Moderation of associations between interparental stress and (mal)adaptation by adolescents' personality: Contrasting differential susceptibility and diathesis-stress models.

OBJECTIVE: This study aimed to contrast differential susceptibility and diathesis-stress models in examining adolescents' Big Five personality dimensions as moderators of longitudinal associations between interparental stress and (mal)adaptation in emerging adulthood (i.e., self-efficacy, externalizing and internalizing behavior). METHOD: Data from the large longitudinal Flemish Study on Parenting, Personality and Development were used (475 families, adolescents' Mage  = 15.82, SDage  = 1.15), with both parents reporting on their interparental stress and mothers reporting on the adolescent's personality and in 2009, and emerging adults reporting on their own (mal)adaptive functioning in 2009 and 2015 and their personality in 2015. RESULTS: Multivariate models showed that extraversion, benevolence, emotional stability and imagination were uniquely related to (mal)adaptation across the 6-year interval. In general, our results exhibited no consistent moderating role for adolescents' personality. Only for girls, high levels of extraversion functioned as a "susceptibility maker" in associations between father's interparental stress and self-efficacy, and, low levels of emotional stability functioned as a "vulnerability marker" in associations between parents' interparental stress and self-efficacy. CONCLUSIONS: The interaction effects as well as their (restricted) generalizability across gender should be replicated before drawing firm conclusions. Adolescents' personality characteristics were important predictors of (mal)adaptation during the transition into emerging adulthood.

Psychotherapy for posttraumatic stress disorder in patients with borderline personality disorder: a systematic review and meta-analysis of its efficacy and safety.

Background: Posttraumatic stress disorder (PTSD) is common in patients with personality disorders. This comorbidity is accompanied by a lower quality of life, and a higher risk of suicide attempts than patients with only one of these diagnoses. Objective: The aim of this systematic review and meta-analysis was to evaluate the scientific evidence of the efficacy of PTSD treatments for this population. Method: A literature search was performed from 1946 through June 2020. Standardized mean effect sizes of psychotherapy for PTSD were computed. Results: The literature search revealed that psychotherapy was the only intervention that was systematically explored. Fourteen studies were included. In 12 of these studies solely patients with borderline personality disorder participated. Analysis of the four RCTs showed a significant, moderate to high standardized effect size for reducing PTSD symptom severity (Hedges' g = 0.54), with effects being maintained at least 3 months (Hedges' g = 0.82). Effect sizes for all studies were also significant, with moderate to high standardized values for symptoms of PTSD (Hedges' g = 1.04). PTSD improvements were again maintained at 3-month follow-up and beyond (Hedges' g = 0.98). In addition, a significant decrease in symptoms of depression, anxiety, borderline symptoms, and PTSD in patients with borderline personality disorder could be revealed for all studies (Hedges' g 0.48-1.04). No increase in self-injurious behaviour, suicide attempts, or hospitalization was observed, while the mean weighted dropout rate during PTSD treatment was 17%. Conclusions: Psychotherapy for PTSD is efficacious and safe for patients with borderline personality disorder and should not be withheld from these vulnerable individuals.

Antecedentes: El trastorno de estrés postraumático (TEPT) es común en pacientes con trastornos de la personalidad. Esta comorbilidad se acompaña de una menor calidad de vida y un mayor riesgo de intentos de suicidio que los pacientes con solo uno de estos diagnósticos.Objetivo: El propósito de esta revisión sistemática y metanálisis fue evaluar la evidencia científica de la eficacia de los tratamientos de TEPT para esta población.Método: Se realizó una búsqueda bibliográfica desde 1946 hasta junio de 2020. Se calcularon los tamaños de efecto promedio estandarizados de la psicoterapia para el TEPT.Resultados: La búsqueda de la literatura reveló que la psicoterapia fue la única intervención explorada sistemáticamente. Se incluyeron catorce estudios. En doce de estos estudios participaron únicamente pacientes con trastorno límite de la personalidad. El análisis de los cuatro ECA mostró un tamaño de efecto estandarizado significativo, moderado a alto, para reducir la gravedad de los síntomas de TEPT (Hedges' g = 0.54), con efectos que se se mantenían al menos tres meses (Hedges' g = 0.82). Los tamaños del efecto para todos los estudios también fueron significativos, con valores estandarizados moderados a altos para síntomas de TEPT (Hedges' g = 1.04). Las mejoras del TEPT también se mantuvieron a los 3 meses de seguimiento y más allá (Hedges' g = 0.98). Adicionalmente, en todos los estudios podría ser revelada una disminución significativa de los síntomas de depresión, ansiedad, síntomas límite y trastorno de estrés postraumático en pacientes con trastorno límite de la personalidad (Hedges'g 0.48 ­ 1.04). No se observó aumento en el comportamiento autolesivo, intentos de suicidio u hospitalización, mientras que la tasa de abandono ponderada media durante el tratamiento del TEPT fue del 17%.Conclusiones: La psicoterapia para el trastorno de estrés postraumático es eficaz y segura para pacientes con trastorno límite de la personalidad y no debiera ser negada a estos individuos vulnerables.

The interparental relationship: Meta-analytic associations with children's maladjustment and responses to interparental conflict.

The aim of the current meta-analysis was to aggregate concurrent and longitudinal empirical research on associations between the interparental relationship and both children's maladjustment (i.e., externalizing and internalizing symptoms) and children's responses to interparental conflict (i.e., emotional, behavioral, cognitive, and physiological). Based on major theoretical frameworks, we distinguished between six dimensions of the interparental relationship: relationship quality, conflict frequency, hostile, disengaged, and unconstructive forms of conflict, and child-related conflict. A final selection of 169 studies for child maladjustment and 61 studies for child responses to conflict were included. The findings revealed by the expansive and fine-grained approach of this meta-analysis support and challenge theoretical hypotheses about the relative predictive value of dimensions of the interparental relationship for children's functioning. Although hostility was specifically more strongly associated with children's externalizing behavior and emotional responses to conflict, disengaged and unconstructive conflict behavior posed similar risks for the other domains of child functioning. In addition, relationship quality, conflict frequency, and child-related conflict warrant more attention in theoretical frameworks, as these dimensions posed similar risks to child functioning as the different forms of conflict. Moreover, most associations between the interparental relationship and child functioning endured over time. Also, developmental and gender differences appeared to depend on the specific forms of interparental conflict and the domain of child functioning. In sum, the results support the growing consensus that prevention and intervention programs aimed at children's mental health could benefit from an alternative or additional focus on the interparental relationship. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Nuchal translucency of 3.0-3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review.

INTRODUCTION: Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results. MATERIAL AND METHODS: A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period July 2012 to June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0 and 3.4 mm) tested between September 2015 and December 2018. RESULTS: A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies-1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464). CONCLUSIONS: Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21 to 1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be raised. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinically significant conditions then the genome-wide >10-Mb resolution NIPT test, which detects most aberrations, could be proposed.

Effectiveness of the Air Purification Strategies for the Treatment of Allergic Asthma: A Meta-Analysis.

We updated the meta-analysis published by McDonald et al. [Chest 2002;122;1535-1542] by reviewing the effectiveness of air purification for the treatment of home-related allergic asthma (dust mite, dog, cat, and cockroach). We analysed the trials included by McDonald et al. as well as studies published since 2000. Data on asthma symptoms scores (ASS), medication use, forced expiratory volume in 1 s as a percentage of the predicted value (FEV1 %pred), histamine provocative concentration causing a 20% reduction in FEV1 (PC20), Asthma Quality of Life Questionnaire (AQLQ) scores, and fractional exhaled nitric oxide (FeNO) levels were extracted. The effectiveness was examined using metafor (registered in Prospero CRD42019127227). Ten trials including a total of 482 patients (baseline characteristics: mean FEV1 %pred 83.2%, I2 = 96.7%; mean PC20 4.93 mg/mL, I2 = 44.0%; mean AQLQ 4.67 [max. 7], I2 = 93.7%; mean FeNO 36.5 ppb, I2 = 0%) were included. We assessed the mean differences in the AQLQ scores as +0.36 (95% CI 0.10 to 0.62, p = 0.01, n = 302, I2 = 0%) and the FeNO levels as -6.67 ppb (95% CI -10.56 to -2.77, p = 0.0008, n = 304, I2 = 0%). The standardised mean differences in all other health outcomes were not significant (ASS -0.68, p = 0.20; medication use: -0.01, p = 0.94; FEV1 %pred -0.11, p = 0.34; PC20 +0.24, p = 0.53). We found statistically significant mean differences in the AQLQ scores and FeNO levels in patients with predominantly mild to moderate asthma at baseline. A large trial reported great improvement in the subgroup of patients receiving Global Initiative for Asthma step 4 therapy. We recommend that future studies on air purification focus on patients with severe and poorly controlled allergic asthma.

A meta-analysis of baseline characteristics in trials on mite allergen avoidance in asthmatics: room for improvement.

BACKGROUND: Evidence regarding the clinical effectiveness of mite allergen avoidance for the treatment of asthma is lacking. In previous meta-analyses on mite allergen control, the baseline data were not discussed in detail. This study updates and extends the existing Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187), with a focus on baseline asthma outcomes and allergen exposures. METHODS: We used the existing trials in the original Cochrane review and included newly published studies. The baseline data for the mite allergen load from the mattress, the standardized asthma symptom score (ASS), the forced expiratory volume in 1 s percentage of predicted (FEV1 %pred.), and the histamine provocative concentration causing a 20% drop in FEV1 (PC20) were extracted. First, the mean values of the outcomes were calculated. The influence of the mite allergen load was examined with a random-effect meta-regression using the Metafor package in R. RESULTS: Forty-five trials were included; 39 trials reported strategies for concurrent bedroom interventions, and 6 trails reported strategies for air purification. The mite allergen load ranged from 0.44 to 24.83 µg/g dust, with a mean of 9.86 µg/g dust (95% CI 5.66 to 14.05 µg/g dust, I2 = 99.8%). All health outcomes showed considerable heterogeneity (standardized ASS mean: 0.13, 95% CI 0.08 to 0.18, I2 = 99.9%; FEV1 %pred. mean: 85.3%, 95% CI 80.5 to 90.1%, I2 = 95.8%; PC20 mean: 1.69 mg/mL, 95% CI 0.86 to 2.52 mg/mL, I2 = 95.6%). The covariate mite allergen load did not significantly influence health outcomes. DISCUSSION: This meta-analysis shows that mite avoidance studies are characterized by the inclusion of patients with rather mild to moderate asthma and with varying and sometimes negligible levels of allergen exposure. Future studies should focus on patients with severe asthma and increased levels of allergen exposure.

Personality, depressive symptoms, the interparental relationship and parenting: Prospective associations of an actor-partner interdependency model.

Grounded on Belsky's process model and family systems theories and using an actor-partner interdependency modeling (APIM) approach (Belsky & Jaffee, 2006; Cox & Paley, 2003), the current study was the first to examine whether Big Five personality characteristics and depressive symptoms of parents and their partners are related to adolescent-perceived parenting behavior directly and indirectly via interparental stress experienced by both parents. Longitudinal data (Time 1: 2001; Time 2: 2007; and Time 3: 2009) from a large community sample of Flemish families was used (N = 455; Time 1 children: Mage = 7.10 years). Results revealed that, for both parents, more agreeableness and autonomy predicted more parental warmth, and more depressive symptoms and lower agreeableness predicted more overreactive discipline (i.e., actor effects). Both parents' depressive symptoms predicted their own interparental stress (i.e., actor effects). Regarding partner-effects, paternal overreactive discipline was shaped by mother's extraversion and experienced interparental stress, and paternal warmth was affected by mother's experienced interparental stress in addition to fathers' own psychological resources. In contrast, maternal parenting was affected by their own psychological resources only. Although no consistent mediating role of interparental stress was found, one small dyadic indirect effect indicated that maternal depressive symptoms were related to more paternal overreactive discipline via heightened levels of interparental stress experienced by both parents. These results provide new support for the idea of interdependency between parents and specifically support the fathering vulnerability hypothesis. Tentatively, this study informs clinical practice by showing that family interventions aiming to improve parenting should pay attention to specific personality characteristics affecting parenting behavior and adopt a dyadic approach including both parents, especially when targeting paternal parenting. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Effect of Antiplatelet Drugs on D-Dimer Levels: A Systematic Review and Meta-analysis.

AIMS: D-dimer is a product of fibrinolysis. In clinical practice, D-dimer levels are commonly used to rule out venous thromboembolism. Antiplatelet drugs may influence D-dimer levels, potentially affecting the accuracy of this diagnostic tool. To evaluate the effect of antiplatelet drugs on D-dimer levels, we performed a systematic review and meta-analysis of all published articles on this topic (PROSPERO registration number CRD42017058932). METHODS AND RESULTS: We electronically searched EMBASE, MEDLINE Epub, Cochrane, Web of Science, and Google Scholar (100 top relevance) (last search on October 5, 2017). We included randomized controlled trials, cohort studies, and cross-sectional studies conducted in humans, with a drug exposure time of at least 7 days. Two reviewers independently selected eligible articles and extracted the data. Five controlled trials, 7 cohort studies, and 5 cross-sectional studies were finally included. Meta-analysis involving all 1117 participants showed no change in dimer levels (standardized mean difference: -0.015, 95% confidence interval, 0.182-0.151, P = 0.855). CONCLUSIONS: In conclusion, antiplatelet drugs do not seem to influence D-dimer levels.

A revised systematic review and meta-analysis on the effect of statins on D-dimer levels.

BACKGROUND: D-dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG-CoA reductase inhibitors, more commonly called statins, are known to have effects independent of LDL-cholesterol lowering, including antithrombotic properties. An effect of statins on D-dimer levels has been reported in a prior systematic review and meta-analysis, but methodological shortcomings might have led to an overestimated effect. To re-evaluate the association between statins and D-dimer levels, we systematically reviewed all published articles on the influence of statins on D-dimer levels and conducted a novel meta-analysis (PROSPERO registration number CRD42017058932). MATERIALS AND METHODS: We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (date of last search: 5 October 2017). We included randomized controlled trials, cohort studies and cross-sectional studies. Two reviewers independently screened all articles retrieved and extracted data on study and patient characteristics, study quality and D-dimer levels. RESULTS: Study-level meta-analysis involving 18,052 study participants showed lower D-dimer levels in those receiving statin treatment than controls (SMD: -0.165, 95% CI -0.234; -0.096, P = <0.001). Sensitivity analyses and additional analyses on treatment duration (<12 weeks vs ≥12 weeks) and type of statin (lipophilic or hydrophilic) did not modify this overall result. CONCLUSION: This meta-analysis suggests an association between use of statins and reduction of D-dimer levels, independent of treatment duration and type of statin used. This effect is small but robust, and should be interpreted with caution.

A reintroduction of environmental mite allergen control strategies for asthma treatment and the debate on their effectiveness.

Asthma affects three hundred million people worldwide. The effectiveness of house dust mite allergen control for asthma treatment is debatable. One aspect that has been little discussed in existing meta-analyses is the possible role of environmental strategies. Here, we reintroduce the previously defined strategies for mite allergen control and discuss their importance to the debate on clinical effectiveness. The strategy of concurrent bedroom interventions is related to the combined use of a priori defined interventions, while the strategy of exposure-based control relates to the treatment of relevant textiles after assessing exposure. The air purification strategy aims to purify the human breathing zone of airborne allergens. In Western European patient practice, the use of these strategies differs. A post hoc study of the dominant Cochrane review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187) appears to indicate that a majority of the underlying trials reported on the strategy of concurrent bedroom interventions, which were mainly executed in a minimal manner. Some trials have reported on the air purification strategy and may potentially alter the debate on effectiveness. No trial has reported on the strategy of exposure-based control. We therefore hypothesize that the absence of evidence for the effectiveness of mite allergen control for asthma treatment applies to the strategy of concurrent bedroom interventions. The evidence-based effectiveness of the exposure-based control strategy appears to be undetermined. The results of our post hoc reanalysis urge that future meta-analyses of mite allergen control should a priori define the environmental strategy under study. Future trials of mite allergen control are warranted to test the exposure-based strategy as well as the sparsely tested strategy of air purification.

Impact of intraoperative stimulation mapping on high-grade glioma surgery outcome: a meta-analysis.

BACKGROUND: Intraoperative stimulation mapping (ISM) using electrocortical mapping (awake craniotomy, AC) or evoked potentials has become a solid option for the resection of supratentorial low-grade gliomas in eloquent areas, but not as much for high-grade gliomas. This meta-analysis aims to determine whether the surgeon, when using ISM and AC, is able to achieve improved overall survival and decreased neurological morbidity in patients with high-grade glioma as compared to resection under general anesthesia (GA). METHODS: A systematic search was performed to identify relevant studies. Adult patients were included who had undergone craniotomy for high-grade glioma (WHO grade III or IV) using ISM (among which AC) or GA. Primary outcomes were rate of postoperative complications, overall postoperative survival, and percentage of gross total resections (GTR). Secondary outcomes were extent of resection and percentage of eloquent areas. RESULTS: Review of 2049 articles led to the inclusion of 53 studies in the analysis, including 9102 patients. The overall postoperative median survival in the AC group was significantly longer (16.87 versus 12.04 months; p < 0.001) and the postoperative complication rate was significantly lower (0.13 versus 0.21; p < 0.001). Mean percentage of GTR was significantly higher in the ISM group (79.1% versus 47.7%, p < 0.0001). Extent of resection and preoperative patient KPS were indicated as prognostic factors, whereas patient KPS and involvement of eloquent areas were identified as predictive factors. CONCLUSIONS: These findings suggest that surgeons using ISM and AC during their resections of high-grade glioma in eloquent areas experienced better surgical outcomes: a significantly longer overall postoperative survival, a lower rate of postoperative complications, and a higher percentage of GTR.

The role of the assessment policy in the relation between learning and performance.

CONTEXT: Optimising student learning and academic performance is a continuous challenge for medical schools. The assessment policy may influence both learning and performance. Previously, the joint contribution of self-regulated learning (SRL) and participation in scheduled learning activities towards academic performance has been reported. However, little is known about the relationships between SRL, participation and academic performance under different assessment policies. OBJECTIVES: The goal of this study was to investigate differences in average scores of SRL, participation and academic performance of students under two assessment policies: (i) a conjunctive lower stakes, lower performance standard (old) assessment policy and (ii) a compensatory higher stakes, higher performance standard (new) assessment policy. In addition, this research investigated whether the relationships between academic performance, SRL and participation are similar across both assessment policies. METHODS: Year-1 medical students (i) under the old assessment policy (n = 648) and (ii) under the new assessment policy (n = 529) completed the Motivated Strategies for Learning Questionnaire on SRL, and additional items on participation. Year-1 performance was operationalised as students' average Year-1 course examination grades. manova and structural equation modelling were used for analyses. RESULTS: Generally, students under the new assessment policy showed significantly higher Year-1 performance, SRL and participation, compared with students under the old assessment policy. The relationships between Year-1 performance, SRL and participation were similar across assessment policies. CONCLUSIONS: This study indicates that the higher academic performance under a compensatory higher stakes, higher performance standard assessment policy, results from higher SRL and participation, but not from altered relationships between SRL, participation and performance. In sum, assessment policies have the potential to optimise student learning and performance.

Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis.

Background: : Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.

Efficacy of Tumor Vaccines and Cellular Immunotherapies in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Programmed cell death protein-1- checkpoint blockers have recently been approved as second-line treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, only a subgroup of patients responds and shows long-term survival to these therapies. Tumor vaccines and cellular immunotherapies could synergize with checkpoint blockade, but which of these treatments is most efficacious is unknown. In this meta-analysis, we assessed the efficacy of tumor vaccination and cellular immunotherapy in NSCLC. METHODS: We searched for randomized controlled trials (RCTs) investigating cellular immunotherapy or vaccines in NSCLC. We used random effects models to analyze overall survival (OS) and progression-free survival (PFS), expressed as hazard ratios (HRs), and differences in time (months). The effect of immunotherapy type, disease stage, tumor histology, and concurrent chemotherapy was assessed using subgroup analysis and meta-regression. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: We identified 18 RCTs that matched our selection criteria; these included a total of 6,756 patients. Immunotherapy extended NSCLC survival and PFS, expressed as HR (OS: HR, 0.81, 95% CI, 0.70 to 0.94, P = .01; PFS: HR, 0.83, 95% CI, 0.72 to 0.95, P = .006) and month difference (OS: difference, 5.43 months, 95% CI, 3.20 to 7.65, P < .005; PFS: difference, 3.24 months, 95% CI, 1.61 to 4.88, P < .005). Cellular therapies outperformed tumor vaccines (OS as HR: P = .005, month difference: P < .001; PFS as HR: P = .001, month difference: P = .004). There was a benefit of immunotherapy in low-stage compared with high-stage NSCLC and with concurrent administration of chemotherapy only in one of four outcome measures evaluated (PFS in months: P = .01 and PFS as HR: P = .031, respectively). There was no significant effect of tumor histology on survival or PFS. CONCLUSION: Tumor vaccines and cellular immunotherapies enhanced OS and PFS in NSCLC. Cellular immunotherapy was found to be more effective than tumor vaccination. These findings have implications for future studies investigating combination immunotherapy in NSCLC.

Conversion of Verbal Response Scales: Robustness Across Demographic Categories.

Happiness and life satisfaction have traditionally been measured using verbal response scales, however, these verbal scales have not kept up with the present trend to use numerical response scales. A switch from a verbal scale to a numerical scale, however, causes a severe problem for trend analyses, due to the incomparability of the old and new measurements. The Reference Distribution Method is a method that has been developed recently to deal with this comparison problem. In this method use is made of a reference distribution based on responses to a numerical scale which is used to decide at which point verbally labelled response options transit from one state to another, for example from 'happy' to 'very happy'. Next, for each wave of the time series in which the verbal scale is used, a population mean is estimated for the beta distribution that fits best to these transition points and the responses in this wave. These estimates are on a level that is comparable to that of the mean of the reference distribution and are appropriate for use in an extended time series based on the responses measured using a verbal and a numerical scale. In this paper we address the question of whether the transition points derived for the general population can be used for demographic categories to produce reliable, extended time series to monitor differences in trends among these categories. We conclude that this is possible and that it is not necessary to derive transition points for each demographic category separately.

Pooling Time Series Based on Slightly Different Questions About the Same Topic Forty Years of Survey Research on Happiness and Life Satisfaction in The Netherlands.

Survey research on subjective wellbeing in The Netherlands started in the early 1970s. The time series happiness and life satisfaction that have emerged since then are unfortunately based on slightly different survey items of which one part uses verbal response scales and another part uses numerical response scales. The diversity of the survey items and a number of other measurement issues, such as the effects of changes in survey mode, hamper comparison over time and make it difficult to establish whether life became any better over the last forty years. These problems can be tackled using the recently developed Reference Distribution Method with which responses to equivalent but not identical survey questions can be pooled to obtain long, consistent time series. We applied the Reference Distribution method to pool time series of happiness and life satisfaction. We conclude that in the past 40 years the Dutch have become slightly happier and satisfied with their lives.

Training Medical Specialists to Communicate Better with Patients with Medically Unexplained Physical Symptoms (MUPS). A Randomized, Controlled Trial.

BACKGROUND: Patients with medically unexplained physical symptoms (MUPS) are prevalent 25-50% in general and specialist care. Medical specialists and residents often find patients without underlying pathology difficult to deal with, whereas patients sometimes don't feel understood. We developed an evidence-based communication training, aimed to improve specialists' interviewing, information-giving and planning skills in MUPS consultations, and tested its effectiveness. METHODS: The intervention group in this multi-center randomized controlled trial received a 14-hour training program to which experiential learning and feedback were essential. Using techniques from Cognitive Behavioral Therapy, they were stimulated to seek interrelating factors (symptoms, cognitions, emotions, behavior, and social environment) that reinforced a patient's symptoms. They were taught to explain MUPS understandably, reassure patients effectively and avoid unnecessary diagnostic testing. Before and after the intervention training, specialists videotaped a total of six consultations with different MUPS patients. These were evaluated to assess doctors' MUPS-focused communicating skills using an adapted version of the Four Habit Coding Scheme on five-point Likert scales. Participants evaluated the training by self-report on three-point Likert scales. Doctors in the control group received training after completion of the study. RESULTS: 123 doctors (40% specialists, 60% residents) and 478 MUPS patients from 11 specialties were included; 98 doctors completed the study (80%) and 449 videotaped consultations were assessed. Trained doctors interviewed patients more effectively than untrained ones (p < 0.001), summarized information in a more patient-centered way (p = 0.001), and better explained MUPS and the role of perpetuating factors (p < 0.05). No effects on planning skills were found. On a 3-point scale the training was evaluated with 2.79. CONCLUSION: MUPS-focused communication training increases the interviewing and information-giving skills of medical specialists. We recommend that the training is incorporated in postgraduate education for medical specialists and residents who frequently encounter patients with MUPS. TRIAL REGISTRATION: Dutch Trial Registration NTR2612.

Training specialists to write appropriate reply letters to general practitioners about patients with medically unexplained physical symptoms; A cluster-randomized trial.

OBJECTIVE: To evaluate effects of a communication training for specialists on the quality of their reply letters to general practitioners (GPs) about patients with medically unexplained physical symptoms (MUPS). METHODS: Before randomization, specialists included ≤3 MUPS patients in a multi-center cluster-randomized trial. In 14h of MUPS-specific communication training, 2.5h focused on reply letters. Letters were discussed with regard to reporting and answering GPs' referral questions and patients' questions, and to reporting findings, explaining MUPS with perpetuating factors and giving advice. After the training, all doctors again included ≤3 MUPS patients. Reply letters to GPs were assessed for quality and blindly rated on a digital scale. RESULTS: We recruited 478 MUPS patients and 123 specialists; 80% of the doctors wrote ≥1 reply letters, 285 letters were assessed. Trained doctors reported (61% versus 37%, OR=2.55, F(1281)=6.60, p(group*time)=.01) and answered (63% versus 33%, OR=3.31, F(1281)=5.36, p(group*time)=.02) patients' questions more frequently than untrained doctors. CONCLUSION: Training improves reply letters with regard to patients' questions, but not with regard to the following: GPs' referral questions, somatic findings, additional testing, explaining, and advice. PRACTICE IMPLICATIONS: Training specialists to write appropriate reply letters needs more focus on explanation and advice.

Homogenizing Responses to Different Survey Questions on the Same Topic: Proposal of a Scale Homogenization Method Using a Reference Distribution.

Survey data are often used for comparison purposes, such as comparisons across nations or comparisons over time. To be effective, this would require equivalent questions and equivalent responses options to the questions. Yet there is a lot of variation in the response scales used, which, for example, differ in the number of response options used and the labeling of these options. This is the case in happiness research, and as a result most of the research data in this field is incomparable. Several methods have been proposed to transform ratings on verbal response scales to a common numerical scale, typically ranging from 0 to 10. In this paper we give an overview of the progress made in those Scale Homogenization methods over time. We describe two early methods: Linear Stretch and the Semantic Judgement of Fixed Word Value Method. Next we discuss the Semantic Judgement of Word Value in Context Method in more detail. Based on these discussions we propose a new Reference Distribution Method. We apply the Semantic Judgement of Word Value in Context and the Reference Distribution Methods to data on happiness in The Netherlands for the years 1989-2009. We show that the Reference Distribution Method produces comparable time series on different questions and that it allows discontinuities in data to be corrected.