Asthma management among allergists in Italy: results from a survey

Background

In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy.

Aims and objectives

The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management.

Methods

An anonymous 16 item web questionnaire was available (April–October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy.

Results

One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence.

Conclusions

Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.

     

Corticosteroid plus β<Subscript>2</Subscript>-agonist in a single inhaler as reliever therapy in intermittent and mild asthma: a proof-of-concept systematic review and meta-analysis

Background

Current guidelines recommend a single inhaler maintenance and reliever therapy (SMART) regimen for moderate to severe asthma. However, evidence for the inhaled corticosteroid plus fast-onset-acting β₂-agonist (ICS/FABA) as reliever therapy in management of intermittent and mild asthma patients is lacking.

Objective

To systematically explore efficacy and safety of the proof-of-concept of the ICS plus FABA regimen in a single inhaler as reliever therapy across children and adults with intermittent and mild persistent asthma.

Methods

We searched online bibliographic databases for randomized controlled trials (RCTs) involving the as-needed use of ICS/FABA as monotherapy in intermittent or mild asthma patients. The primary outcomes were exacerbations and the hazard ratio (HR) of the time to first exacerbation.

Results

Six RCTs (n?=?1300) met the inclusion criteria. Compared with the as-needed FABA regimen, the as-needed use of ICS/FABA as monotherapy statistically reduced exacerbations (RR?=?0.56, P?=?0.001). Compared with regular ICS regimen, the as-needed ICS/FABA therapy had slightly higher risk of exacerbations (RR?=?1.39, P?=?0.011). The HR for time to first exacerbations in the ICS/FABA regimen was significant lower when compared with FABA regimen (HR?=?0.52, P?=?0.002) but had no difference when compared with ICS regimen (HR?=?1.30, P?=?0.286). The corticosteroid exposure in the daily ICS regimen was 2- to 5-fold compared with as-needed use of ICS/FABA regimen.

Conclusions

Our analysis shows that the ICS/FABA as a symptom-driven therapy may be a promising alternative regimen for the patients with intermittent or mild asthma, but it needs further real-world RCTs to confirm these findings.

     

Asthma out of control? A structured review of recent patient surveys

Background

An understanding of the needs and behaviors of asthma patients is important in developing an asthma-related healthcare policy. The primary goal of the present review was to assess patient perspectives on key issues in asthma and its management, as captured in patient surveys.

Methods

Local, national, and multinational asthma surveys were reviewed to assess patient perspectives, and where possible healthcare provider (HCP) perspectives, on key issues, including diagnosis, treatment, control, quality of life, and other patient-centered outcomes. Twenty-four surveys, conducted or published between 1997 and 2003 in Europe and North America, were included in this review. Substantial differences among studies prevented a formal meta-analysis; instead, data were pooled to allow for general comparisons and qualitative analysis.

Results

The results indicate that patients' knowledge of the underlying causes of asthma and treatment options remains inadequate. Moreover, patients often tolerate poor symptom control, possess meager knowledge of correct drug usage, and display insufficient adherence to therapy. Many patients have a low expectation of receiving an appropriate therapy or of having a positive encounter with the HCP. Among HCPs, there is evidence of inadequate understanding of disease etiology and poor or unstructured communication with patients, resulting often in inaccurate assessment of disease severity. Moreover, patients often underreport their symptoms and severity, which in turn could lead to misclassification and undertreatment.

Conclusion

Improving patient education about the importance of achieving optimal asthma control, along with improved communication between patients and HCPs, emphasizing treatment options and optimal treatment of inflammation, may lead to better outcomes and improved asthma management in daily practice.

     

Guideline adherence in hospital recruited and population based COPD patients

Background

Evidence from several studies show poor guideline adherence to COPD treatment, but no such study has been undertaken in Norway. The objectives of this study, was to estimate and compare the guideline adherence to COPD treatment in general population-based and hospital-recruited COPD patients, and find possible predictors of guideline adherence.

Methods

From the prospective, observational EconCOPD-study, we analysed guideline adherence for 90 population-based COPD cases compared to 245 hospital-recruited COPD patients. Overall guideline adherence was defined as correct pharmacological treatment, and influenza vaccination the preceding year, and having received smoking cessation advice. Multivariate logistic regression analysis was performed with the dichotomous outcome overall guideline adherence adjusting for relevant variables.

Results

The overall guideline adherence for population-based COPD cases was 6.7%, significantly lower than the 29.8% overall guideline-adherence amongst hospital-recruited COPD patients. Adherence to pharmacological treatment guidelines was 10.0 and 35.5%, for the two recruitment sources, respectively. GOLD-stage 3 to 4 was associated with significantly better guideline adherence compared to GOLD-stage 2 (OR (95% CI) 18.9 (8.37,42.7)). The unadjusted difference between the two recruitment sources was completely explained by degree of airflow obstruction.

Conclusion

Overall guideline adherence was very low for both recruitment sources. We call for increased attention from authorities and healthcare personnel to improve the quality of care given to this patient group.

     

Association between HMGB1 and asthma: a literature review

Background

Recently, some studies demonstrated that HMGB1, as proinflammatory mediator belonging to the alarmin family, has a key role in different acute and chronic immune disorders. Asthma is a complex disease characterised by recurrent and reversible airflow obstruction associated to airway hyper-responsiveness and airway inflammation.

Objective

This literature review aims to analyse advances on HMGB1 role, employment and potential diagnostic application in asthma.

Methods

We reviewed experimental studies that investigated the pathogenetic role of HMGB in bronchial airway hyper-responsiveness, inflammation and the correlation between HMGB1 level and asthma.

Results

A total of 19 studies assessing the association between HMGB1 and asthma were identified.

Conclusions

What emerged from this literature review was the confirmation of HMGB-1 involvement in diseases characterised by chronic inflammation, especially in pulmonary pathologies. Findings reported suggest a potential role of the alarmin in being a stadiation method and a marker of therapeutic efficacy; finally, inhibiting HMGB1 in humans in order to contrast inflammation should be the aim for future further studies.

     

Untargeted Antifungal Treatment Strategies for Invasive Candidiasis in Non-neutropenic Critically Ill Patients: Current Evidence and Insights

Purpose of Review

The purpose of this study was to provide an overview and insights on important new concepts on untargeted antifungal treatment strategies, namely prophylaxis pre-emptive and empiric treatments for the management of invasive candidiasis (IC) in non-neutropenic critically ill patients.

Recent Findings

Recently, clinical practice guidelines provided recommendation for the management of IC. However, results from recent trials and systematic reviews questioned the effect of untargeted antifungal treatment strategies, especially in terms of survival benefits in non-neutropenic patients, even with septic shock.

Summary

Widespread use of untargeted antifungal treatment strategies seems not to be justified anymore. Future research should evaluate comprehensive diagnostic-therapeutic approaches, including the implementation of de-escalation. In the meanwhile, clinicians should take into account all available sources of information including clinical evaluation, risk factor assessment, scores, and surrogate biomarkers to tailor antifungal treatment before definitive microbiological diagnosis.

     

Factors influencing adherence to an app-based exercise program in adolescents with painful hyperkyphosis

Background

Software applications (apps) could potentially promote exercise adherence. However, it is unclear whether adolescents with painful hyperkyphosis will use an app designed for a home exercise program. The purpose of this study is to assess factors regarding adherence to an app-based home exercise program in adolescents with hyperkyphosis and back pain who were provided a one-time exercise treatment.

Methods

Twenty-one participants were instructed in a one-time exercise treatment and asked to complete a home exercise program 3 times a week for 6 months using an app called PT PAL. At a 6-month follow-up, 14 participants completed a survey assessing factors related to their experiences using the app and their treatment engagement.

Results

Although most participants did not use the app, they reported performing their exercises a few times per week. The adolescent participants considered the app to be more of a barrier than a supportive measure for promoting exercise adherence. Most participants still reported bothersome back pain.

Conclusions

Although adherence to the 6-month app-based home exercise program was not successful, adolescents still viewed technology support such as text reminders as a potential solution.

Trial registration

ClinicalTrials.gov Identifier: NCT03212664. Registered 11 July 2017. Retrospectively registered.

     

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background

Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes.

Methods

A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified.

Results

QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials).

Conclusion

The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.

     

Competence of general practitioners in requesting and interpreting ECGs - a case vignette study

Background

Performing electrocardiography is common in general practice, but the quality of indication setting and diagnostic accuracy have been disputed.

Objectives

To assess the competence of general practitioners (GPs) in their decision-making process with regard to recording and interpreting an electrocardiogram (ECG) and evaluating the relevance of the result for management.

Methods

An online case vignette survey was performed among GPs and cardiologists (in 2015). Nine cases describing situations for which Dutch clinical guidelines recommend or advise against recording an ECG were presented. In each case, the participant had to make choices on recording an ECG, interpreting it, and using the result in a management decision. The reference standard for each ECG diagnosis was set by the expert author team.

Results

Fifty GPs who interpret ECGs themselves, eight GPs who do not and 12 cardiologists completed the survey. Adherence to guidelines recommending an ECG was high for suspected atrial fibrillation, suspected arrhythmia present during consultation, including bradycardia, but much lower for progressive heart failure and stable angina. Diagnostic accuracy of GPs was best in atrial fibrillation (96%), sick sinus syndrome (85%) and old myocardial infarction (82%), but poor in left anterior fascicular block (16%) and incomplete right bundle branch block (10%). GPs often acknowledged the low relevance of the results of a non-indicated ECG.

Conclusion

GPs do not fully adhere to Dutch cardiovascular guidelines on indications for recording ECGs. Diagnostic accuracy was high for atrial fibrillation, sick sinus syndrome and old myocardial infarction and poor for left anterior fascicular block and incomplete right bundle branch block.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Hand-assisted laparoscopic surgery versus laparoscopic right colectomy: a meta-analysis

Objective

The objective of this study is to systematically assess the clinical efficacy of hand-assisted laparoscopic surgery (HALS) and laparoscopic right colectomy (LRC).

Methods

The randomized controlled trials (RCTs) and non-RCTs were collected by searching electronic databases (Pubmed, Embase, and the Cochrane Library). The outcomes included intraoperative outcomes, postoperative outcomes, postoperative morbidity, and oncologic outcomes. Meta-analysis was performed using of RevMan 5.3 software.

Results

A total of five studies involving 438 patients were finally included, with 202 cases in HALS group and 236 cases in LRC group. Results of meta-analysis showed that there was no statistical difference between HALS and LRC in terms of conversion rate, length of hospital stay, reoperation rate, postoperative morbidity, and oncologic outcomes. The operative time was 6.5 min shorter in HALS group; however, it was not a clinically significant difference. Although the incision length was longer in HALS, it did not influence the postoperative recovery.

Conclusions

HALS can be considered an alternative to LRC which combines the advantages of open as well as laparoscopic surgery.

     

Treatment of the Midwestern Endemic Mycoses,Blastomycosis and Histoplasmosis

Purpose of Review

The purpose of this review is to assess the recommended treatment regimens for the major endemic mycoses, histoplasmosis and blastomycosis, which occur in the Midwestern USA and to provide information about the use of newer antifungal agents for these diseases.

Recent Findings

The basic approach to treatment of histoplasmosis and blastomycosis outlined in the IDSA Guidelines is helpful in managing these diseases. However, changes since these guidelines were published provide safer and better tolerated treatment regimens. Prolonged treatment with amphotericin B is rarely required, and lipid formulations of this drug have largely replaced the amphotericin B deoxycholate formulation. Although no clinical trials have been performed and the data are anecdotal, voriconazole and posaconazole are increasingly used in patients who cannot tolerate itraconazole. Voriconazole is especially useful when central nervous system infection is present. Posaconazole tablets provide consistently appropriate serum levels and the drug is well tolerated.

Summary

New azole agents provide alternative therapeutic options for histoplasmosis and blastomycosis.

     

Role of genetic variations of <Emphasis Type="Italic">chitinase 3</Emphasis>-<Emphasis Type="Italic">like 1</Emphasis> in bronchial asthmatic patients

Background

Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1) are associated with bronchial severity and pulmonary function. CHI3L1 proteins are involved in both innate and adaptive immune responses; however, to date, the correlation of these SNPs and their age of onset of bronchial asthma has not been demonstrated.

Methods

To address the role of these genetic variations, 390 patients with well-controlled bronchial asthma and living in Japan were recruited, genotyped, and had a pulmonary function test performed on them in this study. To analyze the concentration levels of CHI3L1 protein, bronchial lavage fluids were examined.

Results

Forced expiratory volume in one second, %predicted (%FEV1), was significantly decreased in homozygotes of rs1214194 compared to heterozygotes and wild type. The age of onset of adult bronchial asthma was significantly younger in GG homozygotes of rs4950928 and AA homozygotes of rs1214194 than in the other two genotypes. The concentration of CHI3L1 protein in bronchial lavage fluid increased in both homozygotes of rs4950928 and rs1214194.

Conclusions

Our study demonstrated that the homozygotes of rs4950928 and rs1214194 of CHI3L1 might predict an early onset of bronchial asthma and have the propensity to promote airway remodeling.Trial registration JMA-IIA00045 remodeling-ICS

     

Synthesis and physicochemical characterization of the one-carbon carrier 10-formyltetrahydrofolate; a reference standard for metabolomics

Introduction

Metabolomics analysis depends on the identification and validation of specific metabolites. This task is significantly hampered by the absence of well-characterized reference standards. The one-carbon carrier 10-formyltetrahydrofolate acts as a donor of formyl groups in anabolism, where it is a substrate in formyltransferase reactions in purine biosynthesis. It has been reported as an unstable substance and is currently unavailable as a reference standard for metabolomics analysis.

Objectives

The current study was undertaken to provide the metabolomics community thoroughly characterized 10-formyltetrahydrofolate along with analytical methodology and guidelines for its storage and handling.

Methods

Anaerobic base treatment of 5,10-methenyltetrahydrofolate chloride in the presence of antioxidant was utilized to prepare 10-formyltetrahydrofolate.

Results

Pure 10-formyltetrahydrofolate has been prepared and physicochemically characterized. Conditions toward maintaining the stability of a solution of the dipotassium salt of 10-formyltetrahydrofolate have been determined.

Conclusion

This study describes the facile preparation of pure (>90%) 10-formyltetrahydrofolate, its qualitative physicochemical characterization, as well as conditions to enable its use as a reference standard in physiologic samples.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Undertaking a randomised controlled trial in the police setting: methodological and practical challenges

Background

There has been an increased drive towards Evidence Based Policing in recent years. Unlike in other public sector services, such as health and education, randomised controlled trials in the police setting are relatively rare. This paper discusses some of the methodological and practical challenges of conducting a randomised controlled trial in the police setting in the UK, based on our experience of the Connect trial. This pragmatic, cluster-randomised controlled trial investigated the effectiveness of a face-to-face training intervention for frontline officers in comparison to routine training. The primary outcome was the number of incidents which resulted in a police response reported to North Yorkshire Police control room in a 1-month period up to 6 months after delivery of training.

Main text

The methodological and practical challenges that we experienced whilst conducting the Connect trial are discussed under six headings: establishing the unit of randomisation; population of interest and sample size; co-production of evidence; time frame; outcomes; and organisational issues.

Conclusion

Recommendations on the conduct of future randomised controlled trials in the police setting are made. To understand the context in which research is undertaken, collaboration between police and academia is needed and police officers should be embedded within trial management groups. Engagement with police data analysts to understand what data is available and facilitate obtaining trial data is also recommended. Police forces may wish to review their IT systems and recording practices. Pragmatic trials are encouraged and time frames need to allow for trial set-up and obtaining relevant ethical approvals.

Trial registration

ISRCTN Registry, ID: ISRCTN11685602. Retrospectively registered on 13 May 2016.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

Mapping data elements to terminological resources for integrating biomedical data sources

Background

Data integration is a crucial task in the biomedical domain and integrating data sources is one approach to integrating data. Data elements (DEs) in particular play an important role in data integration. We combine schema- and instance-based approaches to mapping DEs to terminological resources in order to facilitate data sources integration.

Methods

We extracted DEs from eleven disparate biomedical sources. We compared these DEs to concepts and/or terms in biomedical controlled vocabularies and to reference DEs. We also exploited DE values to disambiguate underspecified DEs and to identify additional mappings.

Results

82.5% of the 474 DEs studied are mapped to entries of a terminological resource and 74.7% of the whole set can be associated with reference DEs. Only 6.6% of the DEs had values that could be semantically typed.

Conclusion

Our study suggests that the integration of biomedical sources can be achieved automatically with limited precision and largely facilitated by mapping DEs to terminological resources.