The Importance of Self-Management in the Context of Personalized Care in COPD.

Despite current guidelines and decades of evidence on the benefits of a self-management approach, self-management of COPD remains relatively under-utilized in clinical care compared with other chronic diseases. However, self-management interventions can play a valuable role in supporting people with COPD to respond to changing symptoms, and thereby make appropriate decisions regarding the management of their own chronic condition. In this review, we discuss the history and evolution of the concept of self-management, assess current multidisciplinary support programs and clinical interactions designed to optimize self-management, and reflect on how effective these are in terms of clinical and humanistic outcomes. We also evaluate the mechanisms for encouraging change from protocol-based care towards a more personalized care approach, and discuss the role of digital self-management interventions and the importance of addressing health inequalities in COPD treatment, which have been accelerated by the COVID-19 pandemic. Reflecting on the importance of self-management in the context of symptom monitoring and provision of educational support, including information from patient organizations and charities, we discuss the ideal components of a self-management plan for COPD and provide six key recommendations for its implementation: 1) better education for healthcare professionals on disease management and consultation skills; 2) new targets and priorities for patient-focused outcomes; 3) skills gap audits to identify barriers to self-management; 4) best practice sharing within primary care networks and ongoing professional development; 5) enhanced initial consultations to establish optimal self-management from the outset; and 6) negotiation and sharing of self-management plans at the point of diagnosis.

Efficacy of Triprolidine in the Treatment of Temporary Sleep Disturbance.

Triprolidine, a first-generation antihistamine for allergic rhinitis, has a shorter half-life and fewer persistent effects relative to other antihistamines and may be useful in the treatment of temporary sleep disturbance. Patients aged ≥18 years old were randomized 1:1:1 to receive either triprolidine 2.5 mg (n = 65), triprolidine 5 mg (n = 66), or placebo (n = 67) on 3 consecutive nights. Sleep disturbance index was monitored via wrist actimeter. Subjective measures were assessed via diary card. Triprolidine 2.5 mg had a significantly lower sleep disturbance index versus placebo on night 1 (P = .02); however, when adjusted for outliers, sleep disturbance index did not significantly differ between either dose of triprolidine versus placebo on night 1. Adjusted sleep disturbance index was significantly lower with triprolidine 2.5 and 5 mg versus placebo on night 3 (P = .0017 and P = .011, respectively) and for the mean of all 3 nights (P = .01 and P = .015, respectively). Sleep latency was significantly improved for triprolidine 2.5 mg versus placebo on nights 2 and 3 and for the mean of all 3 nights and for triprolidine 5 mg versus placebo for the mean of all 3 nights. Subjective measures showed those on both doses of triprolidine felt more refreshed on awakening versus placebo for the mean of all 3 nights, with no increase in daytime sleepiness. The frequency of adverse events was similar across groups. The optimum dose of triprolidine for treatment of temporary sleep disturbance was 2.5 mg. There were improvements in both objective and subjective measures of sleep quality versus placebo, with no safety concerns raised.

Bioavailability of Triprolidine as a Single Agent or in Combination With Pseudoephedrine: A Randomized, Open-Label Crossover Study in Healthy Volunteers.

Antihistamines have been in clinical use for more than 70 years to treat allergic and nonallergic symptoms including relief from cold and flu symptoms. Despite their widespread use, pharmacokinetic (PK) data are sparse for older, first-generation antihistamines. This phase 1 single-center open-label, randomized, single-dose, 3-way crossover trial evaluated the PK profiles of 2 doses of film-coated triprolidine caplets (2.5 and 5 mg) compared with a reference combination tablet (triprolidine 2.5 mg + pseudoephedrine 60 mg) in 24 healthy adults. Blood samples were collected predose and at specified intervals across a 24-hour period after administration, and triprolidine was quantified using liquid chromatography-tandem mass spectrometry. Maximum plasma concentration of triprolidine for the 2.5 mg and dose-normalized 5 mg single-agent tablets were comparable (8.4 versus 7.1 ng/mL, respectively) and higher for the combination tablet (9.5 ng/mL). PK parameters, including time to maximum plasma concentration (∼1.5 hours) and elimination half-life (∼4 hours), were comparable between the 3 treatment arms. The safety profile of this sedating antihistamine was as expected; however, adverse effects were reported in a markedly higher proportion of women than men. There were no significant sex differences in any of the measured PK parameters.

Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and achieved PsARC response more rapidly than late PsA. In this cohort, comedication with csDMARDs was beneficial over 2 years.

A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks.

A randomised, parallel group clinical study was performed to evaluate the safety profile of an e-vapour product (EVP; 2.0% nicotine) in smokers of conventional cigarettes (CCs) switching to use the EVP for 12 weeks. During the study, no clinically significant product-related findings were observed in terms of vital signs, electrocardiogram, lung function tests and standard clinical laboratory parameters. Adverse events (AEs) reported by EVP subjects were more frequent during the first week after switching to the EVP. The frequency of AEs reduced thereafter and out of a total of 1515 reported AEs, 495 were judged as being related to nicotine withdrawal symptoms. The most frequently stated AEs were headache, sore throat, desire to smoke and cough reported by 47.4, 27.8, 27.5 and 17.0% of subjects, respectively. Only 6% of AEs were judged as probably or definitely related to the EVP. Additional observations in EVP subjects included a decrease in the level of urine nicotine equivalents by up to 33.8%, and decreases in the level of three biomarkers of exposure to toxicants known to be present in CC smoke (benzene, acrolein and 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone). The decrease in nicotine equivalents coincided with an increase in nicotine withdrawal symptoms, measured by a questionnaire, which subsided after two weeks. The data presented here shows the potential EVPs may offer smokers looking for an alternative to CCs.

Hippo pathway elements Co-localize with Occludin: A possible sensor system in pancreatic epithelial cells.

External adherens junction-based cell-cell contacts involving E-cadherin interactions function to sense planar cell status and modulate epithelial cell proliferation through Hippo (Hpo) and non-canonical Wnt pathways signaling. We hypothesized these regulatory processes should also be sensitive to a similar cell-cell contact sensor associated with apical-basal polarity events at epithelial surfaces. We used 2 human pancreatic cancer cell lines to explore this hypothesis: one with the capacity to form functional tight junction structures and polarize (HPAFII) and one lacking this capacity (AsPc1). Occludin (Ocln), a tetraspanning protein associated with TJ structures and capable of establishing external cell-cell contacts, was observed to partially co-localize with Hpo elements YAP (c-yes associated protein) and TEAD (TEA-dependent), which function to drive a proliferative transcription program. Treatment with dobutamine, known to affect YAP, was shown to suppress proliferation in an Ocln-dependent manner. Blockade of protein kinase C-zeta (PKC-ζ) diminished transepithelial electrical resistance (TER) of HPAFII monolayers that was not corrected by dobutamine treatment while the loss of TER resulting from inhibition of ROCK1 could be partially recovered. Examination of normal and cancerous human pancreatic biopsies showed that the cellular localization of Ocln, c-Yes, YAP, and TEAD were similar to HPAFII for normal cells and AsPc1 for cancerous cells. Together, these results suggest a link between Hpo and signals emanating from cell-cell contacts involving Ocln that may regulate pancreatic cell proliferation through the coordination of planar cell polarity with apical-basal polarity events.

[Portuguese recommendations for pain management by pharmocotherapy in inflammatory arthritis]. / Recomendações portuguesas para o tratamento e controlo farmacológico da dor nas artropatias inflamatórias.

OBJECTIVES: To develop Portuguese evidence-based recommendations for pain management by pharmocotherapy in inflammatory arthritis. METHODS: The Portuguese project was integrated in the multinational 3E Initiative (Evidence, Expertise, Exchange) 2010 where a total of 453 rheumatologists from 17 countries have participated. The clinical questions concerning pain were formulated and the Portuguese group added 2 more questions. A systematic literature search was performed in Medline, Embase, Cochrane Library and 2008-2009 EULAR and ACR abstracts. The selected articles were systematically reviewed and the evidence was defined according to the Oxford Levels of Evidence. In each country a group of experts joined to discuss their national recommendations. In Portugal, the national meeting was held in October 2010, where 33 rheumatologists discussed and voted by Delphi method the national recommendations. Finally, the agreement among the rheumatologists and the potential impact on their clinical practice was assessed. RESULTS: Thirteen national recommendations were formulated: pain measure scores; analgesic combination therapy; pharmacotherapy in preconception, pregnancy and lactation periods; pharmacotherapy according to comorbilities; safety of NSAIDs and/or paracetamol with methotrexate combination therapy; efficacy and safety of continuous/on-demand NSAIDs; opioids, paracetamol, corticosteroids, antidepressants, neuromodulators and muscle relaxants role and effectiveness; risk factors for the development of chronic pain and the role of topic analgesics. CONCLUSION: The portuguese recommendations for the pain management by pharmacotherapy in inflammatory arthritis were formulated according to the best evidence and supported by a panel of 63 rheumatologists. The differences between the national and international recommendations are reported in this article.

2011 Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis.

OBJECTIVE: To develop recommendations for the treatment of psoriatic arthritis (PsA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. At a national meeting the recommendations were discussed and all attending rheumatologists voted on the level of agreement for each recommendation. A second draft was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with PsA. Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis--December 2011 update.

OBJECTIVE: To develop recommendations for the treatment of axial spondyloarthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations and supporting evidence was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. Secondly, at a national meeting the recommendations were presented, discussed and revised. Finally, the document resulting from this meeting was again circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with axial spondyloarthritis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with axial spondyloarthritis should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - October 2011 update.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of nonresponders. Biological treatment (with a tumour necrosis factor antagonist, abatacept or tocilizumab) should be considered in RA patients with a disease activity score 28 (DAS 28) equal to or greater than 3.2 despite treatment with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 3 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, defined by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of at least 0.6 in the DAS28 score. After 6 months of treatment res­ponse criteria is defined as a decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

[Practical guide for the use of biological agents in rheumatoid arthritis - December 2011 update]. / Guia prático de utilização de terapêuticas biotecnológicas na artrite reumatóide - actualização de Dezembro 2011.

The authors review the practical aspects of biological therapy use for rheumatoid arthritis patients, commenting safety issues before and after treatment initiation and the best treatment strategies to optimize efficacy.

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 2010 update.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

Increased efficacy of infliximab associated with methotrexate in ankylosing spondylitis.

OBJECTIVES: The aims of this study were to assess the efficacy of infliximab (IFX) combined with methotrexate (MTX) versus IFX alone in the treatment of ankylosing spondylitis (AS). METHODS: The study was a 30weeks open label and prospective study of parallel groups in 19 patients with active AS. These patients had shown incomplete therapeutic response to standard therapy (full dose of non-steroidal anti-inflammatory drugs: NSAIDs) and disease modifying antirheumatic drugs: DMARDs (MTX or sulfasalazine: SLZ) for a period of at least 12 weeks and were treated with IFX (5mg/kg). Patients were divided into two treatment groups according to the previous treatment: in Group A, 9 patients previously treated with 7.5mg/week of MTX were treated with IFX in addition to MTX (IFX+MTX); in Group B, 10 patients previously treated only with NSAIDs were treated with IFX (5mg/kg) as monotherapy (IFX). The primary outcome was improvement in disease activity shown by the BASDAI50 at week 30; the secondary outcome included comparison of the proportions of subjects in each group achieving response criteria proposed by the ASAS group. BASDAI, BASFI, ESR, CRP, pain, inflammation and Patient Global Assessment were also recorded. RESULTS: Both groups were similar in sex ratio, clinical forms and B27. Differences between groups occurred only in the disease duration and age of the patient. At 14 and 30 weeks only 50% and 10% respectively of the patients from the IFX group achieved BASDAI50 response compared to 89% of patients from the IFX+MTX group. The difference between groups at 30 weeks was statistically significant (p=0.001; percentage of difference: 79%; 95% confidence interval (CI): 26-93%:). ASAS50 was reached in 67% and 55.6% of patients from the IFX+MTX group at 14 and 30 weeks respectively, compared with 30% and 0% of patients from the IFX group The difference between groups at 30 weeks was statistically significant (p=0.011; percentage of difference: 57%; 95% CI: 8-84.7%). CONCLUSION: Infliximab in combination with MTX seems to increase the efficacy of the therapeutic response in active AS patients, but more wide-ranging studies are necessary, mainly long-term studies.

[Anti-TNF alfa therapy in ankylosing spondylitis]. / Terapêutica anti-TNF alfa na espondilite anquilosante.

Ankylosing spondylitis (AS) is an inflammatory chronic disease that affects young males and in more than 90% of cases is associated with HLA B27 antigen. Therapeutic options for those patients with spondyloarthropathies have been limited during the last decades. Infliximab and etanercept are both approved for the treatment of patients with active disease that does not respond to conventional therapies. Anti-TNF therapy is very effective in AS, and eventually can be more effective than in rheumatoid arthritis. In 2003 Assessments in Ankylosing Spondylitis Group (ASAS) published international recommendations about the use of these agents in AS, which can be used as guidance in taking decisions and elaborating guidelines. To define their utilization it is necessary more studies about efficacy, toxicity and about ways of use.

[Osteopoikilosis: 2 clinical cases]. / Osteopoiquilose: dois casos clinícos.

Osteopoikilosis is a rare, benign and autosomal dominant bone disease. It is usually asymptomatic and diagnosed as a radiological finding. Plain X- Ray films show multiple sclerotic lesions on periarticular areas, epiphyses and metaphyses of long tubular bones. The authors describe two cases of osteopoikilosis in subjects belonging to the same family (brothers).

[Back pain and dorsal kyphosis in childhood]. / Raquialgias e cifose dorsal na infância.

Juvenile idiopathic osteoporosis (JIO) is a rare condition of unknown aetiology, with pre-pubertal onset and frequently spontaneous remission after puberty. We report a case of a 14 years old boy, which two years before began dorso-lumbar pain with dorsal kyphosis. At the age of 12, he was on percentil 25 for height and had no other symptoms or alterations on physical exam. He had multiple vertebral fractures, a low serum vitamin D, and a Z-score in lumbar spine of -5,3. Diagnosis of JIO was made after excluding other causes of juvenile osteoporosis. He was submitted to pamidronate therapy and after six months showed clinical and bone mineral density improvement. At the age of 14 he is asymptomatic. The authors present this clinical case because of is rarity and to point out that although many cases have spontaneous remission, without any therapy, some may persist and become more serious, with pain and multiple fractures, justifying therapeutic intervention.