Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis.

INTRODUCTION: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis. METHODS: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population. RESULTS: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6. CONCLUSIONS: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.

The Impact of the COVID Pandemic on the Incidence of Presentations with Cancer-Related Symptoms in Primary Care.

Introduction: In the Netherlands, the onset of the coronavirus pandemic saw shifts in primary health service provision away from physical consultations, cancer-screening programs were temporarily halted, and government messaging focused on remaining at home. In March and April 2020, weekly cancer diagnoses decreased to 73% of their pre-COVID levels, and 39% for skin cancer. This study aims to explore the effect of the COVID pandemic on patient presentations for cancer-related symptoms in primary care in The Netherlands. Methods: Retrospective cohort study using routine clinical primary care data. Monthly incidences of patient presentations for cancer-related symptoms in five clinical databases in The Netherlands were analysed from March 2018 to February 2021. Results: Data demonstrated reductions in the incidence of cancer-related symptom presentations to primary care during the first COVID wave (March-June 2020) of -34% (95% CI: -43 to -23%) for all symptoms combined. In the second wave (October 2020-February 2021) there was no change in incidence observed (-8%, 95% CI -20% to 6%). Alarm-symptoms demonstrated decreases in incidence in the first wave with subsequent incidences that continued to rise in the second wave, such as: first wave: breast lump -17% (95% CI: -27 to -6%) and haematuria -15% (95% CI -24% to -6%); and second wave: rectal bleeding +14% (95% CI: 0 to 30%) and breast lump +14% (95% CI: 2 to 27%). Presentations of common non-alarm symptom such as tiredness and naevus demonstrated decreased in-cidences in the first wave of 45% (95% CI: -55% to -33%) and 37% (95% CI -47% to -25%). In the second wave, tiredness incidence was reduced by 20% (95% CI: -33% to -3%). Subgroup analy-sis did not demonstrate difference in incidence according to sex, age groups, comorbidity status, or previous history of cancer. Conclusions: These data describe large-scale primary care avoidance that did not increase until the end of the first COVID year for many cancer-related symptoms, suggestive that substantial numbers of patients delayed presenting to primary care. For those patients who had underlying cancer, this may have had impacted the cancer stage at diagnosis, treatment, and mortality.

Quality of Life and Survival of Metastatic Colorectal Cancer Patients Treated With Trifluridine-Tipiracil (QUALITAS).

INTRODUCTION: The RECOURSE trial demonstrated a modest benefit in overall survival (OS) for trifluridine/tipiracil (FTD/TPI) versus placebo in pretreated metastatic colorectal cancer (mCRC) patients. Unfortunately, quality of life (QoL) was not assessed. We evaluated QoL and survival of patients treated with FTD/TPI in daily practice. PATIENTS AND METHODS: QUALITAS is a substudy of the Prospective Dutch CRC cohort (PLCRC). From 150 mCRC patients treated with FTD/TPI, QoL (EORTC QLQ-C30 and QLQ-CR29) was assessed monthly from study entry, and linked to clinical data of the Netherlands Cancer Registry. Joint models were constructed combining mixed effects models with Cox PH models. Primary endpoint was difference in QoL over time (which was deemed clinically relevant if ≥10 points). Secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), and OS. We analyzed the association between QLQ-C30 Summary Score (QoL-SS) at FTD/TPI initiation (baseline) and survival. RESULTS: There was no clinically relevant change in QoL-SS from baseline to 10 months post-baseline (i.e. the cut-off point after which 90% of patients had discontinued FTD/TPI treatment): -5.3 [95% CI -8.7;-1.5]. Patients who were treated with FTD/TPI for ≥ 3 months (n = 85) reported 6.3 [1.6;11.1] points higher baseline QoL, compared to patients treated < 3 months (n = 65, "poor responders"). In the latter, time to a clinically relevant QoL deterioration was < 2 months. Median PFS, TTF and OS were 2.9 [2.7;3.1], 3.1 [2.9;3.2] and 7.7 [6.6;8.8] months, respectively. Worse baseline QoL-SS was independently associated with shorter OS (HR 0.45 [0.32;0.63]), PFS (0.63 [0.48;0.83]), and TTF (0.64 [0.47;0.86]). CONCLUSION: The maintenance of QoL during FTD/TPI treatment in daily practice supports its use. The QoL deterioration in "poor responders" is likely due to disease progression. The strong association between worse baseline QoL and shorter survival suggests that clinicians should take QoL into account when determining prognosis and treatment strategy for individual patients.

Methodological aspects of a randomized within-patient concurrent controlled design for clinical trials in spine surgery.

INTRODUCTION: Randomized controlled trials are considered the highest level of evidence, but their feasibility in the surgical field is severely hampered by methodological and practical issues. Concurrent comparison between the experimental and control conditions within the same patient can be an effective strategy to mitigate some of these challenges and improve generalizability, mainly by the elimination of between-patient variability and reduction of the required sample size. This article aims (1) to describe the methodological aspects of a randomized within-patient controlled trial and (2) to quantify the added value of this design, based on a recently completed randomized within-patient controlled trial on bone grafts in instrumented lumbar posterolateral spinal fusion. METHODS: Boundary conditions for the application of the randomized within-patient controlled trial design were identified. Between-patient variability was quantified by the intraclass correlation coefficient and concordance in the primary fusion outcome. Sample size, study duration and costs were compared with a classic randomized controlled trial design. RESULTS: Boundary conditions include the concurrent application of the experimental and control conditions to identical but physically separated sites. Moreover, the outcome of interest should be local, uncorrelated and independently assessable. The spinal fusion outcomes within a patient were found to be more similar than between different patients (intraclass correlation coefficient 32% and concordance 64%), demonstrating a clear effect of patient-related factors. The randomized within-patient controlled trial design allowed a reduction of the sample size to one-third of a parallel-group randomized controlled trial, thereby halving the trial duration and costs. CONCLUSION: When suitable, the randomized within-patient controlled trial is an efficient design that provides a solution to some of the considerable challenges of a classic randomized controlled trial in (spine) surgery. This design holds specific promise for efficacy studies of non-active bone grafts in instrumented posterolateral fusion surgery.

Exploring the relation between modelled and perceived workload of nurses and related job demands, job resources and personal resources; a longitudinal study.

AIM: Calculating a modelled workload based on objective measures. Exploring the relation between this modelled workload and workload as perceived by nurses, including the effects of specific job demands, job resources and personal resources on the relation. DESIGN: Academic hospital in the Netherlands. Six surgical wards, capacity 15-30 beds. Data collected over 15 consecutive day shifts. METHODS: Modelled workload is calculated as a ratio of required care time, based on patient characteristics, baseline care time and time for non-patient related activities, and allocated care time, based on the amount of available nurses. Both required and allocated care time are corrected for nurse proficiency. Five dimensions of perceived workload were determined by questionnaires. Both the modelled and the perceived workloads were measured on a daily basis. Linear mixed effects models study the longitudinal relation between this modelled and workload as perceived by nurses and the effects of personal resources, job resources and job demands. ANOVA and post-hoc tests were used to identify differences in modelled workload between wards. RESULTS: Modelled workload varies roughly between 70 and 170%. Significant differences in modelled workload between wards were found but confidence intervals were wide. Modelled workload is positively associated with all five perceived workload measures (work pace, amount of work, mental load, emotional load, physical load). In addition to modelled workload, the job resource support of colleagues and job demands time spent on direct patient care and time spent on registration had the biggest significant effects on perceived workload. CONCLUSIONS: The modelled workload does not exactly predict perceived workload, however there is a correlation between the two. The modelled workload can be used to detect differences in workload between wards, which may be useful in distributing workload more evenly in order prevent issues of over- and understaffing and organizational justice. Extra effort to promote team work is likely to have a positive effect on perceived workload. Nurse management can stimulate team cohesion, especially when workload is high. Registered nurses perceive a higher workload than other nurses. When the proportion of direct patient care in a workday is higher, the perceived workload is also higher. Further research is recommended. The findings of this research can help nursing management in allocating resources and directing their attention to the most relevant factors for balancing workload.

Five-Year Outcome of Laparoscopic Fundoplication in Pediatric GERD Patients: a Multicenter, Prospective Cohort Study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease in children. When drug treatment fails, laparoscopic anti-reflux surgery (LARS) is considered. Short-term follow-up studies report high success rates; however, few studies report long-term results. The aim of this study was to describe the long-term effects of LARS in pediatric patients. METHODS: A prospective, multicenter study of 25 laparoscopic fundoplication patients was performed. At 3 months and 1, 2, and 5 years postoperatively, patients and caregivers were asked to complete the gastroesophageal reflux symptom questionnaire to assess symptoms and the PedsQL™ to assess health-related quality of life (HRQoL). RESULTS: Reflux symptom severity was still significantly improved 5 years after LARS compared with preoperative levels (p < 0.0001). However, 26% of patients reported moderate or severe reflux symptoms. Dysphagia was reported in 13% of patients 5 years after LARS and was more common in children with neurologic impairment and children who underwent a Nissen procedure. The increase in HRQoL 3 months postoperatively appears to decline over time: 5 years after surgery, HRQoL was lower, though not significantly, than 3 months postoperatively. HRQoL at 5 years was still higher, though also not significantly, than preoperative levels. The presence of reflux symptoms after surgery was not significantly associated with lower HRQoL. CONCLUSIONS: LARS is effective for therapy-resistant GERD in children. Five years after surgery, reflux symptoms are still improved. However, we observed a decline in symptom-free patients over time. The initial increase in HRQoL shortly after LARS appears to decline over time. TRIAL REGISTRATION: Dutch national trial registry Identifier: 2934 ( www.trialregister.nl ).

Informing metastatic colorectal cancer patients by quantifying multiple scenarios for survival time based on real-life data.

Reported median overall survival (mOS) in metastatic colorectal cancer (mCRC) patients participating in systemic therapy trials has increased to over 30 months. It is uncertain whether trial results translate to real-life populations. Moreover, patients prefer presentation of multiple survival scenarios. Population-based data of all stage IV CRC patients diagnosed between 2008 and 2016 were obtained from the Netherlands Cancer Registry, which has a case ascertainment completeness surpassing 95%. We calculated the following percentiles (scenarios) of OS per year of diagnosis for the total population, and for treatment subgroups: 10th (best-case), 25th (upper-typical), 50th (median), 75th (lower-typical) and 90th (worst-case). Twenty-five percent of patients did not receive any antitumor treatment. From 2008 to 2016, mOS of the total population (n = 27275) remained unchanged at approximately 12 months. OS improved only for the upper-typical and best-case patients; by 4.2 to 29.1 months (P < .001), and by 6 to 62 months (P < .001), respectively. No clinically relevant change was observed among patients who received systemic therapy, with mOS close to 15 months and best-case scenario approximately 40 months. A clinically relevant improvement in survival over time was observed in patients who initially received metastasectomy and/or HIPEC only. In contrast to the wide belief based on trial data that mOS of mCRC patients receiving systemic therapy has improved substantially, improvement could not be demonstrated in our real-life population. Clinicians should consider quoting multiple survival scenarios based on real-life data instead of point estimates from clinical trials, when informing patients about their life expectancy.

Anti-Müllerian hormone levels and risk of type 2 diabetes in women.

AIMS/HYPOTHESIS: Given its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women. METHODS: We measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20-59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH-age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes. RESULTS: During a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HRT2vsT3 1.24 [95% CI 0.81, 1.92]; HRT1vsT3 1.62 [95% CI 1.06, 2.48]; ptrend = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant. CONCLUSIONS/INTERPRETATION: We observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes. Graphical abstract.

Anti-Müllerian Hormone Levels and Risk of Cancer in Women.

OBJECTIVES: To examine if age-specific anti-Müllerian hormone (AMH) levels are associated with cancer risk; and to investigate if age-related AMH trajectories differ between women who develop cancer and women who do not. More specifically, we examined associations with breast cancer, cancers in other tissues expressing AMH receptor AMHR2, and cancers in non-AMHR2-expressing tissues. STUDY DESIGN: We included longitudinal data from 3025 women in the prospective Doetinchem Cohort Study. Cox proportional hazards models were used to assess the association of baseline age-specific AMH tertiles with cancer. We applied linear mixed models to compare age-related AMH trajectories between women who were diagnosed with cancer and women who were not. MAIN OUTCOME MEASURES: Cancer (n = 385; 139 breast cancers, 112 cancers in other AMHR2-expressing tissues, 134 cancers in non-AMHR2-expressing tissues). RESULTS: Overall, baseline age-specific AMH levels were not associated with cancer risk, although in women ≤ 40 years an increased risk was suggested for breast cancer (HRT2:T1 = 2.06, 95%CI = 0.95-4.48; HRT3:T1 = 2.03, 95%CI = 0.91-4.50). Analysis of age-related AMH trajectories suggested that AMH levels were higher at younger ages and declined faster in women who were diagnosed with cancer compared with women who were not, but our results did not provide evidence for actual differences in trajectories. CONCLUSIONS: Our results did not provide evidence for an association between age-specific AMH levels and age-related trajectories and risk of cancer. However, effect estimates for breast cancer were in line with risk-increasing effects found in previous studies.

Two-Year Outcome after Laparoscopic Fundoplication in Pediatric Patients with Gastroesophageal Reflux Disease.

Introduction: Many studies on short-term efficacy of laparoscopic antireflux surgery (LARS) have shown good to excellent results on reflux symptom control and health-related quality of life (HRQoL). Prospective studies on the long-term efficacy, however, are scarce and indicate that the efficacy of symptom control may decline over time. The aim of this study is to assess the 2-year outcome on reflux symptoms and HRQoL after LARS. Materials and Methods: Between 2011 and 2013, 25 children (12 males, median age 6 [2-18] years) with proton pump inhibitor-resistant gastroesophageal reflux disease were included in a prospective longitudinal cohort study. To assess reflux symptoms and HRQoL, patients and/or their caregivers were asked to fill out the validated age-appropriate gastroesophageal reflux symptom questionnaire and Pediatric Quality of Life Inventory™ before, 3 months, 1 year, and 2 years after LARS. Results: Two years after LARS, 29% of patients had moderate to severe reflux symptoms compared with 92% (P < .001) before operation and 12% 3-4 months after operation (P = .219). The significant increase in HRQoL shortly after fundoplication (80.0 compared with 69.5 (P = .004)) is not observed after 2 years (72.0 compared with 69.5, P = .312). Correlation between the impaired HRQoL scores and the recurrence of symptoms could not be verified. Conclusions: Although the efficacy of LARS tends to deteriorate after 2 years, LARS is still effective in controlling reflux symptoms in the majority of patients. The short-term improvement in HRQoL after LARS appears to be transient.

Increasing Fusion Rate Between 1 and 2 Years After Instrumented Posterolateral Spinal Fusion and the Role of Bone Grafting.

STUDY DESIGN: Two-year clinical and radiographic follow-up of a double-blind, multicenter, randomized, intra-patient controlled, non-inferiority trial comparing a bone graft substitute (AttraX Putty) with autograft in instrumented posterolateral fusion (PLF) surgery. OBJECTIVES: The aim of this study was to compare PLF rates between 1 and 2 years of follow-up and between graft types, and to explore the role of bone grafting based on the location of the PLF mass. SUMMARY OF BACKGROUND DATA: There are indications that bony fusion proceeds over time, but it is unknown to what extent this can be related to bone grafting. METHODS: A total of 100 adult patients underwent a primary, single- or multilevel, thoracolumbar PLF. After instrumentation and preparation for grafting, the randomized allocation side of AttraX Putty was disclosed. The contralateral posterolateral gutters were grafted with autograft. At 1-year follow-up, and in case of no fusion at 2 years, the fusion status of both sides of each segment was blindly assessed on CT scans. Intertransverse and facet fusion were scored separately. Difference in fusion rates after 1 and 2 years and between grafts were analyzed with a Generalized Estimating Equations (GEE) model (P < 0.05). RESULTS: The 2-year PLF rate (66 patients) was 70% at the AttraX Putty and 68% at the autograft side, compared to 55% and 52% after 1 year (87 patients). GEE analysis demonstrated a significant increase for both conditions (odds ratio 2.0, 95% confidence interval 1.5-2.7, P < 0.001), but no difference between the grafts (P = 0.595). Ongoing bone formation was only observed between the facet joints. CONCLUSION: This intra-patient controlled trial demonstrated a significant increase in PLF rate between 1 and 2 years after instrumented thoracolumbar fusion, but no difference between AttraX Putty and autograft. Based on the location of the PLF mass, this increase is most likely the result of immobilization instead of grafting. LEVEL OF EVIDENCE: 1.

Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study.

PURPOSE: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. METHODS AND MATERIALS: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. RESULTS: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. CONCLUSIONS: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.

Efficacy of a Standalone Microporous Ceramic Versus Autograft in Instrumented Posterolateral Spinal Fusion: A Multicenter, Randomized, Intrapatient Controlled, Noninferiority Trial.

STUDY DESIGN: in the rest of the article written as patient- and observer-blinded, multicenter, randomized, intrapatient controlled, noninferiority trial. OBJECTIVE: The aim of this study was to determine noninferiority of a biphasic calcium-phosphate (AttraX® Putty) as a bone graft substitute for autograft in instrumented posterolateral fusion (PLF). SUMMARY OF BACKGROUND DATA: Spinal fusion with autologous bone graft is a frequently performed surgical treatment. Several drawbacks of autografting have driven the development of numerous alternatives including synthetic ceramics. However, clinical evidence for the standalone use of these materials is limited. METHODS: This study included 100 nontraumatic adults who underwent a primary, single- or multilevel, thoracolumbar, instrumented PLF. After instrumentation and preparation for grafting, the randomized allocation side of AttraX® Putty was disclosed. Autograft was applied to the contralateral side of the fusion trajectory, so each patient served as his/her own control. For the primary efficacy outcome, PLF was assessed at 1-year follow-up on computed tomography scans. Each segment and side was scored as fused, doubtful fusion, or nonunion. After correction for multilevel fusions, resulting in a single score per side, the fusion performance of AttraX Putty was tested with a noninferiority margin of 15% using a 90% confidence interval (CI). RESULTS: There were 49 males and 51 females with a mean age of 55.4 ±â€Š12.0 (range 27-79) years. Two-third of the patients underwent a single-level fusion and 62% an additional interbody fusion procedure. The primary analysis was based on 87 patients, including 146 instrumented segments. The fusion rate of AttraX Putty was 55% versus 52% at the autograft side, with an overall fusion rate of 71%. The 90% CI around the difference in fusion performance excluded the noninferiority margin (difference = 2.3%, 90% CI = -9.1% to +13.7%). CONCLUSION: The results of this noninferiority trial support the use of AttraX Putty as a standalone bone graft substitute for autograft in instrumented thoracolumbar PLF. LEVEL OF EVIDENCE: 1.

Gastro-esophageal Reflux After Laparoscopic Gastrostomy Placement in Children.

OBJECTIVES: Gastrostomy placement is frequently performed in pediatric patients who require long-term enteral tube feeding. Evidence on the influence of gastrostomy placement on gastro-oesophageal reflux disease has been inconsistent. The aim of this study was to investigate the influence of gastrostomy on gastro-oesophageal reflux. METHODS: A prospective, longitudinal cohort study was performed including 50 patients who underwent laparoscopic gastrostomy between May 2012 and April 2014. Before and 3 months after surgery 24-hour multichannel intraluminal impedance pH monitoring was performed and caregivers filled out reflux symptom questionnaires. RESULTS: Gastro-oesophageal reflux symptoms were present in a comparable number of patients before (44%) and after gastrostomy placement (40%; P = 0.73). Twenty-five of the patients (50%) underwent both the preoperative and postoperative tests and were included in impedance-pH analysis. Acid exposure time (percentage of time with pH below 4) did not change significantly after gastrostomy placement: from 6.2% (3.0-18.1) to 6.1% (2.6-14.9). The number of reflux episodes did not significantly change, for either liquid [mean difference 4.3 (-4.5 to 13.2)] or mixed liquid-gas reflux [mean difference 2.0 (-9.3 to 13.3)]. Before gastrostomy placement, 18 out of 25 patients had pathological reflux (72%) on pH-impedance measurement. In 4 patients, pathological reflux dissolved, whereas 4 patients newly developed pathological reflux. A low preoperative weight-for-height percentile was associated with increased acid exposure after gastrostomy placement. CONCLUSIONS: Overall, gastrostomy placement was not associated with an increase in acid exposure on 24-hour multichannel intraluminal impedance pH monitoring. Similarly, the prevalence of gastro-oesophageal reflux-related symptoms did not change after gastrostomy.

Health-related quality of life in children after laparoscopic gastrostomy placement.

INTRODUCTION: A gastrostomy placement (GP) is an established treatment to provide enteral feeding in pediatric patients with feeding difficulties aiming to improve nutritional status and health-related quality of life (HRQoL). The aim of this study was to evaluate HRQoL in children with severe feeding difficulties who have undergone GP. MATERIALS AND METHODS: A cross-sectional study was performed including 128 patients who had undergone laparoscopic GP (2004-2011). HRQoL was evaluated using the validated Pediatric Quality of Life 4.0 Inventory. Multiple regression analysis was performed to identify predictors of HRQoL. RESULTS: After a mean follow-up of 4.0 years (interquartile range 2.9-6.2) after GP, mean HRQoL was 53.0 out of 100 (standard deviation 21.1). HRQoL was significantly lower in children with neurologic impairment, with a mean difference of -21.4 points between neurologically impaired and neurologically normal children (p < 0.001). HRQoL was also lower in children with cardiac disease (-19.0 points; p = 0.01) and in children with a history of previous gastrointestinal surgery (-15.2 points; p = 0.03). Feeding through a gastrojejunostomy tube (-33.0 points; p = 0.01) and higher age at the time of operation (-1.2 points per year; p = 0.03) were also associated with lower HRQoL. GP-related complications requiring reintervention were associated with lower HRQoL, although this association was not statistically significant (p = 0.06). CONCLUSIONS: Children with severe feeding difficulty, who have undergone GP, have significantly lower HRQoL compared to a healthy pediatric population. Neurologic impairment, cardiac disease, a history of gastrointestinal surgery, older age, and the need for jejunal feeding through the gastrostomy were predictive of even lower HRQoL.

Balancing workload of nurses: Linear mixed effects modelling to estimate required nursing time on surgical wards.

Aim: Quantifying the relation between patient characteristics and care time and explaining differences in nursing time between wards. Design: Academic hospital in the Netherlands. Six surgical wards, capacity 15-30 beds, 2012-2014. Methods: Linear mixed effects model to study the relation between patient characteristics and care time. Estimated marginal means to estimate baseline care time and differences between wards. Results: Nine patient characteristics significantly related to care time. Most required between 18 and 35 min extra, except "two or more IV/drip/drain" (8) and "one-on-one care" (156). Care time for minimum patient profile: 44-57 min and for average patient profile: 75-88 min. Sources of variation: nurse proficiency, patients, day-to-day variation within patients. The set of characteristics is short, simple and useful for planning and comparing workload. Explained variance up to 36%. Calculating estimated means per ward has not been done before. Nurse proficiency is an important factor.

Trajectory of body mass and skeletal muscle indices and disease progression in metastatic colorectal cancer patients.

BACKGROUND: Knowledge of the evolution of BMI and skeletal muscle index (SMI) measurements during advanced cancer and their relationships with disease progression (PD) is relevant to improve the timing of interventions that may improve cachexia-associated outcomes. OBJECTIVES: We investigated BMI and SMI trajectories and their associations with PD in metastatic colorectal cancer (mCRC) patients during consecutive palliative systemic regimens. METHODS: In a secondary analysis of the primary CAIRO3 trial, we included 533 mCRC patients with BMI measurements repeated every 3 wk and 95 randomly selected patients with SMI measurements repeated every 9 wk. We studied 2 periods: p1, during first-line maintenance capecitabine + bevacizumab or observation until the first progression of disease (PD1); and p2, during capecitabine + oxaliplatin + bevacizumab or another reintroduction treatment from PD1 until the second progression of disease (PD2). BMI and SMI trajectories were modeled separately throughout both periods, and joint longitudinal-survival modeling was used to investigate the relationships between slopes in BMI and SMI with PD at 9 and 3 wk pre-PD. A multivariate longitudinal joint model was used to investigate the association between the BMI trajectory and PD at time of PD, independent of SMI. RESULTS: During p1, the slopes in BMI and SMI were associated with early PD1 [HRs for 9-wk BMI: 1.54 (95% CI: 1.33, 1.76); 9-wk SMI: 1.38 (95% CI: 0.87, 1.89), NS; 3-wk BMI: 1.74 (95% CI: 1.48, 1.99); 3-wk SMI: 2.65 (95% CI: 1.97, 3.32)]. During p2, only the slope in SMI was related to PD2 [9-wk BMI: 1.09 (95%: CI: 0.73, 1.45), NS; 9-wk SMI: 1.64 (95% CI: 1.25, 2.04); 3-wk BMI: 1.17 (95% CI: 0.77, 1.57); 3-wk SMI: 1.11 (95% CI: 0.70, 1.53)]. In models mutually adjusting for BMI and SMI, SMI was associated with PD in p1 [p1 ( n = 95), HR BMI: 1.32 (95% CI: 0.74, 2.39), NS; p1, HR SMI: 1.50 (95% CI: 1.04, 2.14); p2 ( n = 50), BMI: 0.98 (95% CI: 0.55, 1.75), NS; p2, HR SMI: 1.11 (95% CI: 0.61, 2.05), NS]. CONCLUSIONS: In mCRC patients during palliative systemic treatment, SMI losses, irrespective of BMI losses, may be a marker for the early initiation of cachexia interventions.

The Effect of Gastrostomy Placement on Health-Related Quality of Life in Children.

BACKGROUND AND PURPOSE: A gastrostomy placement (GP) aims to improve nutritional status and health-related quality of life (HRQoL) in children who require long-term enteral tube feeding. We evaluated the effect of GP on HRQoL. METHODS: A prospective, longitudinal cohort study was performed including patients referred for laparoscopic GP. Children and/or caregivers were asked to fill out the validated PedsQL™ questionnaire before and 3 months after surgery. The aim was to compare preoperative with postoperative HRQoL and to identify predictors of HRQoL. RESULTS: Fifty patients were included with a median age of 3.4 years (interquartile range 1.4-5.6). After GP, total HRQoL did not significantly increase (p = 0.30). However, psychosocial health significantly increased: 55.8 (standard deviation ±20.8) to 61.2 (±19.6; p = 0.03) on a 100-point scale. This was mainly owing to an increase in social HRQoL: 58.2 (±32.3) to 68.3 (±27.9; p = 0.04). HRQoL both before and after GP was significantly lower in children with neurologic impairment (p < 0.0005). However, neurologic impairment did not influence the effect of surgery on HRQoL (p = 0.66). Low preoperative body mass index was a predictor for improvement in HRQoL after GP. CONCLUSIONS: After GP in children, psychosocial HRQoL improved significantly. This was mainly owing to an improvement in social HRQoL. LEVEL OF EVIDENCE: IV.

Barriers to ideal palliative care in multiple care settings: the nurses' point of view.

BACKGROUND: Nurses and certified nursing assistants (CNA) have a crucial role in 24/7 continuity of palliative care for many vulnerable patients and families, however, their perspective has been largely omitted in reported barriers to palliative care. AIM: To describe barriers to ideal palliative care that are specific to nurses and CNAs working in all care settings. METHODS: A cross-sectional, online survey was distributed to members of the Dutch Nurses' Association. FINDINGS: Almost 50% of the participating 2377 nurses and CNAs experienced more than five barriers to ideal palliative care in their work situation; nurses and CNAs employed in regional hospitals, mental healthcare and nursing home settings encountered more barriers than those working in other settings. CONCLUSION: The three most common barriers were: lack of proactive care planning, lack of internal consultation possibilities and lack of assessment of care recipients' preferences and needs for a seamless transition to another setting.

Skeletal muscle mass loss and dose-limiting toxicities in metastatic colorectal cancer patients.

BACKGROUND: Increasing evidence suggests that severe skeletal muscle index (SMI) loss (sarcopenia) is associated with poor overall survival in metastatic colorectal cancer patients, but its mechanisms are unknown. We recently found, using data of the randomized phase 3 CAIRO3 study, that SMI loss was related with shorter time to disease progression and overall survival during first-line maintenance treatment with capecitabine + bevacizumab (CAP-B) or observation and during more intensive capecitabine + oxaliplatin + bevacizumab (CAPOX-B) reintroduction treatment. As a potential risk factor for reduced survival, we explored whether sarcopenia and SMI loss were associated with dose-limiting toxicities (DLTs) during CAP-B and CAPOX-B. METHODS: Sarcopenia status and SMI loss were assessed by using consecutive computed tomography scans. DLTs were defined as any dose delay/reduction/discontinuation of systemic treatment because of reported CTCAE (version 3.0) toxicities at the start or during treatment. Poisson regression models were used to study whether sarcopenia and body mass index (BMI) at the start of treatment and SMI and BMI loss during treatment were associated with DLTs. RESULTS: One hundred eighty-two patients (mean age 63.0 ± 8.8 years, 37% female) received CAP-B, and 232 patients (mean age 63.0 ± 9.0 years, 34% female) received CAPOX-B. At the start of CAP-B and CAPOX-B, 54% and 46% of patients were sarcopenic, respectively. Mean BMI was lower in sarcopenic patients, although patients were on average still overweight (sarcopenic vs. non-sarcopenic at the start of CAP-B 25.0 ± 3.9 vs. 26.7 ± 4.1 and CAPOX-B 25.8 ± 3.8 vs. 27.1 ± 3.8 kg/m2 ). Sarcopenia at the start of CAP-B was not associated with DLTs [relative risk 0.87 (95% confidence interval 0.64-1.19)], whereas patients with >2% SMI loss had a significantly higher risk of DLTs [1.29 (1.01-1.66)]. At the start of subsequent CAPOX-B, 25% of patients received a dose reduction, and the risk of dose reduction was significantly higher for patients with preceding SMI loss [1.78 (1.06-3.01)] or sarcopenia [1.75 (1.08-2.86)]. After the received dose reductions, sarcopenia or SMI loss was not significantly associated with a higher risk of DLTs during CAPOX-B [sarcopenia vs. non-sarcopenic: 0.86 (0.69-1.08) and SMI loss vs. stable/gain: 0.83 (0.65-1.07)]. In contrast, BMI (loss) at the start or during either treatment was not associated with an increased risk of DLTs. CONCLUSIONS: In this large longitudinal study in metastatic colorectal cancer patients during palliative systemic treatment, sarcopenia and/or muscle loss was associated with an increased risk of DLTs. BMI was not associated with DLTs and could not detect sarcopenia or SMI loss. Prospective (randomized) studies should reveal whether normalizing chemotherapeutic doses to muscle mass or muscle mass preservation (by exercise and nutritional interventions) increases chemotherapeutic tolerance and improves survival.