Regular Maintenance Therapy Research Articles

Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50μg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5μg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disease of hematopoietic cells with a variable clinical spectrum characterized by intravascular hemolysis, high risk of thrombosis, and cytopenias. To understand the biochemical shifts underlying PNH, this study aimed to search for the dysfunctional pathways involved in PNH physiopathology by comparing the systemic metabolic profiles of affected patients to healthy controls and the metabolomic profiles before and after the administration of eculizumab in PNH patients undergoing treatment. Plasma metabolic profiles, comprising 186 specific annotated metabolites, were quantified using targeted quantitative electrospray ionization tandem mass spectrometry in 23 PNH patients and 166 population-based controls. In addition, samples from 12 PNH patients on regular eculizumab maintenance therapy collected before and 24 hours after eculizumab infusion were also analyzed. In the PNH group, levels of the long-chain acylcarnitines metabolites were significantly higher as compared to the controls, while levels of histidine, taurine, glutamate, glutamine, aspartate and phosphatidylcholines were significantly lower in the PNH group. These differences suggest altered acylcarnitine balance, reduction in the amino acids participating in the glycogenesis pathway and impaired glutaminolysis. In 12 PNH patients who were receiving regular eculizumab therapy, the concentrations of acylcarnitine C6:1, the C14:1/C6 ratio (reflecting the impaired action of the medium-chain acyl-Co A dehydrogenase), and the C4/C6 ratio (reflecting the impaired action of short-chain acyl-Co A dehydrogenase) were significantly reduced immediately before eculizumab infusion, revealing impairments in the Acyl CoA metabolism, and reached levels similar to those in the healthy controls 24 hours after infusion. We demonstrated significant differences in the metabolomes of the PNH patients compared to healthy controls. Eculizumab infusion seemed to improve deficiencies in the acyl CoA metabolism and may have a role in the mitochondrial oxidative process of long and medium-chain fatty acids, reducing oxidative stress, and inflammation.

NON-SURGICAL TREATMENT OF PERI-IMPLANTITIS: CASE REPORT

Background: Dental implants are an effective, reliable and widely implemented clinical treatment option for the replacement of missing teeth. But although showing predictable successful outcomes, problems are not rare, and nowadays intensively are discussed the related biological complications. And while peri-implant diseases are becoming frequent health issues in dental offices, commonly accepted and applied treatment protocols are still missing. Materials and methods: In this article, we present a case of acute peri-implantitis. A male patient, 50 years old, systemically healthy and non-smoker, complained of pain, oedema and bleeding in the site of an implant placed 5 years ago. The clinical evaluation revealed red and swollen mucous and the presence of a peri-implant abscess. After probing, extensive bleeding and suppuration were observed. The probing depth on the distal site of 4.5 implant was 7mm and the X-ray evaluation showed significant bone loss at this site. The case was resolved completely with non-surgical mechanical debridement combined with systemic antibiotic therapy and subsequent regular peri-implant maintenance therapy. Results: The case demonstrates satisfactory results with a gain of radiographic bone level as it is seen on the X ray imaging, comparing the initial bone level and the bone level 6 months after active treatment. Resolution of peri-implant soft tissue inflammation (no bleeding on probing, no suppuration) is also observed. Conclusion: Non-surgical therapy of peri-implantitis is effective in arresting progressive bone loss and can achieve radiographic bone fill.

The Changing Asthma Management Landscape and Need for Appropriate SABA Prescription.

Short-acting β2 agonists (SABAs) have been a mainstay of asthma treatment since the 1950s, and have been mainly recommended as-needed for symptom relief alongside daily inhaled corticosteroid (ICS)-based maintenance treatment for the past 30years. However, patient adherence to regular ICS-based anti-inflammatory maintenance therapy is frequently poor, leading to SABA overuse for symptom relief and associated poor outcomes. At present, there is a lack of consensus between treatment guidelines on how SABA should be used, and as-needed ICS-formoterol is suggested by some as an alternative reliever therapy. Here, we examine the pharmacology and current use of inhaled SABAs, identify that regular dosing of ICS can encourage appropriate SABA use, and appraise the evidence used to support the changing reliever treatment recommendations. We conclude that SABA continues to play an important role in the asthma management landscape, and give our views on how it should be used in patients with mild-moderate asthma, to complement regular ICS-based maintenance treatment.

Pharmacology Versus Convenience: A Benefit/Risk Analysis of Regular Maintenance Versus Infrequent or As-Needed Inhaled Corticosteroid Use in Mild Asthma.

IntroductionThis study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma.MethodsA pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV1) (AMP PC20)], for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD). For regular ICS maintenance therapy (100% and 50% adherence) and infrequent or as-needed use (dosing 3–4 times per week), treatment effectiveness was expressed as percent time during 28 days when bronchoprotection exceeded either the threshold for a treatment-related bronchoprotective effect (AMP PC20 ≥ 0.25 doubling dose) or the threshold for a clinically significant bronchoprotective effect (AMP PC20 ≥ 1.0 doubling dose). This value was divided by the total ICS dose administered expressed in prednisolone equivalents to give a therapeutic index (TI).ResultsThe model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1–100), 99.9% (8.0–100) and 100% (58.2–100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4–89.1), 52.3% (0.7–69.2) and 51.3% (28.6–58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6–87.0), 25.5% (0.0–38.0) and 26.2% (14.3–31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD.ConclusionsAt doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3–4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection.

Risk factors for the flare of systemic lupus erythematosus and its influence on prognosis: a single-center retrospective analysis

ObjectivesTo explore the risk factors for systemic lupus erythematosus (SLE) flare and their impact on prognosis.MethodsThe clinical characteristics, laboratory results, and treatment plans of 121 patients with SLE flare were retrospectively analyzed. Ninety-eight SLE outpatients with sustained remission during the same period were selected as controls. Logistic multivariate regression analysis was employed to screen for risk factors for SLE flare.ResultsInfection, thrombocytopenia, arthritis, anti-nucleosome antibodies positive, anti-β2-glycoprotein I (IgG) antibodies positive, and patient’s self-discontinuation of medicine maintenance therapy might be risk factors for SLE flare. Patients who discontinued medicine maintenance therapy by themselves had a significantly higher rate of severe SLE flare than patients with regular medicine maintenance therapy (P = 0.033). The incidence of anemia associated with SLE (P = 0.001), serositis (P = 0.005), and pulmonary hypertension (P = 0.003) in patients who discontinued medicine maintenance therapy were significantly higher than patients with regular medicine maintenance therapy. SLE patients with regular medicine maintenance therapy for less than 3 years had a higher risk of pulmonary hypertension than those with regular medicine maintenance therapy longer than 3 years (P = 0.034).ConclusionsThe accompanying thrombocytopenia, arthritis, anti-nucleosome antibodies positive and anti-β2-glycoprotein I (IgG) antibodies positive at the onset of SLE may affect the prognosis of SLE. Patient’s self-discontinuation of medicine maintenance therapy is the main cause of SLE flare, which may induce severe flare in SLE patients and lead to a significantly higher incidence of pulmonary hypertension.

Asthma patients' and physicians’ perspectives on the burden and management of asthma

BackgroundThe 2021 Global Initiative for Asthma (GINA) report recommends as-needed inhaled corticosteroid (ICS)/formoterol irrespective of severity, and maintenance and reliever treatment (MART) from GINA Step 3 as part of Treatment Track 1, partly based on the SYGMA studies. We investigated how current clinical practice in Australia, Canada, China and the Philippines relates to latest GINA recommendations. MethodsPatients and physicians were recruited from online panels between July and August 2020 and invited to complete an online survey. Inclusion criteria: age ≥18 years, current/past physician diagnosis of asthma (patients); primary care (Canada also included respirologists/respiratory therapists), treating ≥4 patients with asthma per month, ≥3 years in clinical practice (physicians). ResultsOverall, 1216/70,183 patients and 803/8376 physicians replied and were eligible for inclusion. Only 8–15% of patients were using MART; 66–81% used regular maintenance therapy with/without an as-needed reliever. Across the four countries, physicians classified 48–63% of their patients as mild (GINA Steps 1–2) and 28–36% as moderate (GINA Steps 3–4). Generally, physicians rated symptom control over exacerbation reduction as their main treatment goal; patients also ranked symptom relief as very important. Approximately 9–29% of patients and 24–45% of physicians were unaware of MART, and among those who prescribed MART, 80–95% prescribed an additional (non-ICS) as-needed reliever. InterpretationMost physicians prioritized managing asthma symptoms over exacerbations. A lack of awareness and understanding of MART dosing exists among physicians. Practical strategies are required to implement GINA recommendations effectively in real-world clinical practice and to identify appropriate patients for MART.

Systematic literature review of long-term efficacy data for topical psoriasis treatments

Objective To identify long-term efficacy evidence that supports use of topical therapies as regular maintenance therapy in the prevention of psoriasis relapse. Methods A systematic literature review identified clinical trials and observational studies that reported efficacy outcomes for topical psoriasis therapies with treatment durations of at least 12 weeks. For therapies with long-term data, the approved treatment schedules in product labels were reviewed. Results Forty-six studies with at least 12-week efficacy outcomes were identified. Eight randomized controlled trials and six observational studies or single-arm open-label studies reported efficacy data for >12-week treatment periods. Most studies used treatment regimens that reflect current standard of care of repeated treatment of relapses. The PSO-LONG study is the only identified randomized controlled trial to have compared regular proactive maintenance use of a topical treatment (calcipotriol/betamethasone foam) with reactive management in response to psoriasis relapses. Conclusions Limited high-quality long-term efficacy data are available for topical psoriasis therapies. While some product labels mention clinical experience of up to 12 months, they do not provide specific recommendations on the optimal long-term regimen. Calcipotriol/betamethasone foam is the only treatment for which the approved label allows either reactive treatment of relapse or regular (twice weekly) maintenance use.

Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.

Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.

Direct healthcare costs associated with management of asthma: comparison of two treatment regimens in Indonesia, Thailand and Vietnam

Objective Daily inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) combinations comprising either regular maintenance therapy with ICS/LABA plus as-needed short-acting beta-2-agonist (SABA) or ICS-formoterol combinations used as maintenance and reliever therapy (MART) are recommended for moderate asthma. This analysis compares the direct costs of twice-daily fluticasone propionate/salmeterol (FP/salm) and budesonide/formoterol MART in three Southeast Asian countries. Methods A literature review identified three randomized trials in patients with asthma (≥ 12 years) comparing regular twice-daily FP/salm with as-needed SABA versus MART in moderate asthma: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-039-0735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Economic analyses, conducted from a healthcare sector perspective (medication costs + healthcare utilization costs), applied unit costs from countries where healthcare costs are publicly available: Indonesia, Thailand and Vietnam. Results are expressed in British pound sterling (GBP/patient/year). Results Annual exacerbation rates were low and differences between treatment strategies were small (range, FP/salm: 0.31–0.38, MART: 0.24–0.25) although statistically significant in favor of MART. Total average (minimum-maximum) direct costs (in GBP/patient/year) across the three studies were £187 (£137–£284), £158 (£125–£190), and £151 (£141–£164) for those who used FP/salm, and £242 (£217–£267), £284 (£237–£340) and £266 (£224–£315) for MART in Indonesia, Thailand and Vietnam, respectively. On average, total direct costs/patient/year with FP/salm were 22.8%, 44.6% and 43.0% lower than with MART for Indonesia, Thailand and Vietnam, respectively. Conclusions In the three countries evaluated, total treatment costs with regular twice-daily FP/salm were consistently lower than with budesonide/formoterol MART due to lower direct healthcare costs.

Analysis of Non-genetic Factors Influencing the Overall Survival of Multiple Myeloma Patients

To explore the non-genetic factors of overall survival in patients with multiple myeloma (MM). Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 51 patients who were newly diagnosed with MM and had complete follow-up data in the Department of Hematology, the Affiliated Jiangning Hospital of Nanjing Medical University from November 2011 to October 2019. Fifty-one patients included 29 males and 22 females. Followed up to December 2019, 21 cases died and 30 cases survived. The univariate analysis showed that the overall survival time of the patients was influenced by age, disease stage, standard treatment, new drugs, maintenance treatment, hypercalcemia, globulin, albumin, and hemoglobin. The overall survival time of patients with age <65 years old, ISS stage I and II, standardized treatment, new drugs, normal or below normal blood calcium, normal or below normal globulin, albumin ≥35 g/L or hemoglobin ≥100 g/L was prolonged significantly (P<0.05). The multivariate analysis showed that maintenance treatment, hypercalcemia (≥2.6 mmol/L), and hemoglobin (<100 g/L) were independent risk factors influencing the prognosis of MM patients. Patients with blood calcium ≥2.6 mmol/L, hemoglobin <100 g/L, and who do not undergo regular maintenance therapy show a poor prognosis.

Influencing Factors of Non-Genetic Factors Influencing the Overall Survival of Multiple Myeloma Patients

Objective: To explore the non-genetic prognostic factors in patients with multiple myeloma (MM). Methods: Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters of 51 MM patients who were newly diagnosed with MM and had complete follow-up data in the Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing From November 2011 to October 2012. Results: Of the 51 patients, 29 were male and 22 were female. Followed up to December 2019, 21 died and 30 survived. The univariate analysis showed the prognosis was influenced by factors including age, disease stage, standard treatment, new drugs, maintenance treatment, hypercalcemia, globulin, albumin, hemoglobin. Patients aged &amp;lt;65 years, with ISS stage I and II, with standardized treatment, with new drugs, with normal or below normal blood calcium, with normal or below normal globulin, with albumin ≥ 35g/L or patients with hemoglobin ≥100g/L have longer survival time. The multivariate analysis showed that maintenance treatment, hypercalcemia and hemoglobin were independent risk factors influencing the prognosis of MM patients. Conclusion: Patients with blood calcium ≥ 2.6mmol/L, hemoglobin &amp;lt;100g/L and those who do not undergo regular maintenance therapy have a poor prognosis. Key words multiple myeloma; overall survival; non-genetic; prognostic factors Disclosures No relevant conflicts of interest to declare.

Palmoplantar hyperkeratotic projections

Palmoplantar hyperkeratotic projections

A multinational observational study identifying primary care patients at risk of overestimation of asthma control

Factors related to the discrepancy between patient-perceived and actual disease control remain unclear. Identifying patients at risk of overestimation of asthma control remains elusive. This study aimed to (i) investigate the relationship between patient-reported and actual level of asthma control (ii), compare the characteristics between patients who believe their asthma is well controlled that accurately report ‘well-controlled’ asthma with those that do not, and (iii) identify factors associated with inaccurately reported ‘well-controlled’ asthma. A historical, multinational, cross-sectional study using data from the iHARP (initiative Helping Asthma in Real-life Patients) review service for adults with asthma prescribed fixed-dose combination therapy. Data from 4274 patients were analysed. A major discrepancy between patient-reported and Global Initiative for Asthma defined asthma control was detected; 71.1% of patients who reported ‘well-controlled’ asthma were inaccurate in their perception despite receiving regular maintenance therapy. Significant differences were noted in age, gender, body mass index, education level, medication use, side effects, attitudes to preventer inhaler use, inhaler technique review and respiratory specialist review between patients who accurately reported ‘well-controlled’ asthma and those who did not. Independent risk factors associated with inaccurately reported ‘well-controlled’ asthma were: having taken a maximum of 5–12 puffs or more of reliever inhaler on at least one day within the previous 4 weeks; being female; having seen a respiratory specialist more than a year ago (rather than in the previous year); and having required oral corticosteroids for worsening asthma in the previous year. The study highlighted the significant hidden burden associated with under-recognition of poor asthma control, on the part of the patient and the need for targeted interventions designed to address the continuing discrepancy between perceived and actual disease control.

Budesonide/formoterol Turbuhaler® as needed in mild asthma: results of SYGMA-1 and SYGMA-2 trials (SYmbicort® Given as needed in Mild Asthma)

According to the modern concepts, asthma is a heterogeneous disease characterized by chronic airway inflammation and respiratory symptoms, which vary in time and intensity and manifest together with variable obstruction of the airways. Asthma is responsible for the deterioration of health status and quality of life in approximately 339 million of adult patients and children worldwide. Despite the fact that asthma is a chronic inflammatory disease, patients with asthma generally inadequately receive anti-inflammatory therapy in real clinical practice and rely on short-acting beta2-agonists (SABA) too much; this can “mimic” worsening of asthma symptoms. SABA monotherapy “on demand” does not affect chronic airway inflammation, underlying asthma occurrence and progression. As a result, such patients still have the risk of asthma exacerbation and disease progression. Therefore, the need of a new therapeutic strategy for patients with milder asthma (steps 1 and 2), which would provide anti-inflammatory treatment considering the low adherence to the regular maintenance therapy and high dependency on SABA, is obvious. Such approach has become available after the SYGMA (SYmbicort® Given as needed in Mild Asthma) trial was completed. According to the results of this trial, budesonide/formoterol 160/4.5 µg/dose as needed was superior to as needed SABA in better asthma control and decrease in severe asthma exacerbation rate by 64% (p &lt; 0.001). Results of SYGMA 1 and 2 trials also demonstrated that budesonide/formoterol 160/4.5 µg/dose as needed was noninferior compared to regular treatment with budesonide in preventing severe asthma exacerbations while the cumulative dose of budesonide was reduced by ≥75%.

Asthma adherence and the overuse of short-acting inhalers

The UK has one of the highest mortality rates for young people who die from asthma compared to other high-income countries. Yet, despite the risks of the condition, many people living with asthma have poor adherence to their medication, explains Rosemary Adsley Asthma is a chronic respiratory condition affecting 5.4 million people in the UK, of whom 1.1 million are children ( Asthma UK, 2017 ). However, the UK has one of the highest mortality rates for those aged 5–34 years old who die as a result of asthma, in comparison to other high-income countries ( Global Asthma Network, 2018 ; Gupta et al, 2018 ). Many asthma patients require regular maintenance therapy, such as corticosteroid inhalers, but a significant number of patients are non-adherent to their medication regime. Identifying patients and tackling their reasons for non-adherence is crucial in order to optimise their care and reduce the risk of exacerbations ( Le and Simon, 2006 ; Murphy, 2014 ). This article will discuss some of the reasons for non-adherence and suggest possible methods to engage patients and improve adherence. It will also discuss how healthcare teams can work together and investigate some of the new and emerging technologies available that may aid in patient adherence.

Long-term efficacy of infliximab treatment and the predictors of treatment outcomes in patients with refractory uveitis associated with Behçet's disease.

To assess the long-term efficacy and safety of infliximab (IFX) treatment for refractory uveitis associated with Behçet's disease (BD) and to identify predictors of long-term IFX therapy outcomes. We retrospectively studied 44 consecutive BD patients with uveitis who were started on IFX therapy and analyzed the efficacy and safety of IFX and the treatment continuation rate. To determine predictors of IFX responsiveness, we analyzed the clinical characteristics of the patients who received regular maintenance therapy and those who required treatment intensification. The serum cytokine levels prior to IFX were measured through the Bio-Plex human cytokine assays. IFX significantly reduced the frequency of ocular attacks and improved the visual acuity of patients with BD-related uveitis. However, approximately half of the patients required dose escalations, necessitating a shortening of the intervals between IFX infusions due to loss of efficacy during the 5-year treatment. The frequency of ocular attacks was significantly higher in patients with complete BD than in patients with incomplete BD. A multiplex cytokine analysis revealed that patients with BD-related uveitis exhibited increased serum IL-2, IL-6, IL-8, and MCP-1 levels. Moreover, among BD patients, the serum IL-2 and IL-6 levels were particularly high in those who maintained remission and received regular IFX treatments. We confirmed the long-term efficacy and tolerability of IFX in patients with BD-related uveitis. Our results indicate that complete BD may be less responsive to IFX and that the pretreatment serum cytokine profiles may be useful for predicting the long-term IFX therapy outcomes.

National Osteoporosis Society vitamin D guideline summary.

The National Osteoporosis Society (NOS) published its document, Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management, in 2013 as a practical clinical guideline on the management of vitamin D deficiency in adult patients with, or at risk of developing, bone disease. There has been no clear consensus in the UK on vitamin D deficiency its assessment and treatment, and clinical practice is inconsistent. This guideline is aimed at clinicians, including doctors, nurses and dieticians. It recommends the measurement of serum 25 (OH) vitamin D (25OHD) to estimate vitamin D status in the following clinical scenarios: bone diseases that may be improved with vitamin D treatment; bone diseases, prior to specific treatment where correcting vitamin D deficiency is appropriate; musculoskeletal symptoms that could be attributed to vitamin D deficiency. The guideline also states that routine vitamin D testing is unnecessary where vitamin D supplementation with an oral antiresorptive treatment is already planned and sets the following serum 25OHD thresholds: <30 nmol/l is deficient; 30-50 nmol/l may be inadequate in some people; >50 nmol/l is sufficient for almost the whole population. For treatment, oral vitamin D3 is recommended with fixed loading doses of oral vitamin D3 followed by regular maintenance therapy when rapid correction of vitamin D deficiency is required, although loading doses are not necessary where correction of deficiency is less urgent or when co-prescribing with an oral antiresorptive agent. For monitoring, serum calcium (adjusted for albumin) should be checked 1 month after completing a loading regimen, or after starting vitamin D supplementation, in case primary hyperparathyroidism has been unmasked. However, routine monitoring of serum 25OHD is generally unnecessary but may be appropriate in patients with symptomatic vitamin D deficiency or malabsorption and where poor compliance with medication is suspected. The guideline focuses on bone health as, although there are numerous putative effects of vitamin D on immunity modulation, cancer prevention and the risks of cardiovascular disease and multiple sclerosis, there remains considerable debate about the evaluation of extraskeletal factors and optimal vitamin D status in these circumstances.

Combination ICS/fast-onset LABA inhaler as maintenance and reliever therapy: the future for uncontrolled adult asthma?

In the Single combination inhaler as Maintenance And Reliever Therapy (SMART) regimen, asthma patients use a corticosteroid/fast-onset long-acting beta-agonist inhaler as both regular maintenance and reliever therapy. In this multicenter, double-blind randomized controlled trial, Papi et al. have demonstrated that treatment with the combination beclometasone/formoterol hydrofluoroalkane (HFA)-MDI when used as both maintenance and reliever therapy significantly prolongs the time to the first severe asthma exacerbation and reduces severe exacerbations compared with the same fixed dose of maintenance beclometasone/formoterol HFA-MDI with salbutamol MDI for relief. These findings are consistent with those of the prior studies of the SMART regimen with the budesonide/formoterol DPI and extend the evidence for use of the SMART regimen to the extrafine beclometasone/formoterol HFA-MDI, to patients with high baseline reliever use, and to patients in whom the SMART regimen results in a step up, step down or no change in baseline inhaled corticosteroid dose.

Constipation in children

Constipation in children is a universal problem, occurring in 0.7-28% of the population. The exact aetiology is unknown, but the majority of children have a functional, rather than organic, aetiology. Symptoms associated with constipation include abdominal pain, a poor appetite and faecal incontinence, all of which interfere with the quality of life of the child and his or her family. Early intervention with appropriate management is necessary to prevent ongoing sequelae. Once an organic cause has been excluded, a programme of intervention should be implemented, namely evacuation of any faecal mass present, followed by regular maintenance therapy to encourage evacuation of a daily soft stool for at least 2-3 months, prior to gradual withdrawal. Emotional support, exercise and dietary modification are linked to the therapy and will ensure a successful outcome. Failure to implement the protocol may result in ongoing problems in up to 50% of children as they enter adulthood.