Trends in C reactive protein testing: a retrospective cohort study in paediatric ambulatory care settings.

OBJECTIVES: This study aims to investigate C reactive protein (CRP) testing practices in paediatric ambulatory care across British primary care and accident and emergency (A&E) departments. DESIGN, SETTING, PARTICIPANTS: This retrospective cohort study included children <18 years old having ≥1 CRP test at primary care or A&E departments in Oxfordshire between 2007 and 2021. OUTCOMES: We estimated the frequency and annual changes in CRP testing in both settings and evaluated referral and admission patterns based on CRP levels: low (<20 mg/L), intermediate or high (≥80 mg/L). RESULTS: Over 15 years, 91 540 CRP tests were requested in 63 226 children, with 33 882 (53.6%) in primary care and 29 344 (46.4%) in A&E. Both settings showed rising trends in test requests, with average annual percentage change of 3.0% (95% CI 1.2% to 4.7%) in primary care and 11.5% (95% CI 8.6% to 14.6%) in A&E. The proportion of intermediate/high-test results remained stable. In primary care, 50 709 (95.8%) of CRP tests were <20 mg/L, with 99.0% of these children managed at home. High and intermediate CRP values increased odds of referral versus low CRP (OR adjusted for age=21.80; 95% CI 16.49 to 28.81 and 4.77; 3.78 to 6.02, respectively). At A&E, 27 610 (71.5%) children had CRP<20 mg/L, of whom 42.5% were admitted while 3776 (9.8%) had CRP≥80 mg/L with 57.9% admission rate. High and intermediate CRP values increased odds of admission versus low CRP (OR adjusted for age=1.90; 95% CI 1.78 to 2.04 and 1.39; 1.32 to 1.46, respectively). CONCLUSION: There are rising trends of CRP test requests in paediatric ambulatory care settings, with no evidence of increases in proportion of intermediate/high-test results in primary care. Low CRP values at primary care were linked to children managed at home, while almost half of children with low CRP values at A&E were admitted to the hospital.

Accuracy of diagnostic tests for acute diverticulitis that are feasible in primary care: a systematic review and meta-analysis.

BACKGROUND: Recognition of acute diverticulitis is important to determine an adequate management strategy. Differentiating it from other gastrointestinal disorders is challenging as symptoms overlap. Clinical tests might assist the clinician with this diagnostic challenge. Previous reviews have focussed on prognostic questions and imaging examinations in secondary care. OBJECTIVE: To evaluate the diagnostic accuracy of clinical tests feasible in primary care for acute diverticulitis in suspected patients. METHOD: We have systematically searched multiple databases for diagnostic accuracy studies of tests feasible in primary care compared to a reference standard in suspected patients. Two reviewers independently selected studies, extracted data, and assessed study quality with the QUADAS-2 tool. We have meta-analysed the results in the case of more than four studies per index test. RESULTS: Seventeen studies were included, all studies were performed in secondary care (median prevalence 48%). Individual signs and symptoms showed a wide range in sensitivity (range 0.00-0.98) and specificity (range 0.08-1.00). Of the four laboratory tests evaluated, CRP >10 mg/l had the highest sensitivity (range 0.89-0.96) with specificity ranging from 0.28 to 0.61. Ultrasound had the highest pooled sensitivity and specificity of 0.92 (95% CI 0.86-0.96) and 0.94 (95% CI 0.88-0.97), respectively. CONCLUSION: None of the studies were performed in primary care. Individual signs and symptoms alone are insufficiently informative for acute diverticulitis diagnosis. CRP showed potential for ruling out and ultrasound had a high diagnostic accuracy. More research is needed about the diagnostic accuracy of these tests in primary care. PROSPERO REGISTRATION NUMBER: CRD42021230622.

What is important to the GP in recognizing acute appendicitis in children: a delphi study.

BACKGROUND: For diagnostic research on appendicitis in registration data, insight is needed in the way GPs generate medical records. We aimed to reach a consensus on the features that GPs consider important in the consultation and medical records when evaluating a child with suspected appendicitis. METHODS: We performed a three-round Delphi study among Dutch GPs selected by purposive sampling. An initial feature list was created based on a literature search and features in the relevant Dutch guideline. Finally, using a vignette describing a child who needed later reassessment, we asked participants to complete an online questionnaire about which consultation features should be addressed and recorded. RESULTS: A literature review and Dutch guideline yielded 95 consultation features. All three rounds were completed by 22 GPs, with the final consensus list containing 26 symptoms, 29 physical assessments and signs, 2 additional tests, and 8 further actions (including safety-netting, i.e., informing the patient about when to contact the GP again). Of these, participants reached consensus that 37 should be actively addressed and that 20 need to be recorded if findings are negative. CONCLUSIONS: GPs agreed that negative findings do not need to be recorded for most features and that records should include the prognostic and safety-netting advice given. The results have implications in three main domains: for research, that negative findings are likely to be missing; for medicolegal purposes, that documentation cannot be expected to be complete; and for clinical practice, that safety-netting advice should be given and documented.

Challenges In Performing An Individual Participant-level Data Meta-analysis.

Individual participant-data meta-analysis (IPDMA) uses data at the participant level to synthesize evidence on clinical decision-making. We discuss the differences from aggregate-data meta-analysis and the advantages and challenges of IPDMA. IPDMA provides an opportunity to study effect modifiers at the participant level and can reduce bias in comparison to aggregate-data meta-analysis. A challenge with IPDMA is that it often requires considerable effort to obtain all the data, and an inability to obtain data for all the studies can lead to availability bias. PATIENT SUMMARY: Systematic reviews of the literature are performed to summarize available evidence regarding clinical decisions. Here we explain the differences between reviews that use aggregated data from published studies and reviews that use the participant-level data from those studies.

A care substitution service in the Netherlands: impact on referral, cost, and patient satisfaction.

BACKGROUND: In care substitution services, medical specialists offer brief consultations to provide general practitioners (GPs) with advice on diagnosis, treatment, or hospital referral. When GPs serve as gatekeepers to secondary care, these regional services could reduce pressures on healthcare systems. The aim is to determine the impact of implementing a care substitution service for dermatology, orthopaedics, and cardiology on the hospital referral rate, health care costs, and patient satisfaction. METHODS: A before-after study was used to evaluate hospital referral rates and health care costs during a follow-up period of 1 year. The study population comprised patients with eligible International Classification of Primary Care codes for referral to the care substitution service (only dermatology, orthopaedic, cardiology indications), as pre-defined by GPs and medical specialists. We compared referral rates before and after implementation by χ2 tests and evaluated patient preference by qualitative analysis. RESULTS: In total, 4,930 patients were included, 2,408 before and 2,522 after implementation. The care substitution service decreased hospital referrals during the follow-up period from 15 to 11%. The referral rate decreased most for dermatology (from 15 to 9%), resulting in a cost reduction of €10.59 per patient, while the other two specialisms experienced smaller reductions in referral rates. Patients reported being satisfied, mainly because of the null cost, improved organisation, improved care, and positive experience of the consultation. CONCLUSIONS: The care substitution service showed promise for specialisms that require fewer hospital facilities, as exemplified by dermatology.

Acute Gastroenteritis: A Qualitative Study of Parental Motivations, Expectations, and Experiences During Out-of-Hours Primary Care.

PURPOSE: Acute gastroenteritis is a common infectious disease in children younger than 6 years of age. Although it is a self-limiting disease, it nevertheless has a high consultation rate in primary care, especially during out-of-hours primary care (OOH-PC). Reasons for this high consultation rate remain unclear. METHODS: The aim of this qualitative study was to explore parental motivations, expectations, and experiences of OOH-PC contacts for children with acute gastroenteritis. We conducted 14 semistructured interviews with parents who contacted OOH-PC in the Netherlands. Interviews were audio-recorded, transcribed, and analyzed using elements of grounded theory and a constant-comparison approach. RESULTS: Unusual behavior of the sick child, absent micturition, and ongoing vomiting and/or diarrhea, with decreased or no fluid intake, motivated parents to contact OOH-PC. Parents initiated contact to prevent symptom deterioration and to be reassured by a general practitioner (GP), expecting them to perform a thorough physical examination, provide information, and make follow-up plans. Parents reported dissatisfaction if they felt unheard, misunderstood, or not taken seriously, and this increased their likelihood of seeking another consultation. General practitioners did not always meet parental expectations. CONCLUSION: Multiple factors affect the decision for parents to contact OOH-PC for their child with gastroenteritis. There is a mismatch between parental expectations and actions of the GP. Awareness regarding parental feelings and understanding their expectations can guide GPs in the interaction with parents, which could improve satisfaction with primary health care and OOH-PC specifically.

Irritable bowel syndrome in children with chronic gastrointestinal symptoms in primary care.

BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in children. However, in primary care, it is still unknown whether there are differences in the prognosis of children with IBS compared to other diagnostic subgroups. Therefore, our aim was to describe the course of symptoms and health-related quality of life (HRQoL) for children with chronic gastrointestinal symptoms who either do or do not fulfil the Rome criteria for IBS in primary care. Second, we compared the diagnosis of the general practitioner (GP) with the Rome criteria. METHODS: We conducted a prospective cohort study with 1-year follow-up, including children aged 4-18 years with chronic diarrhoea and/or chronic abdominal pain in primary care. During follow-up, the Rome III questionnaire, Child Health Questionnaire, and symptom questionnaires were completed. RESULTS: A total of 60/104 children (57.7%) fulfilled the Rome criteria for IBS at baseline. Compared to children without IBS, children with IBS were more commonly referred to secondary care, used more laxatives, and more often developed chronic diarrhoea and low physical HRQoL during 1 year. The diagnosis "IBS" from the GP matched the Rome criteria for only 10% of children, as most were diagnosed with "Constipation." CONCLUSIONS: There seems to be a difference in the treatment and prognosis of symptoms and HRQoL between children with and without IBS in primary care. This suggests that it is relevant to differentiate between these groups. The evaluation and use of feasible criteria to define IBS in different healthcare settings remains subject for further studies.

Management of children with non-acute abdominal pain and diarrhea in Dutch primary care: a retrospective cohort study based on a routine primary care database (AHON).

OBJECTIVE: To describe the testing, prescription, referral, and follow-up management by general practitioners (GPs) for children presenting with non-acute abdominal pain and/or diarrhea in primary care. DESIGN: Retrospective cohort study with one-year follow-up. SETTING: Registry data from a Dutch primary care database (AHON) between 2015 and 2019. SUBJECTS: Children aged 4-18 years old who presented by face-to-face consultation in primary care for non-acute abdominal pain and/or diarrhea (>7 days). MAIN OUTCOME MEASURES: We recorded the proportions of children who received (1) diagnostic testing, medicine prescriptions, follow-up consultations, and referrals at their first visit and (2) repeat consultations and referrals by one-year of follow-up. RESULTS: Among the 2200 children (median age, 10.5 years; interquartile range, 7.0-14.6) presenting to a GP with non-acute abdominal pain and/or diarrhea, most reported abdominal pain (78.7%). At the first visit, GPs performed diagnostic testing for 32.2%, provided a prescription to 34.5%, and referred 2.5% to secondary care. Twenty-five percent of the children had a follow-up consultation within four weeks and 20.8% had a repeat consultation between four weeks and one year. Thirteen percent of the children were referred to secondary care by one year. However, only 1% of all children had documentation of an organic diagnosis needing management in secondary care. CONCLUSION: One-third of children received diagnostic testing or a medicine prescription. Few had a follow-up consultation and >10% was referred to pediatric care. Future research should explore the motivations of GPs why and which children receive diagnostic and medical interventions.

General practitioners (GPs) often manage children with non-acute abdominal pain and/or diarrhea, which is typically due to a functional gastrointestinal disorder (FGID).Nearly one-third of all children underwent diagnostic testing at their first visit.Although recommended by the guideline of the Dutch Society of GPs, we found that only a quarter of children received a follow-up consultation.Thirteen percent of children were referred to pediatric specialist care by one year.

Qualitative study evaluating the expectations and experiences of Dutch parents of children with chronic gastrointestinal symptoms visiting their general practitioner.

OBJECTIVES: Chronic gastrointestinal symptoms are common among children and affect their daily activities and quality of life. The majority will be diagnosed with a functional gastrointestinal disorder. Effective reassurance and education are, therefore, key components of the physician's management. Qualitative studies have shown how parents and children experience specialist paediatric care, yet less is known about general practitioners (GPs), who manage most cases in the Netherlands and have a more personal and enduring relationship with their patients. Therefore, this study evaluates the expectations and experiences of parents of children visiting a GP for chronic gastrointestinal symptoms. DESIGN: We conducted a qualitative interview study. Online interviews were audio and video recorded, transcribed verbatim and independently analysed by the first two authors. Data were collected and analysed concurrently until data saturation was reached. Using thematic analysis, we developed a conceptual framework reflecting respondent expectations and experiences. We performed a member check of the interview synopsis and the conceptual framework. SETTING: Dutch primary care. PARTICIPANTS: We purposively sampled participants from a randomised controlled trial evaluating the effectiveness of faecal calprotectin testing in children with chronic gastrointestinal complaints in primary care. Thirteen parents and two children participated. RESULTS: Three key themes emerged: disease burden, GP-patient relationship and reassurance. Often, the experienced disease burden and the pre-existing GP-patient relationship influenced expectations (eg, for further investigations or a sympathetic ear), and when a GP fulfilled these expectations, a trusting GP-patient relationship ensued that facilitated reassurance. We found that individual needs influenced these themes and their interrelationships. CONCLUSION: Insights provided by this framework could help GPs managing children with chronic gastrointestinal symptoms in daily practice and may therewith improve the consultation experience for parents. Further research should evaluate whether this framework also holds true for children. TRIAL REGISTRATION NUMBER: NL7690.

Health-related quality of life and mortality in the 'Seguimiento Universidad de Navarra' prospective cohort study.

OBJECTIVE: To study the association between health-related quality of life (HRQoL) and all-cause mortality in a healthy middle-aged Mediterranean cohort. METHODS: We included 15,390 participants -mean age 42.8 years at first HRQoL ascertainment, all university graduates-. HRQoL was assessed with the self-administered Medical Outcomes Study Short Form-36 (SF-36) twice, with a 4-year gap. We used multivariable-adjusted Cox regression models to address the relation between self-reported health and Physical or Mental Component Summary (PCS-36 or MCS-36) and mortality, and their interaction with prior comorbidities or adherence to the Mediterranean diet (MedDiet). RESULTS: Over 8.7 years of median follow-up time, 266 deaths were identified. Hazard ratio (HR) for the excellent vs. poor/fair category in self-reported health was 0.30 (95 % confidence interval (CI), 0.16-0.57) in the model with repeated measurements of HRQoL. Both the PCS-36 (HRquartile4(Q4)vs.Q1 0.57 [95%CI, 0.36-0.90], ptrend < 0.001; HRper+10points: 0.64 [95%CI, 0.54-0.75]) and the MCS-36 (HRQ4vs.Q1 0.67 [95%CI, 0.46-0.97], ptrend = 0.025; HRper+10points: 0.86 [95%CI, 0.74-0.99]) were inversely associated with mortality in the model with repeated measurements of HRQoL. Previous comorbidities or adherence to the MedDiet did not modify these associations. CONCLUSIONS: Self-reported HRQoL -assessed as self-reported health, PCS-36 and MCS-36- obtained with the Spanish version of the SF-36 were inversely associated with mortality risk, regardless of the presence of previous comorbidities or adherence to the MedDiet.

Online cognitive-behavioral group intervention for young adult survivors of childhood cancer: a pilot study.

BACKGROUND: Young adult childhood cancer survivors (YACCS) are a vulnerable group in need of psychosocial support, but tailored interventions are lacking. AIM: To examine feasibility and satisfaction, and to explore preliminary effectiveness of an online group intervention (Op Koers Online for YACCS) aimed at teaching active coping skills and providing peer-contact, thereby reducing and preventing psychosocial problems in YACCS. The intervention is based on psycho-education, cognitive behavioral therapy, and aspects of acceptance and commitment therapy. METHODS: YACCS completed questionnaires pre- and post-intervention. Feasibility was based on attendance, drop-out, and an evaluation questionnaire was administered to assess satisfaction. Preliminary effectiveness was evaluated with the Mastery Scale, Illness Cognition Questionnaire, Distress Thermometer, Impact of Cancer - Childhood Survivors, and Pediatric Quality of Life Inventory. Preliminary effectiveness was investigated by testing differences on the psychosocial outcomes (coping and psychosocial wellbeing) between T0 and T1 within respondents, using paired samples t tests and Cohen's d. RESULTS: 10 YACCS participated in the intervention and completed all questionnaires. There was no drop-out; 90% of participants attended five out of six sessions. Overall, participants were satisfied with the intervention; 7.6 on a 0-10 scale. Distress (Cohen's d=-.6, p=.030) and feelings of helplessness (Cohen's d=-.8, p=.001) reduced from T0 to T1, while self-efficacy (Cohen's d=.8, p=.013,) improved. Other outcomes displayed small effects, but did not change significantly. CONCLUSIONS: This first, small pilot study showed short-term decrease in distress and feelings of helplessness and improvement of self-efficacy. Op Koers Online was positively evaluated by YACCS and course leaders, filling a gap in psychosocial services for YACCS.

Diagnostic accuracy of blood tests of inflammation in paediatric appendicitis: a systematic review and meta-analysis.

OBJECTIVE: Possible childhood appendicitis is a common emergency presentation. The exact value of blood tests is debated. This study sought to determine the diagnostic accuracy of four blood tests (white cell count (WCC), neutrophil(count or percentage), C reactive protein (CRP) and/or procalcitonin) for childhood appendicitis. DESIGN: A systematic review and diagnostic meta-analysis. Data sources included MEDLINE, EMBASE, Central, Web of Science searched from inception-March 2022 with reference searching and authors contacted for missing/unclear data. Eligibility criteria was studies reporting the diagnostic accuracy of the four blood tests compared to the reference standard (histology or follow-up). Risk of bias was assessed (QUADAS-2), pooled sensitivity and specificity were generated for each test and commonly presented cut-offs. To provide insight into clinical impact, we present strategies using a hypothetical cohort. RESULTS: 67 studies were included (34 839 children, 13 342 with appendicitis), all in the hospital setting. The most sensitive tests were WCC (≥10 000 cells/µL, 53 studies sensitivity 0.85 (95% CI 0.80 to 0.89)) and absolute neutrophil count (ANC) (≥7500 cells/µL, five studies sensitivity 0.90 (95% CI 0.85 to 0.94)). Combination of WCC or CRP increased sensitivity further(≥10 000 cells/µL or ≥10 mg/L, individual patient data (IPD) of 6 studies, 0.97 (95% CI 0.93 to 0.99)).Applying results to a hypothetical cohort(1000 children with appendicitis symptoms, of whom 400 have appendicitis) 60 and 40 children would be wrongly discharged based solely on WCC and ANC, respectively, 12 with combination of WCC or CRP.The most specific tests were CRP alone (≥50 mg/L, 38 studies, specificity 0.87 (95% CI 0.80 to 0.91)) or combined with WCC (≥10 000 cells/µL and ≥50 mg/L, IPD of six studies, 0.93 (95% CI 0.91 to 0.95)). CONCLUSIONS: The best performing single blood tests for ruling-out paediatric appendicitis are WCC or ANC; with accuracy improved combining WCC and CRP. These tests could be used at the point of care in combination with clinical prediction rules. We provide insight into the best cut-offs for clinical application. PROSPERO REGISTRATION NUMBER: CRD42017080036.

The Intracellularly Acting Effector Foa3 Suppresses Defense Responses When Infiltrated Into the Apoplast.

Plant pathogens employ secreted proteins, among which are effectors, to manipulate and colonize their hosts. A large fraction of effectors is translocated into host cells, where they can suppress defense signaling. Bacterial pathogens directly inject effectors into host cells via the type three secretion system, but it is little understood how eukaryotic pathogens, such as fungi, accomplish this critical process and how their secreted effectors enter host cells. The root-infecting fungus Fusarium oxysporum (Fo) secrets numerous effectors into the extracellular space. Some of these, such as Foa3, function inside the plant cell to suppress host defenses. Here, we show that Foa3 suppresses pattern-triggered defense responses to the same extent when it is produced in planta irrespective of whether the protein carries the PR1 secretory signal peptide or not. When a GFP-tagged Foa3 was targeted for secretion it localized, among other locations, to mobile subcellular structures of unknown identity. Furthermore, like the well-known cell penetrating peptide Arginine 9, Foa3 was found to deliver an orthotospovirus avirulence protein-derived peptide into the cytosol, resulting in the activation of the matching resistance protein. Finally, we show that infiltrating Foa3 into the apoplast results in strong suppression of the pattern-triggered immune responses, potentially indicating its uptake by the host cells in absence of a pathogen.

Added value of CRP to clinical features when assessing appendicitis in children.

BACKGROUND: The diagnostic value of C-reactive protein (CRP) for appendicitis in children has not been evaluated in primary care. As biochemical responses and differential diagnoses vary with age, separate evaluation in children and adults is needed. OBJECTIVES: To determine whether adding CRP to symptoms and signs improves the diagnosis of appendicitis in children with acute abdominal pain in primary care. METHODS: A retrospective cohort study in Dutch general practice. Data was collected from the Integrated Primary Care Information database between 2010 and 2016. We included children aged 4-18 years, with no history of appendicitis, presenting with acute abdominal pain, and having a CRP test. Initial CRP levels were related to the specialist's diagnosis of appendicitis, and the test's characteristics were calculated for multiple cut-offs. The value of adding CRP to signs and symptoms was analysed by logistic regression. RESULTS: We identified 1076 eligible children, among whom 203 were referred for specialist evaluation and 70 had appendicitis. The sensitivity and specificity of a CRP cut-off ≥10 mg/L were 0.87 (95%CI, 0.77-0.94) and 0.77 (95%CI, 0.74-0.79), respectively. When symptoms lasted > 48 h, this sensitivity increased to 1.00. Positive predictive values for CRP alone were low (0.18-0.38) for all cut-off values (6-100 mg/L). Adding CRP increased the area under the curve from 0.82 (95%CI, 0.78-0.87) to 0.88 (95%CI, 0.84-0.91), and decision curve analysis confirmed that its addition provided the highest net benefit. CONCLUSION: CRP adds value to history and physical examination when diagnosing appendicitis in children presenting acute abdominal pain in primary care. Appendicitis is least likely if the CRP value is < 10 mg/L and symptoms have been present for > 48 h.

Psychosocial developmental milestones of young adult survivors of childhood cancer.

PURPOSE: The study aimed to compare the psychosocial development of young adult survivors of childhood cancer (YACCS) with a norm group of young adults from the general population. METHODS: From 2017 to 2020, 558 YACCS (18-30 years, 51% female, 10.9% CNS cancer) who participated in the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort (diagnosed 1963-2001) part 2 completed the Course of Life Questionnaire (CoLQ), assessing the achievement of milestones. Items were grouped into the scales autonomy, psychosexual, and social development. Differences between YACCS and norm group were examined with ANOVA and Cohen's d (CoLQ scales) and with logistic regression analysis and odds ratio (OR) (CoLQ items), for the total group and YACCS of CNS cancer. RESULTS: The total group of YACCS did not report a less favorable psychosocial development than the norm group. YACCS of CNS cancer scored lower than the norm group (p < 0.001) on the scales autonomy (d = - 0.36) and psychosexual (d = - 0.46). Additionally, on half of the items of autonomy (0.25 ≤ OR ≤ 0.34), psychosexual (0.30 ≤ OR ≤ 0.48), and social (0.23 ≤ OR ≤ 0.47) development, YACCS of CNS cancer were less likely (p < 0.01) than the norm group to have achieved the milestones. CONCLUSION: Overall, psychosocial development of YACCS was as favorable as the norm, but YACCS of CNS cancer were at risk of an unfavorable psychosocial development in all domains. Monitoring psychosocial development should be included in the standards of psychosocial care, especially for CNS cancer patients and survivors, to be able to trace delay. Personalized interventions should be offered to improve the psychosocial development in an early stage.

Course of uncomplicated acute gastroenteritis in children presenting to out-of-hours primary care.

BACKGROUND: The aim of this article is to describe the courses of vomiting, diarrhea, fever, and clinical deterioration, in children with uncomplicated gastroenteritis at presentation. This study was performed as a 7-day prospective follow-up study in an out-of-hours primary care service. The course of vomiting, diarrhea, and fever was analyzed by generalized linear mixed modeling. Because young children (≤ 12 months) and children with severe vomiting are at increased risk of dehydration, the potentially more complicated courses of these groups are described separately. The day(s) most frequently associated with deterioration and the symptoms present in children who deteriorated during follow-up were also described. RESULTS: In total, 359 children presented with uncomplicated acute gastroenteritis to the out-of-hours primary care service. Of these, 31 (8.6%) developed a complicated illness and needed referral or hospitalization. All symptoms decreased within 5 days in most children (> 90%). Vomiting and fever decreased rapidly, but diarrhea decreased at a somewhat slower pace, especially among children aged 6-12 months. Children who deteriorated during follow-up had a higher frequency of vomiting at presentation and higher frequencies of vomiting and fever during follow-up. CONCLUSIONS: The frequency of vomiting, not its duration, appears to be the more important predictor of deterioration. When advising parents, it is important to explain the typical symptom duration and to focus on alarm symptoms. Clinicians should be vigilant for children with higher vomiting frequencies at presentation and during follow-up because these children are more likely to deteriorate.

Cost-effectiveness of physiotherapy in childhood functional constipation: a randomized controlled trial in primary care.

OBJECTIVE: Health care expenditures for children with functional constipation (FC) are high, while conservative management is successful in only 50% of the children. The aim is to evaluate whether adding physiotherapy to conventional treatment (CT) is a cost-effective strategy in the management of children with FC aged 4-18 years in primary care. METHODS: A cost-effectiveness analysis was performed alongside a randomized controlled trial (RCT) with 8-month follow-up. Costs were assessed from a societal perspective, effectiveness included both the primary outcome (treatment success defined as the absence of FC and no laxative use) and the secondary outcome (absence of FC irrespective of laxative use). Uncertainty was assessed by bootstrapping and cost-effectiveness acceptability curves (CEACs) were displayed. RESULTS: One hundred and thirty-four children were randomized. The incremental cost-effectiveness ratio (ICER) for one additional successfully treated child in the physiotherapy group compared with the CT group was €24,060 (95% confidence interval [CI] €-16,275 to €31,390) and for the secondary outcome €1,221 (95% CI €-12,905 to €10,956). Subgroup analyses showed that for children with chronic laxative use the ICER was €2,134 (95% CI -24,975 to 17,192) and €571 (95% CI 11 to 3,566), respectively. At a value of €1,000, the CEAC showed a probability of 0.53 of cost-effectiveness for the primary outcome, and 0.90 for the secondary outcome. CONCLUSIONS: Physiotherapy added to CT as first-line treatment for all children with FC is not cost-effective compared with CT alone. Future studies should consider the cost-effectiveness of physiotherapy added to CT in children with chronic laxative use. TRIAL REGISTRATION: The RCT is registered in the Netherlands Trial Register (NTR4797), on the 8th of September 2014. The first child was enrolled on the 2nd of December 2014. https://www.trialregister.nl/trial/4654.

Mediterranean diet and the risk of COVID-19 in the 'Seguimiento Universidad de Navarra' cohort.

BACKGROUND & AIMS: A potential protection against COVID-19 by a high-quality dietary pattern is to be expected given the biological plausibility supporting the beneficial effects of an adequate dietary intake on the immune system. However, knowledge on the relationship between long-term maintained healthy dietary patterns, such as the Mediterranean diet, and the risk of SARS-CoV-2 infection is still sparse. We longitudinally assessed this association in a well-known Mediterranean cohort. METHODS: We assessed 9,677 participants from the SUN Project, a prospective cohort of middle-aged university graduates in Spain. We inquired about a positive result in a COVID-19 diagnostic test during the months of February to December 2020. After excluding health professionals (HP), 5,194 participants were included in the statistical analyses (mean age: 52.6, SD: 12.4; 55.2% women). Food habits were assessed at baseline using a previously validated semiquantitative 136-item food frequency questionnaire. Adherence to the Mediterranean diet (cumulative average of 2 repeated measurements 10 years apart) was assessed using the 0-to-9 Mediterranean Diet Score (MDS). We used multivariable logistic regression models to estimate odds ratios and 95% confidence intervals for incident COVID-19 according to the MDS. RESULTS: Among 5,194 non-HP participants, 122 reported to have received a positive COVID-19 diagnostic test. Participants with intermediate adherence to the Mediterranean diet (3 < MDS ≤ 6) had a significantly lower odds of developing COVID-19 (multivariable-adjusted OR = 0.50, 95% CI: 0.34-0.73), and those with the highest adherence (MDS > 6) exhibited the lowest risk (multivariable-adjusted OR = 0.36, 95% CI: 0.16-0.84, p for trend < 0.001) as compared with participants with MDS ≤ 3. This inverse association remained robust within subgroups and in sensitivity analyses. Notwithstanding, no significant associations were observed for health professionals (p for interaction = 0.06). CONCLUSION: In conclusion, better adherence to the Mediterranean diet may be associated with a lower risk of COVID-19. Our results are applicable only to persons who are not health professionals.

Increased health-related quality of life impairments of male and female survivors of childhood cancer: DCCSS LATER 2 psycho-oncology study.

BACKGROUND: The objective of this study was to compare the health-related quality of life (HRQOL) of Dutch adult male and female childhood cancer survivors (CCSs) to general population references and to study medical determinants. METHODS: CCSs from the Dutch Childhood Cancer Survivor Study LATER cohort (1963-2001) part 2, who were 18 years old or older (time since diagnosis ≥ 5 years), were invited to complete the TNO-AZL Questionnaire for Adult Health-Related Quality of Life. Domain scores and proportions of CCSs with impaired HRQOL (score < 25th percentile of the reference scores) were compared with references via Mann-Whitney U tests and logistic regression analyses corrected for age and sex (P < .004). Interactions of group with sex were included if they were significant (P < .05). Moreover, medical determinants were analyzed with multivariable logistic regression analyses. RESULTS: HRQOL scores for 1766 CCSs (mean age, 35.9 years [standard deviation, 9.4 years]; male, 51%; response rate, 71%) differed from references on most domains with small effect sizes. Both male and female CCSs were more often impaired in gross and fine motor functioning, cognitive functioning, sleep, and vitality with odds ratios (ORs) > 1.4. In addition, female CCSs were more often impaired in daily activities, pain, and sexuality (ORs, 1.4-1.9) and were less often aggressive (OR, 0.6). CCCs of central nervous system (CNS) tumors, bone tumors, and retinoblastoma and those with cranial, abdominopelvic, or lower extremity radiotherapy were at increased risk of impairment in 1 or more domains. CONCLUSIONS: Dutch adult CCSs, especially females, have impaired HRQOL in several domains; this is most pronounced in cognitive functioning. The vulnerabilities of subgroups at risk, such as CCSs of CNS tumors, were confirmed. Surveillance of HRQOL and multidisciplinary survivor care are recommended. LAY SUMMARY: The health-related quality of life in a Dutch nationwide cohort of 1766 survivors of childhood cancer was studied. Survivors of childhood cancer were found to have lower health-related quality of life in several domains (eg, motor functioning and vitality) in comparison with the general population. They most often reported low cognitive functioning (eg, memory and attention). Females had low health-related quality of life in more domains than males. Survivors of brain tumors had low health-related quality of life in most domains. Monitoring health-related quality of life regularly and collaborating between disciplines in survivor care is recommended.