Biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer

Evidence-based recommendations on biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer. This involves pushing the rectum slightly away from the prostate by inserting a balloon or injecting a gel (spacer) between them.

Effects of modifying visual inhaler spacer usage instructions on correct usage rate of untrained users.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) used with spacers are considered the method of choice for delivery of inhaled drugs in preschool-age children. The aim of this study was to determine the effects of modifying the visual inhaler spacer usage guidelines on the correct usage rate. METHODS: The parents and caregivers of patients <6 years old who were prescribed inhalers with spacers for the first time were included in our study. The participants were randomly divided into a modified visual inhaler spacer usage guidelines group and an unmodified visual inhaler spacer usage guidelines group. All study participants underwent face-to-face interviews and completed questionnaires. RESULTS: A total of 510 participants with a median age of 31 (range, 20-46) years were included in this study. The modified visual guidelines group included 254 (49.6%) participants, and the unmodified visual guidelines group included 256 (50.4%) participants. One hundred sixty-five (65.2%) of the 254 participants in the modified visual guidelines group correctly demonstrated the inhaler spacer technique. In contrast, only 21 (8.2%) of the 256 participants in the unmodified visual guidelines group correctly demonstrated the inhaler spacer technique (p < 0.001). When comparing the inhaler spacer usage steps between the 2 groups, the modified visual guidelines group demonstrated the steps more correctly and more quickly (p < 0.001). CONCLUSION: The current visual inhaler spacer usage guidelines are insufficient. We believe that improving the visual inhaler spacer usage guidelines, in particular, will increase the correct usage rate and decrease the number of usage errors.

In vitro and clinical characterization of the valved holding chamber AeroChamber Plus® Flow-Vu® for administrating tiotropium Respimat® in 1-5-year-old children with persistent asthmatic symptoms.

BACKGROUND: When characterizing inhalation products, a comprehensive assessment including in vitro, pharmacokinetic (PK), and clinical data is required. We conducted a characterization of tiotropium Respimat® when administered with AeroChamber Plus® Flow-Vu® anti-static valved holding chamber (test VHC) with face mask in 1-5-year-olds with persistent asthmatic symptoms. METHODS: In vitro tiotropium dose and particle size distribution delivered into a cascade impactor were evaluated under fixed paediatric and adult flow rates between actuation and samplings. The tiotropium mass likely to reach children's lungs was assessed by tidal breathing simulations and an ADAM-III Child Model. PK exposure to tiotropium in preschool children with persistent asthmatic symptoms (using test VHC) was compared with pooled data from nine Phase 2/3 trials in older children, adolescents, and adults with symptomatic persistent asthma not using test VHC. RESULTS: At fixed inspiratory flow rates, emitted mass and fine particle dose decreased under lower flow conditions; dose reduction was observed when Respimat® was administered by test VHC at paediatric flow rates. In <5-year-old children, such a dose reduction is appropriate. In terms of dose per kg/body weight, in vitro-delivered dosing in children was comparable with adults. Transmission and aerosol holding properties of Respimat® when administered with test VHC were fully sufficient for aerosol delivery to patients. At zero delay, particles <5 µm (most relevant fraction) exhibited a transfer efficacy of ≥60%. The half-time was>10 s, allowing multiple breaths. Standardized tidal inhalation resulted in an emitted mass from the test VHC of approximately one-third of labelled dose, independent of coordination and face mask use, indicating predictable tiotropium administration by test VHC with Respimat®. Tiotropium exposure in 1-5-year-old patients using the test VHC, when adjusted by height or body surface, was comparable with that in older age groups without VHCs; no overexposure was observed. Adverse events were less frequent with tiotropium (2.5 µg, n = 20 [55.6%]; 5 µg, n = 18 [58.1%]) than placebo (n = 25 [73.5%]). CONCLUSIONS: Our findings provide good initial evidence to suggest that tiotropium Respimat® may be administered with AeroChamber Plus® Flow-Vu® VHC in 1-5-year-old patients with persistent asthmatic symptoms. To confirm the clinical efficacy and safety in these patients, additional trials are required. CLINICAL TRIALS REGISTRY NUMBER: The trial was registered under NCT01634113 at http://www.clinicaltrials.gov.

Enhancing Asthma Medication Delivery: Spacers and Valved Holding Chambers.

Asthma is one of the most prevalent chronic diseases managed by school nurses, and its management often includes the administration of bronchodilators delivered via a metered dose inhaler (MDI). The use of an MDI requires coordination and mastery of steps that must be performed correctly and in the proper order. These steps are greatly enhanced, especially in the pediatric population, through the use of medical devices-spacers and valved holding chambers. The purpose of this article is to review the rationale and implications for the use of these devices in the school setting.

[Critical evaluation of inhalation spacer devices available in France]. / Évaluation critique des chambres d'inhalation commercialisées en France.

OBJECTIVE: To identify the spacer devices sold in France and to provide a critical evaluation in the light of the published data. MATERIALS AND METHODS: We contacted the pharmaceutical companies, manufacturers and distributors of each spacer in order to obtain their technical parameters and the results of any in vitro or in vivo studies. A review of the literature via PubMed completed the first set of data. We were interested in the quantity of fine particles (less than 5 µm diameter) obtained with a cascade impactor at paediatric flow rates, for all inhaled drugs available in France. RESULTS: Eleven spacer devices were available in 2013 in France (Ablespacer®, Aerochamber Plus®, Babyhaler®, VHC Arrow®, L'Espace®, Funhaler®, Inhaler®, Itinhaler®, OptiChamber Diamond®, Tipshaler® and Vortex®), but three are no longer manufactured (Babyhaler®, Funhaler® and Inhaler®). All were small volume spacers, sold with facial masks of several different sizes. Four were antistatic (Aerochamber Plus®, Intinhaler®, OptiChamber Diamond® and Vortex®). Only salbutamol was tested with all the devices. Inhaled corticosteroids were tested with some and combinations were studied only with Ablespacer®, Aerochamber Plus®, Itinhaler®, and Vortex®. The results were difficult to interpret because the studies were conducted with very different protocols. The only clinical studies were conducted with Aerochamber Plus®, L'Espace® and Vortex®. CONCLUSION: There was a great disparity between commercialized spacer devices in terms of the available data describing their in vitro performance.

Considerations for Designing In Vitro Bioequivalence (IVBE) Studies for Pressurized Metered Dose Inhalers (pMDIs) with Spacer or Valved Holding Chamber (S/VHC) Add-on Devices.

BACKGROUND: The choice of analytical test methods and associated statistical considerations are considered for the laboratory testing of pressurized metered dose inhaler-spacer/valved holding chamber (pMDI-S/VHC) combinations for in vitro bioequivalence (IVBE). METHODS: Four scenarios are presented for comparing TEST ("second entry" or "generic") versus REF ("innovator"): (1) innovator and second entry product pMDI alone without any S/VHC (baseline comparison); (2) innovator and second entry pMDI product with the same S/VHC; (3) innovator pMDI product with existing S/VHC and second entry product with a different S/VHC; and (4) introduction of a second, different S/VHC to be used with a given innovator pMDI product. The following aspects should be reviewed in the preparatory stage of designing experiments to establish IVBE: (a) the inclusion of delayed inhalation; (b) the utilization of age-appropriate flow rates; and (c) the use of anatomically appropriate face models for evaluation of devices with a facemask. Statistical considerations that fit in with such experimental methods include: selection of pMDI batches and S/VHC lots; choice of sample size and acceptance criteria; bracketing or worst case approaches; and balanced/paired designs. A stepwise approach for selection of impactor stage groupings is presented, and an approach to determine realistic acceptance criteria based on REF product characteristics is suggested. RESULTS: An example of an efficient statistical design of experiment is provided for each scenario, together with alternate approaches for calculation of confidence intervals for the mean TEST/REF relationship. It is important to appreciate that the optimal design depends on balancing numerous considerations and will thus likely differ from case to case; hence, the designs presented here should be seen as illustrations rather than the only option available. More effective approaches may be found that suit a particular case at hand. CONCLUSIONS: The information provided will assist in developing correlations in support of IVBE for these add-on devices.

Evaluation of MDI-spacer utilization and technique in caregivers of urban minority children with persistent asthma.

OBJECTIVE: Incorrect Metered-Dose Inhaler (MDI)-spacer technique can result in decreased drug delivery to distal airways and poor asthma outcomes. There is lack of research to examine whether the caregivers utilize proper technique when applying an MDI-spacer delivery system for young minority children with persistent asthma in the United States. The objective of this study was to evaluate MDI-spacer utilization and technique among the caregivers of Bronx minority children with persistent asthma and to determine characteristics associated with correct use. METHODS: We analyzed data from 169 caregivers of urban minority children with persistent asthma (aged 2-9 years). MDI-spacer device technique was assessed using a 10-step checklist derived from the national guidelines, literature and manufacturers' instructions. Based on the median MDI-technique score of six steps demonstrated accurately, caregivers were categorized as correct (seven or more) or incorrect (six or less) users. RESULTS: Of the 169 caregivers, 95% were mothers, mean age 32.3 years (SD 7.6), 56% were unemployed; 74% of the children were Hispanic, 87% had either "not well controlled" or "very poorly controlled" asthma, 92% had a spacer at home and 71% used it "all" or "most" of the time. Only one caregiver correctly demonstrated all 10 steps of the MDI-spacer technique. Child's having one or more asthma-related hospitalizations in the past 12 months and higher caregiver educational level were independent predictors of correct MDI-spacer technique. CONCLUSIONS AND RELEVANCE: The caregivers of urban, minority children with persistent asthma lack proper MDI-spacer technique, suggesting the potential value of both targeted short- and long-term educational interventions.

Respirable dose delivery of fluticasone propionate from a small valved holding chamber, a compact breath actuated integrated vortex device and a metered dose inhaler.

AIMS: To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro-Breathe (SB) device, and pMDI Evohaler (EH). METHODS: Seventeen mild to moderate asthmatics completed the study using a randomized, double-blind, double-dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose. RESULTS: Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively). CONCLUSIONS: The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA-FP.

Effective inhaled drug administration to mechanically ventilated patients.

Inhaled therapy is commonly employed in mechanically ventilated patients with chronic obstructive pulmonary disease or asthma. The efficacy of inhaled drugs is comparable to that achieved with systemic routes of administration, but the dose of drug required to achieve a therapeutic effect is generally much smaller. Moreover, limited systemic absorption of inhaled drugs minimises systemic side effects. Aerosol administration to ventilated patients differs from that in ambulatory patients in several respects. Optimal techniques for using pressurised metered-dose inhalers and nebulisers in ventilator circuits have been developed. With these techniques, the efficiency of inhaled drug delivery in mechanically ventilated patients is now comparable to that in ambulatory patients. Pressurised metered-dose inhalers are chiefly used to deliver bronchodilator and corticosteroid aerosols, and are more efficient and convenient to use than nebulisers for routine therapy in ventilated patients. However, nebulisers are more versatile and are employed to generate aerosols of bronchodilators, corticosteroids, antibiotics, prostaglandins, surfactant and mucolytic agents. Improvements in drug formulations and the design and efficiency of aerosol generating devices have led to increasing application of inhaled therapies in mechanically ventilated patients.

A new small volume holding chamber for asthmatic children: comparison with Babyhaler spacer.

When a new holding chamber for administrating inhaled medication is to be marketed, it needs to be compared with existing chambers with two questions in mind: is this chamber well accepted by patients and is there an in vitro equivalence? We compared the new small volume non-electrostatic valved holding chamber, usable with all pressurized metered-dose inhalers and equipped with a funny facemask, Vortex (Pari GmbH, Germany), to the most frequently prescribed holding chamber in France, Babyhaler (GlaxoSmithKline Laboratories). Preferences were studied for 75 families with a child no more than 4 yr old, using standard questionnaires. An in vitro study assessed the delivered dose and the particle size distribution of two HFA beclomethasone dipropionate pressurized metered dose inhalers (Becotide 250 microg per dose and Nexxair 100 microg per dose) by dose uniformity sample apparatus and cascade impactor according to the European Pharmacopoeia. Vortex was preferred by 95% of the families because of its small size, its duck facemask, and its robust appearance. Among children able to give their opinion, 86% preferred Vortex to Babyhaler. In vitro, both holding chambers reduced the delivered dose of beclomethasone dipropionate and increased the quantity of particles smaller than 5 microm in diameter with both medications. A higher proportion of fine particles was obtained with Nexxair than with Becotide (p < 0.05) and with Vortex than with Babyhaler (p < 0.05). As expected, throat deposition is dramatically reduced for both drugs with both holding chambers. The in vitro difference in the particle size distribution of beclomethasone dipropionate with both holding chambers probably has no clinical influence.

[Different inhaler devices in acute asthma attacks: a randomized, double-blind, placebo-controlled study]. / Diferentes dispositivos inalatórios na crise aguda de asma: um estudo randomizado, duplo-cego e controlado com placebo.

OBJECTIVE: To verify the efficacy, side effects, and cost of treatment of acute asthma attacks, using different inhaler devices. METHODS: This is a randomized, double-blind, placebo-controlled study. Salbutamol was administered via a nebulizer, a metered-dose inhaler (attached to a commercially available spacer device), a homemade non-valved spacer device, or a dry powder inhaler. Assessments were made at zero, 20, 40 and 60 minutes, followed by the application of salbutamol and placebo with another device. Forty children (mean age of 11+/-3.5 years) with acute asthma attacks, were evaluated. Clinical score, forced expiratory volume in one second and side effects were analyzed. The costs for medication and spacer devices were calculated. RESULTS: There is no difference between groups regarding clinical score and variation of forced expiratory volume in one second. There was a major variation in the heart rate response to the nebulizer (35%) compared to the commercially available spacer and dry powder inhaler (15 and 17%) and between the homemade spacer and the commercially available spacer (28 and 15%) (p = 0.004). The nebulizer and homemade spacer caused more tremor (p = 0.02). The cost of treatment was higher for the nebulizer and commercially available spacer (p = 0.0001). CONCLUSIONS: The nebulizer was more expensive and used more medicine, showing the same efficiency. The homemade spacer was cheaper, but presented more side effects. The commercially available spacer was as expensive as the nebulizer, although safer. The dry powder inhaler was cheaper, but, just as the homemade spacer, it also caused tachycardia.

Diferentes dispositivos inalatórios na crise aguda de asma: um estudo randomizado, duplo-cego e controlado com placebo / Different inhaler devices in acute asthma attacks: a randomized, double-blind, placebo-controlled study

OBJETIVO: Verificar a eficácia, eventos adversos e custo do tratamento da crise aguda de asma, utilizando diferentes dispositivos inalatórios. MÉTODOS: Estudo randomizado, duplo-cego e controlado com placebo. Foi utilizado salbutamol em nebulizador, inalador dosimetrado com espaçadores industrial e artesanal e inalador em pó. As avaliações foram feitas em 0, 20, 40 e 60 minutos, seguidas da aplicação de salbutamol e placebo em outro dispositivo. Foram avaliadas 40 crianças em crise aguda de asma, com média de idade = 11±3,5 anos. Utilizou-se escore clínico e função pulmonar, e foram verificados eventos adversos. Foram calculados gastos com o medicamento e o dispositivo inalatório. RESULTADOS: O escore clínico e a variação no volume expiratório forçado no primeiro segundo foram semelhantes entre os grupos ao final do estudo. Foi encontrada uma variação maior na freqüência cardíaca com o uso de nebulizador (35 por cento) do que nos grupos que fizeram uso do espaçador industrial (15 por cento) e do inalador em pó (17 por cento), e também entre os espaçadores artesanal e industrial, 28 e 15 por cento, respectivamente (p = 0,004). O nebulizador e o espaçador artesanal provocaram mais tremores (p = 0,02). O custo do tratamento por paciente foi maior nos grupos nebulizador e espaçador industrial, R$ 22,31 e R$ 16,58, respectivamente (p = 0,0001). CONCLUSÕES: O nebulizador foi o mais caro e consumiu mais droga para apresentar a mesma eficácia. O espaçador artesanal foi o mais barato. No entanto, apresentou mais eventos adversos do que o espaçador industrial e o inalador em pó. O espaçador industrial foi tão caro quanto o nebulizador, porém mais seguro. O inalador em pó foi mais barato e apresentou menos tremores, mas taquicardia semelhante ao espaçador artesanal.

Canadian Standards Association standard CAN/CSA/Z264.1-02:2002: a new voluntary standard for spacers and holding chambers used with pressurized metered-dose inhalers.

A new Canadian standard (CAN/CSA/Z264.1-02:2002) has been published with the purpose of helping to ensure the safety, efficacy and functionality of spacers and/or holding chambers. They are prescribed for use by spontaneously breathing patients for the treatment of various respiratory diseases where medication is delivered to the lungs using pressurized-metered dose inhalers. This consensus standard was developed with the support of pharmaceutical companies and manufacturers of spacers and holding chambers, and with the help of clinicians, retail pharmacists and representatives of patient advocate bodies associated with respiratory diseases and the dissemination of information related to the treatment and the delivery of inhaled medications. Advice was also sought from expert groups outside of Canada to ensure that the standard would be relevant internationally. Whereas monographs in the pharmaceutical compendia and guidance documents published by regulatory bodies provide information that is largely about the drug product and inhaler, this is the only standard whose focus is primarily on these add-on devices. The purpose of the present review is to highlight the main features of the standard for clinicians by describing its scope, the tests that are intended to assure the robustness of the construction of these devices, the type of testing that is specified to establish in vitro efficacy, and the recommendations for the marking and labelling of the device and its associated packaging. Manufacturers who test their products to this Canadian Standards Association standard will be able to provide performance information about add-on devices to the clinician, facilitating an informed decision when selecting devices for patients.