Classification of child abuse by motive and degree rather than type of injury.

The protection of children may be enhanced if ill treatment is classified by motive and degree rather than by type of injury. Four categories are proposed: A, abuse: premeditated ill treatment undertaken for gain by disturbed, dangerous, and manipulative individuals; B, active ill treatment: impulsively undertaken because of socioeconomic pressures, lack of education, resources, and support, or mental illnesses; C, universal mild ill treatment: behaviour undertaken by all normal caring parents in all societies; and D, neglect: defined here as an unintentional failure to supply the child's needs. Such a classification could clarify the procedures for investigation and protection, and support the creation of a Special Interagency Taskforce on Criminal Abuse (SITCA) for those suspected of abuse (category A).

How to distinguish between neglect and deprivational abuse.

Neglect is a major cause of inadequate childcare in all societies and should be differentiated from abuse. "Neglect" is defined here, as the "neglectful" failure to supply the needs of the child, including emotional needs. It does not include the deliberate and malicious withholding of needs, which is a form of abuse. Neglect has its roots in ignorance of a child's needs and competing priorities; it is passive and usually sustained. The carer is without motive and unaware of the damage being caused. Malnutrition is a prime example of neglect; the stigma associated with the term abuse should never be applied to the poor struggling or uneducated mother whose child, that she loves dearly, becomes malnourished. Education of the mother and society and relief from the vicissitudes of poverty are required to alleviate most neglect of the world's children.

Variation among Escherichia coli O157:H7 strains relative to their growth, survival, thermal inactivation, and toxin production in broth.

To estimate the potential outcomes of food processing on the fate of foodborne pathogens. variations in microbial parameters such as growth rate, survival time, thermal inactivation time, and toxin production must be known. Previous microbial studies using single strains or cocktails provide error estimates for the uncertainty of the experimental and statistical procedures, but not for variations among strains. In this study, the behavior of 17 strains of Escherichia coli O157:H7 were followed when placed in synthetic media that permitted growth, survival, or thermal inactivation. The parameter values were not rejected as being normal, lognormal, gamma, or Weibull distributions. The ratio of the standard deviation to mean (normal distribution) for the exponential growth rate was 0.16 and for the lag phase duration, it was 0.38. The ratios of times to achieve a 4-log10 reduction at two survival conditions were 0.39 and 0.46; ratios of thermal D values at 55 and 60 degrees C were 0.42 and 0.33, respectively. The ratio of the negative log10 of toxin production was 0.24. These distributions are larger than the coefficient of variations observed for experimental errors in single strain and cocktail experiments. This indicates the limitations in precision that predictions of future population numbers can have when the potential presence of all strains needs to be considered. This variation among strains is applicable whether predictions are made by traditional subjective and point estimates or by using models and risk assessments.

The effect of folic acid supplementation on plasma homocysteine in an elderly population.

BACKGROUND: Increased plasma homocysteine is associated with coronary artery disease, peripheral vascular disease and venous thrombosis. Folic acid is the most effective therapy for reducing homocysteine levels. The lowest effective supplement of folic acid is not known, particularly for the elderly who have the highest prevalence of these conditions. AIM: To explore the effects of daily supplements of 0, 50, 100, 200, 400 and 600 microg folic acid on plasma homocysteine in an elderly population. DESIGN: Randomized double-blind placebo-controlled trial. METHODS: Participants (n=368) aged 65-75 years were randomly allocated to receive one of the treatments for 6 weeks. Plasma homocysteine was recorded after 3 weeks and 6 weeks of supplementation. RESULTS: Only the 400 microg and 600 microg groups had significantly lower homocysteine levels compared to placebo (p=0.038 and p<0.001, respectively). Using multiple linear regression and each individual's total folic acid intake (diet plus supplement), a total daily folic acid intake of 926 microg per day would be required to ensure that 95% of the elderly population would be without cardiovascular risk from folate deficiency. DISCUSSION: A daily folic acid intake of 926 microg is unlikely to be achieved by diet alone. Individual supplementation or fortification of food with folic acid will be required to reach this target.

Urinary excretion of pyridinium crosslinks in short children treated with growth hormone.

The aim of this study was to evaluate the effect of growth hormone (GH) treatment on bone resorption in children with GH deficiency and those with idiopathic short stature. The study population included seven children with subnormal spontaneous GH secretion and 13 children with idiopathic short stature, all of them pre-pubertal. Anthropometric measurements, free, protein-bound and total urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), serum GH, and serum immunoreactive PTH were measured at baseline and months 1, 3, 6 and 12 of GH treatment. The urinary excretion of total Pyd and Dpd, standardized by the cube of height (m3) in overnight, 24-hour urine collections was not different from age-matched healthy controls at baseline in either group of patients. During treatment with human recombinant GH, both pyridinium crosslinks increased above normal values, reaching a peak after one month in children with GH deficiency and later (after 3-6 months) in children with short stature. Free and total crosslink forms were correlated, and GH treatment did not affect the proportion of free to bound crosslinks. Serum concentrations of iPTH showed a moderate but not statistically significant increase. This study provides no evidence of reduced bone resorption in untreated GH deficiency or in idiopathic short stature. GH treatment induced a marked, but temporary, increase of bone resorption in both groups of patients.

Time-resolved fluorescence immunoassay (TRFIA) for the detection of Escherichia coli O157:H7 in apple cider.

An immunoassay based on immunomagnetic separation and time-resolved fluorometry was developed for the detection of E. coli O157:H7 in apple cider. The time-resolved fluorescent immunoassay (TRFIA) uses a polyclonal antibody bound to immunomagnetic beads as the capture antibody and the same antibody labeled with europium as the detection antibody. Cell suspensions of 10(1) to 10(8) E. coli O157:H7 and K-12 organisms per ml were used to test the sensitivity and specificity of the assay. The sensitivity of the assay was 10(3) E. coli O157:H7 cells with no cross-reaction with K-12. Pure cultures of E. coli O157:H7 (10(1) to 10(5) CFU/ml) in apple cider could be detected within 6 h, including 4 h for incubation in modified EC broth with novobiocin and 2 h for the immunoassay. When apple cider was spiked with 1 to 10(3) CFU/ml of E. coli O157:H7 and 10(6) CFU/ml of K-12, our data show that the high level of K-12 in apple cider did not impede the detection of low levels of O157:H7. The minimum detectable numbers of cells present in the initial inoculum were 10(2) and 10(1) CFU/ml after 4- and 6-h enrichment. The TRFIA provides a rapid and sensitive means of detecting E. coli O157:H7 in apple cider.

COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss.

Genetic factors play an important role in the pathogenesis of osteoporosis but the genes that determine susceptibility to poor bone health are defined incompletely. Previous work has shown that a polymorphism that affects an Spl binding site in the COLIA1 gene is associated with reduced bone mineral density (BMD) and an increased risk of osteoporotic fracture in several populations. Data from cross-sectional studies have indicated that COLIA1 Sp1 alleles also may be associated with increased rates of bone loss with age, but longitudinal studies, which have examined bone loss in relation to COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 Sp1 alleles and early postmenopausal bone loss measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of 734 Scottish women who were followed up over a 5- to 7-year period. The distribution of genotypes was as expected in a white population with 484 "SS" homozygotes (65.9%); 225 "Ss" heterozygotes (30.7%), and 25 "ss" homozygotes (3.4%). Women taking hormone-replacement therapy (HRT; n = 239) had considerably reduced rates of bone loss at the spine (-0.40 +/- 0.06%/year) and hip (-0.56 +/- 0.06%/year) when compared with non-HRT users (n = 352; spine, -1.36 +/- 0.06%/year; hip, -1.21 +/- 0.05%/year; p < 0.001 for both sites). There was no significant difference in baseline BMD values at the lumbar spine (LS) or femoral neck (FN) between genotypes or in the rates of bone loss between genotypes in HRT users. However, in non-HRT users (n = 352), we found that ss homozygotes (n = 12) lost significantly more bone at the lumbar site than the other genotype groups in which ss = -2.26 +/- 0.31%/year compared with SS = -1.38 +/- 0.07%/year and Ss = -1.22 +/- 0.10%/year (p = 0.004; analysis of variance [ANOVA]) and a similar trend was observed at the FN in which ss = -1.78 +/- 0.19%/year compared with SS = -1.21 +/- 0.06%/year and Ss = -1.16 +/- 0.08%/year (p = 0.06; ANOVA). The differences in spine BMD loss remained significant after correcting for confounding factors. Stepwise multiple regression analysis showed that COLIA1 genotype independently accounted for a further 3.0% of the variation in spine BMD change after age (4.0%), weight (5.0%), and baseline BMD (2.8%). We conclude that women homozygous for the Sp1 polymorphism are at significantly increased risk of excess rates of bone loss at the spine, but this effect may be nullified by the use of HRT.

Malnutrition: trials and triumphs.

Severe malnutrition is uncommon but often fatal, particularly in very young infants or when oedema is present. Another major contributor to mortality is undiagnosed infection. Three pilot studies have recently been performed in severely malnourished patients in therapeutic feeding centres in sub-Saharan Africa. In each, a practical management problem was addressed and a potential solution tested. Three conclusions were reached: young breastfeeding infants were best managed using a supplemented suckling technique; routine antibiotics from admission reduced mortality; and in adults with oedematous malnutrition, therapeutic diets with a lower-than-usual protein:energy ratio were effective in reducing mortality and permitting catch-up weight gain.

Nutritional differences in patients with proximal femoral fractures.

BACKGROUND: The reason why elderly human hips tend to break in one of two anatomical regions is uncertain. Nutritional factors may affect the site of fracture. OBJECTIVE: To assess possible nutritional differences in patients with proximal femoral fractures. DESIGN: Prospective observational cohort study. SETTING: University teaching hospital. SUBJECTS: 119 consecutive patients over the age of 65 with a hip fracture admitted to the trauma wards in a single centre. METHODS: One researcher measured triceps, biceps and supra-iliac skinfold thickness, and mid upper arm circumference on admission and on the fifth post-operative day. Body mass index was calculated for each patient, and used to classify patients as severely, moderately or mildly malnourished, normal, overweight or obese. Logistic regression was used to determine the influence of various factors on fracture site. RESULTS: According to their body mass index, 31% of patients were classified as malnourished and 11% as severely malnourished. Patients with intracapsular fractures were significantly more malnourished than patients with trochanteric fractures (P < 0.008). Nutritional status was not related to post-operative complications. Ability to weigh a patient on the fifth post-operative day was the single most important prognostic indicator for complications. CONCLUSIONS: Patients with intracapsular fractures are more malnourished. Those with trochanteric fractures tend to be overweight.

Epidemiological study of hip fracture in Shenyang, People's Republic of China.

The aim of this study was to investigate the incidence and epidemiology in 1994 of hip fracture in Shenyang, a large city in the northeast of The People's Republic of China, using register information and medical records collected from the 36 hospitals in Shenyang. The hip fracture data were restricted to cervical or trochanteric types. A subset (59% of total) of medical records of hip fracture was used to investigate the causes of hip fracture. The causes were classified as simple fall, fall from a bicycle during cycling, bicycle accident, car accident, and fall from a height. There was a total of 453 hip fractures (206 in women and 247 in men) in the population over 50 years of age. The age-adjusted 1 year cumulative incidence rate was 67/100,000 (95% confidence interval [CI] = 58-76/100,000) for women and 81/100,000 (95% CI = 71-91/100,000) for men. The standardized incidence rate against the 1985 U.S. population was 87/100,000 (95% CI = 77-97/100,000) for women and 100/100,000 (95% CI = 89-111/100,000) for men. The mean (+/-standard deviation) age of patients with a hip fracture was 67.5+/-9.8 years for men and 66.9+/-9.0 years for women. The overall male-to-female ratio of hip fracture was 1.21:1 for age-adjusted hip fracture incidence and 1.15:1 for standardized incidence. Simple fall accounted for 70% hip fractures in women but caused only 49% in men (chi2 = 11.2, degrees of freedom [df] = 1,p = 0.0008). The frequency of hip fractures caused by a fall from a bicycle was higher in men (28%) than women (10%) (chi2 = 13.0, df = 1,p = 0.0003). The results of this study indicate (1) a low incidence of hip fracture in a Chinese population compared with more affluent countries, and (b) a higher incidence in men than women that is related in part to a higher incidence of accidents, especially bicycle-related ones.

Dietary nitrate in man: friend or foe?

Based on the premise that dietary nitrate is detrimental to human health, increasingly stringent regulations are being instituted to lower nitrate levels in food and water. Not only does this pose a financial challenge to water boards and a threat to vegetable production in Northern Europe, but also may be eliminating an important non-immune mechanism for host defence. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Epidemiological studies have failed to substantiate this. It has been shown that dietary nitrate undergoes enterosalivary circulation. It is recirculated in the blood, concentrated by the salivary glands, secreted in the saliva and reduced to nitrite by facultative Gram-positive anaerobes (Staphylococcus sciuri and S. intermedius) on the tongue. Salivary nitrite is swallowed into the acidic stomach where it is reduced to large quantities of NO and other oxides of N and, conceivably, also contributes to the formation of systemic S-nitrosothiols. NO and solutions of acidified nitrite, mimicking gastric conditions, have been shown to have antimicrobial activity against a wide range of organisms. In particular, acidified nitrite is bactericidal for a variety of gastrointestinal pathogens such as Yersinia and Salmonella. NO is known to have vasodilator properties and to modulate platelet function, as are S-nitrosothiols. Thus, nitrate in the diet, which determines reactive nitrogen oxide species production in the stomach (McKnight et al. 1997), is emerging as an effective host defence against gastrointestinal pathogens, as a modulator of platelet activity and possibly even of gastrointestinal motility and microcirculation. Therefore dietary nitrate may have an important therapeutic role to play, not least in the immunocompromised and in refugees who are at particular risk of contracting gastroenteritides.

Oedematous malnutrition.

Oedematous malnutrition in the child or adult is not caused by protein deficiency; such a concept can lead to fatal therapeutic error in oedematous malnutrition treatment. On the other hand, deficiency of protein, or the other type II nutrients, is common and causes stunting and wasting. In kwashiorkor, the deficiency is more likely to be due to one or several type I nutrients, particularly those involved with anti-oxidant protection.

[Definition and evaluation of therapeutic food for severely malnourished children in situations of humanitarian emergencies]. / Définition et évaluation d'un aliment thérapeutique pour les enfants sévèrement malnutris, en situation d'urgence humanitaire.

Nowadays, median case fatality rate of severely malnourished children treated in hospitals is 23.5%, a rate which has not changed for the last 50 years. This is probably related to the use of inappropriate or even unsafe treatment protocols. This work aimed at reducing case fatality rates of severe malnutrition by developing a treatment protocol and assessing its effectiveness during humanitarian crises. A therapeutic food was designed from pathophysiologic studies and its use adapted to therapeutic feeding centres. This food (F100) contains 100 Kcal/100 ml, with 10% of its energy derived from proteins; it has a low sodium and iron content but is fortified with vitamins and minerals. It can be prepared either at the treatment centre or at an industrial level. Industrial production, which started in 1993 reached 1,500 MT in 1997. In refugee camps, F100 was used according to a strict protocol adapted to local conditions. Intakes started at 100 Kcal/kg/day and reached 200 kcal/kg/day once appetite was restored. A model to assess the risk of death according to weight, height and oedema was developed. First results show that mortality was often below 5%. Hence, it is possible to standardise and evaluate a nutritional treatment in such unfavourable conditions as a refugee camp. Standardised use of F100 can markedly reduce mortality of severely malnourished children.

A model to standardise mortality of severely malnourished children using nutritional status on admission to therapeutic feeding centres.

OBJECTIVE: To determine a simple model to calculate the number of deaths which could be expected in a therapeutic feeding centre from the height, weight and oedema of children on admission. DESIGN: Admission weight, height, presence of oedema of the children and outcome were prospectively recorded. SETTING: Data were recorded in 18 feeding centres set-up during emergency operations in Africa. Ten of the feeding centres were selected, a priori, as reference centres and eight centres as test centres. SUBJECTS: Data for 3858 children were recorded. 837 children absconded from the centres and were excluded from the analysis. Analysis was performed on data from 2753 children who left the centre after recovery and 268 children who died during treatment. INTERVENTIONS: The relation between the risk of death and, anthropometric measurements and presence of oedema has been determined in a previous paper. The maximum likelihood estimate of the constant of the model was determined from global analysis of the data of the reference centres. The model was applied to the data of the reference and test centres. RESULTS: The model to predict the individual probability of death was: P(death) = 1/(1 + exp[-(20.63 - 9.99 1n(weight/height1.74) + 1.36 oedema)]) The predicted number of deaths was close to the recorded number of deaths for each reference centre. For three of the eight test centres there was a significant excess of observed deaths over predicted. CONCLUSION: This model can be easily used by the supervisor of a centre to assess the expected number of deaths during treatment of malnutrition from simple measurements on children that are routinely taken on admission and thus help to determine the nature of variation in observed mortality rates.

PIP: Data on children treated at 18 emergency feeding centers in 9 African countries were used to develop a simple model to calculate the number of child deaths expectable in severely malnourished children on the basis of height, weight, and edema at admission. Overall crude mortality was 7.6% at the 10 reference centers and 11.3% in the 8 test centers. Included in the analysis were 2753 children treated at the feeding centers and released and 268 children who died during treatment. The association between mortality and the anthropometric measurements and presence of edema had been determined in a previous study. The maximum likelihood estimate of the constant of the model was determined from global analysis of data from the reference centers. The model to predict the individual probability of death was: P(death) = 1/(1 = exp[-(20.63 - 9.99 in optimal ratio of weight to height + 1.36 edema)]). The predicted number of deaths closely approximated the actual number at each reference center, while there was a significant excess of observed over predicted deaths at 3 of the 8 test centers. This simple tool can be used to calculate the predicted number of deaths, evaluate the efficacy of a feeding center, and examine mortality trends over time or in relation to administrative changes.

Expanded models for the non-thermal inactivation of Listeria monocytogenes.

Previously developed four-variable response surface models for describing the effects of temperature, pH/lactic acid, sodium chloride and sodium nitrite on the time to achieve a 4-log, non-thermal inactivation (t4D) of Listeria monocytogenes in aerobic, acidic environments were expanded to five-variable models that distinguish the effects of pH and acidulant concentration. A total of 18 new variable combinations were evaluated and the inactivation kinetics data appended onto a consolidation of two data sets from earlier studies. The consolidated data set, which included 315 inactivation curves representing 209 unique combinations of the five variables, was analysed by response surface analysis. The quadratic model without backward elimination regression was selected for further evaluation. Three additional quadratic models were generated using the concentrations of undissociated lactic and/or nitrous acids as variables in place of percentage lactic acid and sodium nitrite concentration. Comparison of predicted t4D values against literature values for various food systems indicated that the models provide reasonable initial estimates of the inactivation of L. monocytogenes. The models based on the concentration of undissociated lactic and nitrous acids support the hypothesis that antimicrobial activity is associated with this form of the compounds. Evaluation of several examples suggests that these models may be useful for predicting the equivalent of the compounds' "minimal inhibitory concentrations' for accelerating inactivation under various conditions.

Protein-energy interactions in the management of severe malnutrition.

The three syndromes of childhood malnutrition are contrasted with respect to protein. It is concluded that stunting and wasting are the outcomes of protein deficiency, and that kwashiorkor is not due to protein deficiency, rather it is related to unopposed oxidant stress. Formula for the energy and protein requirements are derived and contour plots of the amounts needed to sustain high rates of weight gain at different body compositions generated. It is suggested that all nutrients be expressed with energy as the denominator. No more than 12.5% of protein energy is required to sustain maximum likely rates of weight gain. Using this approach to design a diet, high rates of weight gain are achieved under field conditions in refugee camps.

Comparison of weight- and height-based indices for assessing the risk of death in severely malnourished children.

To compare the effectiveness of treating malnourished children in different centers, the authors believe there is a need to have a simple method of adjusting mortality rates so that differences in the nutritional status of the children are taken into account. The authors compared different anthropometric indices based on weight and height to predict the risk of death among severely malnourished children. Anthropometric data from 1,047 children who survived were compared with those of 147 children who died during treatment in therapeutic feeding centers set up in African countries in 1993. The optimal ratio of weight to height determined by logistic regression was weight (kg)/height (m)1.74 (95% confidence interval of beta estimate 1.65-1.84). The receiver operating curves (sensitivity vs. specificity) showed that the body mass index (weight (kg)/height (m)2), optimal ratio of weight to height, and weight/height index expressed as the percentage of the median of the National Center for Health Statistics' standard were equivalent and superior to the weight/height index expressed as the z score of the National Center for Health Statistics' standard to predict death. As the optimal ratio of weight to height is easier to calculate than the weight/height index expressed as the percentage of the median or z score and does not depend upon either standards or tables, the optimal ratio of weight to height could be conveniently used to adjust mortality rates for nutritional status in therapeutic feeding centers.

PIP: The development of a simple anthropometric index closely related to child survival prognosis could enhance the treatment of severely malnourished children at therapeutic feeding centers in Africa. This study examined whether simple ratios of weight to powers of height could be used to adjust the observed mortality rates for differences in the anthropometric state of 1194 children 6-59 months of age admitted to 9 feeding centers in Sierra Leone, Rwanda, and Madagascar. 147 of these children died during treatment. The optimal ratio of weight to height determined by logistic regression was weight (kg)/height (m). The receiver operating curves showed that the body mass index (weight (kg)/height (m)2), optimal ratio of weight to height, and weight/height index expressed as the percentage of the median of the US National Center for Health Statistics (NCHS) standard were equivalent and superior to the weight/height index expressed as the z score of the NCHS standard to predict death. Edema was a significant risk factor for death (odds ratio, 3.8; 95% confidence interval, 2.2-6.6). The optimal ratio of weight to height can be computed on a pocket calculator and does not require reference to standards or tables, making it appropriate for conditions in the feeding centers.

A matrixed approach to long-term stability testing of pharmaceutical products.

A matrixed approach to long-term stability testing of pharmaceutical products is presented. The basic matrix design, suitable for testing three lots at one storage condition, may be extended to multiple product presentations or storage conditions. The design has full testing at the endpoints (0 and 36 months) and partial testing at the interim time points (3, 6, 9, 12, 18, and 24 months). The test points were selected with the assistance of a statistical search algorithm. The proposed matrix design provides a 37.5% reduction in analytical testing, while still permitting a reliable interim expiry estimate based on 12-month stability data. The expiration dating periods estimated using the matrixed approach are typically more conservative than estimates derived from a full-testing approach. A comparison of expiration dating period estimates for a metered-dose inhaler and capsule drug product using the matrixed and full-testing approaches is presented.

Electrophysiological assessment of brain function in severe malnutrition.

Brain function in 10 severely malnourished children and matched controls was assessed using spectral analysis of electroencephalographic responses to photic driving during slow-wave sleep. The percentage power in the classical EEG broad-band domains was derived from temporo-occipital records. The malnourished group (5-23 months old; z-score height-for-age -3.2 +/- 0.3, weight-for-height -2.5 +/- 0.3) were tested on admission and on discharge from hospital. No significant differences were found between admission and discharge. Significant differences were found between malnourished and control groups, in the alpha 1 band in the undriven EEG, and in the alpha/beta 1 power ratio while driving at 8 Hz. These electrophysiological abnormalities, persisting despite somatic rehabilitation, must be associated with the chronic rather than the acute aspects of malnutrition, and can index the deviation of brain function from normality.