Glycomacropeptide: long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU.

In phenylketonuria, casein glycomacropeptide (CGMP) requires modification with the addition of some essential and semi essential amino acids to ensure suitability as a protein substitute. The optimal amount and ratio of additional amino acids is undefined. AIM: A longitudinal, parallel, controlled study over 12 months evaluating a CGMP (CGMP-AA2) formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU. The CGMP-AA2 contained 36 mg Phe per 20 g protein equivalent. METHODS: Children with PKU, with a median age of 9.2 y (5-16y) were divided into 2 groups: 29 were given CGMP-AA2, 19 remained on Phe-free L-AA. The CGMP-AA2 formula gradually replaced L-AA, providing blood Phe concentrations were maintained within target range. Median blood Phe, Tyr, Phe:Tyr ratio and anthropometry, were compared within and between the two groups at baseline, 26 and 52 weeks. Nutritional biochemistry was studied at baseline and 26 weeks only. RESULTS: At the end of 52 weeks only 48% of subjects were able to completely use CGMP-AA2 as their single source of protein substitute. At 52 weeks CGMP-AA2 provided a median of 75% (30-100) of the total protein substitute with the remainder being given as L-AA. Within the CGMP-AA2 group, blood Phe increased significantly between baseline and 52 weeks: [baseline to 26 weeks; baseline Phe 270 µmol/L (170-430); 26 weeks, Phe 300 µmol/L (125-485) p = 0.06; baseline to 52 weeks: baseline, Phe 270 µmol/L (170-430), 52 weeks Phe 300 µmol/L (200-490), p < 0.001)]. However, there were no differences between the CGMP-AA2 and L-AA group for Phe, Tyr, Phe:Tyr ratio or anthropometry at any of the three measured time points. Within the CGMP-AA2 group only weight (p = 0.0001) and BMI z scores (p = 0.0001) increased significantly between baseline to 52 weeks. Whole blood and plasma selenium were significantly higher (whole blood selenium [p = 0.0002]; plasma selenium [p = 0.0007]) at 26 weeks in the CGMP-AA2 group compared L-AA. No differences were observed within the L-AA group for any of the nutritional markers. CONCLUSIONS: CGMP-AA increases blood Phe concentrations and so it can only be used partly to contribute to protein substitute in some children with PKU. CGMP-AA should be carefully introduced in children with PKU and close monitoring of blood Phe control is essential.

A holistic approach to healthy ageing: how can people live longer, healthier lives?

BACKGROUND: Although lifespan is increasing, there is no evidence to suggest that older people are experiencing better health in their later years than previous generations. Nutrition, at all stages of life, plays an important role in determining health and wellbeing. METHODS: A roundtable meeting of UK experts on nutrition and ageing considered key aspects of the diet-ageing relationship and developed a consensus position on the main priorities for research and public health actions that are required to help people live healthier lives as they age. RESULTS: The group consensus highlighted the requirement for a life course approach, recognising the multifactorial nature of the impact of ageing. Environmental and lifestyle influences at any life stage are modified by genetic factors and early development. The response to the environment at each stage of life can determine the impact of lifestyle later on. There are no key factors that act in isolation to determine patterns of ageing and it is a combination of environmental and social factors that drives healthy or unhealthy ageing. Too little is known about how contemporary dietary patterns and sedentary lifestyles will impact upon healthy ageing in future generations and this is a priority for future research. CONCLUSIONS: There is good evidence to support change to lifestyle (i.e. diet, nutrition and physical) activity in relation to maintaining or improving body composition, cognitive health and emotional intelligence, immune function and vascular health. Lifestyle change at any stage of life may extend healthy lifespan, although the impact of early changes appears to be greatest.

International practices in the dietary management of fructose 1-6 biphosphatase deficiency.

BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. CONCLUSIONS: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.

Fifteen years of using a second stage protein substitute for weaning in phenylketonuria: a retrospective study.

BACKGROUND: In phenylketonuria (PKU), during weaning, it is necessary to introduce a second stage phenylalanine (Phe)-free protein substitute (PS) to help meet non-Phe protein requirements. Semi-solid weaning Phe-free PS have been available for >15 years, although no long-term studies have reported their efficacy. METHODS: Retrospective data from 31 children with PKU who commenced a weaning PS were collected from clinical records from age of weaning to 2 years, on: gender; birth order; weaning age; anthropometry; blood Phe levels; age commenced and dosage of weaning PS and Phe-free infant L-amino acid formula; natural protein intake; and issues with administration of PS or food. RESULTS: Median commencement age for weaning was 17 weeks (range 12-25 weeks) and, for weaning PS, 20 weeks (range 13-37 weeks). Median natural protein was 4 g day-1 (range 3-11 g day-1 ) and total protein intake was >2 g kg-1 day-1 from weaning to 2 years of age. Children started on 2-4 g day-1 protein equivalent (5-10 g day-1 of powder) from weaning PS, increasing by 0.2 g kg-1 day-1 (2 g day-1 ) monthly to 12 months of age. Teething and illness adversely affected the administration of weaning PS and the acceptance of solid foods. Altogether, 32% of children had delayed introduction of more textured foods, associated with birth order (firstborn 80% versus 38%; P = 0.05) and food refusal when teething (80% versus 29%; P = 0.02). CONCLUSIONS: Timing of introduction of solid foods and weaning PS, progression onto more textured foods and consistent feeding routines were important in aiding their acceptance. Any negative behaviour with weaning PS was mainly associated with food refusal, teething and illness. Parental approach influenced the acceptance of weaning PS.

Refining low protein modular feeds for children on low protein tube feeds with organic acidaemias.

Children with inherited metabolic disorders (IMD) who are dependent on tube feeding and require a protein restriction are commonly fed by 'modular tube feeds' consisting of several ingredients. A longitudinal, prospective two-phase study, conducted over 18 months assessed the long-term efficacy of a pre-measured protein-free composite feed. This was specifically designed to meet the non-protein nutritional requirements of children (aged over 1 year) with organic acidaemias on low protein enteral feeds and to be used as a supplement with an enteral feeding protein source. METHODOLOGY: All non-protein individual feed ingredients were replaced with one protein-free composite feed supplying fat, carbohydrate, and micronutrients. Thirteen subjects, median age 7.4y (3-15.5y), all nutritionally tube dependent (supplying nutritional intake: ≥ 90%, n = 12; 75%, n = 1), and diagnosed with organic acidaemias (Propionic acidaemia, n = 6; Vitamin B12 non-responsive methyl malonic acidaemia, n = 4; Isovaleric acidaemia, n = 2; Glutaric aciduria type1, n = 1); were studied. Nutritional intake, biochemistry and anthropometry were monitored at week - 8, 0, 12, 26 and 79. RESULTS: Energy intake remained unchanged, providing 76% of estimated energy requirements. Dietary intakes of vitamins, minerals and essential fatty acids significantly increased from week 0 to week 79, but sodium, potassium, magnesium, decosahexanoic acid and fibre did not meet suggested requirements. Plasma zinc, selenium, haemoglobin and MCV significantly improved, and growth remained satisfactory. Natural protein intake met WHO/FAO/UNU 2007 recommendations. CONCLUSIONS: A protein-free composite feed formulated to meet the non-protein nutritional requirements of children aged over 1 year improved nutritional intake, biochemical nutritional status, and simplified enteral tube feeding regimens in children with organic acidaemias.

Antenatal Weight Management: Women's Experiences, Behaviours, and Expectations of Weighing in Early Pregnancy.

The current emphasis on obstetric risk management helps to frame gestational weight gain as problematic and encourages intervention by healthcare professionals. However pregnant women have reported confusion, distrust, and negative effects associated with antenatal weight management interactions. The MAGIC study (MAnaging weiGht In pregnanCy) sought to examine women's self-reported experiences of usual-care antenatal weight management in early pregnancy and consider these alongside weight monitoring behaviours and future expectations. 193 women (18 yrs+) were recruited from routine antenatal clinics at the Nottingham University Hospital NHS Trust. Self-reported gestation was 10-27 weeks, with 41.5% (n = 80) between 12 and 14 and 43.0% (n = 83) between 20 and 22 weeks. At recruitment 50.3% of participants (n = 97) could be classified as overweight or obese. 69.4% of highest weight women (≥30 kg/m2) did not report receiving advice about weight, although they were significantly more likely compared to women with BMI < 30 kg/m2. The majority of women (regardless of BMI) did not express any barriers to being weighed and 40.8% reported weighing themselves at home. Women across the BMI categories expressed a desire for more engagement from healthcare professionals on the issue of bodyweight. Women are clearly not being served appropriately in the current situation which simultaneously problematizes and fails to offer constructive dialogue.

The challenges of vitamin and mineral supplementation in children with inherited metabolic disorders: a prospective trial.

BACKGROUND: In order to achieve metabolic stability, dietary treatment of inborn errors of metabolism may require restriction of protein, fat or carbohydrate. Manipulation of dietary intake potentially reduces micronutrient status, and provision of a comprehensive vitamin and mineral supplement becomes an essential adjunct to dietary treatment. AIM: To review the efficacy of a new complete vitamin and mineral supplement [Fruitivits, Vitaflo Ltd] in 14 subjects in an open prospective 26-week study. METHOD: All subjects had dietary restrictions: low protein diets (57%, n = 8), regular daytime cornstarch and overnight glucose polymer tube feeds (29%, n = 4), low fat diet (7%, n = 1) and modified Atkins diet (7%, n = 1). Plasma nutritional biochemistry, anthropometry and food frequency questionnaires were collected at week 0, 12 and 26 weeks respectively. RESULTS: Five nutritional parameters showed a significant improvement from baseline (week 0) to study end (week 26): folate (P = 0.01), vitamin E (P = 0.04), plasma selenium (P = 0.002), whole blood selenium (P = 0.04) and total vitamin D (P = 0.008). All the other nutritional markers did not significantly change. Even with regular monitoring, 37% of the product remained unused. CONCLUSIONS: Despite improvements in some nutritional markers, overall use of the vitamin and mineral supplement was less than prescribed. New methods are needed to guarantee delivery of micronutrients in children at risk of deficiencies as a result of an essential manipulation of diet in inborn disorders of metabolism.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Limiting antenatal weight gain improves maternal health outcomes in severely obese pregnant women: findings of a pragmatic evaluation of a midwife-led intervention.

BACKGROUND: Antenatal obesity in pregnancy is associated with complications of pregnancy and poor obstetric outcomes. Although most guidance on pregnancy weight is focused on the prepregnancy period, pregnancy is widely viewed as a period where women are open to lifestyle change to optimise their health. METHODS: The hospital-based Bumps and Beyond intervention invited all pregnant women with a body mass index (BMI) >35 kg m(-2) to take part in a programme of health education around diet and exercise, accompanied by one-to-one guidance and monitoring of dietary change. This service evaluation compares 89 women who completed at a programme of seven sessions with healthy lifestyle midwives and advisors (intervention) versus a group of 89 women who chose not to attend (non-intervention). RESULTS: Mean (SD) weight gain in the intervention group [4.5 (4.6) kg] was less than in the non-intervention group [10.3 (4.4) kg] between antenatal booking and 36 weeks of gestation (< 0.001). This was associated with a 95% reduction in the risk of gestational hypertension during pregnancy and a general reduction in pregnancy complications. There was no effect of the intervention upon gestational diabetes or complications in labour other than post-partum haemorrhage (reduced by 55%). The impact of the intervention on gestational weight gain was greater in women with BMI >40 kg m(-2) at booking. There were no adverse effects of the intervention, even though 21% of the intervention group lost weight during their pregnancy. CONCLUSIONS: Intensive, personalised weight management intervention may be an effective strategy for the prevention of hypertensive disorders during pregnancy.

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes.

PURPOSE: This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. METHODS: Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scattered photons at the maze entrance. The dose of the backscattered photons from a concrete wall was measured for various scattering angles. The dose was also calculated by the FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. RESULTS: It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscattered photons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. CONCLUSIONS: This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose.

Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

The impact of ingested potato type II inhibitors on the production of the major serine proteases in the gut of Helicoverpa armigera.

The flowers of the ornamental tobacco produce high levels of a series of 6 kDa serine protease inhibitors (NaPIs) that are effective inhibitors of trypsins and chymotrypsins from lepidopteran species. These inhibitors have a negative impact on the growth and development of lepidopteran larvae and have a potential role in plant protection. Here we investigate the effect of NaPIs on the activity and levels of serine proteases in the gut of Helicoverpa armigera larvae and explore the adaptive mechanisms larvae employ to overcome the negative effects of NaPIs in the diet. Polyclonal antibodies were raised against a Helicoverpa punctigera trypsin that is a target for NaPIs and two H. punctigera chymotrypsins; one that is resistant and one that is susceptible to inhibition by NaPIs. The antibodies were used to optimize procedures for extraction of proteases for immunoblot analysis and to assess the effect of NaPIs on the relative levels of the proteases in the gut and frass. We discovered that consumption of NaPIs did not lead to over-production of trypsins or chymotrypsins but did result in excessive loss of proteases to the frass.

Dietary management of urea cycle disorders: UK practice.

BACKGROUND: There is no published data describing UK dietary management of urea cycle disorders (UCD). The present study describes dietary practices in UK inherited metabolic disorder (IMD) centres. METHODS: Cross-sectional data from 16 IMD centres were collected by a questionnaire describing the management of UCD patients on prescribed protein-restricted diets. RESULTS: One hundred and seventy-five patients [N-acetylglutamate synthase deficiency, n = 3; carbamoyl phosphate synthase deficiency (CPS), n = 8; ornithine transcarbamoylase deficiency (OTC), n = 75; citrullinaemia, n = 41; argininosuccinic aciduria (ASA), n = 36; arginase deficiency, n = 12] were reported; 70% (n = 123) aged 0-16 years; 30% (n = 52) >16 years. Prescribed median protein intake decreased with age (0-6 months: 2 g kg(-1) day(-1); 7-12 months: 1.6 g kg(-1) day(-1); 1-10 years: 1.3 g kg(-1) day(-1); 11-16 years: 0.9 g kg(-1) day(-1) and >16 years: 0.8 g kg(-1) day(-1)) with little variation between disorders. Adult protein prescription ranged 0.4-1.2 g kg(-1) day(-1) (40-60 g day(-1)). In the previous 2 years, 30% (n = 53) were given essential amino acid supplements (EAAs) (CPS, n = 2; OTC, n = 20; citrullinaemia, n = 15; ASA, n = 7; arginase deficiency, n = 9). EAAs were prescribed for low plasma quantitative essential amino acids (n = 13 centres); inadequate natural protein intake (n = 11) and poor metabolic control (n = 9). From diagnosis, one centre prescribed EAAs for all patients and one centre for severe defects only. Only 3% (n = 6) were given branch chain amino acid supplements. Enteral feeding tubes were used by 25% (n = 44) for feeds and 3% (n = 6) for medications. Oral energy supplements were prescribed in 17% (n = 30) of cases. CONCLUSIONS: In the UK, protein restriction based on World Health Organization 'safe intakes of protein', is the principle dietary treatment for UCD. EAA supplements are prescribed mainly on clinical need. Multicentre collaborative research is required to define optimal dietary treatments.

Weaning infants with phenylketonuria: a review.

Careful weaning is particularly important in phenylketonuria (PKU). Dietary phenylalanine intake is severely restricted, and the diet is supplemented with phenylalanine-free amino acids and special low protein foods. In PKU, there are no evidence-based weaning guidelines and no studies assessing the introduction of solid foods. We critically review the literature and examine current UK weaning practices. Ideally, weaning in PKU should closely reflect the 'model' for healthy infants. However, the requirement for optimal blood phenylalanine control and the demands of diet therapy overshadow the social aspects of weaning. Solid food intake is established with very low protein foods first, and then 50 mg phenylalanine exchanges (equivalent to 1 g of intact protein) gradually replace breast/formula feeds. Introducing solids before the recommended 6 months of age may be advantageous because there is a less persistent neophobic food response, possibly leading to better food acceptance. Infants with PKU also require a special phenylalanine-free protein substitute. Between 6 and 12 months, a second concentrated source of phenylalanine-free protein substitute is required. This is commonly given as an additional liquid, although the prescribed volume may adversely affect appetite. Alternatively, a second-stage protein substitute administered as a paste may better suit feeding development. Further research aiming to examine the weaning process in PKU with a focus on biological, maternal, infant, social and environmental factors is required. This will help provide evidence for the effect of protein substitute on appetite and help in the development of evidence-based guidelines.

Diagnostic radiation procedures and risk of prostate cancer.

Exposure to ionising radiation is an established risk factor for many cancers. We conducted a case-control study to investigate whether exposure to low dose ionisation radiation from diagnostic x-ray procedures could be established as a risk factor for prostate cancer. In all 431 young-onset prostate cancer cases and 409 controls frequency matched by age were included. Exposures to barium meal, barium enema, hip x-rays, leg x-rays and intravenous pyelogram (IVP) were considered. Exposures to barium enema (adjusted odds ratio (OR) 2.06, 95% confidence interval (CI) 1.01-4.20) and hip x-rays (adjusted OR 2.23, 95% CI 1.42-3.49) at least 5 years before diagnosis were significantly associated with increased prostate cancer. For those with a family history of cancer, exposures to hip x-rays dating 10 or 20 years before diagnosis were associated with a significantly increased risk of prostate cancer: adjusted OR 5.01, 95% CI 1.64-15.31 and adjusted OR 14.23, 95% CI 1.83-110.74, respectively. Our findings show that exposure of the prostate gland to diagnostic radiological procedures may be associated with increased cancer risk. This effect seems to be modified by a positive family history of cancer suggesting that genetic factors may play a role in this risk association.

Integrating health and social care in community mental health teams in the UK: a study of assessments and eligibility criteria in England.

The purpose of this cross-sectional survey was to examine the relationship between assessments and eligibility decisions made by health and social care staff in multidisciplinary community teams in England. The data were collected between December 2004 and August 2005. The study was a replication of a study that took place in the same eight locations in England before the modernization of health and social care by the present government. Four hundred and thirteen care coordinators responded from 71 teams to produce a total of 1481 clients. Sixty per cent (n = 884) of the sample of clients were categorised as having a psychotic illness compared to 63% in 1997 to 1998. Fair Access to Care Services (FACS) criteria determine access to social care services, and the Care Programme Approach (CPA) determines the level of mental health services provided. There was a close but an incomplete association between FACS and CPA judgements (kappa = 0.37; 95% confidence interval 0.31-0.43). Compared to the standardised Matching Resources to Care version 2 indication of complex needs, social workers' judgements were the most closely aligned to FACS judgements (F = 5.80; d.f. = 2 and 1203; P < 0.01). This raises the question of the need for training for health professionals in order to make decisions about social assessment and eligibility determination.

Randomized comparison of a nutrient-dense formula with an energy-supplemented formula for infants with faltering growth.

INTRODUCTION: The practice of supplementing standard infant formula with energy for infants with faltering growth has been widespread. This increases energy density but disturbs the protein : energy ratio, and increases risks of microbial contamination and errors in feed preparation. This study aimed to compare the effectiveness of a nutrient-dense formula (NDF) with an energy-supplemented formula (ESF) in infants with faltering growth. METHODS: In an open, parallel, randomized study, 49 infants with faltering growth were randomized to receive a NDF (4.2 kJ mL(-1)) or an ESF (4.2 kJ mL(-1)), for 6 weeks. Anthropometry, biochemistry, feed intake, stool and vomit frequency were collected. RESULTS: No significant differences in tolerance, feed volumes or energy intakes were recorded but the NDF group received 42% more protein and 15-40% more vitamins and minerals. Blood urea concentration in the ESF group fell by 50% over the trial period, suggesting a suboptimal protein : energy ratio in the ESF feed. The NDF group retained a normal mean blood urea concentration, a higher urinary potassium concentration and did not have the significant fall in length z-score seen in the ESF group. CONCLUSION: Increasing the energy content of normal infant formula without also increasing protein and micronutrients should not be practiced in infants with faltering growth.

Home delivery of dietary products in inherited metabolic disorders reduces prescription and dispensing errors.

UNLABELLED: In the UK, for patients with inherited metabolic disorders (IMD) the traditional system for acquiring essential dietary products [patient prompted prescriptions generated by a medical general practitioner (GP) and dispensed by a chemist] is problematic. OBJECTIVE: To investigate the efficacy of a home delivery service (HDS) for essential dietary products (EDP) (i.e. protein substitutes, milk replacements, energy and vitamin and mineral supplements) for subjects with IMD, particularly examining any prescription and dispensing errors, metabolic control and consumer satisfaction. METHODS: A prospective, controlled, home delivery trial for EDP was conducted in patients with IMD for 12 months. Sixty-two patients with IMD [50 with phenylketonuria (PKU); 12 with other IMD: aged 6 months-30 years] were recruited. Thirty subjects used a monthly HDS (Homeward: Nutricia) to receive EDP, 32 remained on the traditional system. Each month, the HDS checked home stock levels of EDP, obtained their prescriptions directly from GP's, and then delivered them to the subjects' homes. An independent researcher completed monthly telephone interviews with patients/parents about any EDP prescription errors or delay in receipt. RESULTS: Incorrect protein substitute was dispensed once by the HDS compared with nine subjects who had 12 errors in the control group (P = 0.01); incorrect flavours of protein substitute were dispensed to the home delivery group once compared with eight subjects getting 11 errors via the chemist (P = 0.03). The HDS delayed delivery of protein substitute for one subject on three occasions compared with 39 occasions in 16 subjects via the chemist (P = 0.001). In patients with PKU, plasma phenylalanine control deteriorated in the control group (P < 0.05) but not in the HDS group. CONCLUSIONS: The long-term use of a HDS for EDP in IMD is safer, effective and more reliable than conventional systems.

'Ready to drink' protein substitute is easier is for people with phenylketonuria.

UNLABELLED: In phenylketonuria (PKU), compliance with taking protein substitute is an issue in teenage and older patients. A 'ready to drink' protein substitute may overcome many of the practical issues associated with its administration. OBJECTIVE: To investigate the efficacy of a liquid protein substitute in a 6-week, three-part, randomized, crossover, controlled study. METHODS: 27 subjects (15 female; 12 male) with PKU with a median age of 30 years (range 8-49 years) were recruited. One subject withdrew from the study. Their median daily dose of protein equivalent was 60 g (range 45-75 g). In parts 1 and 2, subjects were randomized to either a liquid or a powder protein substitute with the same nutritional composition per unit (each 130 ml liquid pouch or 25 g powder sachet contained 15 g protein equivalent). In part 3, subjects chose liquid, powder or a combination of both. Weekly blood phenylalanine (Phe) concentrations were estimated, and during weeks 2, 4 and 6 subjects completed a daily questionnaire on administration issues. RESULTS: All but one of 26 subjects chose the liquid in part 3 as either their sole (69%, n = 18) or partial source (28%, n = 7) of protein substitute. Blood Phe concentrations were significantly better on the liquid (p = 0.03). With the liquid protein substitute, subjects were less self-consciousness (p = 0.003) and found it easier to take away from home (p = 0.001). Overall, the liquid was easier (p < 0.0001), more convenient (p = 0.002) and resulted in less wastage of protein substitute (p = 0.001). CONCLUSION: Liquid protein substitute was popular and efficacious, reduced self-consciousness and overall improved compliance of teenagers and adults with PKU.