Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus.

BACKGROUND: Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain. METHODS: In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks' gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell's stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points. RESULTS: A total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, -17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], -7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, -6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, -17.6 percentage points; two-sided 95% CI, -30.2 to -5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, -4.3 percentage points; two-sided 95% CI, -13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups. CONCLUSIONS: Expectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.).

Prophylactic Mesh Placement During Formation of an End-colostomy: Long-term Randomized Controlled Trial on Effectiveness and Safety.

OBJECTIVE: The aim of this study was to determine if prophylactic mesh placement is an effective, safe, and cost-effective procedure to prevent parastomal hernia (PSH) formation in the long term. BACKGROUND: A PSH is the most frequent complication after stoma formation. Prophylactic placement of a mesh has been suggested to prevent PSH, but long-term evidence to support this approach is scarce. METHODS: In this multicentre superiority trial patients undergoing the formation of a permanent colostomy were randomly assigned to either retromuscular polypropylene mesh reinforcement or conventional colostomy formation. Primary endpoint was the incidence of a PSH after 5 years. Secondary endpoints were morbidity, mortality, quality of life, and cost-effectiveness. RESULTS: A total of 150 patients were randomly assigned to the mesh group (n = 72) or nonmesh group (n = 78). For the long-term follow-up, 113 patients were analyzed, and 37 patients were lost to follow-up. After a median follow-up of 60 months (interquartile range: 48.6-64.4), 49 patients developed a PSH, 20 (27.8%) in the mesh group and 29 (37.2%) in the nonmesh group ( P = 0.22; RD: -9.4%; 95% CI: -24, 5.5). The cost related to the meshing strategy was € 2.239 lower than the nonmesh strategy (95% CI: 491.18, 3985.49), and quality-adjusted life years did not differ significantly between groups ( P = 0.959; 95% CI: -0.066, 0.070). CONCLUSIONS: Prophylactic mesh placement during the formation of an end-colostomy is a safe procedure but does not reduce the incidence of PSH after 5 years of follow-up. It does, however, delay the onset of PSH without a significant difference in morbidity, mortality, or quality of life, and seems to be cost-effective.

Short-term effects of an elimination diet and healthy diet in children with attention-deficit/hyperactivity disorder: a randomized-controlled trial.

An Elimination Diet (ED) may be effective in reducing symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), but has never been compared to an active control condition [i.e., Healthy Diet (HD)]. In a two-armed RCT, a total of N = 165 children (5-12 years) with ADHD were randomized by means of minimization (1:1) to either an ED (N = 84) or HD (N = 81) within two Dutch child and adolescent psychiatry centers. The design included a non-randomized comparator arm including N = 58 children being treated with Care as Usual (CAU). Treatment allocation was unblinded. The primary outcome was a 5-point ordinal measure of respondership based on a combination of parent and teacher ratings on ADHD and emotion regulation, determined after 5 weeks of treatment. Ordinal regression analyses were done on an intention-to-treat basis. Fewer ED (35%) than HD (51%) participants showed a partial to full response, despite overall good-to-excellent treatment adherence (> 88%) and comparable high parental prior believes. A younger age and higher problem severity predicted a better respondership. CAU-preferring participants responded more often favorably (56%) compared to ED-but not HD-participants. Small-to-medium improvements in physical health (blood pressure, heart rate, and somatic complaints) were found in response to ED/HD versus decrements in response to CAU (74% received psychostimulants). The lack of superiority of the ED versus HD suggests that for the majority of children, dietary treatment response is not rooted in food-allergies/-sensitivities. The comparable results for treatment with HD and CAU are remarkable given that CAU participants were probably 'easier to treat' than HD (and ED) participants with proportionally fewer with a (suboptimal/non-response to) prior treatment with medication (4% versus 20%). Further assessment of long-term effects is needed to evaluate the potential place of dietary treatment within clinical guidelines. The trial is closed and registered in the Dutch trial registry, number NL5324 ( https://www.onderzoekmetmensen.nl/en/trial/25997 ).

Variability in clinicians' prediction accuracy for outcomes of adult cochlear implant users.

OBJECTIVE: The variability in outcomes among adult cochlear implant (CI) users poses challenges for clinicians in accurately predicting the benefits of the implant for individual candidates. This study aimed to investigate the accuracy and confidence of clinicians in predicting speech perception outcomes for adult CI users one-year post-implantation. DESIGN: Participants were presented with comprehensive information on pre-implantation, one-month post-implantation, and six-month post-implantation data for 10 case studies. The cases encompassed a range of one-year post-implantation phoneme scores, from low performers (27%) to high performers (92%). Participants were tasked with predicting the speech perception outcomes for these cases one year after implantation. STUDY SAMPLE: Forty-one clinicians completed the full outcome prediction survey. RESULTS: Our findings revealed a significant over-prediction of low performance by clinicians. Interestingly, clinicians tended to predict average performance (73-76% phoneme score) even when provided with information suggesting lower-than-average performance. Most clinicians expressed confidence in their predictions, irrespective of their accuracy. CONCLUSIONS: Identifying signs of low performance, particularly in the early post-implantation period, can enable clinicians to implement early interventions. Further research into accurate outcome prediction is essential for managing expectations, providing counselling, increasing CI adoption, and optimising clinical care for both high and low performers.

The effect of chemotherapy on the exposure-response relation of abiraterone in metastatic castration-resistant prostate cancer.

AIMS: To assess whether the exposure-response relation for abiraterone is different in pre-chemotherapy patients compared to post-chemotherapy patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Data were collected from three clinical studies in mCRPC patients treated with abiraterone acetate. Cox regression analysis was used to determine the relation between abiraterone exposure and survival (progression-free survival [PFS] and overall survival [OS]). An interaction term was used to test whether chemotherapy pretreatment was an effect modifier. To investigate the effect of the previously defined exposure threshold of 8.4 ng/mL on survival, Kaplan-Meier analysis was used. RESULTS: In total, 98 mCRPC patients were included, of which 78 were pre-chemotherapy and 20 were post-chemotherapy patients. Chemotherapy pretreatment in mCRPC setting appears to be an effect modifier. In pre-chemotherapy patients, no significant association between abiraterone exposure and survival was observed (HR 0.68 [95% CI 0.42-1.10], P = .12 and HR 0.85 [95% CI 0.46-1.60], P = .61, PFS and OS, respectively) and no longer survival was seen for patients with an abiraterone exposure above the predefined threshold. In contrast, a significant association was seen in post-chemotherapy patients (HR 0.30 [95% CI 0.12-0.74], P = .01 and HR 0.38 [95% CI 0.18-0.82] P = .01, PFS and OS, respectively), with an increased survival when exposed above this threshold. CONCLUSION: Chemotherapy pretreatment in mCRPC setting modifies the abiraterone exposure-response relation. No relation between abiraterone exposure and survival was seen for pre-chemotherapy patients. Therefore, potentially lower doses can be used in this setting to prevent overtreatment and reduce financial toxicity.

A threshold explanation for the lack of variation in negative composite time trade-off values.

BACKGROUND: Recent studies concluded that for health states considered worse than dead (WTD), as measured with the time trade-off (cTTO) method, negative mean values were insensitive to health state severity, which represents a validity problem for the cTTO. However, the aforementioned studies analysed negative values in isolation, which causes selection bias as the value distribution is truncated. AIM: To investigate the validity of aforementioned studies and of negative values in general. METHODS: The 'threshold explanation' was formulated: beyond a certain severity threshold, preferences change from better than dead (BTD) to WTD. This threshold differs between respondents. Thus, negative values across severity are obtained from different respondents, and responses added for higher severity contribute negative values close to zero, explaining the aforementioned insensitivity. This explanation was tested using data from the Dutch EQ-5D-5L valuation study. Respondents valued 10 health states. Based on respondents' number of WTD preferences, segments were constructed, containing respondents with similar severity thresholds. Using regression models for each individual respondent, we examined the relation between values and severity and compared respondents between segments. RESULTS: Negative values, when analysed in isolation, were insensitive to severity. However, for individual respondents and within most segments, cTTO values and severity were negatively related. For individual respondents, negative slopes were steeper for segments with more WTD preferences, as predicted by the threshold explanation. DISCUSSION: Analysing negative values in isolation leads to biased estimates. Analyses of cTTO values for individual respondents refute the insensitivity of negative cTTO values.

Does a regular nurse-led distress screening and discussion improve quality of life of breast cancer patients treated with curative intent? A randomized controlled trial.

OBJECTIVE: We performed a randomized controlled trial (RCT) to investigate whether regular screening with the distress thermometer (DT) by a nurse improved global quality of life (QOL) of patients with breast cancer (BC) treated with curative intent. METHODS: BC patients were randomized between regular screening for distress with a nurse-led DT intervention (NDTI) and usual care (UC). Both groups filled out questionnaires at baseline, after each received treatment modality and at follow-up visits up to 2 years. At these points, the intervention group received also the NDTI. The primary outcome was the global QOL of the EORTC QLQ C30 at 2 years after the end of treatment. Analyses were done on an intention-to-treat basis, using analysis of covariance (ANCOVA), generalized least squares, and interaction analyses. RESULTS: Of 194 randomized patients, 153 filled out the questionnaires up to 2 years after treatment. There was no significant difference between NDTI and UC in global QOL 2 years after the end of treatment (mean diff. = -1∙273, P = .610; 95% CI [-6.195; 3.649]). Subgroup analysis of patients who received multimodality treatment (surgery, radiotherapy, and chemotherapy, n = 66) showed a significant between-group difference in global QOL over time (mean diff. = -10, P < .001; 95% CI [-14.835; -5.167]) together with other secondary outcome measures in favor of the NDTI. CONCLUSION: NDTI did not lead to a significant improvement in global QOL 2 years after the end of treatment for patients with BC. However, the findings indicate that BC patients who received multimodality treatment may benefit from NDTI.

A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods.

BACKGROUND: Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. METHODS: A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. DISCUSSION: This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. TRIAL REGISTRATION: www.trialregister.nl, NTR5434. Registered at October 11th, 2015.

The Interactive Web-Based Program MSmonitor for Self-Management and Multidisciplinary Care in Persons With Multiple Sclerosis: Quasi-Experimental Study of Short-Term Effects on Patient Empowerment.

BACKGROUND: Empowerment helps persons with a chronic disease to self-manage their condition and increase their autonomy and participation. MSmonitor (Curavista bv) is an interactive Web-based program for self-management and multidisciplinary care in multiple sclerosis (MS). It includes, among others, short questionnaires on fatigue (Modified Fatigue Impact Scale-5 [MFIS-5]) and health-related quality of life (HRQoL, Leeds Multiple Sclerosis Quality of Life [LMSQoL]); long questionnaires on disabilities, perception of disabilities (Multiple Sclerosis Impact Profile), and HRQoL (Multiple Sclerosis Quality of Life-54); a Medication and Adherence Inventory and an Activity Diary. The combination MFIS-5, LMSQoL, and Medication and Adherence Inventory constitutes the Quick Scan. OBJECTIVE: This study aimed to investigate the short-term effects of MSmonitor on empowerment in patients with MS. METHODS: We conducted a quasi-experimental study in a general hospital. Of the 180 patients with MS, 125 were eligible, 30 used MSmonitor, and 21 participated in the study (mean age 45.4 years, SD 10.2 years). A total of 24 eligible patients who did not use MSmonitor constituted the control group (mean age 49.3 years, SD 11.4 years). At baseline and at 4 months, we assessed self-efficacy (Multiple Sclerosis Self-Efficacy Scale [MSSES]), participation and autonomy (Impact on Participation and Autonomy [IPA] questionnaire), and self-management (Partners In Health [PIH] questionnaire). Differences between time points and groups were tested with paired t tests and χ² tests. RESULTS: In the MSmonitor group, follow-up values remained unchanged for MSSES control (P=.19), MSSES function (P=.62), IPA limitations (P=.26), IPA problems (P=.40), PIH recognition and management of symptoms (P=.52), PIH adherence to treatment (P=.80), and PIH coping (P=.73), whereas the PIH knowledge score had improved (mean 27.8, SD 1.7 vs mean 28.7, SD 2.0; P=.02). The overall utilization rate of the program components was 83% and that of the Quick Scan was 95%. In the control group, all outcomes had remained unchanged. CONCLUSIONS: The results suggest that for first-time users of the MSmonitor program and their health care providers, it may not be justified to expect a short-term improvement in empowerment in terms of self-efficacy, self-management, autonomy, or participation. Furthermore, a lack of effect on empowerment is not because of nonusage of the program components.

Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis.

Reduced target attainment of ß-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial. Children with meningococcal septic shock (1 month to 18 years) included in this study received cefotaxime 100-150 mg/kg/day as antibiotic treatment. Left-over plasma samples were analyzed using LC-MS/MS to determine cefotaxime concentrations. MIC values from EUCAST were used to determine target attainment of cefotaxime for Neisseria meningitidis (0.125 mg/l), but also for Streptococcus pneumoniae (0.5 mg/l), Enterobacteriaceae (1 mg/l), and Staphylococcus aureus (4 mg/l). Target attainment was adequate when all samples exceeded MIC or fourfold MIC values. One thirty-six plasma samples of 37 severe septic shock patients were analyzed for cefotaxime concentrations. Median age was 2 years with a median PRISM-score of 24 and mortality of 24.8%. The median unbound cefotaxime concentration was 4.8 mg/l (range 0-48.7). Target attainment ranged from 94.6% for the MIC of N. meningitidis to 16.2% for fourfold the MIC S. aureus. Creatinine levels were significantly correlated with cefotaxime levels. Target attainment of cefotaxime with current dosing guidelines seems to be adequate for N. meningitidis but seems to fail for more frequently encountered pathogens in severely ill children.

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BACKGROUND: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. METHODS: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. DISCUSSION: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks. TRIAL REGISTRATION: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .

Decreased Cognitive Functioning After Electroconvulsive Therapy Is Related to Increased Hippocampal Volume: Exploring the Role of Brain Plasticity.

OBJECTIVE: Electroconvulsive therapy (ECT) is still the most effective treatment of severe and therapy-refractory major depressive disorder. Cognitive side effects are the major disadvantage of ECT. Cognitive deficits are generally temporary in nature and may be mediated by the hippocampus. Recent studies have shown a temporary increase in hippocampal volume and a temporary decrease in cognitive functioning post-ECT compared with pre-ECT. This study investigates whether these volumetric changes are related to changes in cognitive functioning after ECT. METHODS: Nineteen medication-free patients with treatment-resistant major depressive disorder underwent a whole-brain magnetic resonance imaging scan and a neuropsychological examination (including the Rey auditory verbal learning task, Wechsler Memory Scale Visual Reproduction, fluency, Trail Making Task) within 1 week before and within 1 week after the course of ECT. Electroconvulsive therapy was administered twice a week bitemporally with a brief pulse. A matched healthy control group (n = 18) received the same neuropsychological examination and at a similar interval to that of the patients. RESULTS: Hippocampal volumes increased significantly from pretreatment to posttreatment in patients. Mean performance on cognitive tasks declined, or remained stable, whereas performance in controls generally improved because of retesting effects. The increase in hippocampal volume was related to changes in cognitive performance, indicating that this increase co-occurred with a decrease in cognitive functioning. CONCLUSIONS: Our findings tentatively suggest that the temporal increase in hippocampal volume after treatment, which may result from neurotrophic processes and is thought to be crucial for the antidepressive effect, is also related to the temporary cognitive side effects of ECT.

Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial.

Background: Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS). The objective of this randomized controlled clinical trial was to assess the efficacy of either long-term treatment with doxycycline or cognitive-behavioral therapy (CBT) in reducing fatigue severity in patients with QFS. Methods: Adult patients were included who met the QFS criteria according to the Dutch guideline: a new onset of severe fatigue lasting ≥6 months with significant disabilities, related to an acute Q fever infection, without other somatic or psychiatric comorbidity explaining the fatigue. Using block randomization, patients were randomized between oral study medication and CBT (2:1) for 24 weeks. Second, a double-blind randomization between doxycycline (200 mg/day, once daily) and placebo was performed in the medication group. Primary outcome was fatigue severity at end of treatment (EOT; week 26), assessed with the Checklist Individual Strength subscale Fatigue Severity. Results: Of 155 patients randomized, 154 were included in the intention-to-treat analysis (doxycycline, 52; placebo, 52; CBT, 50). At EOT, fatigue severity was similar between doxycycline (40.8 [95% confidence interval {CI}, 37.3-44.3]) and placebo (37.8 [95% CI, 34.3-41.2]; difference, doxycycline vs placebo, -3.0 [97.5% CI, -8.7 to 2.6]; P = .45). Fatigue severity was significantly lower after CBT (31.6 [95% CI, 28.0-35.1]) than after placebo (difference, CBT vs placebo, 6.2 [97.5% CI, .5-11.9]; P = .03). Conclusions: CBT is effective in reducing fatigue severity in QFS patients. Long-term treatment with doxycycline does not reduce fatigue severity in QFS patients compared to placebo. Clinical Trials Registration: NCT01318356.

The efficacy of Internet-based cognitive behavioral therapy for severely fatigued survivors of breast cancer compared with care as usual: A randomized controlled trial.

BACKGROUND: Severe fatigue is a common and distressing symptom affecting approximately one in four survivors of breast cancer. The current study examined the efficacy of Internet-based cognitive behavioral therapy (ICBT) for severe fatigue in survivors of breast cancer compared with care as usual (CAU). METHODS: The authors conducted a parallel-group randomized controlled trial. Severely fatigued, disease-free survivors of breast cancer who had completed cancer treatment at least 3 months previously were eligible. Participants were randomly allocated to ICBT or CAU using computer-generated stratified block randomization. The primary outcome of fatigue severity was assessed at baseline and after 6 months, as were the secondary outcomes of functional impairment, psychological distress, and quality of life. Statistical effects were tested with analyses of covariance (intention-to-treat analysis). RESULTS: Participants were recruited between January 2014 and March 2016 and assigned to ICBT (66 patients) or CAU (66 patients). Compared with the participants who had received CAU, those who had received ICBT reported lower fatigue scores at 6 months (mean difference [Δ], 11.5; 95% confidence interval [95% CI], 7.7-15.3) and a large effect size (Cohen d = 1.0), with the majority of patients (73%) demonstrating clinically significant improvement. ICBT also was found to lead to lower functional impairment (Δ, 297.8; 95% CI, 145.5-450.1) and psychological distress scores (Δ, 5.7; 95% CI, 3.4-7.9) and higher quality-of-life scores (Δ, 11.7; 95% CI, 5.8-17.7) compared with CAU, with medium to large effect sizes (Cohen d = 0.6-0.8). CONCLUSIONS: ICBT appears to be effective in reducing severe fatigue and related symptoms and meets the current need for easy accessible and more efficient evidence-based treatment options for severely fatigued survivors of breast cancer. Cancer 2017;123:3825-34. © 2017 American Cancer Society.

Glatiramer acetate treatment persistence - but not adherence - in multiple sclerosis patients is predicted by health-related quality of life and self-efficacy: a prospective web-based patient-centred study (CAIR study).

BACKGROUND: In patients with relapsing remitting multiple sclerosis (RRMS) the persistence of and adherence to disease modifying drug (DMD) treatment is inadequate. To take individualised measures there is a need to identify patients with a high risk of non-persistence or non-adherence. As patient-related factors have a major influence on persistence and adherence, we investigated whether health-related quality of life (HRQoL) and self-efficacy could predict persistence or adherence. METHODS: In a prospective web-based patient-centred study in 203 RRMS patients, starting treatment with glatiramer acatete (GA) 20 mg subcutaneously daily, we measured physical and mental HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire), functional and control self-efficacy (Multiple Sclerosis Self-Efficacy Scale), the 12-month persistence rate and, in persistent patients, the percentage of missed doses. HRQoL and self-efficacy were compared between persistent and non-persistent patients, and between adherent and non-adherent patients. Logistic regression analysis was used to assess whether persistence and adherence were explained by HRQoL and self-efficacy. RESULTS: Persistent patients had higher baseline physical (mean 58.1 [standard deviation, SD] 16.9) and mental HRQoL (63.8 [16.8]) than non-persistent patients (49.5 [17.6]; 55.9 [20.4]) (P = 0.001; P = 0.003) with no differences between adherent and non-adherent patients (P = 0.46; P = 0.54). Likewise, in persistent patients function (752 [156]) and control self-efficacy (568 [178]) were higher than in non-persistent patients (689 [173]; 491 [192]) (P = 0.009; P = 0.004), but not in adherent vs. non-adherent patients (P = 0.26; P = 0.82). Logistic regression modelling identified physical HRQoL and control self-efficacy as factors that explained persistence. Based on predicted scores from the model, patients were classified into quartiles and the percentage of non-persistent patients per quartile was calculated: non-persistence in the highest quartile was 23.4 vs. 53.2% in the lowest quartile. Risk differentiation with respect to adherence was not possible. Based on these findings we propose a practical work-up scheme to identify patients with a high risk of non-persistence and to identify persistence-related factors. CONCLUSIONS: Findings suggest that pre-treatment physical HRQoL and control self-efficacy may identify RRMS patients with a high risk of early discontinuation of injectable DMD treatment. Targeting of high-risk patients may enable the efficient use of persistence-promoting measures. TRIAL REGISTRATION: Nederlands Trial Register code: NTR2432 .

Cultural values: can they explain self-reported health?

PURPOSE: Self-reported health (SRH) is a measure widely used in health research and population studies. Differences in SRH have been observed between countries and cultural values have been hypothesized to partly explain such differences. Cultural values can be operationalized by two cultural dimensions using the World Values Survey (WVS), namely the traditional/rational-secular and the survival/self-expression dimension. We investigate whether there is an association between the WVS cultural dimensions and SRH, both within and between countries. METHODS: Data from 51 countries in the WVS is used and combined with macroeconomic data from the Worldbank database. The association between SRH and the WVS cultural dimensions is tested within each of the 51 countries and multilevel mixed models are used to test differences between these countries. Socio-demographic and macroeconomic variables are used to correct for non-cultural variables related to SRH. RESULTS: Within countries, the survival/self-expression dimension was positively associated with SRH, while in most countries there was a negative association for the traditional/rational-secular dimension. Values range between 4 and 17% within countries. Further analyses show that the associations within countries and between countries are similar. Controlling for macroeconomic and socio-demographic factors did not change our results. DISCUSSION: The WVS cultural dimensions predict SRH within and between countries. Contrary to our expectations, traditional/rational-secular values were negatively associated with SRH. As SRH is associated with cultural values between countries, cultural values could be considered when interpreting SRH between countries.

Quality of Recovery After Low-Pressure Laparoscopic Donor Nephrectomy Facilitated by Deep Neuromuscular Blockade: A Randomized Controlled Study.

BACKGROUND: The use of low intra-abdominal pressure (<10 mmHg) reduces postoperative pain scores after laparoscopic surgery. OBJECTIVE: To investigate whether low-pressure pneumoperitoneum with deep neuromuscular blockade improves the quality of recovery after laparoscopic donor nephrectomy (LDN). DESIGN, SETTING AND PARTICIPANTS: In a single-center randomized controlled trial, 64 live kidney donors were randomly assigned to 6 or 12 mmHg insufflation pressure. A deep neuromuscular block was used in both groups. Surgical conditions were rated by the five-point Leiden-surgical rating scale (L-SRS), ranging from 5 (optimal) to 1 (extremely poor) conditions. If the L-SRS was insufficient, the pressure was increased stepwise. MAIN OUTCOME MEASURE: The primary outcome measure was the overall score on the quality of recovery-40 (QOR-40) questionnaire at postoperative day 1. RESULTS: The difference in the QOR-40 scores on day 1 between the low- and standard-pressure group was not significant (p = .06). Also the overall pain scores and analgesic consumption did not differ. Eight procedures (24%), initially started with low pressure, were converted to a standard pressure (≥10 mmHg). A L-SRS score of 5 was significantly more prevalent in the standard pressure as compared to the low-pressure group at 30 min after insufflation (p < .01). CONCLUSIONS: Low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade during LDN does not reduce postoperative pain scores nor improve the quality of recovery in the early postoperative phase. The question whether the use of deep neuromuscular blockade during laparoscopic surgery reduces postoperative pain scores independent of the intra-abdominal pressure should be pursued in future studies. TRIAL REGISTRATION: The trial was registered at clinicaltrial.gov before the start of the trial (NCT02146417).

Nighttime kidney transplantation is associated with less pure technical graft failure.

PURPOSE: To minimize cold ischemia time, transplantations with kidneys from deceased donors are frequently performed during the night. However, sleep deprivation of those who perform the transplantation may have adverse effects on cognitive and psychomotor performance and may cause reduced cognitive flexibility. We hypothesize that renal transplantations performed during the night are associated with an increased incidence of pure technical graft failure. METHODS: A retrospective analysis of data of the Dutch Organ Transplant Registry concerning all transplants from deceased donors between 2000 and 2013 was performed. Nighttime surgery was defined as the start of the procedure between 8 p.m. and 8 a.m. The primary outcome measure was technical graft failure, defined as graft loss within 10 days after surgery without signs of (hyper)acute rejection. RESULTS: Of 4.519 renal transplantations in adult recipients, 1.480 were performed during the night. The incidence of pure technical graft failure was 1.0 % for procedures started during the night versus 2.6 % for daytime surgery (p = .001). In a multivariable model, correcting for relevant donor, recipient and graft factors, daytime surgery was an independent predictor of pure technical graft failure (p < .001). CONCLUSIONS: Limitation of this study is mainly to its retrospective design, and the influence of some relevant variables, such as the experience level of the surgeon, could not be assessed. We conclude that nighttime surgery is associated with less pure technical graft failures. Further research is required to explore factors that may positively influence the performance of the surgical team during the night.

A multidimensional 'path analysis' model of factors explaining fatigue in rheumatoid arthritis.

OBJECTIVES: Fatigue is one of the most commonly reported symptoms in rheumatoid arthritis (RA). Many factors may play a causal role on fatigue in RA patients, but their contribution and interplay is barely understood. The objective was to develop a multidimensional model of factors that explain fatigue severity in RA. METHODS: A cross-sectional study (n=228) of consecutive patients with RA was performed. Fatigue, disease characteristics and psychosocial and behavioural outcomes were collected. Baseline differences between non severely fatigued patients (CIS-fatigue <35) and severely fatigued patients (CIS-fatigue ≥35) were tested. Structural equation modeling was used to test a hypothesised model for fatigue. RESULTS: The final model includes pain, physical functioning, mood, sense of control, sleep quality and fatigue, with good fit (CFI=0.976) explaining 74% of the variance in RA fatigue. Accordingly, poor sleep quality (ß=0.42, p<0.001) and less physical functioning (ß=0.65, p<0.001) are directly related to a higher level of fatigue. Less sense of control is related to more mood disturbance (ß=0.64, p<0.001), more pain (ß=0.389, p<0.001) and less physical functioning (ß=-0.24, p<0.001). More mood disturbance is related to poor sleep quality (ß=0.78, p<0.001) and higher pain level is related to less physical functioning (ß=0.75, p<0.001). CONCLUSIONS: RA fatigue is directly influenced by poor sleep quality and physical functioning, and indirectly by sense of control, mood and pain. Treatment of these factors by psychological interventions and physical exercise could help to improve fatigue in patients with RA.

An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol.

BACKGROUND: In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-related quality of life 6 months after treatment in those people with MS who had relapsing remitting disease and low disability. METHODS/DESIGN: CDT is a sociologically oriented approach, its goal is to uncover and promote existing capabilities, and the notion "stressor" is the central concept. CDT's components are plenary group sessions, small group sessions, consultations, a theatre evening, and start of the day with a joint activity. The small group sessions form the actual training. Depending on their individual goals the participants join the training groups 'Body', 'Feeling' or 'Life', to work out their aims and to reduce their stressors. The multidisciplinary team includes a psychiatrist, psychiatric nurse, neurologist, specialized MS nurse, physiotherapist, dance therapist, and a person with MS. To evaluate the (cost)effectiveness of CDT in persons with relapsing remitting MS and low disability we perform a single-centre, randomized controlled trial in 140 patients, with or without support partners. The primary outcome is self-efficacy control. The secondary outcomes are self-efficacy function, health-related quality of life, autonomy and participation, anxiety, depression, cost effectiveness and cost utility. The tertiary outcome is care-related strain to support partners. Outcomes are assessed at baseline and at 1, 3 and 6 months after CDT. DISCUSSION: This randomized controlled trial will adequately evaluate the clinical and cost effectiveness of a 3-day intensive social cognitive program in people with relapsing remitting MS and low disability, with self-efficacy control as primary outcome. DUTCH TRIAL REGISTRY: Application number: 22444.