mg daily for 12 weeks (induction), followed by 30 mg daily maintenance through week 52. Primary endpoints included endoscopic response (≥50% SES-CD reduction or ≥2-point decrease from baseline for baseline SES-CD ≤ 4) and clinical remission (Harvey–Bradshaw Index [HBI] ≤ 4). Secondary endpoints included endoscopic remission, clinical response (HBI decrease ≥ 3 points), and quality of life (IBD-Disk). Statistical analysis used the Wilcoxon signed-rank test with 95% confidence intervals (CIs). Results: Median patient age was 37 years; 75% had ≥3 prior biologic failures. Clinical remission rates (HBI) were 59% (95% CI: 41–75%) at week 12, 44% (95% CI: 27–63%) at week 26, and 53% (95% CI: 29–76%) at week 52. Endoscopic response rates were 48% (95% CI: 44–52%) at week 26 and 46% (95% CI: 21–72%) at week 52. Endoscopic remission was achieved in 43% (95% CI: 40–48%) at week 26 and 27% (95% CI: 10–57%) at week 52. Clinical response (HBI) improved progressively from 65% at week 2 to 71% at week 52. Quality of life, as assessed by the IBD-Disk, showed significant improvement: Reduced Disease Burden (defined as a decrease of 70% or a CED-Disk Score of ≤15) was observed in 33% of patients at week 12 and 35% at week 52. Median SES-CD decreased from 9 points (IQR: 6–17) at baseline to 5 points (IQR: 1–12, p = 0.005) at week 52. Adverse events occurred in 11% of patients (4% lymphopenia, 7% skin disease), with no serious adverse events or deaths. Conclusions: Upadacitinib demonstrates significant clinical and endoscopic efficacy in biologic-experienced, anti-TNF-pretreated patients with CD, achieving remission rates comparable to or exceeding those of the pivotal trials despite a highly refractory population (75% with ≥3 prior biologic failures). The favorable safety profile supports upadacitinib as an important therapeutic option in sequential treatment of refractory CD. Full article

Postsocialist peri-urban spaces are characterized by a chaotic development as a result of the transition from communism to capitalism. Recent research has highlighted that liveability in peri-urban spaces encounters challenges of adaptation to the peri-urban areas. The aim of the present study is to identify and analyze patterns and contrasts that occur between age groups and gender in relation to the level of liveability as well as to better understand the daily mobility practices and commuting dependencies and how mobility shapes key contrasts and emerging tensions within Timișoara’s postsocialist peri-urban spaces. As liveability relates to local development, commuting, and accessibility to service facilities in the residential environment, the identification of patterns and differences is imperative when considering the perception of local residents on potential (un)sustainable liveability in peri-urban areas. This study utilizes a quantitative analysis, informed by a survey of considerable size (N = 954) conducted in peri-urban settlements of Timisoara, Romania, with a view to elucidating the distinctions and commonalities in the perceptions held by the local populace. The findings indicate that the elderly population exhibits a greater reluctance to adapt to the emerging peri-urban environment. In contrast, the younger and more educated demographic demonstrates a higher degree of adaptability to the contemporary challenges posed by peri-urban expansion and hazardous development. Daily mobility, including commuting, is directly influenced by the effects of dispersed and chaotic development (e.g., more than 79% of respondents rely on private cars for commuting), as well as the lack of facilities and services (e.g., 2.21 level of satisfaction regarding cultural events). This highlights Timisoara’s dependence on external services, as well as the significant role of personal vehicles in providing access to the city center and its neighborhoods. Therefore, we can observe the peri-urban area undergoing a transitional phase as it navigates the initial stages of sustainable urban development and pursues an enhanced quality of life. Finally, we propose several policy recommendations for local authorities, offering solutions for enhancing liveability in peri-urban areas. Full article

Roses held profound cultural and economic significance in ancient Greece and Rome, yet comprehensive documentation of their species diversity, cultivation practices, and horticultural innovations remains fragmented across archaeological, iconographic, and textual sources. This multidisciplinary study synthesizes evidence from classical texts, archaeological remains including recently identified rose stem fragments from Oplontis, and iconographic materials—including frescoes, coins, and mosaics—to reconstruct the horticultural systems and cultural landscape of roses in classical antiquity. Analysis of literary sources, particularly Theophrastus’s fourth-century BCE taxonomic descriptions, reveals systematic cultivation of diverse rose varieties with flowers ranging from white to deep crimson, including yellow variants, characterized by morphologies from simple to double forms and valued for fragrance intensity and re-blooming capacity. Archaeological evidence from sites such as Paestum, Pompeii, and Oplontis, including pollen samples, preserved wood fragments with diagnostic prickle patterns, and fresco representations, documents commercial rose production and specialized cultivation techniques that demonstrate significantly greater morphological diversity than textual sources alone indicate. Field research and collection documentation establish the origins of Mediterranean rose cultivation, while iconographic analysis identifies roses in religious ceremonies, festivals, and daily life contexts. Textual sources provide detailed propagation methods, seasonal management practices, and evidence of Mediterranean hybridization events, alongside extensive documentation of medicinal and cosmetic applications. Economic analysis reveals specialized trade networks, commercial production centers, and diverse applications in perfumery, garland making, and pharmaceutical industries. This research establishes that Greek and Roman civilizations developed sophisticated rose cultivation systems integrating botanical selection, horticultural innovation, and cultural symbolism that directly influenced medieval and Renaissance practices and informed modern trait categorization systems. These findings demonstrate the foundational role of classical antiquity in European rose heritage, revealing how ancient horticultural knowledge, species diversification through hybridization, and cultivation techniques created an unbroken transmission that shaped contemporary rose industries and established conservation priorities for this horticultural heritage. Full article

The increase in population and demand for the various needs of citizens increases the interaction with the geo-environment. Thus, the rate of natural events affecting daily human life increases. Such an event occurred on a rock cliff in a densely populated area in İstanbul (Türkiye). More than four rock blocks (approximately 3–5 m³) belonging to the Paleozoic sequence of İstanbul, composed of nodular limestone with sandy-clay interlayers, detached and fell. The blocks traveled along a path of approximately 60 m and stopped by crushing a couple of buildings downslope. The path was rough and contained various surface conditions (e.g., bedrock, talus, and plants). This study was initiated by the examination of the dimensions of failed rock blocks, their paths, and topographic conditions. Unmanned vehicles (drones) facilitated the generation of 3D numerical models of topographic changes on the site. Quantifying discontinuity properties (such as persistence, spacing, roughness, etc.) and defining weathering properties comprises the second stage, along with sampling. Based on digital topographic data and field observations, cross-sections were defined by means of possible rockfall areas within the area of potentially unstable blocks. Numerical analysis and rockfall analysis were conducted along these critical sections. Interpretation of laboratory data and results obtained from numerical studies leads to an understanding of the mechanism of the recent rockfall event and demonstrates the most critical areas to be considered and reinforced. The research comprises proposing appropriate reinforcement techniques due to the strong Turkish regulations along the “Bosphorus Waterfront Protected Zone”. The study advises pre-cleaning of potentially unstable blocks after a fence production on paths where rocks could fall, and rock anchors in some localities with varying lengths. The latest part of the research covers the re-assessment of mitigation processes with numerical models, which shows that the factor of safety increased to the desired levels. The reinforcement applications at the site match well with the proposed prevention methods. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Revodiol Calming Cream^® (RCC) is a novel dermocosmetic product containing cannabidiol (CBD) and Annona cherimola fruit extract, designed for the management of atopic-prone and sensitive skin. Objective: Clinically assess the efficacy and safety of RCC in the management of atopic-prone and/or sensitive skin. Materials and methods: A prospective study included 20 adults and 22 children with mild-to-moderate atopic-prone skin. RCC was applied daily, for 56 days. Clinical evaluation included the SCORAD index, pruritus and dryness scales; and a Visual Analog Scale (VAS). Biometric assessments (Mexameter^®, Tewameter^®, Visioscan^®, Corneofix^®) were performed. Subjective satisfaction and quality of life (DLQI) were also recorded. Results: RCC was well tolerated, with no significant adverse events. After 56 days, SCORAD scores decreased by 55% in adults and 60% in children. Pruritus and dryness were significantly reduced, and VAS scores indicated a 65% decrease in discomfort. Biometric assessments demonstrated improvements in erythema, skin barrier function, topography, and desquamation. Subjective satisfaction reached 75% in both populations, and DLQI improved by 23%. Conclusions: The synergistic combination of CBD, Annona cherimola extract, and natural humectants offers a safe and effective daily dermocosmetic care for both adults and children. Full article

Background: Thalassotherapy, which combines seawater, marine mud, and maritime climate, has been traditionally used to support musculoskeletal recovery. Its thermal, biochemical, and mechanical properties may enhance tissue healing and modulate inflammation. This study aimed to evaluate the short-term clinical effects of a standardized two-week thalassotherapy program compared with conventional rehabilitation in post-traumatic patients. Methods: A matched controlled cohort study was conducted at the Corpore Sano Sanatorium, Techirghiol, Romania. Post-traumatic patients followed identical physiotherapy and hydrokinetic exercise routines; additionally, the thalassotherapy group received daily seawater baths, sapropelic mud applications, and exposure to marine aerosols. Pain levels, joint mobility, inflammatory status, and quality of life were assessed before and after the intervention. Adverse events and treatment tolerance were monitored throughout the study. Results: Patients undergoing thalassotherapy experienced more pronounced improvements in musculoskeletal function, pain relief, inflammatory balance, and quality-of-life outcomes compared with those receiving standard rehabilitation alone. Both interventions contributed to clinical progress, but the magnitude of change was consistently greater among patients treated with marine-based therapies. No adverse events or intolerance reactions were recorded, and all participants completed the program. Conclusions: Thalassotherapy may provide complementary short-term benefits in post-traumatic rehabilitation, enhancing functional recovery, symptom relief, and perceived well-being. However, due to the non-randomized design and short follow-up period, these findings should be interpreted cautiously. Further randomized studies with long-term outcomes are required to confirm the therapeutic role of thalassotherapy in modern rehabilitation practice. Full article

Background/Objectives: Introducing a demanding home-based program (HBP) of Vojta therapy (VT) into their daily activities is a life-altering event for parents of children with global developmental delay (GDD). This study aims to document the experiences of parents of children with GDD administering a HBP of VT. Methods: A multicentre study with a qualitative case design based on an interpretative approach is presented. Interviews were conducted with 10 parents using photo-elicitation (PE). Inductive and thematic analyses were used. Results: Four common experiential themes were identified. Firstly, crying was identified as the most significant barrier to administering therapy (despite parents accepting that crying was not pain-related). Secondly, parents described the intense and variable emotional impact of being responsible for the therapy and its effects on their child. Thirdly, parents unanimously felt that their involvement was worthwhile, with the developmental results they perceived outweighing the emotional, physical and time demands of administering the VT. Finally, parents developed a narrative of hope stemming from the therapy and its observed effects. Conclusions: The physical, emotional and time demands on parents when administering a HBP of VT are very significant. The main barriers to adherence to the program are identified as the child’s crying during therapy and time management. Intense emotional experiences, both positive and negative, arise while administering a HBP of VT. Parents are not only able to overcome all emotional and logistical challenges when they recognize improvements in their child, but they also begin to hope for further improvement. Implications for the professional design of HBPs of VT include the following: advanced warning that crying is normal, part of the therapy and not pain-related; training and ongoing support from a qualified therapist; training in recognising developmental improvement; and psychological support to deal with the emotional journey. Full article

The loss of a limb is an event that significantly affects an individual’s quality of life, with implications not only for autonomy in daily activities but also for their ability to interact with others. At the same time, current prostheses often fail to meet the user’s needs, resulting in high drop-out rates. In this review, we investigated the primary causes of prosthesis abandonment and analyzed them by highlighting the technological and psychological aspects associated with current devices. Technological issues due to reliability, functionality and comfort, together with psychological issues related to anxiety and depression, are among the main factors contributing to prosthesis rejection. Social aspects, sport, and community activities play crucial roles in improving the sense of belonging and acceptance of prosthesis users. Although research has often prioritized functionality, prosthesis development should follow patient-centered models that address the individual needs and requirements of patients, emphasizing psychological, rehabilitative, and technological support. Full article

Classical thermodynamics (CT) has become integrated into everyday life, especially through its applications in engineering. In contrast, out-of-equilibrium thermodynamics (OET) is often viewed as a fundamental science that seems distant from daily experiences. While “energy” is a familiar term in households, “entropy,” which refers to degraded energy, remains enigmatic. This gap in understanding has significant implications for developing effective sustainability practices. CT typically emphasizes the efficiency of individual systems that produce work, often overlooking the entropy production that occurs within larger, interconnected systems. This paper aims to establish a philosophical framework that transforms OET into what is referred to as “lived thermodynamics.” This framework is grounded in pragmatism, particularly drawing from the early synthesis of thermodynamics and evolutionary theory proposed by Charles S. Peirce. A central aspect of this approach involves shifting the focus from traditional “systems” to out-of-equilibrium assemblages. In these assemblages, the physical trends of entropy production are often interrupted and redirected by evolutionary innovations and random events. The evolving envelope of open systems within these assemblages manifests an increasing rate of entropy production. This synthesis of thermodynamics and evolutionary theory builds on Lotka’s pioneering contributions and contemporary theories, particularly Vermeij’s work on the evolution of power. The framework introduces a sustainability criterion based on entropy. By applying this criterion, OET can evolve into “lived thermodynamics,” fostering a holistic understanding of energy use in devices and technological systems while considering the broader implications of entropy production in the out-of-equilibrium assemblages in which we live. Full article

Background: Childhood growth hormone deficiency (GHD) and idiopathic short stature (ISS) are endocrine disorders characterized by impaired linear growth due to insufficient or ineffective growth hormone (GH) activity. While daily recombinant human GH (rhGH) therapy effectively restores growth, treatment adherence remains suboptimal owing to the burden of daily injections. Long-acting formulations such as pegylated recombinant human GH (PEG-rhGH) have been developed to improve convenience and compliance while maintaining therapeutic efficacy. This systematic review and meta-analysis aimed to evaluate the comparative effectiveness and safety of once-weekly PEG-rhGH versus daily rhGH and to assess dose–response outcomes between higher- and lower-dose PEG-rhGH regimens in pediatric GHD and ISS. Methods: This study followed PRISMA 2020 guidelines. Comprehensive searches were conducted in PubMed, Web of Science, and Scopus from inception to September 2025 using MeSH terms and free-text keywords for “PEGylated recombinant human growth hormone,” “long-acting growth hormone,” and “growth hormone deficiency.” Eligible studies included randomized controlled trials (RCTs) and cohort studies evaluating PEG-rhGH in children (≤18 years) with GHD or ISS, comparing either once-weekly PEG-rhGH with daily rhGH or different PEG-rhGH doses. Data extraction included study design, participant characteristics, intervention details, and key outcomes (height SDS, height velocity, IGF-1 SDS). Meta-analysis was conducted using Review Manager with a random-effects model, and heterogeneity was quantified using the I² statistic. Results: Eight studies, comprising 2549 children, met the inclusion criteria. Once-weekly PEG-rhGH demonstrated comparable short-term growth outcomes to daily rhGH at 6 and 12 months, with modest but significant superiority in height SDS (MD = 0.10, 95% CI 0.01–0.19) and height velocity (MD = 0.74 cm/year, 95% CI 0.42–1.05) by 24 months. IGF-1 SDS did not differ significantly at 6 or 12 months. In dose comparisons, 0.2 mg/kg/week PEG-rhGH produced substantially greater gains in height SDS and IGF-1 SDS than 0.1 mg/kg/week, with a time-dependent increase in the magnitude of the effect. Safety analyses revealed no increase in adverse or serious adverse events with PEG-rhGH compared to daily rhGH; reactions were generally mild and transient. Conclusions: Once-weekly PEG-rhGH is as effective as daily rhGH for promoting growth in pediatric GHD and ISS, with possible long-term advantages in growth outcomes and similar safety. The higher PEG-rhGH dose (0.2 mg/kg/week) appears to optimize efficacy without compromising tolerability. Weekly administration may enhance adherence and quality of life, supporting PEG-rhGH as a viable alternative to daily GH therapy. Full article

Background and Clinical Significance: Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by airflow limitation and a significant impact on functional capacity, emotional well-being, and quality of life. Pulmonary rehabilitation improves functional capacity and psychosocial outcomes in individuals with COPD, but evidence on its implementation in primary care is limited. This case report describes the functional and emotional outcomes of a structured pulmonary rehabilitation program delivered in a primary care setting for a patient with moderate COPD, indicating potential feasibility and clinical relevance, while recognizing that evidence from a single case cannot be generalized; Case Presentation: A 73-year-old man, an ex-smoker for 10 years, with a history of moderate COPD (GOLD 2/B), controlled hypertension, and recurrent respiratory infections, presented after discontinuation of regular exercise following a previous hospital-based rehabilitation program completed 26 months earlier. The patient reported dyspnea on exertion and functional decline. He completed a 16-week pulmonary rehabilitation program delivered in a primary care setting. The intervention included weekly supervised sessions (breathing exercises, aerobic and resistance training, and education) and twice-weekly home exercises. Outcomes were assessed pre- and post-intervention. Dyspnea improved (mMRC 2 → 1), 6-Minute Walk Test distance increased (303 → 380 m), lower-limb strength improved (10× Sit-to-Stand: 10 → 18 repetitions), perceived exertion decreased (Borg 7 → 4), daily activity limitations were reduced (LCADL 28 → 20), and anxiety decreased (HADS 10 → 6). No adverse events occurred, and adherence was 100%. Conclusions: This single case shows that a structured pulmonary rehabilitation program delivered in primary care was feasible and associated with meaningful improvements in functional performance and emotional well-being in a patient with moderate COPD. Full article

Background/Objectives: Systemic Lupus Erythematosus (SLE) is a multifactorial disease that significantly affects patients’ quality of life (QoL) and poses management challenges. This project combined a nationwide patient listening initiative with an Advisory Board (AB) to identify unmet needs and perceptions, aiming to integrate patient perspectives into decision-making and enhance SLE care. Methods: The “PaLESiamoci!” project, conducted by IQVIA with two patient organizations (Gruppo LES Italiano and APMARR), included both qualitative and quantitative phases. Ten patients completed disease diaries and one-hour interviews, while 151 others voluntarily filled a PO-administered survey including the validated 12-item Medical Outcome Short Form (SF-12) and items on physical, emotional, and daily life impact. Insights from these phases informed the AB discussion involving clinicians and patient representatives on six key topics. Results: Patients with SLE showed lower Physical (−13.4) and Mental (−14.0) Component Summary scores than the Italian population, indicating reduced social and work functioning. Despite EULAR recommendations to minimize corticosteroid use, 64% of patients remained on corticosteroids. The AB discussions revealed key unmet needs, including differing awareness of organ damage risks, corticosteroid-related adverse events, and adherence challenges, as well as the need for non-pharmacological and multidisciplinary support. Conclusions: The project highlighted major gaps and opportunities in SLE management. Patient organizations and rheumatologists emphasized developing tailored educational materials, strengthening rheumatologist–patient communication, and promoting multidisciplinary, patient-centered approaches to improve overall care. Full article

Patients with diabetes and chronic kidney disease (CKD-DM) often have residual albuminuria despite pharmacological treatment. Finerenone targets mineralocorticoid overactivation, but real-world evidence remains limited. This study evaluated the impact of finerenone in a cohort of patients with CKD-DM. This was a real-life study including patients with CKD-DM and an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m², treated with finerenone, aged ≥ 18 years, and followed at the Nephrology Department of Vall d’Hebron Hospital. Clinical and laboratory data were collected at baseline and at 1, 3, and 6 months of treatment. Changes in albuminuria and eGFR were analyzed in patients who completed 6 months of follow-up. A total of 60 patients were included in the analysis; 39 (65%) were male, with a median age of 79 ± 10.12 years. Finerenone was initiated at 10 mg daily in 57 patients (95%), with 38.3% escalating to 20 mg after 1 month. After 6 months, the urinary albumin-to-creatinine ratio (UACR) decreased by 37.1% (p = 0.012, n = 34). Patients with an initial eGFR drop > 20% showed a greater UACR decrease of around 43% at 3 (p = 0.012) and 6 months (p = 0.013). A significant 9.5% decline in eGFR was observed at 1 month, followed by stabilization at 3 and 6 months. Finerenone was discontinued in 10% of the patients due to adverse events. Hyperkalemia occurred in 18.3% of the patients, but no hospitalizations for adverse events or heart failure were reported. In summary, finerenone induced a significant 37.1% reduction in albuminuria after 6 months of treatment. This reduction was more pronounced in patients who experienced an initial eGFR dip ≥ 20%. Finerenone was generally well tolerated and appears to be a promising therapeutic strategy for reducing albuminuria in this population. Full article

Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-COVID Syndrome (PCS) are chronic conditions that share relevant pathophysiological mechanisms. Conventional rehabilitation programs have often been associated with patient dissatisfaction and frequent adverse events (AEs), highlighting the need for safer and more effective clinical approaches. This study aims to compare the effects of a telerehabilitation program based on conscious movement with those of conventional low-intensity exercise in individuals with ME/CFS or PCS. Methods: This is a prospective, single-blind, three-arm, parallel, superiority randomized clinical trial. A total of 147 participants (aged 18–70) with ME/CFS or PCS will be recruited and randomly assigned to one of three groups: (a) conscious movement; (b) low-intensity exercise; or c) usual care. All interventions will be delivered via telehealth over 12 weeks, with weekly 45-min sessions combining health education and individually tailored exercises. Participants will be encouraged to practice daily using the provided materials. Adherence rates and potential AEs will be recorded. The primary outcome is the total score on the 14-item Chalder Fatigue Scale at 12 weeks (post-intervention). Secondary outcomes include heart rate variability, functional performance, pain intensity and interference, mental health, interoceptive awareness, quality of life, sleep quality and fear of movement. Measurements will be collected at baseline, post-intervention, and at 3-month follow-up. Discussion: Recent evidence suggests that both autonomic and cognitive activity modulate immune function. Conscious movement, which integrates exercise with interoception and mindfulness-based strategies, may provide greater benefits than low-intensity exercise alone. Study limitations should be considered when interpreting the results. Trial registration: Registered at ClinicalTrials.gov on 15 May 2025 (NCT06978582). Protocol version 4 (29 September 2025). Ethics Committee code: 2025-0180. Full article

Background: Breast cancer-related lymphedema (BCRL) remains a challenging complication for breast cancer survivors. Currently, there are no effective pharmacological options available to address this condition. Emerging research highlights the critical role of inflammation, lymphatic dysfunction, and T-cell activity in the development of BCRL. Tacrolimus, a calcineurin inhibitor, has demonstrated promising results in preclinical studies for reducing inflammation, enhancing lymphatic function, and modulating T-cell activity—key mechanisms implicated in BCRL pathogenesis. This study investigates whether topical tacrolimus ointment can reduce the incidence and severity of BCRL, providing a novel approach to mitigate this debilitating condition. Methods: A parallel, open-label non-randomized controlled multicenter clinical pilot trial was conducted from February 2020 to June 2022. Female participants undergoing axillary lymph node dissection (ALND) were recruited and divided into an intervention group (n = 22) receiving topical tacrolimus 0.1% ointment daily for 12 months and a control group (n = 39). Outcomes included lymphedema diagnosis (primary), arm volume, bioimpedance spectroscopy, quality of life (QOL) scores, and adverse events. Assessments were performed at baseline and at 3, 6, 9, and 12 months. Results: At 12 months, lymphedema was diagnosed in 3 of 18 patients (16.7%) in the intervention group and 4 of 37 patients (10.8%) in the control group (p > 0.05). Mean increase in at-risk arm volume was 80.7 mL in the intervention group versus 116.1 mL in the control group (p > 0.05). Disease-specific quality of life scores worsened in both groups, but scores returned to baseline at 12 months in the intervention group only. Adverse events were mild and manageable, with no serious events reported. Conclusions: While topical tacrolimus did not significantly reduce the incidence of lymphedema, exploratory patterns in symptom onset and quality-of-life measures indicate that further investigation in larger randomized trials may be warranted. Full article