Valoración externa de las recomendaciones de la GEMA2009 por un panel multiprofesional de expertos en asma

Objectives

To assess the level of agreement on the GEMA 2009 clinical recommendations by a Spanish expert panel on asthma.

Materials and methods

The study was divided into four stages: 1) establishment of a 9 member scientific committee (GEMA authors) for selection of GEMA recommendations to use in the survey; 2) formation of a panel of 74 professionals with expertise in this field (pulmonologists, allergists, family doctors, ear, nose and throat and paediatric specialists); 3) Delphi survey in two rounds, sent by mail, with intermediate processing of opinions and a report to the panel members; and 4) analysis and discussion of results for the Scientific Committee.

Results

Seventy four participants completed the two rounds of survey. During the first round, a consensus was reached in 49 out of 56 questions analysed. Following discussion by the panel, the consensus was increased to a total of 53 items in the survey. With respect to the remaining questions, Insufficient consensus was obtained on the rest of the questions, due to differing views between sub-specialists, or lack of criteria by most of the experts.

Conclusions

The external analysis by asthma experts from different specialities showed a high level of professional agreement with the GEMA 2009 recommendations in Spain (96.5%). The disagreement shown in three recommendations reflect the lack of a high level evidence. These issues represent areas of interest for future research.     

Nationwide Experience With Off‐Label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Objective

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Methods

In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti–IL‐1 treatment for at least 6 months were reviewed.

Results

In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18–68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1–48), and the mean colchicine dose was 1.7 mg/day (range 0.5–4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti–IL‐1 treatment was used because of colchicine‐resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6–98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine‐resistant FMF patients were attack free. Serum levels of C‐reactive protein, erythrocyte sedimentation rate, and 24‐hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced.

Conclusion

Anti–IL‐1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine‐resistant FMF patients.

     

Therapeutic guidelines on ulcerative colitis: A GRADE methodology based effort of GETECCU

Background and aim

Evidence-based clinical guidelines on Ulcerative colitis (UC) have been developed through a consensus, while GRADE methodology is the current standard for guideline development. This is the first one based on GRADE methodology on UC.

Methods

Following GRADE methodology, the Spanish Group of Ulcerative Colitis and Crohn's disease (GETECCU) have developed a guideline on UC treatment. After selection of relevant clinical scenarios, 32 clinical questions were chosen and recommendations were established.

Results

In 2 questions no recommendation was possible. Twenty-two actions were recommended for, 14 strongly and 8 weakly. However, in 8 questions a recommendation against doing something was obtained, weak in 5 and strong in 3. The majority of recommendations were based on moderate quality evidence, and only 5 on high-quality evidence.

Conclusions

With GRADE methodology we find a clear recommendation on possible actions in most clinical decisions in UC treatment, but much more clinical high-quality research is needed.     

Treatment of acute gout: A systematic review

Objective

Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis.

Methods

A systematic search was performed using PubMed and Cochrane database through May 2013. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements.

Results

Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1β inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra.

Conclusion

NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout.     

Colchicine treatment in children with familial Mediterranean fever

Prophylactic colchicine therapy has been shown to be a safe and effective method of eliminating the attacks and preventing the development of amyloidosis in patients with familial Mediterranean fever (FMF). However, information about effective dosages that control FMF attacks and prevent amyloidosis in childhood is not available. The aim of this study is to determine the effective colchicine dose for children in terms of body weight and surface area. Sixty-two (34 male, 28 female) children with FMF were selected and colchicine treatment was initiated by giving 0.5–1 mg/day to each patient. The dose was gradually increased up to a maximum 2 mg/day in unresponsive patients; mean duration of therapy was 45.6 ± 35.5 months. When the optimal effective dosage (i.e. the one that reduced the frequency of attacks and ESR, CRP and fibrinogen levels during the attack-free period) was achieved, the optimal effective dose was calculated according to the body weight and body surface area for each patient. Based on these values mean colchicine dose was computed for the study group and values for different age groups were evaluated. Mean colchicine doses according to the body weight and surface area of the whole group were found to be 0.03 ± 0.02 mg/kg/day and 1.16 ± 0.45 mg/m²/day, respectively. It was shown that children less than 5 years of age might need colchicine doses as high as 0.07 mg/kg/day or 1.9 mg/m²/day. These dosages are approximately 2.5–3 times more than the mean colchicine dose for children aged 16–20 years. These results clearly show that small children need higher doses of colchicine in order to control their attacks. Thus, we conclude that colchicine, when given according to body weight or body surface area, would be more effective in childhood.     

Early valve replacement for aortic stenosis irrespective of symptoms results in better clinical survival: A meta-analysis of the current evidence

Objectives

Patients with severe, but asymptomatic aortic stenosis (AS) present a difficult clinical challenge. The conventional strategy is ‘wait for symptoms’ approach. However, some observational studies have suggested early aortic valve replacement (AVR) results in better outcome compared to late surgery. There are no randomised controlled trials comparing clinical outcome of early and late AVR. This meta-analysis is to examine the effect of the two approaches on clinical outcome in such patients.

Methods

We searched the PubMed for published studies on asymptomatic AS and treatment. Four observational studies (N = 976 patients) were suitable for inclusion in the analysis.

Results

All four studies provided sufficient details. Using the subgroup of asymptomatic patients who underwent early surgery together or separately from the subgroup who had surgery after developing symptoms resulted in ORs of 0.17 and 0.16 respectively (p < 0.00001) in favour of early AVR compared with conservational or late surgery.

Conclusion

Meta-analysis of the available observational studies has demonstrated highly significant clinical outcome in favour of early AVR compared with late surgery, suggesting that early surgical approach offers substantial survival benefit for severe asymptomatic AS patients.     

Increased Risk of Recurrent Gout Attacks with Hospitalization

Background

Although anecdotal evidence suggests that the risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis.

Methods

We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a 1-year period, including onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period before each gout attack. The same exposure information also was obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications.

Results

Of 724 participants (mean age, 54.5 years; 78.5% male), 35 hospitalizations occurred during a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (odds ratio, 4.05; 95% confidence interval, 1.78-9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with the use of allopurinol, colchicine, or nonsteroidal anti-inflammatory drugs, but not statistically significantly.

Conclusions

Our study confirmed that the risk of gout attacks increases among patients with gout during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with preexisting gout.     

Documento de consenso sobre el fenotipo mixto EPOC-asma en la EPOC

Introduction

Although asthma and COPD are different pathologies, many patients share characteristics from both entities. These cases can have different evolutions and responses to treatment. Nevertheless, the evidence available is limited, and it is necessary to evaluate whether they represent a differential phenotype and provide recommendations about diagnosis and treatment, in addition to identifying possible gaps in our understanding of asthma and COPD.

Methods

A nation-wide consensus of experts in COPD in two stages: 1) during an initial meeting, the topics to be dealt with were established and a first draft of statements was elaborated with a structured «brainstorming» method; 2) consensus was reached with two rounds of e-mails, using a Likert-type scale.

Results

Consensus was reached about the existence of a differential clinical phenotype known as «Overlap Phenotype COPD-Asthma», whose diagnosis is made when 2 major criteria and 2 minor criteria are met. The major criteria include very positive bronchodilator test (increase in FEV₁ ≥ 15% and ≥ 400 ml), eosinophilia in sputum and personal history of asthma. Minor criteria include high total IgE, personal history of atopy and positive bronchodilator test (increase in FEV₁ ≥ 12% and ≥ 200 ml) on two or more occasions. The early use of individually-adjusted inhaled corticosteroids is recommended, and caution must be taken with their abrupt withdrawal. Meanwhile, in severe cases the use of triple therapy should be evaluated. Finally, there is an obvious lack of specific studies about the natural history and the treatment of these patients.

Conclusions

It is necessary to expand our knowledge about this phenotype in order to establish adequate guidelines and recommendations for its diagnosis and treatment.     

Diagnostic challenge in a Tunisian patient with Familial Mediterranean Fever,sacroiliitis and coxitis

Introduction

Familial Mediterranean Fever (FMF) is a hereditary auto inflammatory disease. The most common joint attack is an acute large joint monoarthritis most often affecting the knee or hip and lasting for several days. Rarely, a more protracted arthritis may occur.

Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin

Objective

The purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout.

A randomized controlled trial to evaluate the slow‐acting symptom‐modifying effects of colchicine in osteoarthritis of the knee: A preliminary report

Objective

To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.

Methods

Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double‐blind, placebo‐controlled trial over a 5‐month period.

Results

The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel‐Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T² test (P = 0.0115).

Conclusion

Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

     

Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults

Background

Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress – such as diabetes, chronic kidney disease and aging – where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined.

Methods

To test the hypothesis that circulating levels of N^?-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older.

Results

During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95% confidence interval [CI] = 1.03–1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke.

Conclusions

In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML’s value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.     

The effects of body mass index on surface electrocardiograms in young adults

Introduction

While BMI is known to affect ECG measurements, these effects have not been well characterized in young adults.

Methods

We retrospectively reviewed all ECGs performed in adults 18 to 35 years old at a single institution over a 30 year period. ECG measurements were derived electronically and stratified by WHO BMI category.

Results

A total of 55,218 ECGs were included. Increasing BMI led to increased P wave duration and decreasing P, R, and T wave axes. Additionally, while increasing BMI led to less R wave voltage, J point elevation, and T wave amplitude in patients with a BMI ≥ 18.5 kg/m², there was also a decrease in the measured parameters in patients with a BMI < 18.5 kg/m².

Discussion

BMI had significant effects on ECG measurements. For accurate assessment of ECGs, these data should be incorporated into established nomograms. Further investigation into the effects of BMI on the ECG is warranted.     

Possible effect of subclinical inflammation on daily life in familial Mediterranean fever

This study was performed to investigate the attack-free complaints of patients with familial Mediterranean fever (FMF) and the impact of colchicine on these symptoms and on subclinical inflammation. A questionnaire that includes information about the disease course and symptoms during the attack-free period was administered to the parents of 50 FMF patients. For evaluation of the attack-free period, questions were asked about four items concerning daily activities of the children—weakness, lack of appetite, sleep problems, and decreased activity. The respondents rated the items and the total score was taken as the sum of all of the specific items. The laboratory values were noted from the patients files. During the attack-free period, patients with mild disease had higher total scores, higher weakness, and decreased activity scores than patients with moderate disease. When we compared the daily activity scores before and after colchicine therapy, a statistically significant increase was observed in the total scores and in all of the specific item scores. Also a significant decrease was seen in the erythrocyte sedimentation rate and white blood cell counts, and a significant increase was seen in the hemoglobin levels during the attack-free period after colchicine usage. Regression of inflammation together with improvement in daily activities were observed. FMF patients seem to have complaints during the attack-free period that may be related to subclinical inflammation. Moreover, colchicine besides preventing the FMF attacks and the dangerous complication of amyloidosis also seems to hinder the symptoms of the attack-free period in children with FMF.     

Consenso de expertos sobre propuestas para la mejora del manejo de la dislipemia aterogénica

Introduction and objectives

Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up.

Methods

After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues.

Results

After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients.

Conclusions

The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus.Full English text available from:www.revespcardiol.org/en     

The mental health and quality of life of adult patients with congenital heart disease

Background

The quality of life (QoL) of adults with congenital heart disease (CHD) has gained significant interest. In addition to medical problems, many patients with CHD face psychosocial, educational, and behavioral challenges. However, few studies have examined the relationship between disease severity and QoL in adults with CHD.

Methods

Eighty-five patients (50 men, 35 women) aged 20–52 years (median, 26.5 years) were enrolled. Patients underwent a QoL, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) survey. The scores were compared with those of age- and gender-matched population data according to the degree of underlying CHD. Disease severity was classified in relation to initial diagnosis, illness course, and current functional status (New York Heart Association [NYHA] class, ability index, CHD functional index, ventricular ejection fraction, and peak VO₂).

Results

There was no significant correlation between disease severity and current functional status assessed by BDI and BAI. Patients who stated that they were religious had better scores for resilience (p = 0.031), physical QoL (p = 0.008), and environmental QoL (p = 0.025). Environmental QoL scores were higher in patients who fully understood their disease (p = 0.004). Current NYHA functional class was associated with scores for psychological resilience.

Conclusions

CHD severity had a detrimental impact on resilience only when measured in terms of poor functional status. The initial diagnosis and course of the illness influence QoL and perceived health. Good psychosocial adaptation could be the result of close family relationships and involvement, making mental adjustment easier.     

Exploring the periodicity of cardiovascular events in Switzerland: Variation in deaths and hospitalizations across seasons,day of the week and hour of the day

Purpose

The purpose of this study is to explore the periodical patterns of events and deaths related to cardiovascular disease (CVD), acute myocardial infarction (AMI) and stroke in Swiss adults (≥ 18 years).

Methods

Mortality data for period 1969–2007 (N = 869,863 CVD events) and hospitalization data for period 1997–2008 (N = 959,990 CVD events) were used. The annual, weekly and circadian distribution of CVD-related deaths and events were assessed. Multivariate analysis was conducted using multinomial logistic regression adjusting for age, gender and calendar year and considering deaths from respiratory diseases, accidents or other causes as competitive events.

Results

CVD deaths and hospitalizations occurred less frequently in the summer months. Similar patterns were found for AMI and stroke. No significant weekly variation for CVD deaths was found. Stratification by age and gender showed subjects aged < 65 years to present a higher probability of dying on Mondays and Saturday, only for men. This finding was confirmed after multivariate adjustment. Finally, a circadian variation in CVD mortality was observed, with a first peak in the morning (8–12 am) and a smaller second peak in the late afternoon (2–6 pm). This pattern persisted after multivariate adjustment and was more pronounced for AMI than for stroke.

Conclusion

There is a periodicity of hospitalizations and deaths related to CVD, AMI and stroke in Switzerland. This pattern changes slightly according to the age and sex of the subjects. Although the underlying mechanisms are not fully identified, preventive measures should take into account these aspects to develop better strategies of prevention and management of CVD.     

Bone metabolism in obese rats programmed by early weaning

Objective

Obesity and osteoporosis seem to have a common pathogenesis, especially because bone and adipose tissue have common origins. Since early weaning (EW) decreases adipogenesis and osteogenesis in neonate, further programming for obesity and hyperleptinemia, we hypothesized that these changes in adipogenesis could affect bone metabolism.

Materials/Methods

Lactating rats were separated into 3 groups: control — dams whose pups ate milk throughout lactation; mechanical EW (MEW) — dams were involved with a bandage interrupting suckling in the last 3 days of lactation; pharmacological EW (PEW) — dams were bromocriptine-treated (0.5 mg/twice a day via intraperitoneal injection) 3 days before weaning. The adult offspring was subjected to dual-energy X-ray absorptiometry and bone tissue was also evaluated by computed tomography, microcomputed tomography and biomechanical tests, beyond serum analyses.

Results

MEW and PEW presented higher total bone mineral density (BMD), total bone mineral content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both groups also presented increase of these parameters and higher femur BMD and fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral body radiodensity, trabecular number, stiffness and break load; lower trabecular separation, maximal deformation and break deformation, and also hyperleptinemia and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was lower for both groups.

Conclusions

Since both models program for obesity and increased bone mass, and leptin increases plasma vitamin D levels, probably leptin is the link between obesity and higher bone mass.