This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA).n = 663), adalimumab , certolizumab pegol , etanercept , golimumab , infliximab , tocilizumab , and TOF (n = 101/only bDMARDs-switched cases). Drug discontinuation reasons  and rates were estimated at 36 months using Gray’s test and statistically evaluated after adjusted by potential clinical confounders  using the Fine-Gray model.This study assessed 3897 patients and 4415 treatment courses with bDMARDs and TOF from 2001 to 2019 . Treatment courses included abatacept  and the bDMARDs-switched group ; toxic adverse events in the bDMARDs-naïve group  and the bDMARDs-switched group ; and remission in the bDMARDs-naïve group  and the bDMARDs-switched group .Cumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases. Tumor necrosis factor inhibitors (TNFi), such as infliximab (IFX), etanercept (ETN), and adalimumab (ADA), were the first biological disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) that had accumulated evidence of drug retention –5. OtherRandomized controlled trials (RCTs) often recruit patients with fewer comorbidities who are different from those in real-world settings , and cohWe recently reported drug retention rates among bDMARDs used in all age , 17 as wThe Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. Data from RA patients who fulfilled the 1987 RA classification criteria of the American College of Rheumatology  or the 2Treatments were administered by the attending rheumatologists in accordance with the guidelines of the Japan College of Rheumatology –26. The P < 0.05 was considered statistically significant.The estimated cumulative incidence curves and discontinuation ratio of each agent defined by specific reasons at 36 months were examined by Gray’s test , 28. TheBaseline clinical characteristics of the bDMARDs-naïve cases are shown in Table Baseline clinical characteristics of the bDMARDs-switched cases are shown in Table Cause-specific cumulative discontinuation rates were assessed using Gray’s test and statistically compared using Fine-Gray hazard competing risk regression model at 36 months Figs. .Fig. 1EP < 0.001). These rates in the bDMARDs-switched cases were as follows .Drug discontinuation rates due to lack of effectiveness in the bDMARDs-naïve cases were as follows Fig. a: ABT 1P < 0.001P < 0.001). These rates in the bDMARDs-switched cases were as follows .Drug discontinuation rates due to toxic adverse events in the bDMARDs-naïve cases were as follows Fig. a: ABT . These rates in the bDMARDs-switched cases were as follows .Drug discontinuation rates due to remission in the bDMARDs-naïve cases were as follows Fig. a: ETN . These rates in the bDMARDs-switched cases were as follows .Drug discontinuation rates due to non-toxic events in the bDMARDs-naïve cases were as follows . These rates in the bDMARDs-switched cases were as follows .Finally, drug discontinuation rates due to all adverse events (including lack of effectiveness and toxic adverse events) in the bDMARDs-naïve cases were as follows Fig. a: ABT  and 95% confidence intervals (CI) for discontinuation due to each specific cause were calculated using the Fine-Gray hazard competing risk regression model adjusted for confounders Tables  and 4.TP < 0.001), ETN , and IFX  compared with ABT (P < 0.001 between agents). In terms of toxic adverse events, ADA , ETN , GLM , IFX , and TCZ  showed a significantly higher rate compared with ABT (P < 0.001 between agents). HR for discontinuation due to non-toxic reasons was significantly lower with CZP  compared with ABT, although no significant difference was observed between agents (P = 0.07). HRs for discontinuation due to remission were significantly higher with ADA , GLM , IFX , and TCZ  compared with ABT (P < 0.001 between agents). Finally, HRs for all adverse events (including lack of effectiveness and toxic adverse events) were significantly higher with ADA , CZP , ETN , GLM , IFX , and TCZ  compared with ABT (P < 0.001 between agents).In the bDMARDs-naïve cases Table , HRs forP < 0.05), although significantly lower with TCZ  compared with ABT (P < 0.001 between agents). As for all toxic adverse events, ETN  showed a significantly lower rate compared with ABT (P = 0.004 between agents). There were no significant differences in HRs for discontinuation due to non-toxic reasons (P = 0.5) and remission (P = 0.9) between agents. Finally, HRs for all adverse events (including lack of effectiveness and toxic adverse events) were significantly higher with ADA , CZP , and IFX  compared with ABT (P < 0.001 between agents).In the bDMARDs-switched cases Table , HRs forThis multi-center, retrospective study was designed to evaluate retention rates and reasons for discontinuation for 7 bDMARDs and TOF, especially in bDMARDs-naïve and bDMARDs-switched cases.Factors affecting bDMARD retention rates have been reported. Higher age , female In terms of toxic adverse events, 2016 EULAR recommendations concluded that there were no differences in serious infections or malignancies across bDMARDs . HoweverRegarding total retention of TNFi, GLM showed a higher retention rate compared with other TNFi when clinical backgrounds were matched . On the Patients with first TNFi failure, switching to non-TNFi bDMARDs showed higher retention rates due to lack of effectiveness compared with patients switched to a second TNFi . In suchThe efficacy of low-dose MTX in Japanese populations compared with western populations should be mentioned. Intraerythrocyte MTX-polyglutamate concentrations, which are considered a useful biomarker of MTX efficacy, were 65 nmol/L with 13.4 mg/week of MTX in the USA, compared with 94 nmol/L with 10.3 mg/week of MTX in Japanese . Thus, aSome limitations to this study need to be considered. First, the backgrounds of patients differed between agents, which may affect results even after adjustment for potential confounders ; in addition, comorbidities that may affect drug retention could not be evaluated. Second, the judgment and reasons for discontinuation (such as lack of effectiveness or remission) depended on the decisions of each physician, without standardized criteria. Third, the difference between intravenous and subcutaneous bDMARDs and the use of other conventional synthetic DMARDs could not be determined. Fourth, dose changes of bDMARDs, MTX, and PSL could not be monitored. Fifth, among agents available in Japan, CZP and TOF were licensed most recently (2013), which may have led to a small number of prescriptions , which may have affected results. However, the strength of this study is that it is the first study comparing drug retention and discontinuation reasons of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases, based on a real-world setting. These results may provide important evidences for the precision medicine, especially for appropriate use of bDMARDs and TOF in both situations of daily clinical practice.Remarkable differences were observed in drug retention rates of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases. Overall retention rates excluding non-toxic reasons and remission were highest with ABT among the bDMARDs-naïve cases (not including TOF), while TCZ showed the highest total retention rate in the bDMARDs-switched cases.Additional file 1: Figure S1. Estimated cumulative incidence with discontinuation due to non-toxic events in the bDMARDs-naïve cases (a) and the bDMARDs-switched cases (b). ABT = abatacept, ADA = adalimumab, CZP = certolizumab pegol, ETN = etanercept, GLM = golimumab, IFX = infliximab, TCZ = tocilizumab, TOF = tofacitinib, bDMARDs = biological disease-modifying antirheumatic drugs.


Abstract. In this article, we introduce the “CampbellParadigm” as a novel variant of  The sound measurementof attitudes, by contrast, demands a substantial attitude-behaviorrelation because attitude measurement entirely and unconditionally rests upon thelink between an attitude and some manifestations .According to The most common measurement model of (explicit) attitudes is still the venerabletripartite model of attitudes by Due to its limited relevance for overt behavior, scholars have challenged thetripartite model as being problematic and have proposed alternative measurementmodels of individual attitudes  elicitsthree modes or types of manifestations: a person’s cognitive, affective,and behavioral responses to an attitude object  must be displayed asmanifest behavior . According to the tripartite model, these manifestations can takethree generic forms: for example, when the person verbally states that PSV isthe “best” team and will therefore win the championship , when he/she physically attends a PSV game , and when his/her face erupts into expressions of joy whenPSV scores a goal . Conceptually, in this model,the attitude (the latent variable) is linked with three types of manifestations that is believed to control the person’smanifest reactions  verbalexpressions of one’s cognitive valuation of the attitude object , (b) self-reports of one’s affectivereactions , (c) self-reports of one’sbehavioral intentions  or of one’s past behaviorwith respect to the attitude object , or any combination ofthese indicators. Note that the latent attitude can become manifest in many waysand formats, and it is not necessary to consider them all. Ideally, it shouldnot matter which combinations of these indicators are used to measure theunderlying In the next section, we will describe the Campbell Paradigm, which we understandmight be unfamiliar to some readers  can and should be used as the basis for the measurement of individualattitudes.For example, an environmentalist  is typically expected to engage in a set of activities that reflecthis or her attitude. For instance, she/he may publicly acknowledge that climatechange is caused by humans, vote for representatives with a knownpro-environmental record, recycle cardboard regularly, and eliminate foods thatare particularly environmentally harmful  from his/her diet.Generally, the person’s esteem for an attitudinal object  or goal  becomesobvious in the extent to which he/she engages in more and more difficultbehaviors that involve increasingly demanding barriers or progressively morepainful sacrifices . Thus, Campbell’s idea isthat the Consistent with his suggestion that the order of items should be seen asparamount to the measurement of attitudes, I1,I2, …Ik) to measure a latentvariable , then he or she willnecessarily affirm all less demanding indicators  as well. Vice versa, if aperson fails to affirm an undemanding indicator, he or she will not affirmmore demanding ones.The Guttman model is based on the use of a person-invariant ordered set ofitems  by marking a box on a survey. Costs forother behaviors are obviously more substantial, such as when a personactively or financially supports a candidate’s campaign . Behavioral costscome in many different forms, for example, when a behavior involves personaleffort, time, personal sacrifices, or money or when a behavior involvestransgressions of social norms, expectations, or display rules. In aparticular sociocultural context , these costscommonly apply to all people  or goal  becomes clear in the face of the behavioral costs theperson is willing to endure in order to reveal positivity toward the objectin question or to attain the related goal.Campbell’s original proposition was successfully tested with theGuttman model see . Neverthsame behaviors explained by thisattitude on an empirical test. This is why Campbell’s proposal formeasuring individual attitudes was initially regarded as circular, even byCampbell himself  and the consequencesof an attitude .Deriving an environmental attitude measure from the same behavioralindicators that are supposed to subsequently be explained by the attitudewould confound the measure. In other words, if a person’s attitude isestimated through the behaviors that a person enacts, we cannot really besurprised to find the very lf e.g., , and hasWhen indicatorsthat are used to measure an attitude  can bedesigned to be different from the behavioral consequencesthat are modeled as caused by an attitude . It would indeed constitute circular logic if the behavioraleffects – the set of behaviors-to-be-explained – were includedamong the indicators that were used to estimate the attitude. However, whenthere is a logical or a practical  separation between theindicators and the specific behavioral consequences of an attitude, thenthere is no logical fallacy. In other words, Of course, this logical or practical distinction must be examined in eachinstance in which the paradigm is used. In the case of the presidentialelection data, we will see that people’s expressions of theirintentions to vote for a certain candidate and their post-electionself-reports of voting behavior are both – at least, logically– distinct from the same people’s manifest cognitive andaffective indicators of their attitudes. Whereas intentions were, in thiscase, only logically distinct – by means of item wording –from the cognitive and affective indicators, the behavioral self-reportswere both logically and temporally distinct from the cognitive and affectiveindicators of the attitude measure.Whereas probability of engaging in the behavior. In otherwords, the Rasch model reduces the goal of applying the measurement modelfrom predicting people’s engagement in a behavior to predicting theprobability of engaging in a behavior .In contrast to the Guttman model, the Rasch model leaves room forobservational irregularities  because, rather thandirectly modeling a person’s actual engagement in a specific behavior, it models the person’sFor Many attitude measures that apply a Rasch-type model for the measurement ofindividual attitudes already exist in the literature  of the expected relationsbetween the attitude and various manifestations – the tripartitemodel of attitudes – and (b) of the specific connection between eachsingle manifestation and a corresponding attitude – the Rasch model.Regarding the latter, the Campbell Paradigm thus speaks of a genericcompensatory relation between a person’s attitude and the costs thatare involved in engaging in a behavior , or stated somewhat differently,when pursuing a personal attitudinal goal  turnout to be rather undemanding – especially as self-reports , nature  attitudes  that was recently presented in audes see . Note thWe implemented three goals in this section. First, we tested our prime hypothesisderived from the Campbell Paradigm by investigating whether the 44 evaluativereactions to the two presidential candidates  could form a person-invariant ordered set of items that could in fact beused as the basis for a Campbellian measure of pro-Reagan-anti-Mondale attitude. Theresulting one-dimensional Rasch scale represents respondents’ jointexpression of their appreciation for Ronald Reagan and their scorn for WalterMondale.Second, we tested whether a single attitude dimension could sufficiently representall 44 evaluative reactions. Rather than corroborating only the theoreticallyanticipated dimension, we contrasted this one-dimensional Rasch model with two- andthree-dimensional Rasch models to explore whether the information in the 44 itemscould be better represented by a more complex attitudinal model.Third, we examined the predictive validity of the attitudinal measure that wedeveloped. Here, we accounted for people’s intentions to vote for one of thetwo presidential candidates prior to the election and predicted their reports of howthey had voted after the election in 1984. Note that, especially with measures atdifferent levels of aggregation, such as in this case where attitude is measuredwith a multi-item scale and behavior is measured with a single item, expectationsfor comprehensive behavioral explanations  are typicallynot high  is derived represent a single, person-invariant, and orderedRasch-homogenous set of items. This test corresponds to the question of whetherthe Rasch model fits the data reasonably well. Moreover, the extent of aperson’s attitude is derived on the basis of maximum likelihoodestimation, which is the conventional way to score individuals with approachesthat are based on the Rasch model  statisticin assessing item fit but used the effect size interpretation instead  model– a RascWhereas the one-dimensional model used all 44 items to reflect a single attitudetoward the two candidates , thetwo-dimensional model used 22 indicators (for each candidate) to reflect each oftwo distinct attitudes: one pro-Reagan and one pro-Mondale. By contrast, ourthree-dimensional model separated both the pro-Reagan the pro-Mondale attitudes– solely represented by the 15 evaluative statements about each of thetwo candidates – from a “feelings dimension” . The feelingitems were treated as a separate dimension under the assumption that theyreflected some generic response tendencies  = 83,032, was significantlybetter than for the one-dimensional,G2(45) = 90,312, or three-dimensionalmodels,G2(53) = 87,555, with an increase inmodel fit of ΔG2(2) = 7,280(p < .001) andΔG2(6) = 4,523(p < .001), respectively.Model fit was estimated with the uted cf. . As can r = −.44 (disattenuated for measurementerror). On the one hand, this correlation corroborated the discriminant validityof the two attitude measures, and on the other hand, it indicated that a personwho valued Reagan was simultaneously somewhat inclined to denigrate Mondale andvice versa. Separating the two attitudes did not necessarily have much relevancethough, unless it could expand our understanding of people’s votingbehavior.A two-dimensional model that spoke of two separate attitudes  was also implied by the only moderate correlationbetween the two attitudes, which wasIn order to check whether attitude did indeed have an influence on aperson’s intention to vote and on self-reported voting behavior, we usedMplus  to estimN = 1,950) and to predict his or herself-reported actual vote for Ronald Reagan (1) or Walter Mondale (0) after theelection .First, we discuss the results of the two-dimensional attitude model . We usedR2) of voting intentions and 74.5% (NagelkerkeR2) of actual voting behavior. Knowingpeople’s attitudes toward the two candidates raised the probability ofcorrectly recognizing individuals with an intention to vote for Reagan fromp = .58 top = .90 and for correctly discriminating a Reaganfrom a Mondale voter from p = .58 top = .88. The base rate(p = .58) was obviously already slightly in favorof Reagan in the surveyed sample.Jointly, the pro-Reagan and pro-Mondale attitudes accounted for 78.4% . For every logitincrease in a person’s pro-Reagan attitude, the odds ofactually voting for Reagan increased by a factor of 6.4(p < .001).For every logit increase in a person’s pro-Mondaleattitude, the odds of expressing the intention to vote for Reagan decreased by afactor of 7.7 (p < .001). For every logitincrease in a person’s pro-Mondale score, the odds ofactually voting for Reagan decreased by a factor of 4.2(p < .001).For every logit increase in a person’s pro-Reagan dimension(compared to those who were below the mean) were 4.6 times more likely toexpress their intention to vote for Reagan rather than Mondale(p < .001). They were also 4.3 times morelikely (again compared to those who were below the mean) to actually vote forReagan rather than Mondale (p < .001).Those who were above the mean on the pro-Mondale dimension(compared to those below the mean) were about 5.7 times more likely to expresstheir intention to vote for Mondale rather than Reagan(p < .001). They were also 5.5 times morelikely (again compared to those below the mean) to actually vote for Mondalerather than Reagan (p < .001).Those who were above the mean on the R2) of voting intentions and for72.0% (Nagelkerke R2) of actual voting behavior.Knowing people’s attitudes toward the two candidates raised theprobability of correctly recognizing individuals with an intention to vote forReagan from p = .58 top = .90 and for correctly discriminating a Reaganfrom a Mondale voter from p = .58 top = .87.Now, consider the model in pro-Reagan-anti-Mondale attitude, the odds of expressingthe intention to vote for Reagan increased by a factor of 290(p < .001). For every logit increase in aperson’s pro-Reagan-anti-Mondale score, the odds ofactually voting for Reagan increased by a factor of 52(p < .001).For every logit increase in a person’spro-Reagan-anti-Mondale attitude (compared to those whowere below the mean) were 6.7 times more likely to express their intention tovote for Reagan rather than Mondale(p < .001). They were also about 6.3 timesmore likely (again compared to those below the mean) to actually vote for Reaganrather than Mondale (p < .001).Those who were above the mean on the unidimensionalN = 1,269). Eventhe means for the two attitudes for people who expressed an intention to votefor or who reported voting for either Reagan or Mondale were not significantlydifferent and were thus comparable, which can be seen in the overlapping 95%confidence intervals in Whereas the quantitative gains relative to the one-dimensional view might not besufficient to justify the more sophisticated, two-dimensional view ofpeople’s attitudes toward the two presidential candidates, theexplanation for why someone chose to vote for Reagan or Mondale might. Asexpected, Reagan voters had positive views of their candidate and negative viewsof the challenger, and Mondale voters had positive views of their candidate andnegative views of Reagan, as shown in r = −.44; see Measuring a single pro-Reagan-anti-Mondale attitude would have obscured the factthat people based their decision about which of the two candidates to vote foron two relatively distinct but correlated were barely superior to asingle bipolar pro-Reagan-anti-Mondale attitude in accounting for people’svoting intentions and self-reported voting.p = .60 to a probability of aroundp = .90 for predicting a person’s votingintentions and his or her self-reported past voting for Reagan.As predicted, we found that quantitative knowledge about the extent to which a personwas dedicated to Reagan-electing or Mondale-rejecting goals  substantially increased the probability ofapproximately As a measurement model, the tripartite model describes the link between a latentattitude and some manifest evaluative statements – affective, cognitive, andbehavioral responses – toward an attitude object see . It provsame model used to establish an estimation of the latentattitude is expected to also theoretically account for other forms ofattitude-relevant behavior  a particular behaviorand the extent of an individual’s attitude . Not surAs a measurement model, the Campbell Paradigm formally describes the relation betweena latent concept  and manifest behavior . As a behavior-explanation model, the Campbell Paradigmuses the quantitative estimate  of the latent attitude to explainthe occurrence of the behavior in question. Still, when measurement – linkingmanifest behavioral indicators with individual attitudes – and explanation– predicting behavior with a latent attitude see  – are trWith our research, we implemented the Campbell Paradigm as a reinterpretation of thetripartite model with data that were previously employed by We believe that


Such isotope effects are critical parameters for interpreting natural stable isotope abundances as proxies for biological process rates in the environment across scales. The kinetic isotope effect of ammonia oxidation (AO) to nitrite (NO2–), performed by ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), is generally ascribed to the enzyme ammonia monooxygenase (AMO), which catalyzes the first step in this process. However, the kinetic isotope effect of AMO, or εAMO, has been typically determined based on isotope kinetics during product formation  alone, which may have overestimated εAMO due to possible accumulation of chemical intermediates and alternative sinks of ammonia/ammonium (NH3/NH4+). Here, we analyzed 15N isotope fractionation during archaeal ammonia oxidation based on both isotopic changes in residual substrate  and cumulative product  pools in pure cultures of the soil strain Nitrososphaera viennensis EN76 and in highly enriched cultures of the marine strain Nitrosopumilus adriaticus NF5, under non-limiting substrate conditions. We obtained εAMO values of 31.9–33.1‰ for both strains based on RS (δ15NH4+) and showed that estimates based on CP (δ15NO2–) give larger isotope fractionation factors by 6–8‰. Complementary analyses showed that, at the end of the growth period, microbial biomass was 15N-enriched (10.1‰), whereas nitrous oxide (N2O) was highly 15N depleted (−38.1‰) relative to the initial substrate. Although we did not determine the isotope effect of NH4+ assimilation (biomass formation) and N2O production by AOA, our results nevertheless show that the discrepancy between εAMO estimates based on RS and CP might have derived from the incorporation of 15N-enriched residual NH4+ after AMO reaction into microbial biomass and that N2O production did not affect isotope fractionation estimates significantly.The naturally occurring nitrogen (N) isotopes,  However, εCP estimates reflect the combined fractionation effects of the isotope equilibrium between NH4+ and NH3  remaining in the culture. Plots of ln(f) and of δCP−δS0 versusRS) and product (εAP), respectively. Uncertainties of ε are expressed as standard error of the slope. Differences in isotope fractionation effects between cultures were assessed by testing significant differences between their regression plots, using R  and the product  of ammonia oxidation, and followed typical Rayleigh isotope fractionation kinetics for closed systems  exhibited 15N isotope fractionation factors based on substrate (εRS) between 31.9 and 33.1‰, and based on product (εCP) between 37.7 and 49.1‰  or the product . The N isotope fractionation factors based on δ15NO2– (εCP) were larger than those based on δ15NH4+ (εRS) by 8.0, 5.8, and 5.9‰ for N. adriaticus, and for N. viennensis grown on 1 mM or 2 mM NH4+, respectively.Based on the oxidation of NHth rates —all cultcultures . Nitroge systems : NH4+ bend 49.1‰ . We foun15N isotope fractionation factors of N. viennensis and N. adriaticus are in the upper range, or higher, than those previously reported for AOA, which might be due to the higher ammonia concentrations applied in our study  to both circumvent and assess potential biases associated with estimates based on δ15NO2– . It should be noted, however, that different apparent isotope effects in whole cells may also be observed in the NH4+ pool, despite constant AMO enzyme-level isotope effects, depending, for example, on the balance between ammonia oxidation rates and ammonia diffusion across the S-layer   or NH4+/NH3 transport. The NH4+/NH3 equilibrium isotope effect has been estimated to be 19.2‰ in aqueous solution  . Publish in AOA) . However systems , whose r unclear . At low solution , whereassolution , have beransport . It is u the AMO , where t3 availability, the apparent isotope effect of the AMO can also be underestimated due to concurrent NH4+ assimilation, which has a smaller isotope effect. This process would alter observed εRS estimates in proportion to the amount of NH4+ assimilated and the isotope effect for NH4+ assimilation  of ammonia oxidized by N. viennensis grown on 2 mM NH4+. Although dissolved inorganic N (DIN) concentrations (sum of [NH4+] and [NO2–]) were relatively constant over the course of ammonia oxidation, we recovered only 81.9% (±1.5 SE) of the initial DIN by the end of incubation of N. adriaticus, and 94.7% (±3.4 SE) and 90.7% (±1.1 SE) of N. viennensis grown on 1 mM NH4+ or 2 mM NH4+, respectively. In N. adriaticus cultures, assimilation of N by contaminant bacteria likely did not contribute substantially to the lower εRS relative to εCP, due to the high enrichment level of the culture (95%) at the time of the experiment, and the fact that εRS of N. adriaticus was similar to that of N. viennensis in pure culture. In addition, the 15N-enrichment of N. viennensis’ biomass shows that AMO preferentially, and primarily, reacts on pseudo-periplasmatic NH3, causing 15N-enrichment of the residual ammonia, which is subsequently assimilated into biomass. We thus propose that under substrate replete conditions, the observed isotope effects of εRS of 31.9–33.1‰ primarily reflect the kinetic isotope effect of the AMO-catalyzed reaction, modified by the NH4+/NH3 equilibrium isotope effect , whereas all other known AOA use the glutamate dehydrogenase (GDH) pathway  are assumed to maintain NH2OH at low steady-state concentrations. Therefore, isotope effects associated with NH2OH oxidation should have a limited impact on δ15NO2–. Second, any process that adds an additional isotope fractionation step, either prior, or subsequent, to NO2– formation, such as the production of the gases NO and N2O, may result in an under- or overestimation of the kinetic isotope fractionation factor. The effect of N2O and NO production on δ15NO2– will depend on their formation pathways, and respective isotope effects and by-product yields. In the N. viennensis culture grown on 2 mM NH4+, we measured cumulative N2O at the end of the incubation, which represented 0.5% (±0.01 SE) of the NH4+ oxidized, or 3.5% (±0.4 SE) of the “missing” N pool. N2O yields of AOA are generally low. For example, N. viennensis has been shown to produce N2O at rates of about 0.1% of those of ammonia oxidation when grown on 1 mM NH4+/NH3   would decrease the apparent kinetic isotope effect of AMO (εCP), instead of increasing it. Using an isotopic mass balance approach, we calculated that the missing N pool , would need to have a δ15N of −18.5‰ (±1.7 SE) in order to account for the difference in isotope fractionation between εRS and εCP  , 3, whiccultures , while N and εCP . Therefo2OH to NO2– in AOA, despite being produced in relatively small amounts . Thus, NH4+ assimilation, but not N2O production, significantly affected the isotope fractionation factor of AMO estimated for N. viennensis .The raw data supporting the conclusion of this article have been deposited at DRYAD (doi: WW designed the study. MMo, RA, BB, MMe, MS, LJ, SR, and MW performed the experiments. MMo, RA, BB, MS, and LJ analyzed the data. GH and CS provided the resources and strains. MMo, RA, and WW wrote the manuscript with contributions from all co-authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


New Heights is a voluntary school-based program that provides a well-defined system of supports for expectant and parenting students in Washington, DC, and was found to be effective at improving educational outcomes. This study explores the program elements and practices that, when used together, improved academic outcomes for New Heights participants and define a possible roadmap for service providers interested in replicating the program’s success.The study team collected data through site visits, key informant interviews, staff surveys, program observations, case files, and program materials.The core design and implementation elements of the New Heights program are (1) placing a trained staff member in the school to provide advocacy, case management, education, and in-kind incentives; (2) bringing community-based service providers into the school; (3) giving trained staff autonomy and a strong grounding in local context; and (4) using a highly collaborative process to hire and support school-based coordinators.Staff and funders interested in improving outcomes for young parents in school could use the experience of New Heights and the key practices that were critical to its success as a guide: (1) ensure that the program is well defined but can be tailored to the needs of schools and students, (2) engage community partners to bring services to participants, (3) hire and train the right staff who are committed to “do whatever it takes,” (4) actively cultivate a culture of collaboration among program staff, and (5) develop buy-in with school staff and illustrate program value. What is already known? Programs designed to address the needs of young expectant or parenting mothers often use multiple components and approaches, involving numerous partners. The body of evidence on the effectiveness of some of these programs is growing, but there is still a lack of knowledge about what drives program success.What does this article add? This paper defines and explores the key program design and implementation components of New Heights, an effective school-based program for young parents, which was found to increase credit accumulation; reduce absenteeism; and, to some extent, increase school completion rates. We share key lessons learned for the field based on the program’s successful implementation in Washington, DC.Programs designed to address the needs of young expectant or parenting mothers often use multiple components and approaches, involving numerous partners , we identified one Pregnancy Assistance Fund (PAF) funded program—New Heights—that has strong and positive impacts for expectant or parenting young mothers  navigate the challenges of pregnancy, parenthood, and completing high school. Pregnant or parenting students often face judgment in their communities, in class, with their peers, or on their way to and from school. New Heights aims to reduce some of this stigma and stress, increase school engagement and credit accumulation, and build self-sufficiency and resilience. With a 2010 PAF grant, DCPS central office staff refined and expanded New Heights from just two high schools, where it had operated for nearly two decades, to nine of the district’s large, comprehensive high schools that were also in the city’s poorest neighborhoods with the highest rates of teen births , New Heights program staff (n = 3), school-based coordinators (n = 11), and representatives of several associated community-based providers (n = 12); four focus groups with expecting or parenting young mothers who had participated in the program (n = 29); observations of program delivery in three schools; and review of select participant case files (n = 28). All respondents consented to participate in the study. A team of five site visitors conducted three site visits to Washington, DC, to collect in-depth data on (1) the intended program design for New Heights, (2) the program as implemented at the time of data collection in spring and summer 2015, (3) staff and young mothers’ experiences with the program, and (4) lessons learned from implementation.The New Heights program database, which contains administrative data on program participants and the number and types of workshops delivered through the program.1A paper and pencil survey completed by 11 New Heights coordinators .New Heights program materials, including the New Heights manual for program managers (updated January 2015), criteria for vetting and approving community-based providers for educational workshops, video of five-day preservice training of New Heights coordinators, evaluation reports, meeting agendas and notes, and New Heights summit brochures and plans.This study of New Heights implementation examined program delivery in nine schools into which the program expanded in 2010 and incorporated input from staff at the two original New Heights high schools. The research was conducted in accord with prevailing ethical principles and approved by an Institutional Review Board. This manuscript is not based upon clinical study or patient data. The study relied on the following data sources:Qualitative analysis of interviews, focus groups, observation data, and key program materials described above involved an iterative process of identifying key themes and triangulating data sources. Trained staff used a qualitative analysis software package, Atlas.ti, to facilitate organizing and synthesizing the qualitative data according to themes and key research questions. We used administrative data from the New Heights database to analyze the number of workshops offered and the average workshop attendance rate for female participants in the nine study schools in 2014–2015.In this article, we present the key findings that emerged from our analysis of these data sources.The New Heights program model is not an off-the-shelf program with a one-size-fits-all curriculum. It clearly defines several core components Fig.  and thenThe New Heights program’s key feature is placing a coordinator in every school. The coordinators are trained staff, employed by the district, who operate primarily out of a designated office or classroom space in each school. The coordinator leads the delivery of the program’s multiple components, serving as a resource for his or her school, assessing the academic and personal needs of participating students, and helping them identify concrete strategies to meet their goals.Advocacy Expectant and parenting students typically have needs that make it challenging for them to participate fully in school activities and manage their academic workload. They must make frequent visits to the doctor for which they may have to miss some or all of their school day. Because of their changing bodies, expecting mothers also find their existing uniform shirts or pants no longer fit, or they prefer to wear loose-fitting clothes to avoid undue attention, which can make it difficult to meet the school dress code requirements. Coordinators help reduce stigma and school-based discrimination by educating school staff and students; they also ensure that administrative rules, such as those for excused versus unexcused absences, dress code, or access to an elevator, are modified to accommodate expectant and parenting students.Case management Coordinators are expected to (1) monitor and promote academic progress for each participant in close collaboration with teachers, counselors, and school administrators; (2) help students manage all logistical or personal challenges—such as referrals to transportation, child care, or housing needs—to ensure that they can attend school every day; and (3) empower students to become self-sufficient by providing them with the tools and skills to advocate for themselves.Educational workshops Held at least three times a week, lunchtime workshops provide supplemental education on parenting skills, career and financial planning, prenatal care, early childhood development, and healthy relationships. Although the logistics of the workshops are organized by the coordinators, most workshops are delivered by community-based partners. Given the district’s rich environment of nonprofits, New Heights has a well-developed system of community partners to provide students with access to legal assistance, early childhood education, mental health counseling, and college or career planning guidance. Funding permitting, the program also conducts a culminating one-day event, called the Youth Summit, at the end of the year to celebrate participating youth, alumni/ae, and community partners’ achievements.Baby Bonus Bucks New Heights uses a system of in-kind incentives, or points, called Baby Bonus Bucks to help improve attendance, grades, and class participation. Coordinators develop benchmarks individualized for each student, and students earn these incentives when they meet their goals. Students can use their Baby Bonus Bucks toward “purchasing” items from New Heights staff such as maternity supplies, baby clothes or toys, diapers, formula, and other items.New Heights does not have a scripted curriculum; rather, coordinators integrate and deliver four main components in their particular schools, which are located in an urban environment rich with invested community partners.Taken together, these components ultimately aim to help expectant and parenting students achieve educational success Fig. . In the Identifying and recruiting pregnant and parenting youth are large barriers community-based programs face to improving outcomes in areas with high rates of teen births. Nonprofits and clinics know these youth are there and in need of services, but unless young expectant or parenting mothers or fathers voluntarily walk through nonprofit or clinic doors, it is hard to identify and serve them. New Heights used three key strategies to overcome this challenge.First, the program is based in the schools, where nurses, counselors, and students can identify pregnant and parenting females and serve them where they are. The impact study found that 75% of the parenting mothers in the New Heights schools take advantage of the program . Access to these providers during the school day allows students to easily make connections when they need specific resources. In keeping with this approach, New Heights leadership ensured that when making hiring decisions, coordinators had strong connections in the local communities.For New Heights, the role of the school-based coordinator was central to the program’s operation and highly individualized to the needs of each school and student that the coordinator served. The coordinator’s role required staff who not only supported students but treated them as individuals with strengths and skill sets to help themselves. As one coordinator said, “We don’t provide a service to students—they don’t just come to get the voucher. They come and we teach them how to get a child care voucher. We will step in if there is a problem, but we really want them to learn to advocate for themselves.” For this reason, program leaders balanced two considerations in hiring coordinators: the capacity to deliver an intensive wraparound program and their ability to adapt quickly to the needs of their students and school.Believing that an interdisciplinary mix of coordinators would build on one another’s strengths and help address different challenges, New Heights leadership staff looked for candidates from varied professional backgrounds whose skills and characteristics would complement each other. Another factor they considered was experience working in DCPS or community-based organizations that would allow coordinators to leverage those prior relationships to more effectively advocate with school administrators on behalf of their students and identify appropriate resources to address challenges. Program leaders also looked for staff who were passionate about helping expectant and parenting students, had experience working with young people (or had been young parents themselves), or had lived and worked in the communities they would be serving and could therefore relate to the challenges expecting or parenting students faced while in school. As one student highlighted, “It is really difficult to try and parent and also do all your schoolwork. There are times when I wanted to give up. You have to care for yourself, and it makes a big difference to know that there are people who care about you.” Finally, when interviewing and meeting candidates, program leaders and veteran staff asked candidates questions to assess personal fit in addition to their professional and academic qualifications. In order to “do whatever it takes” to help their students, a coordinator needed to be adaptable, empathetic, collaborative, an innovative problem-solver, and willing to mentor and coach others  funded their positions, program leaders recognized the importance of involving schools in the hiring process of each coordinator. When expanding to new schools under the PAF grant, New Heights central office staff invited school principals to meet the short-listed candidates and engaged them in the interview process. Based on their discussions, each coordinator candidate and school principal then ranked their top three choices, ensuring that both the schools and the coordinators had buy-in. Two veteran New Heights coordinators were also a critical part of the hiring teams, and their years of experience added important value to the staff recruitment and selection process. New Heights staff also considered any unique student needs or contexts across the expansion schools, emphasizing that in making a hiring decision for each school it was important for them to “see potential candidates through [our] students’ eyes to determine their fit for the program.” The program also offered competitive salaries and relied on a network of existing community partners to attract the right candidate.New Heights central office staff used a highly intentional approach in providing tailored supervision and support to each coordinator on an ongoing basis. First, staff who designed and conducted the 5-day preservice and annual refresher trainings had been with the district for many years, and their deep knowledge of the schools and communities helped coordinators get a clear picture of the ground realities and expectations for their role in each school. Veteran staff walked new coordinators through a typical day, the different types of school staff with whom they would have to build relationships, and the types of information and resources they would need.In addition, the New Heights program manager served as a supervisor, who was embedded in the schools side-by-side with the coordinators throughout the academic year, learning along with them and serving as an integral and trusted source of support when necessary. Coordinators received ongoing monitoring and one-on-one feedback from the supervisor, who rotated her time among schools year-round. Each week, she aimed to spend four days at a single school to observe its culture, the needs of the students, and the activities of the coordinator. The program manager could then provide more targeted support to each coordinator based on the specific needs and context of their schools and students.Finally, a collaborative spirit, rather than hierarchy, defined New Heights daily operations. Monthly staff meetings focused on topics coordinators wanted to prioritize, and regularly focused on the self-care strategies coordinators could use to manage the demands of this intensive work.The experience of New Heights provides important guiding principles that could be customized by service providers and funders looking to replicate the model and achieve similar outcomes in their own context. The following recommendations draw on the study of the program’s implementation to present lessons learned for helping young mothers overcome significant challenges and thrive in school:New Heights developed a well-integrated system, led by a school-based coordinator and consisting of advocacy, case management, weekly education, and in-kind incentives, that supports female students in overcoming barriers to attending and completing school. A key aspect of this system is meeting each student where she is and tailoring the system of tools and services to address her needs. These components do not operate in silos—rather, program staff must be given the autonomy and training to customize and combine the different components for the context of their schools and students.Weekly workshops allowed New Heights to provide supplemental education on relevant topics and facilitate in-school connections with community-based providers and services. Developing relationships with invested community partners is important for increasing access and removing barriers to needed services and for providing information on parenting, housing, financial literacy, and reproductive health. Program staff can tailor workshop content and frequency depending on the needs of their students and get their input in selecting the topics and the providers.The New Heights coordinators formed the backbone of the program. According to participants, New Heights felt like “home,” a safe space for them to shed the stress and stigma of being a young parent. Participants truly appreciated the targeted support and guidance they received from coordinators.Program leaders should be thoughtful about defining program requirements and expectations for staff early in the process, to help identify and recruit staff with the appropriate skills and personalities to fit the role. Look for staff who are self-motivated, empathetic, and willing to adapt to different school environments and cultures. Envision who the students would want to work with: hiring from local communities, where staff know and can connect with the population, is important. Finally, ensure that the selection process provides opportunities for multiple stakeholders  to share input so that there is buy-in from the start.Fostering a spirit of collaboration and ownership among frontline staff, supervisors, and program leadership can go a long way in building a strong system for implementation and addressing early challenges. For New Heights, this collaborative spirit was driven by highly supportive leaders and experienced peers. Program leaders should incorporate regular opportunities for meaningful engagement as a team, sharing challenges and concerns as a group to brainstorm solutions and encouraging self-care. Clear communication and a safe space to share their perspectives helps staff develop a strong connection to the program model, and to the families they are serving, and believe in what they are trying to achieve together.Cultivating and building trust with school staff and local partners were critical for New Heights and formed the foundation for successful program delivery on the ground. Program leaders and staff based in the school should invest in understanding the local context and develop relationships with teachers, administrators, support staff, and students. To secure their support, coordinators can highlight program benefits and find ways in which program staff can relieve burdens for teachers and administrators to help them more easily serve their most challenging students. Volunteering at school events, sharing progress at administrative meetings, and offering assistance and resources can increase buy-in and help meet the needs of young parents.This study builds on and adds to the existing research with lessons that can be drawn from programs serving expectant and parenting youth.After its federal grant ended, New Heights had to reduce the number of school-based coordinators and prioritize schools with the greatest number of expectant and parenting students. Staff adjusted their model and sustained their program by using rotating coordinators for schools with a smaller number of potential participants (Asheer et al. This study had some limitations. Its findings are based on the program’s implementation in a specific setting. When considering replication, program leaders should keep in mind that the staffing and structural elements described here were designed for expectant and parenting mothers in schools in Washington, DC, with large student populations and a plethora of community-based resources in an urban setting, so they may not be generalizable to other contexts or populations. In addition, the program aims to serve both mothers and fathers, but the study focused primarily on female participants and thus cannot draw conclusions about the program’s components that would be effective for working with fathers.


The support of people with profound intellectual and multiple disabilities (PIMD) rarely focused on motor activity, which might have negative consequences for the quality of life of these people. Evidence-based motor activity programs that present individually tailored and structural motor activity for these people are, regretfully, lacking. This study developed such a program for these people and evaluated the implementation process.n = 9). Process evaluation included the delivered fidelity, dose, reach, and adaptations made during the program. In addition, mechanisms of impact and the influence of contextual factors were evaluated. Data collection included researcher logbooks, individual program content, and staff reports.The motor activity program is developed in accordance with the theoretical premises of the educational program and consists of four methodological steps in which the content is individually filled with: motor activity structurally embedded within the activities of daily living, and 3–5 motor activities aimed at a specific goal, which is evaluated. Program delivery consisted of a manual, explanation to the teams, and coaching of one contact person per participant  study was registered at the Netherlands Trial Register (number 6627) on February 10, 2017:  In order to improve the functioning and participation in daily activities of people with profound intellectual and multiple disabilities (PIMD) , stimulaTo date, it seems, however, that structural stimulation of the motor domain is often lacking in the daily support of people with PIMD , 12, 13.The integration of motor activities, however, needs to be well considered in the support of a person with PIMD. The group of people with PIMD is heterogeneous and particularly vulnerable with each person having their own special needs, abilities and preferences . To ensuThere are, however, only early indications of the effects of specific motor activities  for people with PIMD , 23, 24.To date, there is no program that presents motor activity opportunities for structural integration in a methodical, individually focused, and goal-oriented way including systematic monitoring and evaluation of outcomes at an individual level in people with PIMD. Such a program is important to ensure that people with PIMD optimally benefit from motor activity to contribute to the quality of life of these people. In addition, this will increase the available body of knowledge on the relationships between specific motor activities and specific outcomes for people with PIMD. Therefore, the aim of this study was to develop a program which has the purpose to ensure structural and goal-oriented motor activity of people with PIMD within an individual tailored and continuing program and from the perspective that motor activities can contribute also above and beyond the motor domain. In addition, this study aimed to investigate the conditions essential to a successful implementation, by evaluating the process of implementation within the support of people with PIMD at a residential care facility in the Netherlands.The motor activity program was designed to ensure that the use of motor activity optimally contribute to, and enhance the quality of, the support of people with PIMD. The ultimate aim of this program is that consideration is given to the way in which motor activity can contribute to the support of the person with PIMD and that motor activity is structurally embedded within the support using a fixed amount of motor activity. The program can be seen as a framework compromising four steps to ensure working in a methodical and goal-oriented way. Within the program, the content should be filled individually with motor activity structurally imbedded within the activities of daily living and 3–5 motor activities aimed at a specific goal. Capturing the content and focus of the activities together with goal-oriented and systematic evaluation, as part of the program, provides measurable insight into the results on an individual level.The motor activity program is developed from the view that structural stimulation of the motor domain is a prerequisite for the improvement of the quality of life of persons with PIMD . In addiIn the first step, a personal description about individual needs and possibilities on the motor domain is bundled to a motor profile. To create this personal profile, we have relied on the statement of Van der Putten [In the second and third step, based on the motor profile, interdisciplinary consensus is reached on the way of facilitating motor activity of the person with PIMD within five everyday situations  [In the fourth step, evaluation of the performance of activities and goals took place. After 12 weeks of activity performance, staff reports are evaluated by the use of the goal attainment scale  to accomplishing an end goal (+ 2)) and new goals should be formulated [Based on the theoretical premises of the educational program , 27, ther Putten  indicatir Putten . In the ansfers) . In addiansfers) , 19. Theansfers) , 32. In ansfers) –24). As ansfers) , also eaansfers) . This isrmulated , 28.FigThe implementation of the motor activity program was designed consisting of three phases including critical elements within these phases and related to a fixed time schedule  and to check per participant whether study participation was possible. In addition, the living units and activity groups of the participants had to be informed by the internal physical therapist. Also, the purpose and content of the motor activity program had to be explained during the quarterly team meetings of the living units at which parents or legal representatives were also invited. Next, one contact person  had to be provided with the manual and trained to be able to give content to the program. Therefore, program delivery consisted of a manual (including the resources required for each program step), explanation to the teams, and coaching of one contact person per participant. Within the manual, for each of the program steps it was explained what information is needed, who is responsible (attributed to the location), and how to use the forms. In addition, specific attention within program delivery was paid to the normative view and program steps to ensure methodological and interdisciplinary working and monitoring and evaluation of implementation and goals.A period of 8 weeks had been assumed to give content to the individual programs before actual performance of, and reporting on, the activities , implementation dose (the quantity of the program implemented), reach (involvement of devised responsible staff), and adaptations made [Mechanisms of impact referred to the participant outcomes based on the program content and performance and understanding of unexpected pathways and consequences. Context referred to the factors that may have affected the implementation and outcomes. Qualitative and quantitative data were gathered during implementation using the following data sources: individual program content of the motor activity program , staff reports and evaluations as part of the program , and a logbook which included for each of the participants the role of the researcher with all dates of contact with the contact person and other involved professionals, the time schedule of the steps taken, and observed barriers directed by selected potential factors  [ons made . Mechanin staff) , 37.Descriptive statistics (frequencies and percentages) were applied to the quantitative data . Documentary and content analysis were performed on the logbook, individual program content, and staff reports. This documentary and content analysis focused on the execution of the program compared to the intention of the program with regard to the time schedule, critical elements in implementation and content of the program. It was analysed whether the critical elements in implementation and the content of the program were executed as intended (+), executed but not entirely as intended (+/−), or not executed (−). It also focused on intended outcomes vs. actual outcomes and reasons if motor activities were not performed. We also evaluated whether the devised responsible staff were involved in the implementation phases and related critical elements of implementation. In addition, the factors that may have affected the implementation and outcomes were described.introduction of the program, all involved stakeholders were informed and agreement was given for participation. In addition, the quarterly team meetings of the living units were attended to further explain the program. In one case, however, the quarterly team meeting occurred later than intended, because of unforeseen circumstances  (see Table During All contact persons agreed to collect and bundle the required information for the motor profile and to schedule an interdisciplinary meeting. Two contact persons related to four participants (participant 4 and 5 and 8 and 9), however, were unable to fulfill the information for the motor profile and to organize the interdisciplinary meeting. One had to delegate the tasks because she changed jobs and the other contact person conveyed the tasks unclearly (based on communication with involved staff) and was unreachable for a certain period. For these four participants, in consultation with management, assistance by one of the researchers (first author) was given to continue the implementation process by organizing and joining a meeting with a participant representative of the living unit and a participant representative of the activity group. For two of these participants, it was forced to have a meeting with the representative of the living unit and activity group separately, because of non-matching working hours. They were in contact by e-mail and in one case they subsequently involved the health care psychologist to give content to the program. As shown in Tables For most other participants, setting up the motor profile and interdisciplinarity were not entirely executed as intended. Only in the case of four participants (44.4%) the health care psychologist was involved in setting up the motor profile , it took longer than intended to performance of the program started later in time and for none of the participants the program has been fully performed within the timetable set for pilot testing  the performance and reporting on activities went different from intended  was described in relation to involvement in general, and not facilitating motor behaviour, with the argument of the participant being unable to contribute motorically. In addition, in the case of two participants, the way of facilitating motor activity within the 3–5 motor activities integrated in the weekly program included one of the everyday situations already described within the program. In addition, the duration and moment of performance of the motor activities were not described for two of the attending participants. With regard to the content in relation to the goals set, in three participants, previously offered motor activities were described, but without all activities having a clear link with the goal set. In addition, the previously offered motor activity within the weekly programs of four participants (44.4%) were substantially changed after implementation of the program. In the other cases, no changes were made although the already offered 3–5 motor activities were now more explicitly focused because of the goal set.The context likely influenced the implementation and outcomes. It is showed that “contextual problems” in the first steps  directly leads to a program without collaboration between professionals and performing of next steps while previous steps are incomplete , but only in one participant (11.1%) all critical steps in implementation were performed as intended, though later in time. In addition, only of three participants (33.3%), staff reports on the performance and outcomes of motor activities could be evaluated. It is showed that the core components of the program were affected with the conceived implementation plan. The time schedule, critical steps in implementation and program content were influenced by a lack of conditions such as professionals’ motivation and responsibility, methodical working, interdisciplinarity and continuity in staff, leading to a decreased implementation fidelity and dose.The core components of the motor activity program are based on normative and theoretical statements which cannot be dissociated from the program. Methodical and goal-oriented working with explicit and planned actions as well as systematic evaluation within an interdisciplinary context are required to ensure that the support fits the needs and preferences of each individual with PIMD . Based oTo improve the implementation process of the motor activity program in practice, it is important that more attention is paid to the structure for implementation . As the To ensure that the motor activity program will be implemented with quality, the core components of the program should be leading in a training program for a team of professionals. Attention should be paid to the organizational conditions to enable the organization to function better in activities such as an interdisciplinary collaboration and in procedures to achieve the goals  . In addiThe main strength of this study is that an innovative theory-based motor activity program designed to improve the structural and goal-oriented motor activation imbedded in the support of people with PIMD, was implemented in practice. In addition, the process evaluation enabled the identification of factors crucial to preserve the core components of the intervention. In addition, the results provides suggestions to improve future implementation. Moreover, the current results also showed the added value of goal-oriented and methodological working and evaluation of motor activity at an individual level. As there was no program that presents motor activity opportunities for structural integration in a methodical, individually focused, and goal-oriented way including systematic monitoring and evaluation of outcomes at an individual level in people with PIMD, the results form an important step toward evidence based support for motor activity for people with PIMD.The main limitation of this study is that it represents the implementation process in the context of one residential facility, so the results were strongly influenced by the initial situation with regard to the current way of working and based on the vision on the target group as well as on the importance of motor activation. As several projects aimed at motor activity and lifestyle had already been carried at this facility it could be that the added value of capturing the activities and goal-oriented and systematic evaluation should have been more emphasized in order to see its value. In addition, if the facility had already worked with the educational program, this would most likely have facilitated the implementation fidelity and dose. It is not clear whether implementation at another residential facility would have led to similar results. In addition, the implementation process of the motor activity program possibly also improves if all persons from one living unit or activity group are involved within such innovations. The nine participants with PIMD that participated in the current study were recruited based on the criteria from Nakken and Vlaskamp . Due to Moreover, although we would argue that the researchers were close enough to the implementation of the program to record crucial problems and to track why these occurred after all , this stAnother limitation is that the logbook data of the current study were originally intended to be better able to interpret the outcomes of the program during pilot testing. Specific factors have been noted, but data are limited to what has come to the attention of the researcher. Although the first author was on location almost every day during implementation, the logbook data are limited to those that came across at the work floor and which were came up during the contacts with the staff involved. Different methods of data collection and a more thorough devised implementation plan with barriers seen by the location beforehand would probably have led to a more specific data collection. For future research, it is recommended that the process evaluation includes broader data from all stakeholders involved in the development and implementation of the program . This maAnother point to bear in mind is that although the conceived program has been based on a social-behavioural framework , the proAnother point to bear in mind is that the forms of the motor activity program had to be used on paper, because it was not allowed to make adaptations to the online reporting system during pilot testing. Although conclusions cannot be drawn from current data, we suggest that the lack of reporting and performance of activities may have been hampered by inability to use the standard online reporting system. To improve future applications, it is important that we learn from experience and that such resources as the standard reporting system should be available and adapted to innovations .This study presented the development and evaluation of a motor activity program including the lessons learned during implementation. The findings led to substantial changes in the implementation strategy with the recommendation of a training program with specific content for a team of professionals. Moreover, it also indicates that motor activity for people with PIMD can contribute also beyond the motor domain, for example on pleasure, independence and alertness. Further studies can build on these findings towards quality implementation and to increase the knowledge about the relationships between motor activities and specific benefits for persons with PIMD.


Several states are in the process of developing or implementing programs that use a social insurance approach to financing long-term services and supports (LTSS). The National Academy of Social Insurance developed a roadmap that highlights key design parameters for states to consider in crafting a program. It also outlines a range of vetted approaches states could adopt, and describes the building blocks and tradeoffs associated with a range of options. States that establish a new LTSS program will need to make decisions about the integration of the program with other payers and benefit programs as well as address concrete implementation challenges. This presentation summarizes these issues including coordination of benefits with other payers, Federal Medicaid funding issues, integration of LTSS and medical care, and challenges around program startup, administration and monitoring as well as evaluation and modification. Addressing such issues is critical to the success of these type of programs.


Program utilization was 6.4% for all methods combined. Inferring a causal relationship between referral method and program utilization was not possible because the study did not use a randomized design. Innovation is needed to generate higher utilization rates for cancer center smoking cessation programs.Most people who smoke and develop cancer are unable to quit smoking. To address this, many cancer centers have now opened smoking cessation programs specifically designed to help cancer patients to quit. An important question has now emerged—what is the most effective approach for engaging smokers within a cancer center in these smoking cessation programs? We report outcomes from a retrospective observational study comparing three referral methods—traditional referral, best practice advisory (BPA), and direct outreach—on utilization of the Duke Cancer Center Smoking Cessation Program. We found that program utilization rate was higher for direct outreach (5.4%) than traditional referral (0.8%),  Treatment of tobacco dependence is uniquely important in people with cancer. In the United States, smoking causes approximately 28.6% of all cancer deaths  and causA diagnosis of cancer is widely considered to be a teachable moment—a somewhat rare opportunity that arises in a person’s life when major behavioral change is possible . That saThere is a now a wide variety of evidence-based smoking cessation treatments available, including seven FDA-approved smoking cessation medications , and an A key step in helping cancer patients to quit smoking is referral to a smoking cessation program. We discuss three methods of patient referral in this paper—traditional referral, best practice advisory (BPA), and direct outreach . The defWe conducted a retrospective observational study on data from patients referred to the Duke Cancer Center Smoking Cessation Program by traditional referral and BPA over a 1-year period between 1 October 2017 and 30 September 2018. In addition, we conducted pilot testing of direct outreach from 1 July to 31 July 2018. We then used these data to compare all three referral methods—traditional referral, best practice advisory, and direct outreach—on referral rates and program utilization. Primary outcomes for this study were program referral rate (the portion of smokers attending visits at Duke Cancer Center who were referred to the Duke Cancer Center Smoking Cessation Program) and program utilization rate (the portion of cancer center smokers who attended an appointment at the Duke Cancer Center Smoking Cessation Program). Data were analyzed using descriptive analyses and chi-square for comparison of groups. This study was supported by funding from the National Cancer Institute, grant supplement P30-CA014236-43S3. The study was approved by the Duke University Health System Institutional Review Board. As a retrospective observational study on aggregate patient outcomes of routine clinical care, the study did not require notification of or consent from patients or providers.The Duke Cancer Center Smoking Cessation Program employs a team-based approach with collaboration of medical and behavioral providers trained through the Duke-UNC Tobacco Treatment Specialist Training Program. The Duke Cancer Center Smoking Cessation Program exclusively serves the Duke Cancer Center. Current tobacco users who receive care of any kind  at Duke Cancer Center may be referred to the Duke Cancer Center Smoking Cessation Program from any Duke Cancer Center provider . Cancer center providers can refer their patients to the Duke Smoking Cessation Program by placing an order in the electronic health record. In addition, cancer center providers received a BPA  on all of their patients who were current smokers, informing them that their patient was a current smoker, and presenting an electronic link to refer their patient to the program. Cancer center providers were not required to make a program referral and only made a referral if this arose naturally during cancer care. Cancer center providers were unaware that an observational study was being conducted to assess referral outcomes. As such, providers referred patients as they normally do during routine clinical care. Direct outreach was not conducted by medical providers and was conducted by program staff.no answer, patient declined, call back later, and appointment scheduled. All referrals receive a minimum of three call attempts. Patients who decline services are offered referral to QuitlineNC, a national telephonic tobacco quitline [cancel or reschedule; and patients will sometimes be a no show to an appointment. Patients receive a phone call from a Program Coordinator six months after their first scheduled appointment regardless of whether they attended. If that patient is continuing to use tobacco, program services are offered again. A small number of patients received more than one form of referral; these were patients who agreed to an appointment through direct outreach, but their providers also placed a traditional referral. This occurred in 2 patients—one was counted as a traditional referral, the other as direct outreach.Once a patient is referred, they are contacted by a Program Coordinator who describes the program and assists in triage and scheduling. Referral outcomes collected include the following: quitline . QuitlinIn our program, BPA is opt-in, not opt-out, such that the provider must open the BPA alert and place a referral. The alert does not provide a hard stop and may be ignored in order to manage other issues. Nursing staff are encouraged to click the BPA and are able to create a pended order, which can then be signed by the medical provider. To maximize the use of BPA, we provided instructions at all provider and staff presentations. In most cases, training on how to open the BPA alert occurred at the same time as training on how to place a program referral. The BPA build was not time-consuming for our technical staff, and BPAs are commonly used at Duke for other purposes.We conducted a 30-day pilot study on direct outreach. For this study, we generated a list from the electronic health record showing all tobacco users with an appointment at the Duke Cancer Center in the next 30 days and then called these patients by phone to offer services. If there was no response, patients were sent an electronic message through the electronic health record patient communication portal. Direct outreach was conducted by a social worker and a medical assistant, both with training as tobacco treatment specialists. These staff members are intimately familiar with the program and capable of addressing patient questions with a degree of sophistication. The two providers spent 60 h (3 h/day × 20 days) making outreach calls.Duke requires that every patient’s smoking history is updated by nursing staff at each clinical visit. Patients in our program were identified as smokers by accessing the smoking history component of the electronic health record. Duke requires that smoking history be updated for each patient by nursing staff at each clinical visit, although there are currently no data on how well nursing staff complies with this requirement.BPA: Data on BPA outcomes were obtained from an electronic health record dataset designed to track BPA referrals. Direct Outreach: Direct outreach was piloted over a 30-day period with program referral and utilization outcomes tracked on each patient through the pilot study database. Clinical Outcomes: Data entry within the Duke Cancer Center Smoking Cessation Program is algorithmic, such that key data elements are entered into the electronic health record at every visit. Data collected include smoking history, cancer diagnosis, psychiatric history, previous smoking cessation treatment, and carbon monoxide breath testing to assess smoking abstinence and reduction. Analysis: Data were analyzed using descriptive analyses and chi-square for comparison of groups. Data on traditional referral and BPA were compared using 12-month datasets. Data on direct outreach were compared to other referral methods using 30-day datasets. Data presented here are based on unique patients; repeat visits for individuals are not included so as to avoid double counting.Data on program referrals and appointment attendance were collected through a referral database in EPIC, an electronic health record system. In the 12-month assessment period, the roughly 150 Duke Cancer Center clinicians  cared for over 50,000 patients, including 6040 smokers (approximately a 12% rate of current smoking). Of these, patients who attended an appointment with the Duke Cancer Center Smoking Cessation Program had a mean age of 53.8 (SD 10.1); 43.7% were female, 28.1% were African American, 65.6% were Caucasian, and 6.3% were other/unknown/not reported race. Primary insurance providers were 56.3% Medicare/Medicaid, 31.2% private insurance, and 12.5% self-pay.2  = 61.4, p < 0.001. The program utilization rate over a 12-month period was defined as the total number of patients who attended an appointment at the Duke Cancer Center Smoking Cessation Program divided by the total number of current smokers seen at Duke Cancer Center. During the 12-month assessment period, 99 unique patients attended the Duke Cancer Center Smoking Cessation Program for a program utilization rate of 1.6% (99/6040). Of these 99 program attendees, traditional referral resulted in 91 attendees (1.5% utilization rate), significantly higher than BPA, which resulted in 8 program attendees (0.1% utilization rate); X2  = 68.5, p < 0.001. The chance of interaction between referral methods  was low due to low overall utilization rates .Over the 12-month period, 6040 current smokers received care of any kind  by any Duke Cancer Center provider . Duke Cancer Center providers had access through the electronic health record to place an order for their patients to be referred to the Duke Cancer Center Smoking Cessation Program. In addition, cancer center providers received a BPA  on all of their patients who were current smokers, informing them that their patient was a current smoker, and presenting an electronic link to refer patients to the program. The referral rate over a 12-month period was defined as the total number of patients who were referred to the Duke Cancer Center Smoking Cessation Program divided by 6040—the total number of current smokers seen by any provider at the Duke Cancer Center. During the 12-month assessment period, the Duke Cancer Center Smoking Cessation Program received a total of 230 referrals, a referral rate of 3.8% (230/6040). Traditional referral led to 183 of these referrals  and was significantly higher than BPA, which led to 47 referrals ; X2  = 16.1, p < 0.001. Differences in program utilization between traditional referral and direct outreach were not significant, but the numbers were so small (1 attendee vs. 4 attendees) that statistical comparison was not meaningful.Over the 30-day period (1 July–30 July 2018), we pilot-tested direct outreach to assess program referral rate and utilization rate for this referral method . During Carbon monoxide (CO) breath testing was collected at all clinic visits to assess smoking abstinence , but selA comparison of the three referral methods showed that direct outreach led to higher rates of program referral and program utilization than traditional referral, and that traditional referral was associated with higher rates of program utilization than BPA. Although differences in program utilization between these referral methods were fairly large, it was not possible to infer a causal relationship between referral method and program utilization because patients were not randomized to referral methods. An important conclusion from these outcomes is that traditional referral alone may be insufficient for recruitment of patients into a cancer center smoking cessation program. This is an important finding because most smoking cessation programs at least begin by relying on traditional referral as the primary means of referral. Our findings suggest that, if possible, efforts should be made to expand methods of patient outreach beyond traditional referral.A commonly expressed critique of smoking cessation programs is that all outcomes appear to be low. Although there is a need for improvement, it is important to recognize that at any given time, the percentage of smokers who are willing to make a quit attempt is typically only 14–20% ,42,43,44Traditional referral led to a program utilization rate of only 1.5% (12-month data) of all smokers receiving services at the Duke Cancer Center. One reason for this low referral rate could be that oncology providers tend to be busy and often do not feel that there is sufficient time to discuss smoking cessation while providing cancer treatment services . This loAlthough, this study was not randomized and provided no assurance regarding bias, an unexpected finding was that BPA had quite a small effect (0.2% for 12 months) on program utilization. The most common explanation for the relatively low use of the BPA is alert fatigue, in which an electronic health record presents so many alerts that providers ignore them in order to complete more pressing work ,52. StudAlthough this study provided no assurance regarding bias, direct outreach appeared to be associated with higher program utilization. The major challenge to implementation of direct outreach methods within a smoking cessation program is that manual phone calls (our approach) were time-consuming. One solution to this is to develop automated forms of direct outreach. Automated outreach can be conducted through interactive voice response , email aThis study had several limitations. This was a retrospective observational study and patients were not randomized to various referral methods. In a non-randomized trial, it would be impossible to exclude various forms of bias. Another limitation is that the study used two databases  that did not allow for integration of patient-level data; as such, it was not possible to report smoking abstinence for each referral method. This limitation could be overcome in a prospective analysis. The study also included a wide range of patients with varying degrees of illness and barriers to treatment  such that results may not generalize to healthier portions of the general population. Additionally, we provided data on direct outreach for only a 30-day period, with less stability than 12-month outcomes.Smoking cessation is uniquely important for smokers who have cancer; it improves cancer treatment outcomes, reduces cancer recurrence, and reduces overall mortality. It has now been recognized as necessary that cancer centers provide specialized smoking cessation treatment for smokers with cancer. We assessed three approaches to patient recruitment into the Duke Cancer Center Smoking Cessation Program and found that direct outreach  led to the highest rates of program utilization. Traditional referral alone did not lead to high rates of program utilization, and best practice advisory showed rather poor outcomes. Innovative solutions are needed to increase utilization of cancer center smoking cessation programs.