A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson's disease: a study protocol for a randomised controlled trial.

BACKGROUND: Parkinson's disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals' needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. METHODS/DESIGN: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. PRIMARY OUTCOME: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. DISCUSSION: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016.

Somatomedin activity in cerebrospinal fluid.

Somatomedin activity has been demonstrated in the cerebrospinal fluid (CSF) of 12 normal subjects and one patient with acromegaly. In all cases the concentration was lower in the CSF than in the corresponding serum, and a significant correlation was demonstrated between the somatomedin activity in the two body fluids (p smaller than 0.01).

Iron needs during pregnancy: do we need to rethink our targets?

This paper argues that current estimates of the need for absorbed iron, estimates of iron absorption, and hence estimates of iron requirements for pregnant women greatly depend on what is determined as the desirable or target hemoglobin concentration (goal). The existing goal appears to be based on the maximal hemoglobin concentration that can be achieved with iron supplementation of well-nourished women; this is a situation that can be expected to minimize iron absorption efficiency. I am unaware of attempts to define hemoglobin or anemia goals based on functional criteria (health of infant or mother). The current approach may seriously overestimate iron need and discourage food-based programs; furthermore, it may declare operational iron supplementation programs to be failures when, in fact, many programs may be successful in preventing functional effects of iron deficiency anemia. This is illustrated with data from a completed comparative study of daily and weekly iron supplementation. The final plea is to set aside existing traditions and, instead, attempt to develop functional criteria for anemia and establish functional goals of hemoglobin concentrations to be achieved during pregnancy.

Approaches to analysis of dietary data: relationship between planned analyses and choice of methodology.

Dietary intake cannot be estimated without error and probably never will be. The nature and magnitude of the error depends on both the dietary data collection methodology and the subjects studied. The impact of particular types of error depends on the question being asked and the analytical methodology used to address it. Examples of these phenomena are presented in this review paper. The future lies in improved estimation and understanding of the error terms and in the development of analytical and statistical methods of coping with these error terms rather than with "improvements" in dietary methodology per se.

Menstrual-cycle patterns in energy and macronutrient intake.

For 14 subjects drawn from the Beltsville One-Year Dietary Intake Study, patterns of energy, protein, fat, carbohydrate, protein/1000 kcal, fat/1000 kcal, and carbohydrate/1000 kcal were examined across pre- and postmenstrual periods. Individual subjects contributed data for one to four menstrual periods. Energy, fat, and fat/1000 kcal intakes were significantly higher in the 10 premenstrual days than in the 10 postmenstrual days. After elimination of effects attributable to between-subject differences and to balance periods included in the Beltsville study, fitted sine curves explained 14% and 25% of the variance in energy and fat intakes, respectively, across 14 premenstrual and 14 postmenstrual days, and 20% of the variance in fat/1000 kcal. Independent patterns were identified in absolute and relative protein intake. No patterns were discerned for carbohydrate. Physiological or behavioral factors appear to influence both total food intake (energy intake) and food selection (macronutrients/1000 kcal) across the menstrual cycle.

The nature and individuality of within-subject variation in energy intake.

Examinations of observed within-subject variation in the energy intake of 29 adults participating in the Beltsville One-Year Dietary Intake Study suggest that individuals possess characteristic patterns of variability in total food intake (expressed as energy intake). Although the day-to-day variation appears to contain a sizable random component, significant nonrandom components were detected in the observed variation of all but one subject. Up to 37% of the total variance observed for a subject could be explained by the long- and short-term patterns identified in food intake. Both the shape and the amplitude of these patterns were unique to the individual subject, suggesting that observed within-subject variance is a function of the particular combination of environmental and biological pressures on the individual's total food intake at any one time and of the methodological errors inherent in the estimation of this intake.

Protein requirements of infants: a reexamination of concepts and approaches.

Estimates of protein requirements of infants aged 3-4 mo by FAO/WHO/UNU (1.47 +/- 0.26 g.kg-1.d-1 as crude protein, N X 6.25) are judged to be overestimates. From simulation analyses we suggest that 1.1 +/- 0.1 - 0.2 g.kg-1.d-1 is a more reasonable estimate. This is consistent with statements that 1) breast milk that provides an average of 16 g protein/1000 kcal or a fixed-composition formula that contains 17 g protein/1000 kcal is adequate for essentially all such infants and 2) average protein intakes from that milk or formula would be approximately 1.65 or 1.75 g.kg-1.d-1, close to current average requirements estimates. It appears that there has been a difference in the concepts of requirement usually applied to infants and to adults and a systematic misinterpretation of breast-milk data in estimating requirements. A plea is issued for the application of epidemiologic approaches as a part of requirement estimation.

Statistical estimation of dietary parameters: implications of patterns in within-subject variation--a case study of sampling strategies.

Patterns within intraindividual variation in energy intake were described previously. Using case studies based on the same Beltsville One-Year Dietary Intake Study data set, we examined the interaction between random and nonrandom variation and the choice of sampling strategy in estimation of individuals' usual intakes over 1 y. Mean intake estimates derived from adjacent-day samples were less reliable and more likely to be biased than were those based on randomly selected days. A finite adjacent-day sample fails to encompass longer-term trends. Because adjacent-day samples underestimate true within-subject variation, by customary tests they appear more reliable. This may present an interpretational problem. Comparisons of random weekend and week-day samples confirm that failure to proportionately sample both will bias the estimation of the usual (1-y mean) intake and the within-subject variance.

Conceptual and methodological issues regarding the epidemiology of iron deficiency and their implications for studies of the functional consequences of iron deficiency.

This paper reviews the measures of iron status (hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, mean cell volume, free erythrocyte protoporphyrin, serum iron, transferrin saturation, and serum ferritin) that are potentially available for inclusion in field studies of the relationship between iron and mental performance. The characteristics of these measures (sensitivity to iron status, specificity to iron, and diurnal and day-to-day variability) are reviewed and the implications of choice of variable for the design, analysis, and interpretation of studies are discussed. Brief consideration is given to the question of confounding variables and to sources of both false-positive and false-negative conclusions. The explicit message of the paper is that there is no perfect choice of measure of iron status but, given explicit definition of the research question, there are preferred choices that can most effectively combine the choice of variable and the design of the study.

An examination of factors believed to be associated with infantile obesity.

Forty-two normal (25th to 75th percentiles of weight for age) and 47 "obese" (above the 90th percentile) infants, 4 to 9 months of age, were compared with regard to energy and macronutrient intake, breast-feeding history, age of introduction of solids, and maternal reliance on external feeding cues. The study failed to reveal characteristic group differences. The current stereotype of the obese infant as one who is overfed, is given solids very young, is not breast fed, and whose mother is not responsive to his satiety signals is challenged. As a result, the nature of current group counseling for the prevention of infantile obesity is questioned.

Errors in the interpretation of dietary assessments.

Two years ago, I reviewed the analytic effect of error in the estimation of dietary intake, describing the emphasis on the "random" day-to-day variation in reported intake. Interest in this area is increasing and there are signs of progress in analytic strategies. This paper focuses on two concerns about the use of dietary data in analyses. The effect of different methods of adjusting analyses of fat and a health outcome for energy is illustrated through an exploration of the association between fat intake and high body mass index in data sets from the US Department of Agriculture and a Dutch national survey. Both a shift in the analytic question and a change in the error structure occur as analysis strategies are changed, leading to confusion in interpretation. The paper also addresses the growing concern about bias in the estimation of intake and the possibility that differential bias moves with stratification variables of analytic interest. The increasing use of doubly labeled water estimates of energy expenditure as a gold standard for checking on overall bias in reporting is commendable. There will always be error in dietary assessments. The challenge is to understand, estimate, and make use of the error structure during analysis.

Estimated vitamin intakes of toddlers: predicted prevalence of inadequacy in village populations in Egypt, Kenya, and Mexico.

Vitamin intakes of 255 toddlers (aged 18-30 mo) were estimated from food consumption recorded during 1 y at sites in Egypt, Kenya, and Mexico. Mean intakes were compared with requirements standards by using a probability approach to estimate the prevalence of inadequate intakes. There were predicted inadequacies for vitamin A (32%) and riboflavin (20%) in Egypt, vitamins A (68%) and C (63%) and riboflavin (52%) in Mexico, and vitamin B-12 (44%) in Kenya. Vitamin E was inadequate in all diets, but in relation to polyunsaturated fatty acids only the intake in Mexico was low. No diet provided the recommended amount of vitamin D, but its dietary requirement is uncertain. Correlations among nutrient intakes suggest factors that may contribute to reported associations of consumption of animal products with improved growth or development among these children: provision of vitamin B-12 and available minerals, displacement of fiber and phytate-rich energy sources, and increased energy density.

PIP: Data on 255 children, 18-30 months old, in Kalama village on the Nile delta in Egypt, the Embu district in Kenya, and the Solis Valley in Mexico were analyzed over a 1-year period to study the relationships of energy and animal protein intakes with vitamins, minerals, and two factors that affect bioavailability, dietary fiber and phytate. The researchers used the probability approach to determine the prevalence of inadequate intakes. Estimated intake inadequacies were 32% for vitamin A and 20% for riboflavin in Egypt; 68% for vitamin A, 63% for vitamin C, and 52% for riboflavin in Mexico, and 44% for vitamin B12 in Kenya. All the diets were deficient in vitamin E. Yet, when researchers compared vitamin E in relation to polyunsaturated fatty acids, the vitamin E intake was low only in Mexico. None of the diets had the recommended amount of vitamin D, but actual dietary requirements were unknown. Further, the researchers had no information on solar exposure. Provision of vitamin B12 and available minerals, displacement of fiber and phytate-rich energy sources, and increased energy density were associated with improved growth or development among children ingesting animal products (p 0.05). Intakes of folacin, niacin, and thiamin were negatively related to animal protein intake (p 0.05).

Estimated mineral intakes of toddlers: predicted prevalence of inadequacy in village populations in Egypt, Kenya, and Mexico.

Intakes of minerals and factors that might affect their bioavailability were estimated for 255 toddlers aged 18-30 mo living in villages in Egypt, Kenya, and Mexico. Mean intakes over 1 y were compared with international-requirement estimates by using a probability approach. The prevalence of iron intakes likely to be inadequate to prevent anemia was estimated as 35% in Egypt, 13% in Kenya, and 43% in Mexico. The prevalence of zinc intakes likely to be inadequate to meet basal requirements was estimated as 57% and 25% in Kenya and Mexico, respectively, but only 10% in Egypt, where the use of yeast-leavened breads was judged to have improved zinc availability. There was no suggestion that estimated copper or magnesium intakes were inadequate, but calcium intakes in Kenya and Egypt were well below recommended amounts. Studies of factors affecting mineral bioavailability in the diets of these countries' populations could suggest dietary changes that might improve effective mineral intake with minimal cost.

Estimated protein intakes of toddlers: predicted prevalence of inadequate intakes in village populations in Egypt, Kenya, and Mexico.

This paper presents a probability assessment of the adequacy of protein intakes of toddlers (aged 18-30 mo) in study communities in Egypt, Kenya, and Mexico judged in relation to FAO/WHO/UNU estimates of requirements. Effects of supplementing amino acid intakes, or of assuming lower bioavailability for lysine are also considered. In Egypt and Mexico existing protein intakes of toddlers were adequate. In Kenya existing intakes were marginal. Total protein intake was low and often lysine or tryptophan concentration was low. If Kenyan intakes met estimated energy requirements, protein intakes would be adequate. We conclude that protein intake is unlikely to be a primary limiting factor for toddler growth and development, and the benefit to be expected from increasing the intake of limiting amino acids is marginal. Reported associations of animal-source protein and energy with growth, size, and psychologic function of these toddlers are unlikely to be causally attributable to inadequacy of protein intakes.

Source of variance in 24-hour dietary recall data: implications for nutrition study design and interpretation. Carbohydrate sources, vitamins, and minerals.

Beaton et al (Am J Clin Nutr 1979;32:2546-59) reported on the partitioning of variance in 1-day dietary data for the intake of energy, protein, total carbohydrate, total fat, classes of fatty acids, cholesterol, and alcohol. Using the same food intake data and the expanded National Heart, Lung and Blood Institute food composition data base, these analyses of sources of variance have been expanded to include classes of carbohydrate, vitamin A, vitamin C, thiamin, riboflavin, niacin, calcium, iron, total ash, caffeine, and crude fiber. The analyses relate to observed intakes (replicated six times) of 30 adult males and 30 adult females obtained under a paired Graeco-Latin square design with sequence of interview, interviewer, and day of the week as determinants. Neither sequence nor interviewer made consistent contribution to variance. In females, day of the week had a significant effect for several nutrients. The major partitioning of variance was between interindividual variation (between subjects) and intraindividual variation (within subjects) which included both true day-to-day variation in intake and methodological variation. For all except caffeine, the intraindividual variability of 1-day data was larger than the interindividual variability. For vitamin A, almost all of the variance was associated with day-to-day variability. One day data provide a very inadequate estimate of usual intake of individuals. In the design of nutrition studies it is critical that the intended use of dietary data be a major consideration in deciding on methodology. There is no "ideal" dietary method. There may be preferred methods for particular purposes.

Small but healthy? Are we asking the right question?

This paper reviews the development of thinking about anthropometric measures within the nutrition community, suggests that this has led us into some serious misconceptions, and offers a plea for a reconsideration in the use and interpretation of such measures. It is suggested that the 'Small but Healthy?' debate is really the result of the misinterpretations and, as such, is distracting from the true issues. The paper also argues strongly against the notion of 'no-cost' adaptations, and argues instead that present status-quo accommodations may be achieved at the price of potential for change.

Schoolchildren have similar predicted prevalences of inadequate intakes as toddlers in village populations in Egypt, Kenya, and Mexico.

OBJECTIVES: To examine the probability of inadequacy of schoolchild nutrient intakes; to compare the predicted adequacy of schoolchild diets to previously published data for toddler diets and to examine the relative adequacy of the diets of sibling pairs. DESIGN: Food consumption data were measured 2 days per month across approximately one year. Mean nutrient intakes were calculated and compared to international standards using a probability approach. SETTING: Villages in Egypt, Kenya, and Mexico. SUBJECTS: 285 school-age children (7-9 years of age) and 255 toddlers (18-30 months of age) including 94 sibling pairs. RESULTS: Within a country, there was a striking similarity between the nutrients predicted to be inadequate in schoolchild and toddler diets across all nutrients except vitamin B12, which was more likely to be inadequate among schoolchildren. Nutrients of concern for both ages in one or more countries included iron, zinc, calcium, riboflavin, and vitamins B12, D, E, and A. For 94 toddler-schoolchild pairs, siblings at high risk of nutrient inadequacy could be identified from an indicator child with a sensitivity of 43-100% and a specificity of 59-100%. CONCLUSIONS: Nutrient adequacy tends to be a household characteristic for these two ages of children. Nutritional interventions that target the household have a high probability of benefitting multiple age groups of children.

PIP: The authors investigated the probability of inadequacy of schoolchild nutrient intakes in order to compare the predicted adequacy of schoolchild diets to previously published data for toddler diets, and to examine the relative adequacy of the diets of sibling pairs. Food consumption data were measured two days per month for approximately one year for 285 children aged 7-9 years and 255 infants aged 18-30 months, including 94 sibling pairs, in villages in Egypt, Kenya, and Mexico. Mean nutrient intakes were calculated and compared to international standards using a probability approach. Within a country, there was close similarity between the nutrients predicted to be inadequate in schoolchild and toddler diets across all nutrients except vitamin B(12), D, E, and A. For 94 toddler-schoolchild pairs, siblings at high risk of nutrient inadequacy could be identified from an indicator child with a sensitivity of 43-100% and a specificity of 59-100%. Nutritional interventions which target the household have a high probability of benefiting multiple age groups of children.

Nutritional needs during the first year of life. Some concepts and perspectives.

This article reviews some of the recent changes in thinking that are reflected in two reports (Recommended Nutrient Intakes for Canadians and the FAO/WHO/UNU Report on Energy and Protein Requirements) concerning nutrient requirements for infants below one year of age. The author illustrates the concepts underlying the published requirement estimates and hence some of the principles that should underlie the interpretation and application of the estimates.

Household food insecurity and hunger among families using food banks.

Over the past two decades, the demand for charitable food assistance has steadily grown, and a massive ad hoc system of food banks has become established in Canada. To assess the food insecurity and nutritional vulnerability of one subgroup of food bank users, interviews were conducted with a sample of 153 women in families using emergency food relief programs in Metropolitan Toronto. Ninety percent reported household incomes which were less than two thirds of the 'poverty line', and 94% reported some degree of food insecurity over the previous 12 months. Seventy percent reported some level of absolute food deprivation, despite using food banks. The findings highlight the limited capacity of ad hoc, charitable food assistance programs to respond to problems of household food insecurity which arise in the context of severe and chronic poverty.