Capturing Emerging Experiential Knowledge for Vaccination Guidelines Through Natural Language Processing: Proof-of-Concept Study.

BACKGROUND: Experience-based knowledge and value considerations of health professionals, citizens, and patients are essential to formulate public health and clinical guidelines that are relevant and applicable to medical practice. Conventional methods for incorporating such knowledge into guideline development often involve a limited number of representatives and are considered to be time-consuming. Including experiential knowledge can be crucial during rapid guidance production in response to a pandemic but it is difficult to accomplish. OBJECTIVE: This proof-of-concept study explored the potential of artificial intelligence (AI)-based methods to capture experiential knowledge and value considerations from existing data channels to make these insights available for public health guideline development. METHODS: We developed and examined AI-based methods in relation to the COVID-19 vaccination guideline development in the Netherlands. We analyzed Dutch messages shared between December 2020 and June 2021 on social media and on 2 databases from the Dutch National Institute for Public Health and the Environment (RIVM), where experiences and questions regarding COVID-19 vaccination are reported. First, natural language processing (NLP) filtering techniques and an initial supervised machine learning model were developed to identify this type of knowledge in a large data set. Subsequently, structural topic modeling was performed to discern thematic patterns related to experiences with COVID-19 vaccination. RESULTS: NLP methods proved to be able to identify and analyze experience-based knowledge and value considerations in large data sets. They provide insights into a variety of experiential knowledge that is difficult to obtain otherwise for rapid guideline development. Some topics addressed by citizens, patients, and professionals can serve as direct feedback to recommendations in the guideline. For example, a topic pointed out that although travel was not considered as a reason warranting prioritization for vaccination in the national vaccination campaign, there was a considerable need for vaccines for indispensable travel, such as cross-border informal caregiving, work or study, or accessing specialized care abroad. Another example is the ambiguity regarding the definition of medical risk groups prioritized for vaccination, with many citizens not meeting the formal priority criteria while being equally at risk. Such experiential knowledge may help the early identification of problems with the guideline's application and point to frequently occurring exceptions that might initiate a revision of the guideline text. CONCLUSIONS: This proof-of-concept study presents NLP methods as viable tools to access and use experience-based knowledge and value considerations, possibly contributing to robust, equitable, and applicable guidelines. They offer a way for guideline developers to gain insights into health professionals, citizens, and patients' experience-based knowledge, especially when conventional methods are difficult to implement. AI-based methods can thus broaden the evidence and knowledge base available for rapid guideline development and may therefore be considered as an important addition to the toolbox of pandemic preparedness.

Public engagement in decision-making regarding the management of the COVID-19 epidemic: Views and expectations of the 'publics'.

BACKGROUND: In the management of epidemics, like COVID-19, trade-offs have to be made between reducing mortality and morbidity and minimizing socioeconomic and political consequences. Traditionally, epidemic management (EM) has been guided and executed attentively by experts and policymakers. It can, however, still be controversial in the public sphere. In the last decades, public engagement (PE) has been successfully applied in various aspects of healthcare. This leads to the question if PE could be implemented in EM decision-making. METHODS: From June to October 2020, seven deliberative discussion focus groups were executed with 35 Dutch citizens between 19 and 84 years old. Their views on PE in COVID-19 management were explored. The deliberative approach allows for the education of participants on the topic before the discussion. The benefits, barriers, timing and possible forms of PE in EM were discussed. RESULTS: Almost all participants supported PE in EM, as they thought that integrating their experiences and ideas would benefit the quality of EM, and increase awareness and acceptance of measures. A fitting mode for PE was consultation, as it was deemed important to provide the public with possibilities to share ideas and feedback; however, final authority remained with experts. The publics could particularly provide input about communication campaigns and control measures. PE could be executed after the first acute phase of the epidemic and during evaluations. CONCLUSIONS: This paper describes the construction of an empirically informed framework about the values and conditions for PE in EM from the perspective of the public. Participants expressed support to engage certain population groups and considered it valuable for the quality and effectiveness of EM; however, they expressed doubts about the feasibility of PE and the capabilities of citizens. In future studies, these results should be confirmed by a broader audience. PATIENT OR PUBLIC CONTRIBUTION: No patients or members of the public were involved in the construction and execution of this study. This study was very exploratory, to gain a first insight into the views of the public in the Netherlands, and will be used to develop engagement practices accordingly. At this stage, the involvement of the public was not yet appropriate.

Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

OBJECTIVE: The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350 + E) compared to PEG4000 without electrolytes (PEG4000). METHODS: In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350 + E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ≤1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ≥3 per week with <1 episode of fecal incontinence. RESULTS: Ninety-seven subjects were included, of whom 82 completed the study. Mean reduction in TSS was -3.81 (95% CI: -4.96 to -2.65) and -3.74 (95%CI: -5.08 to -2.40), for PEG3350 + E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68). Daily sachet use was: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350 + E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P = 0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. CONCLUSIONS: Noninferiority regarding long-term constipation-related symptoms of PEG3350 + E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents.

The public's considerations about implementing non-pharmaceutical interventions to manage a novel COVID-19 epidemic.

In the future, new variants of the SARS-CoV-2 virus might emerge and cause outbreaks. If this occurs, the implementation of non-pharmaceutical interventions (NPIs) can be reconsidered. Consideration of the potential benefits and harms of implementing NPIs, and ultimately deciding about implementing NPIs, is currently mainly executed by experts and governments. However, general literature on public engagement suggests that integrating public perspectives into decision-making can enhance the quality of decisions and foster greater public understanding of them. In this study, a deliberative mini-public was conducted to integrate this public perspective. The aim was to elicit public considerations regarding non-pharmaceutical interventions by asking a diverse group of citizens to participate as decision-makers and convene, learn and deliberate about implementing non-pharmaceutical interventions during a hypothetical outbreak of a new SARS-CoV-2 variant. Participants emphasized the importance of early implementation during the outbreak, to prevent exceeding healthcare capacity, long-term mental health issues, educational deficits, and bankruptcies. Additionally, participants stressed taking public support into account, and shared ideas on maintaining support. Furthermore, participants wanted to give citizens personal responsibility and freedom in making their own assessment regarding adherence to interventions and how much risk of infection they would be willing to accept. Participants also expressed the need for the government to adopt a learning attitude towards improvements in pandemic response, and to generate more focus on long-term strategies. The deliberative mini-public, revealed public considerations that reflected public values and needs. These considerations might be helpful in better aligning epidemic management policies with public perspectives. Regarding the deliberative mini-public, uncertainties remain about the design and impact on a bigger scale.

Functional nonretentive fecal incontinence: do enemas help?

OBJECTIVE: To assess the current treatment of functional nonretentive fecal incontinence, which consists of education, toilet training, and positive motivation. STUDY DESIGN: Patients, age 6 years and older, referred for fecal incontinence (FI) and diagnosed with functional nonretentive fecal incontinence were eligible candidates. Seventy-one children (76% boys, median age 9.3 years) were randomized to receive conventional therapy (control group) or conventional therapy in addition to daily enemas during 2 weeks. Treatment success was defined as <2 episodes of FI/month without use of enemas. RESULTS: At intake, the median FI frequency was 6.1 per week, whereas the median defecation frequency was 7.0 per week. At the end of the treatment period, the median number of FI episodes was significantly decreased in both groups: from 7.0 (IQR 4.0-11.5) to 1.0 (IQR 0.5-2.0) in the intervention group and from 6.0 (IQR 4.0-10) to 2.0 (IQR 0.5-3.5) in the control group. No statistical difference was found between the groups at the end of the treatment period (P = .08) nor during additional follow-up (average success rate 17% for both groups, P = .99). CONCLUSION: Temporarily application of additional rectal enemas did not significantly improve treatment success compared with conventional therapy alone.

Preferences for public engagement in decision-making regarding four COVID-19 non-pharmaceutical interventions in the Netherlands: A survey study.

BACKGROUND: Worldwide, non-pharmaceutical interventions (NPIs) were implemented during the COVID-19 crisis, which heavily impacted the daily lives of citizens. This study considers public perspectives on whether and how public engagement (PE) can contribute to future decision-making about NPIs. METHODS: An online survey was conducted among a representative sample of the public in the Netherlands from 27 October to 9 November 2021. Perceptions and preferences about PE in decision-making on NPIs to control COVID-19 were collected. Preferences regarding four NPIs were studied: Nightly curfew (NC); Digital Covid Certificate (DCC); Closure of elementary schools and daycares (CED); and physical distancing (1.5M). Engagement was surveyed based on the five participation modes of the IAP2 Spectrum of Public Participation, namely inform, consult, advice, collaborate and empower. RESULTS: Of the 4981 respondents, 25% expressed a desire to engage in decision-making, as they thought engagement could improve their understanding and the quality of NPIs, as well as increase their trust in the government. Especially for the NPIs DCC and NC, respondents found it valuable to engage and provide their perspective on trade-offs in values (e.g. opening up society versus division in society by vaccination status). Respondents agreed that the main responsibility in decision-making should stay with experts and policy-makers. 50% of respondents did not want to engage, as they felt no need to engage or considered themselves insufficiently knowledgeable. Inform was deemed the most preferred mode of engagement, and empower the least preferred mode of engagement. CONCLUSION: We reveal large variations in public preferences regarding engagement in NPI decision-making. With 25% of respondents expressing an explicit desire to engage, and considering the benefit of PE in other areas of (public) health, opportunities for PE in NPI decision-making might have been overlooked during the COVID-19 pandemic. Our results provide guidance into when and how to execute PE in future outbreaks.

Kaleidoscopic integration: Advancing the integration of incommensurable knowledge in healthcare guidelines.

The integration of different types of knowledge in epistemically hierarchical settings remains one of the greatest challenges when developing standards for healthcare practices. In this article, we open up the notion of knowledge integration and empirically examine the various ways in which different types of knowledge interact and can be integrated. To allow us to focus on the diverse forms of knowledge as well as their interaction and integration, we combine Moreira's work on repertoires of evaluation with that of Dewulf and Bouwen on frame interactions. We examine the quest for knowledge integration by studying interactions in the case of the development of the COVID-19 vaccination guideline in the Netherlands, a prime example of the encounter of a wide range and diversity of knowledge that needs to be appraised and integrated into guideline recommendations. Drawing on ethnographic observations of more than 70 guideline development meetings between 2021 and 2022, we first map the different types of knowledge and reasonings used by the guideline developers and subsequently analyze their interactions. We identified eight knowledge interaction patterns, being disconnection, polarization, accommodation, incorporation, reconnection, reconciliation, passive juxtaposition, and kaleidoscopic integration. We hereby draw attention to the various possible knowledge interactions encompassed in the concept of "knowledge integration", especially to those in which integration is achieved while differences and incompatibilities are maintained. Finally, we discuss potential ways to facilitate fruitful knowledge interactions during collaborative work which include the ability to accept and sustain tensions between different types of knowledge and making more explicit use of frame or rather repertoire reflection.

Voices of society: the emergence of civil-society practices aiming to engage in the management of the COVID-19 pandemic in the Netherlands.

During the COVID-19 pandemic, public groups mobilised themselves in civil-society engagement practices (CSEPs) aiming to improve or suggest alternative epidemic management. This study explores the motivation to establish CSEPs and their perceived contributions to epidemic management, to gain insight whether integrating views of CSEPs could add value. A systematic online search was executed to identify CSEPs focused on COVID-19 management between January 2020 and January 2022 in the Netherlands. In order to create a comprehensible overview of the identified CSEPs, relevant characteristics were gathered and mapped, for example, local or national scope, subject of action and goals. A selection of CSEPs was interviewed between April and June 2022 to study their motivators to start the CSEPs and perceived contributions to management. The search resulted in the identification of 22 CSEPs, of which members of 14 CSEPs were interviewed. These members indicated several issues that motivated the start of their CSEP, namely; shortage of equipment, sense of solidarity, and a perceived lack of governmental action, lack of democratic values and lack in diversity of perspectives in epidemic management. All respondents believed to have contributed to policy or society, by influencing opinions, and occasionally by altering policy. However, respondents encountered obstacles in their attempts to contribute such as inability to establish contact with authorities, feeling unheard or undermined, and complications due to the interplay of political interests. In conclusion, CSEPs have fulfilled various roles such as providing alternative management policies, producing equipment, representing the needs of vulnerable populations, and supporting citizens and providing citizens with other viewpoints and information. The identified motivators to establish CSEPs in this study uncover room for improvements in policy. These insights, together with the identified perceived barriers of CSEPs, can be used to improve the connection between (future) epidemic management and public priorities and interests.

No role for increased rectal compliance in pediatric functional constipation.

BACKGROUND & AIMS: Increased rectal compliance has been proposed to contribute to pediatric functional constipation (FC). We evaluated the clinical relevance of increased rectal compliance and assessed whether regular use of enemas improves rectal compliance in children with FC. METHODS: A prospective longitudinal study was conducted on children (8-18 years old) with FC. Pressure-controlled rectal distensions were performed at baseline and at 1 year. Rectal compliance was categorized into 3 groups: normal, moderately increased, or severely increased. Patients were randomly assigned to groups given conventional therapy or rectal enemas and conventional therapy. Clinical success was defined as >or=3 spontaneous defecations per week and fecal incontinence <1 per week. RESULTS: Baseline measurements were performed in 101 children (11.0 +/- 2.1 years); rectal compliance was normal in 36%, moderately increased in 40%, and severely increased in 24%. Patients with severely increased rectal compliance had lower defecation frequency (P = .03), more fecal incontinence (P = .04), and more rectal fecal impaction (P < .001). After 1 year, success values were similar between groups: 42% normal, 41% moderately increased, and 40% with severely increased compliance. Barostat studies performed after 1 year in 80 children (37 conventional therapy and 43 rectal enemas in addition to conventional therapy) revealed that rectal compliance had not changed in either group and had not improved in successfully treated patients. CONCLUSIONS: Constipated children with severely increased rectal compliance have severe symptoms. However, increased rectal compliance is not related to treatment failure. Regular use of enemas to avoid rectal fecal impaction does not improve rectal compliance in pediatric FC.

Magnetic resonance imaging of the lumbosacral spine in children with chronic constipation or non-retentive fecal incontinence: a prospective study.

OBJECTIVE: To determine the prevalence of lumbosacral spine (LSS) abnormalities in children with defecation disorders, intractable constipation, or non-retentive fecal incontinence (NRFI) and evaluate whether LSS abnormalities on magnetic resonance imaging (MRI) are clinically detected by neurologic examination. STUDY DESIGN: MRI of the LSS and complete neurologic examination by a pediatric neurologist blinded to the MRI results were performed in patients with intractable defecation disorders. RESULTS: Patients with intractable constipation (n = 130; 76 males; median age, 11 years; range, 6-18 years), and patients with NRFI (n = 28; 18 males; median age, 10 years; range, 7-15 years) participated. One occult spina bifida (OSB) and 3 terminal filum lipomas were found in patients with a normal neurologic examination. One patient had a terminal filum lipoma and neurologic complaints. Gluteal cleft deviation was found in 3 of 4 patients with LSS abnormalities. Neurosurgical treatment was not required in any patient during the 12-week follow-up. CONCLUSIONS: MRI showed LSS abnormalities in 3% of patients with defecation disorders and normal neurologic examination, all of whom reported symptom relief at the 12-week follow-up without neurosurgical intervention. Thus, whether or not LSS abnormalities play a role in defecation disorders remains unclear.

A randomized controlled trial of enemas in combination with oral laxative therapy for children with chronic constipation.

BACKGROUND & AIMS: After 5 years of intensive oral laxative use, up to 30% of constipated children still have an unsuccessful outcome. Children refractory to oral laxatives might benefit from regular rectal evacuation by enemas. This randomized controlled trial compared the effects of additional treatment with rectal enemas (intervention) with conventional treatment alone (oral laxatives, control) in severely constipated children. METHODS: In a tertiary hospital in the Netherlands, 100 children, aged 8-18 years, with functional constipation for at least 2 years were randomly assigned to intervention or control groups. The control group received education, behavioral strategies, and oral laxatives. The intervention group was also given 3 rectal enemas/week, reduced by 1 enema/week every 3 months. Outcome measures were defecation and fecal incontinence frequency and overall success at 12, 26, 39, and 52 weeks. Overall success was defined as 3 or more defecations/week and less than 1 fecal incontinence episode/week, irrespective of laxative use. RESULTS: Defecation frequency normalized in both groups but was significantly higher in the intervention group compared with controls at 26 and 52 weeks (5.6 vs 3.9/week, P = .02, and 5.3 vs 3.9/week, P = .02, respectively). There were no significant differences between groups in reduction of fecal incontinence episodes (P = .49) and overall success rates (P = .67). After 1 year of treatment, the overall success rate was 47.1% in the intervention group versus 36.1% in the control group. CONCLUSIONS: There is no additional effect of enemas compared with oral laxatives alone as maintenance therapy for severely constipated children.

Health related quality of life in children with constipation-associated fecal incontinence.

OBJECTIVES: With a disease-specific questionnaire, this study aimed to evaluate health-related quality of life (HRQoL) in children with constipation in association with clinical characteristics. STUDY DESIGN: Children with constipation-associated fecal incontinence (n = 114), 8 to 18 years, filled out the Defecation Disorder List at a Dutch tertiary hospital. Correlations and linear regression analysis between clinical characteristics and scores on emotional and social functioning were calculated. Specific concerns of children were described by individual item scores of these domains. RESULTS: Higher frequency of fecal incontinence episodes was associated with lower emotional and social functioning. Linear regression analysis showed a significant association between social functioning and fecal incontinence, but the variance of the model was low (adjusted R(2)= 0.08). Between 70% to 80% of children were concerned about experiencing fecal incontinence unnoticeably and the attendant social consequences. Children did not report having fewer friends and participated well in social events. CONCLUSION: Lower HRQoL regarding disease-specific emotional and social functioning was reported in children with frequent episodes of constipation-associated fecal incontinence. However, other nonspecified factors may also influence HRQoL of these children. Most children reported relatively more emotional concerns than social consequences.

Health-related quality of life in young adults with symptoms of constipation continuing from childhood into adulthood.

BACKGROUND: Children with functional constipation report impaired Health-related Quality of Life (HRQoL) in relation to physical complaints and long duration of symptoms. In about one third of children with constipation, symptoms continue into adulthood. Knowledge on HRQoL in adults with constipation persisting from childhood is lacking. OBJECTIVES: To assess HRQoL in adults with constipation from early childhood in comparison to that of their peers. Furthermore to gain insight into the specific social consequences related to continuing symptoms of constipation and/or fecal incontinence at adult age. METHODS: One HRQoL questionnaire and one self-developed questionnaire focusing on specific consequences of symptoms of constipation continuing into adulthood were administrated to 182 adults with a history of childhood constipation. Successful clinical outcome was defined as a defecation frequency three or more times per week with less than two episodes of fecal incontinence per month, irrespective of laxative use. HRQoL of both adults with unsuccessful and successful clinical outcome were compared to a control group of 361 peers from the general Dutch population. RESULTS: No differences in HRQoL were found between the whole study population and healthy peers, nor between adults with successful clinical outcome (n = 139) and the control group. Adults with an unsuccessful clinical outcome (n = 43) reported significantly lower HRQoL compared to the control group with respect to scores on bodily pain (mean +/- SD 77.4 +/- 19.6 versus 85.7 +/- 19.5, p = 0.01) and general health (67.6 +/- 18.8 versus 74.0 +/- 18.1, p = 0.04). Adults with an unsuccessful clinical outcome reported difficulties with social contact and intimacy (20% and 12.5%, respectively), related to their current symptoms. Current therapy in these adults was more often self-administered treatment (e.g. diet modifications) (60.4%) than laxatives (20.9%). CONCLUSION: Overall, young adults with constipation in childhood report a good quality of life, as HRQoL of adults with successful clinical outcome was comparable to that of their peers. However, when childhood constipation continues into adulthood, it influences HRQoL negatively with social consequences in 20% of these adults.

Functional nonretentive fecal incontinence in children.

Fecal incontinence, the loss of feces in the underwear after age 4 years, is a frustrating phenomenon for children and their parents. It is difficult to treat, presenting as a single symptom without any organic cause or signs of constipation. This review addresses the definition of functional nonretentive fecal incontinence and provides an overview of its epidemiology, pathophysiology, clinical features, diagnostic work-up and prognosis.

The role of a probiotics mixture in the treatment of childhood constipation: a pilot study.

BACKGROUND: Inconsistent data exist about the efficacy of probiotics in the treatment of constipation. Several studies in adults with constipation showed positive effects of probiotics on constipation. Inconsistent data exist regarding the effect of a single probiotic strain in constipated children. The aim of this pilot study was to determine the effect of a mixture of probiotics containing bifidobacteria and lactobacilli in the treatment of childhood constipation. METHODS: Children aged 4-16 years with constipation as defined by the Rome III criteria were eligible for the study. During a 4 week period, children received a daily mix of 4 x 109 colony forming units of a probiotic mixture (Ecologic(R)Relief) containing Bifidobacteria (B.) bifidum, B. infantis, B. longum, Lactobacilli (L.) casei, L. plantarum and L. rhamnosus. Primary outcome measures were frequency of bowel movements (BMs) per week and stool consistency. Secondary outcome measures were number of faecal incontinence episodes per week, abdominal pain and side effects. RESULTS: Twenty children, 50% male, median age 8 (range 4-16) were included. The frequency of BMs per week increased from 2.0 (1.0-5.0) to 4.2 (0.0-16.0) in week 2 (p = 0.10) and 3.8 (2.1-7.0) in week 4 (p = 0.13). In 12 children presenting with <3 BMs/week, BMs per week increased significantly from 1.0 (0.0-2.0) to 3.0 (0.0-7.0) in week 2 (p = 0.01) and 3.0 (0.0-10.0) in week 4 (p = 0.01). The stool consistency was reported as hard in 7 children at baseline, in 4 children at week 2 (p = 0.23) and in 6 children after 4 weeks of treatment (p = 1.00). A significant decrease in number of faecal incontinence episodes per week was found in the entire group: 4.0 (0.0-35.0) to 1.5 (0.0-14.0) in week 2 (p = 0.01) and 0.3 (0.0-7.0) in week 4 (p = 0.001). The presence of abdominal pain decreased significantly from 45% to 25% in week 2 (p = 0.04) and 20% at week 4 (p = 0.006). No side effects were reported. CONCLUSION: This pilot study shows that a mixture of probiotics, has positive effects on symptoms of constipation. To confirm these findings, a large randomised placebo controlled trial is required.

The clinical effect of a new infant formula in term infants with constipation: a double-blind, randomized cross-over trial.

BACKGROUND: Nutrilon Omneo (new formula; NF) contains high concentration of sn-2 palmitic acid, a mixture of prebiotic oligosaccharides and partially hydrolyzed whey protein. It is hypothesized that NF positively affects stool characteristics in constipated infants. METHODS: Thirty-eight constipated infants, aged 3-20 weeks, were included and randomized to NF (n = 20) or a standard formula (SF; n = 18) in period 1 and crossed-over after 3 weeks to treatment period 2. Constipation was defined by at least one of the following symptoms: 1) defecation frequency < 3/week; 2) painful defecation; 3) abdominal or rectal palpable mass. RESULTS: Period 1 was completed by 35 infants. A significant increase in defecation frequency (NF: 3.5 pre versus 5.6/week post treatment; SF 3.6 pre versus 4.9/week post treatment) was found in both groups, but was not significantly different between the two formulas (p = 0.36). Improvement of hard stool consistency to soft stool consistency was found more often with NF than SF, but did not reach statistical significance (90% versus 50%; RR, 1.8; 95% CI, 0.9-3.5; p = 0.14). No difference was found in painful defecation or the presence of an abdominal or rectal mass between the two groups. Twenty-four infants completed period 2. Only stool consistency was significantly different between the two formulas (17% had soft stools on NF and hard stools on SF; no infants had soft stools on SF and hard stools on NF, McNemar test p = 0.046). CONCLUSION: The addition of a high concentration sn-2 palmitic acid, prebiotic oligosaccharides and partially hydrolyzed whey protein resulted in a strong tendency of softer stools in constipated infants, but not in a difference in defecation frequency. Formula transition to NF may be considered as treatment in constipated infants with hard stools.

Inhibition of histone acetylation as a tool in bone tissue engineering.

Our approach to bone tissue engineering is the in vitro expansion and osteogenic differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) and their subsequent implantation on porous ceramic materials. Current osteogenic differentiation protocols use dexamethasone to initiate the osteogenic process, thus ignoring the multiple signaling pathways that control osteogenesis in vivo. Supporting osteogenesis at multiple stages might further enhance the bone-forming capacity of hMSCs. As reported previously, inhibition of so-called histone deacetylases (HDACs) stimulates osteoblast maturation, and in this report, we investigated whether trichostatin A (TSA), a widely used HDAC inhibitor, can be implemented in bone tissue engineering. We confirmed that TSA treatment of hMSCs results in increased expression of alkaline phosphatase (ALP) with concomitant increase in mineralization. Flow cytometry demonstrated that TSA increases the percentage of ALP-positive hMSCs as well as their average ALP expression level, but the robustness of the response differs between donors. Unfortunately, TSA has a profound negative effect on cell proliferation, so we investigated whether hMSCs respond to TSA after reaching confluence. Confluent hMSCs on tissue culture plastic displayed enhanced ALP expression. Therefore, we seeded TSA-treated hMSCs onto ceramic particles and analyzed ectopic bone formation upon implantation in immune-deficient mice. Unfortunately, TSA-treated hMSCs did not display better bone formation in vivo than control cells. Finally, we observed that TSA treatment strongly enhanced bone formation of ex vivo cultured mouse calvaria, which warrants further exploration of TSA in bone tissue engineering.

The value of the abdominal radiograph in children with functional gastrointestinal disorders.

Functional gastrointestinal disorder is a common problem in childhood. The symptoms vary from a relative mild gastrointestinal problem such as abdominal pain or infrequent defecation to severe problems with fecal impaction and fecal incontinence. The aim of this review is to describe and evaluate the value of the different existing methods to assess fecal loading on an abdominal radiograph with or without the use of radio-opaque markers in the diagnosis of functional abdominal pain, functional constipation and functional non-retentive fecal incontinence. In our opinion, the abdominal radiograph has limited value in the diagnostic work-up of children with functional gastrointestinal disorders.

Long-term prognosis for childhood constipation: clinical outcomes in adulthood.

OBJECTIVES: This study examines long-term prognoses for children with constipation in adulthood and identifies prognostic factors associated with clinical outcomes. METHODS: In a Dutch tertiary hospital, children (5-18 years of age) who were diagnosed as having functional constipation were eligible for inclusion. After a 6-week treatment protocol, prospective follow-up evaluations were conducted at 6 and 12 months and annually thereafter. Good clinical outcomes were defined as > or =3 bowel movements per week for > or =4 weeks, with < or =2 fecal incontinence episodes per month, irrespective of laxative use. RESULTS: A total of 401 children (260 boys; median age: 8 years [interquartile range: 6-9 years]) were included, with a median follow-up period of 11 years (interquartile range: 9-13 years). The dropout rate during follow-up was 15%. Good clinical outcomes were achieved by 80% of patients at 16 years of age. Thereafter, this proportion remained constant at 75%. Poor clinical outcomes at adult age were associated with: older age at onset (odds ratio [OR]: 1.15 [95% confidence interval [CI]: 1.02-1.30]; P = .04), longer delay between onset and first visit to our outpatient clinic (OR: 1.24 [95% CI: 1.10-1.40]; P = .001), and lower defecation frequency at study entry (OR: 0.92 [95% CI: 0.84-1.00]; P = .03). CONCLUSIONS: One-fourth of children with functional constipation continued to experience symptoms at adult age. Certain risk factors for poor clinical outcomes in adulthood were identified. Referral to a specialized clinic should be considered at an early stage for children who are unresponsive to first-line treatment.

Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG.

OBJECTIVE: We hypothesized that enemas and polyethylene glycol (PEG) would be equally effective in treating rectal fecal impaction (RFI) but enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction. METHODS: Children (4-16 years) with functional constipation and RFI participated. One week before disimpaction, a rectal examination was performed, symptoms of constipation were recorded, and the first CTT measurement was started. If RFI was determined, then patients were assigned randomly to receive enemas once daily or PEG (1.5 g/kg per day) for 6 consecutive days. During this period, the second CTT measurement was started and a child's behavior questionnaire was administered. Successful rectal disimpaction, defecation and fecal incontinence frequencies, occurrence of abdominal pain and watery stools, CTTs (before and after disimpaction), and behavior scores were assessed. RESULTS: Ninety-five patients were eligible, of whom 90 participated (male, n = 60; mean age: 7.5 +/- 2.8 years). Forty-six patients received enemas and 44 PEG, with 5 dropouts in each group. Successful disimpaction was achieved with enemas (80%) and PEG (68%; P = .28). Fecal incontinence and watery stools were reported more frequently with PEG (P < .01), but defecation frequency (P = .64), abdominal pain (P = .33), and behavior scores were comparable between groups. CTT normalized equally (P = .85) in the 2 groups. CONCLUSION: Enemas and PEG were equally effective in treating RFI in children. Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI.