The effect of two lottery-style incentives on response rates to postal questionnaires in a prospective cohort study in preschool children at high risk of asthma: A randomized trial

Background: In research with long-term follow-up and repeated measurements, quick and complete response to questionnaires helps ensure a study's validity, precision and efficiency. Evidence on the effect of non-monetary incentives on response rates in observational longitudinal research is scarce. Objectives. To study the impact of two strategies to enhance completeness and efficiency in observational cohort studies with follow-up durations of around 2 years. Method and intervention. In a factorial design, 771 children between 2 and 5 years old and their parents participating in a prospective cohort study were randomized to three intervention groups and a control group. Three types of lotteries were run: (i) daytrip tickets for the whole family to a popular amusement park if they returned all postal questionnaires, (ii) 12.50-worth gift vouchers for sending back the questionnaire on time after each questionnaire round and (iii) a combination of (i) and (ii). Main outcome measures. Primary outcome was the proportion of participants who returned all questionnaires without any reminder. Secondary outcomes were '100% returned with or without reminder', 'probability of 100% non-response', 'probability of withdrawal', 'proportion of returned questionnaires' and 'overall number of reminders sent'. Statistical analysis. After testing for interaction between the two lottery interventions, the two trials were analysed separately. We calculated risk differences (RD) and numbers needed to "treat" and their 95% confidence intervals. Results: Daytrip nor voucher intervention had an effect on the proportion of participants who returned all questionnaires (RD -0.01; 95% CI-0.07 - 0.06) and (RD 0.02; 95% CI-0.50 - 0.08), respectively. No effects were found on the secondary outcomes. Conclusion: Our findings do not support the idea that lottery-style incentives lead to more complete response to postal questionnaires in observational cohort studies with repeated data collection and follow-up durations of around 2 years

Predicting asthma in preschool children at high risk presenting in primary care: Development of a clinical asthma prediction score

Background: A setting-specific asthma prediction score for preschool children with wheezing and/or dyspnoea presenting in primary healthcare is needed since existing indices are mainly based on general populations. Aims: To find an optimally informative yet practical set of predictors for the prediction of asthma in preschool children at high risk who present in primary healthcare. Methods: A total of 771 Dutch preschool children at high risk of asthma were followed prospectively until the age of six years. Data on asthma symptoms and environmental conditions were obtained using validated questionnaires and specific IgE was measured. At the age of six years the presence of asthma was assessed based on asthma symptoms, medication, and bronchial hyper-responsiveness. A clinical asthma prediction score (CAPS) was developed using bootstrapped multivariable regression methods. Results: In all, 438 children (56.8%) completed the study; the asthma prevalence at six years was 42.7%. Five parameters optimally predicted asthma: age, family history of asthma or allergy, wheezing-induced sleep disturbances, wheezing in the absence of common colds, and specific IgE. CAPS scores range from 0 to 11 points; scores <3 signified a negative predictive value of 78.4% while scores of ≥7 signified a positive predictive value of 74.3%. Conclusions: We have developed an easy-to-use CAPS for preschool children with symptoms suggesting asthma who present in primary healthcare. After suitable validation, the CAPS may assist in guiding shared decision-making to tailor the need for medical or non-medical interventions. External validation of the CAPS is needed

A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four

Background: The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness.Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness.Methods: Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments.Results: 8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies.Conclusion: Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation

Defining frequent attendance in general practice

Background: General practitioners (GPs) or researchers sometimes need to identify frequent attenders (FAs) in order to screen them for unidentified problems and to test specific interventions. We wanted to assess different methods for selecting FAs to identify the most feasible and effective one for use in a general (group) practice. Methods: In the second Dutch National Survey of General Practice, data were collected on 375 899 persons registered with 104 practices. Frequent attendance is defined as the top 3% and 10% of enlisted patients in each one-year age-sex group measured during the study year. We used these two selections as our reference standard. We also selected the top 3% and 10% FAs (90 and 97 percentile) based on four selection methods of diminishing preciseness. We compared the test characteristics of these four methods. Results: Of all enlisted patients, 24 % did not consult the practice during the study year. The mean number of contacts in the top 10% FAs increased in men from 5.8 (age 15-24 years) to 17.5 (age 64-75 years) and in women from 9.7 to 19.8. In the top 3% of FAs, contacts increased in men from 9.2 to 24.5 and in women from 14 to 27.8. The selection of FAs becomes more precise when smaller age classes are used. All selection methods show acceptable results (kappa 0.849 - 0.942) except the three group method. Conclusion: To correctly identify frequent attenders in general practice, we recommend dividing patients into at least three age groups per se

Pilot study evaluating the effects of an intervention to enhance culturally appropriate hypertension education among healthcare providers in a primary care setting

Background: To improve hypertension care for ethnic minority patients of African descent in the Netherlands, we developed a provider intervention to facilitate the delivery of culturally appropriate hypertension education. This pilot study evaluates how the intervention affected the attitudes and perceived competence of hypertension care providers with regard to culturally appropriate care.Methods: Pre- and post-intervention questionnaires were used to measure the attitudes, experienced barriers, and self-reported behaviour of healthcare providers with regard to culturally appropriate cardiovascular and general care at three intervention sites (N = 47) and three control sites (N = 35).Results: Forty-nine participants (60%) completed questionnaires at baseline (T0) and nine months later (T1). At T1, healthcare providers who received the intervention found it more important to consider the patient's culture when delivering care than healthcare providers who did not receive the intervention (p = 0.030). The intervention did not influence ex

Inflammatory chemokine receptors regulate CD8+ T cell contraction and memory generation following infection

CD8+ T cells lacking CXCR3 and CCR5 expression have impaired contraction and generate an increased number of memory cells after virus infection

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Culturally Adapted Hypertension Education (CAHE) to Improve Blood Pressure Control and Treatment Adherence in Patients of African Origin with Uncontrolled Hypertension: Cluster-Randomized Trial

<div><p>Objectives</p><p>To evaluate the effect of a practice-based, culturally appropriate patient education intervention on blood pressure (BP) and treatment adherence among patients of African origin with uncontrolled hypertension.</p><p>Methods</p><p>Cluster randomised trial involving four Dutch primary care centres and 146 patients (intervention n = 75, control n = 71), who met the following inclusion criteria: self-identified Surinamese or Ghanaian; ≥20 years; treated for hypertension; SBP≥140 mmHg. All patients received usual hypertension care. The intervention-group was also offered three nurse-led, culturally appropriate hypertension education sessions. BP was assessed with Omron 705-IT and treatment adherence with lifestyle- and medication adherence scales.</p><p>Results</p><p>139 patients (95%) completed the study (intervention n = 71, control n = 68). Baseline characteristics were largely similar for both groups. At six months, we observed a SBP reduction of ≥10 mmHg -primary outcome- in 48% of the intervention group and 43% of the control group. When adjusted for pre-specified covariates age, sex, hypertension duration, education, baseline measurement and clustering effect, the between-group difference was not significant (OR; 0.42; 95% CI: 0.11 to 1.54; P = 0.19). At six months, the mean SBP/DBD had dropped by 10/5.7 (SD 14.3/9.2)mmHg in the intervention group and by 6.3/1.7 (SD 13.4/8.6)mmHg in the control group. After adjustment, between-group differences in SBP and DBP reduction were −1.69 mmHg (95% CI: −6.01 to 2.62, P = 0.44) and −3.01 mmHg (−5.73 to −0.30, P = 0.03) in favour of the intervention group. Mean scores for adherence to lifestyle recommendations increased in the intervention group, but decreased in the control group. Mean medication adherence scores improved slightly in both groups. After adjustment, the between-group difference for adherence to lifestyle recommendations was 0.34 (0.12 to 0.55; P = 0.003). For medication adherence it was −0.09 (−0.65 to 0.46; P = 0.74).</p><p>Conclusion</p><p>This intervention led to significant improvements in DBP and adherence to lifestyle recommendations, supporting the need for culturally appropriate hypertension care.</p><p>Trial Registration</p><p>Controlled-Trials.com <a href="http://www.controlled-trials.com/ISRCTN35675524" target="_blank">ISRCTN35675524</a></p></div

A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four

Background: The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness. Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness. Methods: Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e. g. through placebo) connections between all treatments. Results: 8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies. Conclusion: Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementatio

Summary of three culturally adapted hypertension education sessions.

<p>(i) Using culturally-sensitive framework for eliciting a patient's explanatory model of hypertension (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090103#pone-0090103-t002" target="_blank">table 2</a>); (ii) using information from hypertension guidelines <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090103#pone.0090103-Smulders1" target="_blank">[35]</a>. (iii) using “5 As” method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090103#pone.0090103-Whitlock1" target="_blank">[18]</a>.</p