Implementing integrated care guidelines in asthma and COPD: It ain't easy!

Objective: To evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic Obstructive Pulmonary Disease (COPD) or Asthma in a real-life situation. Methods: Patients at the outpatient clinic of the department of pulmonary disease were included in a controlled cohort study, comparing the use of diagnostic items and 'Personalised care plans' (PCPs) in patients with obstructive lung disease before (2013) and after (2015) implementation of a personalised diagnostic pathway. Results were compared with reference data (2016) from two control hospitals that used the same guidelines but did not implement this pathway. Results: 100 patients were selected for all three cohorts. After implementing the diagnostic pathway in 2015, 35 % of patients visited attended all pre-planned appointments, whereas 65 % of patients did not: they were diagnosed using usual care. Factors contributing to patients not attending the diagnostic care pathway were: the logistical complexity and intensity of the 2-day pathway, patients willingness to participate in a personalised pathway, and low social economic status or low literacy. After the implementation of the pathway, a significant improvement was seen in the number of PCPs (P < 0.001) and the number of diagnostic items registered recorded in the patients' electronic medical records (P < 0.001). Conclusion: Implementing a standardised diagnostic pathway in a real-life population significantly improved the number of personalised care plans, demonstrating that the implementation of holistic care planning is feasible in this population. Nevertheless, the pathway needs further improvements to maximize the number of patients benefitting from it, including logistical streamlining, removing unnecessary diagnostic tools, and increasing the focus on low literacy. Additionally, we found that implementing existing guidelines in a real life context is complex. Therefore, it is required to prioritize the translation of current guidelines into every-day practice, before expanding existing guidelines and protocols.

Effect of bariatric surgery on lung function and asthma control after 8 years of follow-up.

Background: Bariatric surgery has a proven beneficial effect on asthma symptoms and lung function in patients with class III obesity and asthma. The effects of bariatric surgery on asthma control and small airway function persist for at least 12 months after bariatric surgery. However, long-term follow-up data are lacking. Objectives: To evaluate the very-long term effects of bariatric surgery on asthma symptoms and lung function. Methods: In a prospective, longitudinal follow-up study, we planned an 8-year follow-up visit for patients previously included in the OBAS 1.0 trial, which evaluated the effects of bariatric surgery on asthma control and lung function in patients with asthma and class III obesity in The Netherlands. Results: Fifteen of 78 patients from the OBAS trial completed the 8-year follow-up visit. Nine patients underwent bariatric surgery, and six patients did not. After 8 years of follow-up, asthma control (Asthma Control Questionnaire [ACQ] score at 12 months of 0,4 versus an ACQ score of 0.7 at 8 years of follow-up; p = 0.075) and small airway function (R5-R20 (frequency-dependent resistance at 5Hz-20Hz); score at 12 months of 0,25 versus an ACQ score of 0.07 at 8 years of follow-up; p = 0.345) remained clinically stable compared with 12 months of follow-up. Patients who underwent bariatric surgery had a statistically significant weight regain between 12 months of follow-up and 8 years of follow-up (median [interquartile range] body mass index 30.2 kg/m² [23.9-43.4 kg/m²] versus 32.3 kg/m² [24.0-36.4 kg/m²]; p = 0.025). However, the impact of weight regain on asthma control, and asthma quality of life was clinically insignificant (ACQ, ß (regression coefficient) = 0.04; 95% Confidence Interval [0.02; 0.06]; p < 0.001; and AQLQ; ß = -0.04 CI [-0.07; -0.009]; p = 0.013). Conclusion: These results emphasize the importance of bariatric surgery in treating obesity-related asthma.

Stratification of COPD patients towards personalized medicine: reproduction and formation of clusters.

BACKGROUND: The global initiative for chronic obstructive lung disease (GOLD) 2020 emphasizes that there is only a weak correlation between FEV1, symptoms and impairment of the health status of patients with chronic obstructive pulmonary disease (COPD). Various studies aimed to identify COPD phenotypes by cluster analyses, but behavioral aspects besides smoking were rarely included. METHODS: The aims of the study were to investigate whether (i) clustering analyses are in line with the classification into GOLD ABCD groups; (ii) clustering according to Burgel et al. (Eur Respir J. 36(3):531-9, 2010) can be reproduced in a real-world COPD cohort; and (iii) addition of new behavioral variables alters the clustering outcome. Principal component and hierarchical cluster analyses were applied to real-world clinical data of COPD patients newly referred to secondary care (n = 155). We investigated if the obtained clusters paralleled GOLD ABCD subgroups and determined the impact of adding several variables, including quality of life (QOL), fatigue, satisfaction relationship, air trapping, steps per day and activities of daily living, on clustering. RESULTS: Using the appropriate corresponding variables, we identified clusters that largely reflected the GOLD ABCD groups, but we could not reproduce Burgel's clinical phenotypes. Adding six new variables resulted in the formation of four new clusters that mainly differed from each other in the following parameters: number of steps per day, activities of daily living and QOL. CONCLUSIONS: We could not reproduce previously identified clinical COPD phenotypes in an independent population of COPD patients. Our findings therefore indicate that COPD phenotypes based on cluster analysis may not be a suitable basis for treatment strategies for individual patients.

STOP: an open label crossover trial to study ICS withdrawal in patients with a combination of obesity and low-inflammatory asthma and evaluate its effect on asthma control and quality of life.

BACKGROUND: Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of 'false-negative' T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits. METHODS: The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17-75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m2). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal. DISCUSSION: This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients. Trial registration Netherlands Trial Register, NL8759, registered 2020-07-06, https://www.trialregister.nl/trial/8759 . Protocol version and date: version 2.1, 20 November 2020.

Matrix stimulation in chronic pruritus: A randomized controlled study.

Chronic pruritus is one of the main symptoms in dermatology. We investigated a new intervention for chronic pruritus by neurostimulation through matrix electrodes. In this randomized controlled trial, 29 patients with chronic pruritus caused by a variety of dermatological diseases were allocated to an experimental group (EG; n = 14, 4-Hz neurostimulation of the itching area through matrix electrodes) or the control group (CG; n = 15, placement of matrix electrodes without neurostimulation). Outcome measures were the itching sensation as measured by a Numerical Rating Scale immediately after the intervention and the intermediate effect measured by the average itching sensation on the day before the intervention compared with the average itching sensation on day 1, 2 and 3 after the intervention. Regarding the short-term effect on itching, the anova showed a significant interaction effect for the 5-min stimulation with a larger reduction in the EG with a large effect size of d = 1.10. The average reduction in itching intensity was 78.2% for the EG compared with 34.3% for the CG. For the intermediate effect, no significant interaction was found (F = 1.721, P = 0.199). Comparing the itching sensation at day 0 with day 3, the interaction effect showed a statistical trend toward a greater reduction in the EG (F = 3.178, P = 0.086; statistical trend, d = 0.69). This study proved that neurostimulation through matrix electrodes is effective in the short-term reduction of itching in patients with chronic pruritus caused by dermatological diseases. Additional studies are needed with larger patient pools and covering longer study periods.

Do mask aperture bars of extraglottic airway devices prevent prolapse of epiglottis causing airway obstruction? A randomized crossover trial in anesthetized adult patients.

STUDY OBJECTIVE: The study objective is to determine whether extraglottic airway devices (EADs) with or without mask aperture bars (MABs) result in similar anatomical positions in patients undergoing surgery. DESIGN: Prospective, randomized, crossover comparison of four extraglottic airway devices. SETTING: Operating theatre at a large teaching hospital. PATIENTS: Eighty consenting patients scheduled to undergo surgery with general anesthesia. INTERVENTIONS: Patients were randomly allocated to receive anesthesia with one of four tested EADs. Two versions of each EAD were inserted in random order; one with and one without MABs. MEASUREMENTS AND MAIN RESULTS: Endoscopic evaluation did not demonstrate any difference between the EADs with or without MABs. Contact between MABs and arytenoids (n=15) and herniation of arytenoids (n=7) was restricted to the Cobra-group patients. In nine patients the epiglottis made contact with a MAB, although this contact was very limited and often unilateral. CONCLUSION: This study demonstrated that the anatomical position of the four tested single-use EADs is similar with or without mask aperture bars. We therefore question whether MABs have a protective role in prevention of airway occlusion and whether MABs are essential components. In the overall majority of EADs with MABs, the latter did not prevent contact with the epiglottis. Contact and herniation of the laryngeal structures are seen more frequently when more than two MABs are present.

Predicting leaf traits of herbaceous species from their spectral characteristics.

Trait predictions from leaf spectral properties are mainly applied to tree species, while herbaceous systems received little attention in this topic. Whether similar trait-spectrum relations can be derived for herbaceous plants that differ strongly in growing strategy and environmental constraints is therefore unknown. We used partial least squares regression to relate key traits to leaf spectra (reflectance, transmittance, and absorbance) for 35 herbaceous species, sampled from a wide range of environmental conditions. Specific Leaf Area and nutrient-related traits (N and P content) were poorly predicted from any spectrum, although N prediction improved when expressed on a per area basis (mg/m(2) leaf surface) instead of mass basis (mg/g dry matter). Leaf dry matter content was moderately to good correlated with spectra. We explain our results by the range of environmental constraints encountered by herbaceous species; both N and P limitations as well as a range of light and water availabilities occurred. This weakened the relation between the measured response traits and the leaf constituents that are truly responsible for leaf spectral behavior. Indeed, N predictions improve considering solely upper or under canopy species. Therefore, trait predictions in herbaceous systems should focus on traits relating to dry matter content and the true, underlying drivers of spectral properties.

Relationships between nutrient-related plant traits and combinations of soil N and P fertility measures.

Soil fertility and nutrient-related plant functional traits are in general only moderately related, hindering the progress in trait-based prediction models of vegetation patterns. Although the relationships may have been obscured by suboptimal choices in how soil fertility is expressed, there has never been a systematic investigation into the suitability of fertility measures. This study, therefore, examined the effect of different soil fertility measures on the strength of fertility-trait relationships in 134 natural plant communities. In particular, for eight plot-mean traits we examined (1) whether different elements (N or P) have contrasting or shared influences, (2) which timescale of fertility measures (e.g. mineralization rates for one or five years) has better predictive power, and (3) if integrated fertility measures explain trait variation better than individual fertility measures. Soil N and P had large mutual effects on leaf nutrient concentrations, whereas they had element-specific effects on traits related to species composition (e.g. Grime's CSR strategy). The timescale of fertility measures only had a minor impact on fertility-trait relationships. Two integrated fertility measures (one reflecting overall fertility, another relative availability of soil N and P) were related significantly to most plant traits, but were not better in explaining trait variation than individual fertility measures. Using all fertility measures together, between-site variations of plant traits were explained only moderately for some traits (e.g. 33% for leaf N concentrations) but largely for others (e.g. 66% for whole-canopy P concentration). The moderate relationships were probably due to complex regulation mechanisms of fertility on traits, rather than to a wrong choice of fertility measures. We identified both mutual (i.e. shared) and divergent (i.e. element-specific and stoichiometric) effects of soil N and P on traits, implying the importance of explicitly considering the roles of different elements to properly interpret fertility-trait relationships.

Leaf habit and woodiness regulate different leaf economy traits at a given nutrient supply.

The large variation in the relationships between environmental factors and plant traits observed in natural communities exemplifies the alternative solutions that plants have developed in response to the same environmental limitations. Qualitative attributes, such as growth form, woodiness, and leaf habit can be used to approximate these alternative solutions. Here, we quantified the extent to which these attributes affect leaf trait values at a given resource supply level, using measured plant traits from 105 different species (254 observations) distributed across 50 sites in mesic to wet plant communities in The Netherlands. For each site, soil total N, soil total P, and water supply estimates were obtained by field measurements and modeling. Effects of growth forms, woodiness, and leaf habit on relations between leaf traits (SLA, specific leaf area; LNC, leaf nitrogen concentration; and LPC, leaf phosphorus concentration) vs. nutrient and water supply were quantified using maximum-likelihood methods and Bonferroni post hoc tests. The qualitative attributes explained 8-23% of the variance within sites in leaf traits vs. soil fertility relationships, and therefore they can potentially be used to make better predictions of global patterns of leaf traits in relation to nutrient supply. However, at a given soil fertility, the strength of the effect of each qualitative attribute was not the same for all leaf traits. These differences may imply a differential regulation of the leaf economy traits at a given nutrient supply, in which SLA and LPC seem to be regulated in accordance to changes in plant size and architecture while LNC seems to be primarily regulated at the leaf level by factors related to leaf longevity.

13. Sacroiliac joint pain.

The sacroiliac joint accounts for approximately 16% to 30% of cases of chronic mechanical low back pain. Pain originating in the sacroiliac joint is predominantly perceived in the gluteal region, although pain is often referred into the lower and upper lumbar region, groin, abdomen, and/ or lower limb(s). Because sacroiliac joint pain is difficult to distinguish from other forms of low back pain based on history, different provocative maneuvers have been advocated. Individually, they have weak predictive value, but combined batteries of tests can help ascertain a diagnosis. Radiological imaging is important to exclude "red flags" but contributes little in the diagnosis. Diagnostic blocks are the diagnostic gold standard but must be interpreted with caution, because false-positive as well as false-negative results occur frequently. Treatment of sacroiliac joint pain is best performed in the context of a multidisciplinary approach. Conservative treatments address the underlying causes (posture and gait disturbances) and consist of exercise therapy and manipulation. Intra-articular sacroiliac joint infiltrations with local anesthetic and corticosteroids hold the highest evidence rating (1 B+). If the latter fail or produce only short-term effects, cooled radiofrequency treatment of the lateral branches of S1 to S3 (S4) is recommended (2 B+) if available. When this procedure cannot be used, (pulsed) radiofrequency procedures targeted at L5 dorsal ramus and lateral branches of S1 to S3 may be considered (2 C+).

Resistive-heating or forced-air warming for the prevention of redistribution hypothermia.

BACKGROUND: We evaluated the efficacy of resistive-heating or forced-air warming versus no prewarming, applied before induction of anesthesia for prevention of hypothermia. METHODS: Twenty-seven patients scheduled for laparoscopic colorectal surgery were randomized into 1 of 3 groups: no prewarming; 30 minutes of prewarming with a carbon fiber total body cover at 42 degrees C; or 30 minutes of preoperative forced-air warming at 42 degrees C. The forced-air warming cover excluded the shoulders, ankles, and feet. The prewarming period was exactly 30 minutes. At the 31st minute, a total IV anesthesia technique was initiated, and all patients were actively warmed with a lithotomy blanket. Tympanic and distal esophageal temperatures were measured. Categorical data were analyzed using chi(2) test, and continuous data were analyzed with analysis of variance. P <0.05 was considered statistically significant. RESULTS: The mean esophageal temperatures differed significantly between the control and the carbon fiber group from 40 to 90 minutes of anesthesia. After 50 minutes of anesthesia, the mean esophageal temperatures in the control, carbon fiber, and forced-air groups were 35.9 degrees C +/- 0.3 degrees C, 36.5 degrees C +/- 0.4 degrees C, and 36.2 degrees C +/- 0.3 degrees C, respectively. No statistically significant difference was found between the forced-air and control groups. After 30 minutes of prewarming with resistive heating, patients had an esophageal temperature that was significantly higher than the control group. CONCLUSIONS: Prewarming should be considered part of the anesthetic management when patients are at risk for postoperative hypothermia.

Plant strategies in relation to resource supply in mesic to wet environments: does theory mirror nature?

In ecology, strategy schemes based on propositions about the selection of plant attributes are common, but quantification of such schemes in relation to nutrient and water supply is lacking. Through structural equation modeling, we tested whether plant strategies related to nutrient and water/oxygen supply are reflected in a coordination of traits in natural communities. Structural equation models, based on accepted ecological concepts, were tested with measured plant traits of 105 different species across 50 sites in mesic to wet plant communities in the Netherlands. For each site, nutrient and water supply were measured and modeled. Hypothesized multivariate strategy models only partly reflected current theoretical schemes. Alternative models were consistent, showing that lack of consistency of the original models was because of (i) strong correlations among traits that supposedly belong to different strategy components; (ii) poor understanding of mechanisms determining the covariation of plant maximum height, leaf size, and stem density; and (iii) lack of integrative and long-term measures of nutrient supply needed to predict coordinated plant trait responses. Our main conclusion is that a combination of trade-offs (partly) across different plant organs and diverging effects of resource supply ultimately determines the coordination of plant traits needed to "make a living."

Postoperative residual paralysis in outpatients versus inpatients.

Postoperative residual paralysis is an important complication of the use of neuromuscular blocking drugs. In this prospective study, the incidence of residual paralysis detected as a train-of-four response <90% was less frequent in surgical outpatients (38%) than inpatients (47%) (P = 0.001). This might have been the result of the more frequent use of mivacurium for outpatients. Before undertaking tracheal extubation, the anesthesiologists had applied clinical criteria (outpatients, 49%; inpatients, 45%), pharmacological reversal (26%, 25%), neuromuscular transmission monitoring (12%, 11%), or a combination of these. None of these measures seemed to reduce the incidence of residual paralysis except for quantitative train-of-four monitoring. Postoperatively, eight individual clinical tests or a sum of these tests were also unable to predict residual paralysis by train-of-four. Although the incidence of residual paralysis was less frequent in surgical outpatients, predictive criteria were not evident.

Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis.

In recent years it has become clear that multiple sclerosis (MS) patients benefit from physical exercise as performed in aerobic training but little is known about the effect on functional domains and physiological factors mediating these effects. We studied immunological, endocrine and neurotrophic factors as well as coordinative function and quality of life during an 8-week aerobic bicycle training in a waitlist control design. In the immune-endocrine study (1) 28 patients were included, the coordinative extension study (2) included 39 patients. Training was performed at 60% VO(2)max after determining individual exertion levels through step-by-step ergometry. Metabolic (lactate), endocrine (cortisol, adrendocortico-releasing hormone, epinephrine, norepinephrine), immune (IL-6, soluble IL-6 receptor), and neurotrophic (brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF)) parameters were compared from a prestudy and a poststudy endurance test at 60% VO(2)max for 30 min. In study (1), lowered lactate levels despite higher workload levels indicated a training effect. Disease-specific quality of life (as measured by the Hamburg Quality of Life Questionnaire for Multiple Sclerosis, HAQUAMS) significantly increased in the training group. No significant training effects were seen for endocrine and immune parameters or neurotrophins. In study (2), two out of three coordinative parameters of the lower extremities were significantly improved. In summary, low-level aerobic training in MS improves not only quality of life but also coordinative function and physical fitness.

Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam.

UNLABELLED: Because an oral formulation of midazolam is not approved in certain countries, we evaluated oral alprazolam as an alternative. Forty-five outpatients scheduled for gynecological laparoscopic surgery participated in a double-blinded study to compare the effectiveness and side effects of oral alprazolam 0.5 mg with midazolam 7.5 mg, as a reference drug, and placebo. We evaluated psychomotor function by means of the Trieger Dot Test (TDT) and the Digit-Symbol Substitution Test. Simple memory tests were performed. Data were analyzed with chi(2) or paired Student's t-tests, or with one-way analysis of variance with the Student-Newman-Keuls or Kruskal-Wallis test, as appropriate; P < 0.05 was considered statistically significant. Alprazolam and midazolam both decreased anxiety scores more than placebo (P < 0.05). One hour after premedication, the Digit- Symbol Substitution Test score was similar in all groups, whereas the TDT score was greater (indicating impairment of performance) in the alprazolam group than in the placebo group (P < 0.05). Sedation scores, extubation time, and discharge times in the active drug groups did not differ from placebo. At discharge from the postanesthesia care unit, the TDT score was greater in both active drug groups compared with placebo (P < 0.05). Five patients, exclusively in the midazolam group, had amnesia (P < 0.05). We conclude that alprazolam may be an effective alternative to midazolam for anxiety reduction without causing amnesia. However, it may cause greater impairment of psychomotor function in the early postoperative period. IMPLICATIONS: Oral alprazolam 0.5 mg and midazolam 7.5 mg comparably reduce anxiety in ambulatory surgery patients. Despite early psychomotor impairment, neither drug delays postanesthetic extubation nor prolongs discharge from the postanesthesia care unit.

Critical choices: The United Nations, networks, and the future of global governance

Critical Choices outlines promising ways of how global public policy networks can help to meet the governance challenges of the 21st century and equips policymakers with a practical toolbox to manage globalization. It is in the interest of governments to engage in these "coalitions for change" to better be able to meet their responsibilities toward their citizens. Profound and continuing change in our global environment -- social, political, and economic -- today demands commensurate changes in our institutions of global governance, not least in the institution that lies at the core of the international system, the United Nations. The organization faces a series of critical choices in responding to these fundamental challenges. Creative new arrangements are needed urgently to allow governments, other organizations, both public and private, and individuals around the world to work together to address pressing global problems -- from weapons control, to the lack of adequate global labor standards, to climate change -- as they arise.