Phenylketonuria variants in Ontario.

Since mass screening of the newborn population for phenylketonuria (PKU) by the Guthrie test was begun in Ontario in July 1965 many variants of PKU have been recognized in the 96 to 97% screened. Seventy-one cases of classic PKU were detected (four were missed). Of 48 cases of persistent hyperphenylalaninemia discovered, 18 were classified as atypical PKU and 30 as persistent benign hyperphenylalaninemia. Numerous infants with transient hyperphenylalaninemia (initial values over 10 mg/dl in 12), in many instances the result of transient neonatal tyrosinemia, were discovered. There was a slight predominance of males. Serum phenylalanine values of up to 15 mg/dl seemed to be harmless to the developing brain. A survey of 67 247 adults in the general population revealed 1 person with PKU and 1 with persistent benign hyperphenylalaninemia; both had normal intelligence quotients. Of 1548 mothers of retarded children tested, none had hyperphenylalaninemia.     

Survey of gastroenteritis in children admitted to hospital in Newcastle upon Tyne in 1971-5.

In a survey of 674 children admitted to the main gastroenteritis unit in Newcastle upon Tyne from 1971 to 1975 there was a noticeable reduction in the incidence of severe dehydration and hypernatraemia, though there was no appreciable change in many characteristics of the patients. This period coincided locally (and nationally) with a determined effort on the part of health visitors and doctors to encourage mothers to breast-feed and to advise them to avoid giving concentrated milk feeds and ensure an adequate water intake during febrile illnesses. This may have contributed towards a reduction in the severity of the illness in children with gastroenteritis admitted to hospital. The overall mortality and the incidence of neurological complications in cases of hypernatraemia are low compared with previous reports.     

Health care cost of crusted scabies in Aboriginal communities in the Northern Territory,Australia

BackgroundCrusted scabies is a debilitating dermatological condition. Although still relatively rare in the urban areas of Australia, rates of crusted scabies in remote Aboriginal communities in the Northern Territory (NT) are reported to be among the highest in the world.ObjectiveTo estimate the health system costs associated with diagnosing, treating and managing crusted scabies.MethodsA disease pathway model was developed to identify the major phases of managing crusted scabies. In recognition of the higher resource use required to treat more severe cases, the pathway differentiates between crusted scabies severity grades. The disease pathway model was populated with data from a clinical audit of 42 crusted scabies patients diagnosed in the Top-End of Australia’s Northern Territory between July 1, 2016 and May 1, 2018. These data were combined with standard Australian unit costs to calculate the expected costs per patient over a 12-month period, as well as the overall population cost for treating crusted scabies.FindingsThe expected health care cost per patient diagnosed with crusted scabies is $35,418 Australian dollars (AUD) (95% CI: $27,000 to $43,800), resulting in an overall cost of $1,558,392AUD (95% CI: $1,188,000 to $1,927,200) for managing all patients diagnosed in the Northern Territory in a given year (2018). By far, the biggest component of the health care costs falls on the hospital system.DiscussionThis is the first cost-of-illness analysis for treating crusted scabies. Such analysis will be of value to policy makers and researchers by informing future evaluations of crusted scabies prevention programs and resource allocation decisions. Further research is needed on the wider costs of crusted scabies including non-financial impacts such as the loss in quality of life as well as the burden of care and loss of well-being for patients, families and communities.     

High Levels of Orexin A in the Brain of the Mouse Model for Phenylketonuria: Possible Role of Orexin A in Hyperactivity Seen in Children with PKU

Phenylketonuria (PKU) is a metabolic disorder caused by phenylalanine hydroxylase deficiency leading to increased levels of phenylalanine in the brain. Hyperactivity is reportedly induced by a high level of orexin A, and therefore orexin A content was studied in the PKU mice. Hypothalamus and brain stem had higher levels of orexin A compared to cerebrum and cerebellum both in wild type and PKU mice brains as observed by radioimmunoassay method. Interestingly, all these regions of the brain in PKU mouse showed a higher level of orexin A compared to the wild type. Heart and plasma also had higher levels of orexin A in PKU compared to the wild type. Immunohistochemical analysis revealed an increased number of orexin A–stained cells in the brain and heart of PKU mouse compared to the wild type. This is the first report of increased level of orexin in the PKU mouse brain. Hyperactivity is commonly observed in children with PKU; thus these findings suggest that orexin A is a contributing factor for the hyperactivity.     

Mobile orthoptic service for primary screening of visual disorder in young children.

A mobile orthoptic service was begun in 1976. General practitioners, clinic doctors, and health visitors referred 4544 preschool children to the service in 18 months. Of the children referred, no defect was detected in 3138 (69%), 927 (20%) were recalled for a second assessment within 12 months, and 479 (11%) were referred for treatment. Out of 261 who received treatment in Oxford, 24 (9%) received aftercare. Benefits of the service included a 25% decrease during 1976-7 in inappropriate referrals of preschool children to the specialist hospital. The chance of inappropriate referral was reduced by a factor of 30 if a child was referred to the mobile service instead of to the eye hospital. A prevention programme such as the mobile orthoptic service can improve the rate of detection of visual disorder in young children, while providing the support needed by primary-care doctors and nurses for visual screening of preschool children easily and cheaply.     

Cost analysis of the Kozak protocol as used in an Ontario hospital in the treatment of children with epidermolysis bullosa.

Conventional treatment of epidermolysis bullosa is often unsuccessful. The Kozak protocol is an alternative that has been given considerable public support in Ontario. The incremental cost of this treatment program at the Hospital for Sick Children, Toronto, was examined. The departments of nursing, pharmacy and food services each kept records of salaries and supply costs applicable to the care of nine patients with epidermolysis bullosa who were treated in the fiscal year 1982-83. The selected direct costs to the hospital were compared with the projected costs if these patients had been treated in Dr. Kozak''s clinic in West Germany or under the financial arrangements offered to Dr. Kozak by the Ontario minister of health. At a total incremental cost of +255.92 per patient-day, care at the Hospital for Sick Children may not currently be the least expensive means of offering the Kozak protocol to Ontario children. However, the major expense of the program, the nurses'' salaries, could be reduced if the patients'' parents were to assume many of the nursing tasks; this would make the hospital''s program the most cost-effective method of treating children with epidermolysis bullosa.     

Phenylketonuria: an inborn error of phenylalanine metabolism

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism resulting from deficiency of phenylalanine hydroxylase (PAH). Most forms of PKU and hyperphenylalaninaemia (HPA) are caused by mutations in the PAH gene on chromosome 12q23.2. Untreated PKU is associated with an abnormal phenotype which includes growth failure, poor skin pigmentation, microcephaly, seizures, global developmental delay and severe intellectual impairment. However, since the introduction of newborn screening programs and with early dietary intervention, children born with PKU can now expect to lead relatively normal lives. A better understanding of the biochemistry, genetics and molecular basis of PKU, as well as the need for improved treatment options, has led to the development of new therapeutic strategies.     

The Costs of Delivering Integrated HIV and Sexual Reproductive Health Services in Limited Resource Settings

Objective

To present evidence on the total costs and unit costs of delivering six integrated sexual reproductive health and HIV services in a high and medium HIV prevalence setting, in order to support policy makers and planners scaling up these essential services.

Design

A retrospective facility based costing study conducted in 40 non-government organization and public health facilities in Kenya and Swaziland.

Methods

Economic and financial costs were collected retrospectively for the year 2010/11, from each study site with an aim to estimate the cost per visit of six integrated HIV and SRH services. A full cost analysis using a combination of bottom-up and step-down costing methods was conducted from the health provider’s perspective. The main unit of analysis is the economic unit cost per visit for each service. Costs are converted to 2013 International dollars.

Results

The mean cost per visit for the HIV/SRH services ranged from $Int 14.23 (PNC visit) to $Int 74.21 (HIV treatment visit). We found considerable variation in the unit costs per visit across settings with family planning services exhibiting the least variation ($Int 6.71-52.24) and STI treatment and HIV treatment visits exhibiting the highest variation in unit cost ranging from ($Int 5.44-281.85) and ($Int 0.83-314.95), respectively. Unit costs of visits were driven by fixed costs while variability in visit costs across facilities was explained mainly by technology used and service maturity.

Conclusion

For all services, variability in unit costs and cost components suggest that potential exists to reduce costs through better use of both human and capital resources, despite the high proportion of expenditure on drugs and medical supplies. Further work is required to explore the key drivers of efficiency and interventions that may facilitate efficiency improvements.     

Long-chain polyunsaturated fatty acids profile in plasma phospholipids of hyperphenylalaninemic children on unrestricted diet

IntroductionThe aim of the present study was to examine whether hyperphenylalaninemic children on unrestricted diet (MHP) may exhibit a different LCPUFA profile from PKU or healthy children in plasma phospholipids.Patients and methodsForty-five MHP children (age 9–14 years) were age and sex matched with 45 PKU and 45 healthy children. Fatty acids were determined and expressed as % of total fatty acids.ResultsMHP children showed docosahexaenoic acid (DHA) levels higher than PKU children (mean difference, 0.2%; 95% confidence interval, 0.02%–0.38%), although difference was not significant after correction for multiple comparisons, and lower levels than healthy children (?0.8%; ?1.01% to ?0.59%). Concentration of n-3 PUFA was higher in MHP than PKU children (0.6%; 0.4% to 0.8%),ConclusionsThe results suggest that low DHA levels in plasma phospholipids not only are evident in PKU but also may occur in MHP children, who are on unrestricted diet, as compared to healthy children.     

Folk Phytotherapy in Paediatric Health Care in Central and Southern Italy: a Review

Complementary and alternative medicine (CAM) consists of systems and practices used to prevent or treat illness, and/or promote health and wellbeing, generally with herbal remedies. In recent decades, ethnobotanical and ethnopharmacological surveys have received increased attention among populations in central and southern Italy traditionally highly conservative regarding knowledge of folk medicine. This review highlights the use of wild and cultivated plants in paediatric health care. From a search of articles published between 1978 and 2017 we found a total of 34 containing reports of medicinal plants specifically used for treating children’s diseases, listing 83 taxa belonging to 37 families in 116 recorded cases of medicinal plant use. Tuscany has the highest number of plant use reports and the highest number of species used in a single region, followed by Campania and Sicily. Allium sativum is the most widely reported species, cited in eight regions. We identified eight ailment categories. Plants used as anthelmintics and for gastro-intestinal and skin diseases are widely used.     

PKU screening — Is it worth it?

Ontario''s program for PKU screening of newborn infants reached 94.5% of the newborn population from 1966 to 1971. There were 70 infants identified by the program, 47 of whom were classical cases and 23 atypical cases of phenylketonuria. The incidence was 1:16,700 live births for classical cases and 1:34,000 live births for atypical cases. Since the beginning of the program 44 children have been identified in infancy as having PKU and have been treated successfully. Retardation has become evident in only three infants, two of whom were missed by the screening program.The cost of identification and care of one child for five years is about $7000, much less than the $250,000 needed to provide lifetime institutional care for one severely retarded individual.     

Vision screening at 8 and 18 months. Steering Committee of Oxford Region Child Development Project.

OBJECTIVE--To determine the effectiveness of an existing screening programme based in the community for ocular and vision defects in infants considered at increased risk of such defects. DESIGN--Children with ocular or vision defect by the age of 2 were ascertained by searching records. Those from populations at high risk were matched with their results from screening tests. The characteristics of the cases among this population were compared with those of the cases in the remainder of the population. Patterns of referral and age at referral were studied in both groups. SETTING--The study was conducted within Oxfordshire Health District. SUBJECTS--433 Children at high risk born in 1984 to mothers living in the health district at delivery and who either weighed less than 2000 g or weighed 2000 g and over and required admission to a special care nursery for longer than 24 hours. The low risk population (6254) were infants without these characteristics who were resident in the health district at the time of referral. INTERVENTIONS--Screening tests for vision or ocular defects already routinely used were applied by health visitors at 8 and 18 months to the children at high risk. MAIN OUTCOME MEASURE--Comparison of results of screening tests with vision and ocular defects detected by the age of 2. RESULTS--Screening tests in current use for vision loss and squint in this age group were insensitive and had a low positive predictive value when applied to a high risk population. Defects that were not apparent on direct inspection were unlikely to be detected by these tests. In the high risk group the relative risk of having a defect was 2.8 (95% confidence interval 1.8 to 4.5) but 85% of all cases detected by the age of 2 were in children at low risk. Referral patterns and age of referral differed in the two groups. CONCLUSIONS--Screening by health visitors of high risk populations contributes little to the detection of vision and ocular defects. This type of evaluation needs to be applied also to low risk populations, who have different referral patterns and contribute most of the cases.     

Bereavement counselling after sudden infant death.

Of 14 families who suffered a sudden infant death, eight were followed up intensively over several months and offered individual counselling, parents'' group meetings, and interviews with doctors as a way of helping them come to terms with their feelings of loss. Five couples accepted short term support from their health visitor, and one refused help. Many families experienced considerable stress including marital conflict, difficulties with surviving children, and anxiety about future children becoming victims of the sudden infant death syndrome. It was concluded that medical social workers, health visitors, hospital paediatricians, general practitioners, and parent self help groups are in key positions to help. The success of such help is likely to depend on the confidence that each helper has that his or her contribution will be valued by the bereaved family.     

Visceral larva migrans (toxocariasis) in Toronto.

A 7-year-old child was admitted to Toronto''s Hospital for Sick Children in 1976 with symptoms and laboratory findings compatible with visceral larva migrans, a disease usually caused by Toxocara canis. This prompted a search for other cases seen at the hospital during the period 1952 through 1978. Only 18 cases were discovered that met at least three of six criteria and thus were considered possible or probably cases of the disease. Three possible cases of ocular toxocariasis during the same period were also uncovered. Fever was the commonest presenting symptom. Eosinophilia, leukocytosis and hyperglobulinemia were the most frequent laboratory findings. In view of the small number of cases found in 27 years at this large pediatric hospital with a broad referral base, it is concluded that visceral larva migrans poses little risk to the health of children in the Toronto area.     

The health of children in refuges for women victims of domestic violence: cross sectional descriptive survey

ObjectivesTo describe the health and developmental status of children living in refuges for women victims of domestic violence and to investigate their access to primary healthcare services.DesignCross sectional survey.SettingWomen''s refuges in Cardiff.Participants148 resident children aged under 16 years and their mothers.Results148/257 (58%) children living in refuges between April 1999 and January 2000 were assessed. Child health system data were incorrect (general practitioner and/or address) or unavailable for 85/148 (57%) children. Uptake of all assessments and immunisations was low. 13/68 (19%) children aged <5 years had delayed or questionable development on the Denver test, and 49/101 (49%) children aged 3-15 years had a Rutter score of >10 (indicating probable mental health problems). Concerns were expressed by mothers of 113/148 (76%) children. After leaving the refuge, 22 children were untraceable and 36 returned home to the perpetrator from whom the families had fled.ConclusionsThe children had a high level of need, as well as poor access to services. Time spent in a refuge provides a window of opportunity to review health and developmental status. Specialist health visitors could facilitate and provide support, liaison, and follow up.

What is already known on this topic

A pilot study showed poor uptake of immunisations and surveillance among children who live in refuges for women victims of domestic violenceQualitative studies suggest that these children are at risk of psychological ill health

What this study adds

Baseline health and demographic data show that children in refuges have a high level of unmet health need, particularly in relation to mental health difficultiesTheir families have poor access to health services     

The time has come: a new scene for PKU treatment

Phenylketonuria (PKU) is one of the few genetic diseases in which mental retardation can be prevented. Hence, diagnosis and treatment must be established early. PKU treatment consists of a phenylalanine-restricted diet supplemented with a phenylalanine-free mixture of amino acids. However, it is difficult to adhere to this diet. In the last decade, a better comprehension of the biochemistry, genetics and molecular basis of the disease, as well as the need for easier treatment, led to the development of several new therapeutic strategies for PKU. In the present study, we evaluated these new therapeutic options in terms of theoretical basis, methodologies, efficacy, and costs.     

Efficacy of pertussis vaccination in England. Report from the PHLS Epidemiological Research Laboratory and 21 area health authorities.

A national assessment of the efficacy of pertussis vaccination was made in 21 area health authorities in England. Notification rates for children given either three doses of diphtheria/tetanus/pertussis vaccine or diphtheria/tetanus vaccine were studied during the two and a half-year period January 1978-June 1980. A survey of home circumstances showed that the two vaccine groups could be validly compared. Home visits were made to assess the severity of the illness, the attack rates in home contacts, and to take pernasal swabs. Pertussis vaccination was found to be of outstanding value in preventing serious disease. Nevertheless, its effect in controlling whooping cough is limited by the fact that protection for home contacts is less satisfactory, and by the occurrence of mild cases in vaccinated children which may contribute to the spread of the disease.     

Measles immunisation: results of a local programme to increase vaccine uptake.

Investigations showed that the measles immunisation programme in our health board was a failure. Surveys of health care staff and parents to determine the cause of the problem identified several aspects of concern: the immunisation of children was often left to parental initiative, with only 29% of general practitioners playing an active part in recalling children by the 15th month of age; general practitioners, clinical medical officers, paediatricians, and health visitors all required education on several aspects of measles immunisation; parents also required more information about the importance of preventing this disease. A coordinated effort to remedy these problems was introduced which achieved an increase of 13% in vaccine uptake during 1984. These findings may have implications beyond our own area.     

Immunisation of children by a nurse without a doctor present.

Over 16 months 148 children were referred by health visitors and general practitioners to a specially trained nurse for failing to complete courses of immunisation. A further 91 children of travellers'' families were identified as needing immunisation. The nurse carried out 810 immunisations on 237 of these children in their homes without a doctor being present. There were only two refusals, and one child suffered a mild anaphylactic shock. The cost per immunisation, in nurse''s salary and travel expenses, was pounds 8. This is an effective and fairly inexpensive way of achieving uptake of immunisation in such groups of children, and there seems no reason why trained nurses should not give immunisations either in a child health clinic or at home, without a doctor present.     

Requirements for a minimum standard of care for phenylketonuria: the patients’ perspective

Phenylketonuria (PKU, ORPHA716) is an inherited disorder that affects about one in every 10,000 children born in Europe. Early and continuous application of a modified diet is largely successful in preventing the devastating brain damage associated with untreated PKU. The management of PKU is inconsistent: there are few national guidelines, and these tend to be incomplete and implemented sporadically. In this article, the first-ever pan- European patient/carer perspective on optimal PKU care, the European Society for Phenylketonuria and Allied Disorders (E.S.PKU) proposes recommendations for a minimum standard of care for PKU, to underpin the development of new pan-European guideline for the management of PKU. New standards of best practice should guarantee equal access to screening, treatment and monitoring throughout Europe. Screening protocols and interpretation of screening results should be standardised. Experienced Centres of Expertise are required, in line with current European Union policy, to guarantee a defined standard of multidisciplinary treatment and care for all medical and social aspects of PKU. Women of childbearing age require especially intensive management, due to the risk of severe risks to the foetus conferred by uncontrolled PKU. All aspects of treatment should be reimbursed to ensure uniform access across Europe to guideline-driven, evidence-based care. The E.S.PKU urges PKU healthcare professionals caring for people with PKU to take the lead in developing evidence based guidelines on PKU, while continuing to play an active role in serving as the voice of patients and their families, whose lives are affected by the condition.