Long-term teduglutide associated with improved response in pediatric short bowel syndrome-associated intestinal failure.

OBJECTIVES: Patients with short bowel syndrome-associated intestinal failure (SBS-IF) require long-term parenteral nutrition and/or intravenous fluids (PN/IV) to maintain fluid or nutritional balance. We report the long-term safety, efficacy, and predictors of response in pediatric patients with SBS-IF receiving teduglutide over 96 weeks. METHODS: This was a pooled, post hoc analysis of two open-label, long-term extension (LTE) studies (NCT02949362 and NCT02954458) in children with SBS-IF. Endpoints included treatment-emergent adverse events (TEAEs) and clinical response (≥20% reduction in PN/IV volume from baseline). A multivariable linear regression identified predictors of teduglutide response; the dependent variable was mean change in PN/IV volume at each visit over 96 weeks. RESULTS: Overall, 85 patients were analyzed; 78 patients received teduglutide in the parent and/or LTE studies (any teduglutide [TED] group), while seven patients did not receive teduglutide in either the parent or LTE studies. Most TEAEs were moderate or severe in intensity in both groups. By week 96, 82.1% of patients from the any TED group achieved a clinical response, with a mean fluid decrease of 30.1 mL/kg/day and an energy decrease of 21.6 kcal/kg/day. Colon-in-continuity, non-White race, older age at baseline, longer duration of teduglutide exposure, and increasing length of remaining small intestine were significantly associated with a reduction in mean PN/IV volume requirements. CONCLUSIONS: In pediatric patients with SBS-IF, teduglutide treatment resulted in long-term reductions in PN/IV requirements. The degree of PN/IV volume reduction depended on the duration of teduglutide exposure, underlying bowel anatomy, and demographics.

Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee.

Functional gastrointestinal disorders (FGID), such as infant regurgitation, infant colic, and functional constipation, are common and typically physiological phenomena during the early months of an infant's life and account for frequent consultations with pediatricians. Various infant formulas are marketed for their management and are frequently given by parents to infants before a medical consultation. However, the evidence supporting their effectiveness is limited and some have altered nutritional compositions when compared to standard formulas. Thus, these products should only be used under medical supervision and upon medical advice. Marketing and over-the-counter sales do not ensure proper medical guidance and supervision. The aim of this position paper is to review the current evidence regarding the safety and efficacy of formulas specifically formulated for addressing regurgitation, colic, and constipation, recognized as FGID. The objective is to provide guidance for clinical management based on the highest quality of available evidence. A wide search using Pubmed, MEDLINE, EMBASE and Cochrane Database of Systematic Reviews was performed including the MESH terms infant formula, colic, constipation, regurgitation, reflux, palmitate, lactase, lactose, magnesium, hydrolyzed protein, prebiotics or probiotics. 752 papers were identified and screened. Finally, 72 papers were included in the paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained by multiple e-mail exchange and meetings of the Nutrition Committee. (1) For breastfed infants experiencing FGID such as regurgitation, colic, or constipation, transitioning from breastfeeding to commercial formulas is not recommended. (2) In general, whether an infant is breastfed or formula-fed, it's crucial to reassure parents that FGIDs are normal and typically do not necessitate treatment or change to a special formula. (3) Thickened formulas, often termed anti-reflux formulas, may be considered in specific cases of regurgitation. (4) The usage of specialized formulas for infants with colic is not advised due to a lack of clinical evidence. (5) In the case of constipation in infants, the use of formulas enriched with high ß-palmitate and increased magnesium content may be considered to soften the stool. Generally, there is limited evidence supporting the use of specialized formulas for FGID. Breastfeeding should never be discontinued in favor of formula feeding.

Causes and Outcome of Central Venous Catheter Repair in Children with Intestinal Failure on Home Parenteral Nutrition.

OBJECTIVES: Children requiring a central venous catheter (CVC) for long-term parenteral nutrition (PN) are at risk of CVC breakage. Modern intestinal failure (IF) management aims to preserve vascular access sites. CVC repair rather than removal is hence attempted for broken catheters. The aim of this study was to describe causes and outcomes of CVC repairs in home PN dependent children. METHODS: All patients (ages 0-17 years) with CVC dependency enrolled in the IF rehabilitation program of a pediatric referral center were identified, and those who underwent a CVC repair between January 2019 and November 2020 included. Data on associated cause for breakage and incidence of central line-associated bloodstream infections (CLABSIs) post repair were documented retrospectively. Descriptive statistics including medians, percentages, and frequencies were used. RESULTS: Forty children, 15 males (37%) and 25 females (63%), were identified. Fifteen of 40 (37.5%) patients underwent a total of 29 CVC repairs (0.1 repairs per 1000 catheter days); 8 of 15 (53%; 33% females) were <5 years of age. The most common reason for repair was CVC fracture by biting (41%) followed by catheter occlusion with intraluminal PN deposition (13.2%). Repair was successful in 100% cases. Only 1 patient had a confirmed CLABSI post repair (1/29 repairs; 3%) who presented 3 days late after the initial catheter breakage. Catheter salvage was successful with antibiotics. CONCLUSION: CVC repair in our cohort was very successful and infection rate after repair minimal. CVC repair rather than removal is recommended to preserve central venous access.

Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support.

OBJECTIVES: Our objective was to evaluate the short- and long-term safety and efficacy of teduglutide treatment in infants and children with short bowel syndrome with intestinal failure (SBS-IF). METHODS: Two open-label phase 3 studies and 1 extension study investigated the short- and long-term safety and efficacy of teduglutide (0.05 mg/kg/day) in infants and children with SBS-IF: NCT03571516, 24-week study of infants who were randomized to receive teduglutide or standard of care (SoC); NCT02980666, 24-week study of infants and children who all received teduglutide; and NCT03268811, 24-week extension study of patients who completed NCT02980666 (patients could receive up to 48 weeks of total treatment). RESULTS: Twelve infants and 8 children enrolled in the core studies, and 2 infants and 7 children in the extension study. After 24 weeks of treatment, parenteral support (PS) requirements reduced by ≥20% from baseline for 4 infants (57.1%) and 4 children (66.7%) receiving teduglutide and for 2 infants receiving SoC (50.0%). One infant (50.0%) and 4 children (80.0%) receiving teduglutide maintained the ≥20% reduction in PS at 48 weeks of treatment. Two children receiving teduglutide achieved enteral autonomy, after 12 weeks and 28 weeks of treatment, respectively. All adverse events (AEs) were in line with known impacts of SBS-IF and adverse reactions to teduglutide. Only one serious AE (abdominal pain) was considered related to teduglutide. CONCLUSIONS: Short- and long-term treatment with teduglutide resulted in clinically meaningful reductions in PS requirements for infants and children with SBS-IF. Teduglutide was well tolerated, and efficacy improved with longer-term treatment.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 1: From Intestinal Resection to Home Discharge.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN.

Anaemia in Children Receiving Home Parenteral Nutrition: A Common Problem?

OBJECTIVES: Children receiving home parenteral nutrition (HPN) are at risk of iron deficiency anaemia. Our aim was to determine the incidence of iron deficiency anaemia in paediatric HPN and efficacy of each therapeutic approach. METHODS: Retrospective data collection from children receiving HPN at a tertiary referral centre over a 12-month period (2015). Full blood count, and whenever available, ferritin and C-reactive protein were collected at least 3 times for each patient. Liver function tests were checked at the beginning and end of the study and number of blood transfusions/iron infusions recorded. RESULTS: Forty-one HPN patients (61% girls; 51% motility disorder, 29% enteropathy, 20% short bowel syndrome) were identified. Eighty-three percent of children were anaemic at the beginning of the study with the number decreasing to 73% by the end. Iron deficiency anaemia was most commonly seen and treated with blood transfusion in 46% of cases and iron infusions in 29%. There was no statistical difference in the level of haemoglobin improvement between the 2 treatments (50% vs 33%, P  = 0.657) nor a significant difference in haemoglobin (g/L) level achieved. The results for both were, however, more favourable in the infusion group. Patients receiving transfusions had a significantly higher incidence of abnormal liver function compared with those who hadinfusions (93% vs 37%, P = 0.009). CONCLUSIONS: Iron deficiency anaemia is common in children receiving HPN. A large proportion of patients still receive blood transfusions as first-line therapy but intravenous iron can be a suitable alternative. Treatment guidelines are required.

Patient-level costing analysis of paediatric short bowel syndrome care in a specialist tertiary centre.

PURPOSE: To undertake a pilot study estimating patient-level costs of care for paediatric short bowel syndrome (SBS) from the healthcare provider perspective. METHODS: A pilot group of patients with anatomical SBS was selected at a single specialist tertiary centre in the United Kingdom. The Patient Level Information and Costing System (PLICS) was used to extract costing data for all hospital-based activities related to SBS, from the implementation of PLICS in 2016 to April 2021. Patient-specific and pooled data were reported descriptively in per patient-year terms. RESULTS: Five patients had full PLICS data available for the 5-year study period and 2 patients had 4 years of data. The median cost for hospital care of SBS was £52,834 per patient-year (range £1804-£331,489). The key cost drivers were inpatient beds, pharmacy, and staffing costs, which made up > 60% of annual costs. In the first 3 years following index admission (n = 2), there was a steady decline in the annual cost of care to a level comparable with patients with established SBS. CONCLUSION: Patient-level cost of care analysis for SBS is feasible using PLICS. Hospital-related costs vary widely between and within individual patients over time. Key drivers of cost are related to complications of SBS.

Designing and Implementing a Family Literacy Program Through Smartphones: How Does Recruitment Method Influence Uptake and Attrition?

Texting-based programs are increasingly used to support parents as their child's first teacher and create links between home and school. However, there is scant evidence about the influence of program implementation on parent uptake and attrition-a key component of such programs. This article describes the design and delivery of Kindytxt, a literacy-based text-messaging program for parents with a child at Kindergarten in Western Australia, and examines the influence of recruitment method, area socioeconomic status, and teacher participation on parent uptake and attrition. Results indicate that embedding Kindytxt into a well-established family literacy program provided the infrastructure and mechanism for extensive program reach, and the recruitment method, specifically the involvement of the kindergarten teacher, significantly influenced parent registration. However, attrition rates were not significantly affected by the area socioeconomic status of participating schools, recruitment method, nor teacher participation in Kindytxt. The results suggest that teacher involvement may be the crucial factor in enabling parents to access texting programs, regardless of the socioeconomic status of the school community. The design elements may be used to inform future program development, and the research results highlight the importance of documenting and including the method of delivery as variables in the evaluation of program implementation.

Evaluating the performance of a clinical genome sequencing program for diagnosis of rare genetic disease, seen through the lens of craniosynostosis.

PURPOSE: Genome sequencing (GS) for diagnosis of rare genetic disease is being introduced into the clinic, but the complexity of the data poses challenges for developing pipelines with high diagnostic sensitivity. We evaluated the performance of the Genomics England 100,000 Genomes Project (100kGP) panel-based pipelines, using craniosynostosis as a test disease. METHODS: GS data from 114 probands with craniosynostosis and their relatives (314 samples), negative on routine genetic testing, were scrutinized by a specialized research team, and diagnoses compared with those made by 100kGP. RESULTS: Sixteen likely pathogenic/pathogenic variants were identified by 100kGP. Eighteen additional likely pathogenic/pathogenic variants were identified by the research team, indicating that for craniosynostosis, 100kGP panels had a diagnostic sensitivity of only 47%. Measures that could have augmented diagnoses were improved calling of existing panel genes (+18% sensitivity), review of updated panels (+12%), comprehensive analysis of de novo small variants (+29%), and copy-number/structural variants (+9%). Recent NHS England recommendations that partially incorporate these measures should achieve 85% overall sensitivity (+38%). CONCLUSION: GS identified likely pathogenic/pathogenic variants in 29.8% of previously undiagnosed patients with craniosynostosis. This demonstrates the value of research analysis and the importance of continually improving algorithms to maximize the potential of clinical GS.

Results of an International Survey on Feeding Management in Infants With Short Bowel Syndrome-Associated Intestinal Failure.

OBJECTIVES: Short bowel syndrome (SBS) is a complex and rare condition (incidence 1200/100,000 live births) that requires a multidisciplinary team approach to management. In January 2019, the first European Reference Network on Rare and Inherited Congenital Anomalies (ERNICA) Intestinal Failure (IF) workshop was held. Several questions about the strategies used in managing IF associated with SBS were devised. The aim of our study was to collect data on the enteral feeding strategies adopted by the ERNICA centres. METHODS: A questionnaire (36 questions) about strategies used to introduce enteral nutrition post-operatively and start complementary food/solids in infants with SBS associated IF was developed and sent to 24 centres in 15 countries that participated in the ERNICA-IF workshop. The answers were collated and compared with the literature. RESULTS: There was a 100% response rate. In infants, enteral nutrition was introduced as soon as possible, ideally within 24-48 hours post-small intestinal surgical resection. In 10 of 24 centres, bolus feeding was used, in nine continuous, and in five a combination of both. Twenty-three centres used mothers' own milk as the first choice of feed with extensively hydrolysed feed, amino acid-based feed, donor human milk or standard preterm/term formula as the second choice. Although 22 centres introduced complementary/solid food by 6 months of age, food choice varied greatly between centres and appeared to be culturally based. CONCLUSIONS: There is diversity in post-surgical enteral feeding strategies among centres in Europe. Further multi-centre studies could help to increase evidence-based medicine and management on this topic.

Surgery and opioids: evidence-based expert consensus guidelines on the perioperative use of opioids in the United Kingdom.

There are significant concerns regarding prescription and misuse of prescription opioids in the perioperative period. The Faculty of Pain Medicine at the Royal College of Anaesthetists have produced this evidence-based expert consensus guideline on surgery and opioids along with the Royal College of Surgery, Royal College of Psychiatry, Royal College of Nursing, and the British Pain Society. This expert consensus practice advisory reproduces the Faculty of Pain Medicine guidance. Perioperative stewardship of opioids starts with judicious opioid prescribing in primary and secondary care. Before surgery, it is important to assess risk factors for continued opioid use after surgery and identify those with chronic pain before surgery, some of whom may be taking opioids. A multidisciplinary perioperative care plan that includes a prehabilitation strategy and intraoperative and postoperative care needs to be formulated. This may need the input of a pain specialist. Emphasis is placed on optimum management of pain pre-, intra-, and postoperatively. The use of immediate-release opioids is preferred in the immediate postoperative period. Attention to ensuring a smooth care transition and communication from secondary to primary care for those taking opioids is highlighted. For opioid-naive patients (patients not taking opioids before surgery), no more than 7 days of opioid prescription is recommended. Persistent use of opioid needs a medical evaluation and exclusion of chronic post-surgical pain. The lack of grading of the evidence of each individual recommendation remains a major weakness of this guidance; however, evidence supporting each recommendation has been rigorously reviewed by experts in perioperative pain management.

Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported With Parenteral Nutrition at Home.

OBJECTIVES: The aim of the study was to review long-term outcome of intestinal epithelial dysplasia (IED)/tufting enteropathy (TE) patients treated with parenteral nutrition (PN) at home managed by an intestinal failure (IF) rehabilitation service. METHODS: Infants presenting from 1986 to 2010 with IF, and TE histology were retrospectively reviewed for up to 30 years. Data collected included outcome, presentation, nutrition (parenteral/enteral), country of residence, race, EpCAM gene, growth, bone age, and occupation. RESULTS: Thirteen patients (6 boys) in Malta and the UK with TE histology were established on home PN. Survival was 100% for UK children and 92% overall (1 death aged 13 months). Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements reduced with increasing age and <7 infusions/week were needed by 10/12, 83% by 10 years, 6/8, 75% who had reached 15 years, 5/7, 71% who had reached 20, and all 4, 100% >25 years. Two of 12 cases weaned from PN by 10 years, 1 of 8 by 15 years, 3 of 7 by 20 years, and 3 of 4 or 75% >25 years. Seven Maltese patients homozygous for the same EPCAM gene abnormality had a similar outcome to the other cases. Weight, height, bone mineralization, bone age, and insulin-like growth factor-1 (IGF-1) levels were low, but improved with age. Patients achieved educational levels of parents and were employed. CONCLUSIONS: IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant.

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome.

OBJECTIVE: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). STUDY DESIGN: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. RESULTS: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of -41% and -45%, respectively, with 0.025 mg/kg/d teduglutide and by -25% and -52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and -6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and -1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. CONCLUSIONS: Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.

Content and Evaluation of the Benefits of Effective Exercise for Older Adults With Knee Pain Trial Physiotherapist Training Program.

OBJECTIVE: To explore whether participating in the Benefits of Effective Exercise for knee Pain (BEEP) trial training program increased physiotherapists' self-confidence and changed their intended clinical behavior regarding exercise for knee pain in older adults. DESIGN: Before/after training program evaluation. Physiotherapists were asked to complete a questionnaire before the BEEP trial training program, immediately after, and 12 to 18 months later (postintervention delivery in the BEEP trial). The questionnaire included a case vignette and associated clinical management questions. Questionnaire responses were compared over time and between physiotherapists trained to deliver each intervention within the BEEP trial. SETTING: Primary care. PARTICIPANTS: Physiotherapists (N=53) who completed the BEEP trial training program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self-confidence in the diagnosis and management of knee pain in older adults; and intended clinical behavior measured by a case vignette and associated clinical management questions. RESULTS: Fifty-two physiotherapists (98%) returned the pretraining questionnaire, and 44 (85%) and 39 (74%) returned the posttraining and postintervention questionnaires, respectively. Posttraining, self-confidence in managing older adults with knee pain increased, and intended clinical behavior regarding exercise for knee pain in older adults appeared more in line with clinical guidelines. However, not all positive changes were maintained in the longer-term. CONCLUSIONS: Participating in the BEEP trial training program increased physiotherapists' self-confidence and changed their intended clinical behavior regarding exercise for knee pain, but by 12 to 18 months later, some of these positive changes were lost. This suggests that brief training programs are useful, but additional strategies are likely needed to successfully maintain changes in clinical behavior over time.

A Pharmacokinetic Modeling Approach to Predict the Contribution of Active Metabolites to Human Efficacious Dose.

A preclinical drug candidate, MRK-1 (Merck candidate drug parent compound), was found to elicit tumor regression in a mouse xenograft model. Analysis of samples from these studies revealed significant levels of two circulating metabolites, whose identities were confirmed by comparison with authentic standards using liquid chromatography-tandem mass spectrometry. These metabolites were found to have an in vitro potency similar to that of MRK-1 against the pharmacological target and were therefore thought to contribute to the observed efficacy. To predict this contribution in humans, a pharmacokinetic (PK) modeling approach was developed. At the mouse efficacious dose, the areas under the plasma concentration time curves (AUCs) of the active metabolites were normalized by their in vitro potency compared with MRK-1. These normalized metabolite AUCs were added to that of MRK-1 to yield a composite efficacious unbound AUC, expressed as "parent drug equivalents," which was used as the target AUC for predictions of the human efficacious dose. In vitro and preclinical PK studies afforded predictions of the PK of MRK-1 and the two active metabolites in human as well as the relative pathway flux to each metabolite. These were used to construct a PK model (Berkeley Madonna, version 8.3.18; Berkeley Madonna Inc., University of California, Berkeley, CA) and to predict the human dose required to achieve the target parent equivalent exposure. These predictions were used to inform on the feasibility of the human dose in terms of size, frequency, formulation, and likely safety margins, as well as to aid in the design of preclinical safety studies.

Travelling With Children on Home Parenteral Nutrition.

BACKGROUND: Home parenteral nutrition (HPN) is an established therapy in children with intestinal failure. Parenteral nutrition (PN) management allows most paediatric patients to participate in age-appropriate activities; however, HPN may lead to significant restrictions, particularly going on holiday. We aimed to identify sociodemographic and illness-specific variables that influence if and how families with children on HPN travel. METHODS: A standardised questionnaire was sent to all 40 children on HPN within a large tertiary intestinal failure centre in the United Kingdom. Depending on whether the family had/had not been on holiday since their child had started HPN, questions were asked to understand the reasons for not travelling or to gather information about individual travel experiences. RESULTS: A total of 30 children were enrolled, 20 of 30 went at least once on holiday, and 5 of 30 travelled more than once per year, 70% travelled outside Britain. Going on vacation was more common, the longer the child had been on HPN (P = 0.022); hours spent on PN tolerance of enteral feeds or the child's age did not influence travel behaviour; 80% of parents who went on vacation had a good/worthy experience, 95% would travel again. The biggest reported obstacle was the transportation of PN bags. Ten families sacrificed a holiday over fear that it may be difficult to arrange or because of the child's unstable medical condition. CONCLUSIONS: A significant proportion of families chose to go on holiday away from home despite their child being on HPN. The experience is considered good by most.

Patients Know Best: Qualitative Study on How Families Use Patient-Controlled Personal Health Records.

BACKGROUND: Self-management technologies, such as patient-controlled electronic health records (PCEHRs), have the potential to help people manage and cope with disease. OBJECTIVE: This study set out to investigate patient families' lived experiences of working with a PCEHR. METHODS: We conducted a semistructured qualitative field study with patient families and clinicians at a children's hospital in the UK that uses a PCEHR (Patients Know Best). All families were managing the health of a child with a serious chronic condition, who was typically under the care of multiple clinicians. As data gathering and analysis progressed, it became clear that while much of the literature assumes that patients are willing and waiting to take more responsibility for and control over their health management (eg, with PCEHRs), only a minority of participants in our study responded in this way. Their experiences with the PCEHR were diverse and strongly shaped by their coping styles. Theory on coping identifies a continuum of coping styles, from approach to avoidance oriented, and proposes that patients' information needs depend on their style. RESULTS: We identified 3 groups of patient families and an outlier, distinguished by their coping style and their PCEHR use. We refer to the outlier as controlling (approach oriented, highly motivated to use PCEHR), and the 3 groups as collaborating (approach oriented, motivated to use PCEHR), cooperating (avoidance oriented, less motivated to use PCEHR), and avoiding (very avoidance oriented, not motivated to use PCEHR). CONCLUSIONS: The PCEHR met the needs of controller and collaborators better than the needs of cooperators and avoiders. We draw on the Self-Determination Theory to propose ways in which a PCEHR design might better meet the needs of avoidance-oriented users. Further, we highlight the need for families to also relinquish control at times, and propose ways in which PCEHR design might support a better distribution of control, based on effective training, ease of use, comprehensibility of data security mechanisms, timely information provision (recognizing people's different needs), personalization of use, and easy engagement with clinicians through the PCEHR.

Hormone Therapy and Other Treatments for Symptoms of Menopause.

The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.

Self-management approaches for osteoarthritis in the hand: a 2×2 factorial randomised trial.

BACKGROUND: Osteoarthritis is the leading cause of disability in older adults. Evidence of effectiveness for self-management of hand osteoarthritis is lacking. METHODS: In this randomised, factorial trial, we evaluated the effectiveness of joint protection versus no joint protection, and hand exercise versus no hand exercise in adults, 50 years of age or older, with hand osteoarthritis. Following a population survey (n=12 297), eligible individuals were randomly assigned (1:1:1:1) to: leaflet and advice; joint protection; hand exercise; joint protection plus hand exercise. Joint protection and hand exercises were delivered by nine occupational therapists, over four group sessions. The primary outcome was the OARSI/OMERACT responder criteria at 6 months. Outcomes were collected blind to allocation (3, 6, 12 m). Analysis was by intention to treat. RESULTS: Of 257 participants randomised (65:62:65:65) (mean age (SD) 66 years (9.1); female 66%) follow-up was 85% at 6 m (n=212). Baseline characteristics and loss to follow-up were similar between groups. There were no reported treatment side effects. At 6 m 33% assigned joint protection were responders compared with 21% with no joint protection (p=0.03). Of those assigned hand exercises, 28% were responders compared with 25% with no exercises (n.s.). Differences in secondary outcomes were not statistically significant, except for improvement in pain self-efficacy with joint protection (3 m p=0.002; 6 m p=0.001; 12 m p=0.03). CONCLUSIONS: These findings show that occupational therapists can support self-management in older adults with hand osteoarthritis, and that joint protection provides an effective intervention for medium term outcome. (Funded by the Arthritis Research UK ISRCTN 33870549).