Colistin dry powder inhalation with the Twincer™: An effective and more patient friendly alternative to nebulization.

BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates.

Coexistence of malnutrition, frailty, physical frailty and disability in patients with COPD starting a pulmonary rehabilitation program.

BACKGROUND & AIMS: Malnutrition, frailty, physical frailty, and disability are common conditions in patients with chronic obstructive pulmonary disease (COPD). Insight in the coexistence and relations between these conditions may provide information on the nature of the relationship between malnutrition and frailty. Such information may help to identify required interventions to improve the patient's health status. We therefore aimed to explore whether malnutrition, frailty, physical frailty, and disability coexist in patients with COPD at the start of pulmonary rehabilitation. METHODS: For this cross-sectional study, from March 2015 to May 2017, patients with COPD were assessed at the start of a pulmonary rehabilitation program. Nutritional status was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA) based Pt-Global app. Frailty was assessed by the Evaluative Frailty Index for Physical activity (EFIP), physical frailty by Fried's criteria, and disability by the Dutch version of World Health Organization Disability Assessment Schedule 2.0 (WHODAS). These variables were dichotomized to determine coexistence of malnutrition, frailty, physical frailty, and disability. Associations between PG-SGA score and respectively EFIP score, Fried's criteria, and WHODAS score were analyzed by Pearson's correlation coefficient. Two tailed P-values were used, and significance was set at P < 0.05. RESULTS: Of the 57 participants included (age 61.2 ± 8.7 years), malnutrition and frailty coexisted in 40%. Malnutrition and physical frailty coexisted in 18%, and malnutrition and disability in 21%. EFIP score and PG-SGA score were significantly correlated (r = 0.43, P = 0.001), as well as Fried's criteria and PG-SGA score (r = 0.37, P = 0.005). CONCLUSIONS: In this population, malnutrition substantially (40%) coexists with frailty. Although the prevalence of each of the four conditions is quite high, the coexistence of all four conditions is limited (11%). The results of our study indicate that nutritional interventions should be delivered by health care professionals across multiple disciplines.

Acute effects of cigarette smoke on inflammation and oxidative stress: a review.

Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified 123 studies investigating the acute effects of cigarette smoking on inflammation and oxidative stress in human, animal, and in vitro models. An acute smoking model is a relatively easy and sensitive method of investigating the specific effects of cigarette smoke on oxidative stress and inflammation. Acute smoke exposure can result in tissue damage, as suggested by increased products of lipid peroxidation and degradation products of extracellular matrix proteins. Acute cigarette smoke has a suppressive effect on the number of eosinophils and several inflammatory cytokines, possibly due to the anti-inflammatory effect of carbon monoxide. An acute smoking model can supplement other ways of studying the effects of smoking and is an as yet underinvestigated method for intervention studies in smoking related diseases.

Treatment of patients with long-standing unexplained subfertility with in vitro fertilization.

OBJECTIVE: To evaluate whether IVF is an effective treatment for long-standing unexplained subfertility. DESIGN: Retrospective cohort study. SETTING: Tertiary care infertility center in a university hospital. PATIENT(S): Two hundred two couples with unexplained subfertility of 2 years' duration or more who attended the center for their first IVF attempt. INTERVENTION(S): Couples were placed on a waiting list for IVF. They received no treatment until IVF was started. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) while on the waiting list and PR after IVF treatment. RESULT(S): Complete data sets were available for 131 couples. Seventeen of 131 women became pregnant while waiting for IVF treatment (PR 0.9% per exposure cycle), whereas 45 of 119 receiving IVF treatment became pregnant (PR 17% per IVF attempt). CONCLUSION(S): IVF treatment has substantial added value over waiting and is an efficient treatment for long-standing unexplained subfertility.

Exhaled nitric oxide is higher both at day and night in subjects with nocturnal asthma.

Nitric oxide in exhaled air is thought to reflect airway inflammation. No data have been reported so far on circadian changes in NO in subjects with nocturnal asthma. To determine whether exhaled NO shows a circadian rhythm inverse to the circadian rhythm in airway obstruction in subjects with nocturnal asthma, we conducted a study involving six healthy controls, eight individuals without nocturnal asthma (4-h to 16-h variation in peak expiratory flow [PEF] <= 15%), and six individuals with nocturnal asthma (4-h to 16-h PEF variation > 15%). Smoking, use of corticosteroids, and recent respiratory infections were excluded. NO concentrations were measured at 12, 16, 20, and 24 h, and at 4, 8, and 12 h of the next day, using the single-breath method. At the same times, FEV1 and PEF were also measured. Mean NO concentrations were significantly higher in subjects with nocturnal asthma than in subjects without nocturnal asthma, and higher in both groups than in healthy controls at all time points. Mean exhaled NO levels over 24 h correlated with the 4-h to 16-h variation in PEF (r = 0.61, p < 0.01). Exhaled NO did not show a significant circadian variation in any of the three groups as assessed with cosinor analysis, in contrast to the FEV1 in both asthma groups (p < 0.05). At 4 h, mean +/- SD NO levels were higher than at 16 h in subjects with nocturnal asthma; at 50 +/- 20 ppb versus 42 +/- 15 ppb (p < 0.05); other measurements at all time points were similar. Differences in NO and FEV1 from 4 h to 16 h did not correlate with one another. We conclude that subjects with nocturnal asthma exhale NO at higher levels both at night and during the day, which may reflect more severe diurnal airway-wall inflammation. A circadian rhythm in exhaled NO was not observed. NO levels did not correspond to the circadian rhythm in airway obstruction. The small increase in NO at 4 h may indicate an aspect of inflammation, but it is not associated with increased nocturnal airway obstruction.

A discrete mathematical model of unlabelled granulocyte kinetics. A preliminary study of feedback control.

The equations used in formulating the continuous model of granulocyte kinetics developed by O'Fallon et al. (1971) were analyzed to see if they could be altered to simulate a feedback mechanism operating on the production and development of granulocytes. After extensive study and modification of the continuous model, it was found that a discrete model based on a Leslie matrix procedure was more effective for simulating the feedback system. This discrete model was used to show experimentally, from a mathematical view point, that a feedback mechanism of some kind must be operating on the production and development of granulocytes. Further, the discrete model was subjected to preliminary tests (simultaneous and cascading feedback) to demonstrate that it has the capability of responding to feedback control.

A note on life tables and nonlinear death processes.

This note is viewing survival data of a natural cohort as being generated by a possibly nonlinear, nonhomogeneous death process. It proves that the usual conditional distributions of the number of survivors at a certain age are binomial if and only if the death process is linear. Thus the customary statistical methods for the analysis of life table data are, strictly speaking, invalid whenever the underlying death process is nonlinear. For example, if a contagious disease is the cause of some or all of the deaths, the deaths will not be independent and the death process, not linear. One should then base the statistical analysis on a model for the spread of the disease rather than the routine binomial model.

Conditions under which a number of sinusoids may be instantaneously in phase.

The literature on the phase relationships between frequency components of a Fourier analysis is reviewed, with examples and theories from acoustics and neurophysiology. Given n sinusoids of different frequencies omega1, omega2, .., omegan and phase angles phi1, phi2, .., phin, it is shown that for n greater than or equal to 2 the set of initial phase angles allowing the n sinusoids to be in phase at some time t0 consists of one or more planes of constant dimension 2 and that for n = 2 such a time t0 always exists. The conditions under which the common phase of n sinusoids at one time t0 will be the same as the common phase at another time t0 are also investigated. The importance of incommensurately related frequency components is emphasized by proofs which do not depend on harmonic relationships. Proofs are formulated in a linear algebra format to demonstrate the versatility of the method for analysing long sequences of frequencies and phases.